PA Infectious Disease Bootcamp

Part 0 · Systematic ID Review

Systematic Infectious Disease Review — 35 Modules

The full organism-by-organism teaching pass, presented first. Worked in six blocks: sexually transmitted infections, tick-borne disease, opportunistic infections, high-yield comparison tables, screening and prevention, and a 30-point rapid-fire review. Each module runs etiology → presentation → diagnosis → management → board traps. Part 1 onward then drills the same material through pre-read vignettes and trap-focused topic cards.

Section I · Modules 1–11

Sexually Transmitted Infections

Eleven modules covering the bacterial, viral, and protozoal STIs, plus PID, HIV virology, and hepatitis B. CDC 2021 treatment guidelines throughout.

Tier 1

Module 1

Chlamydia (Chlamydia trachomatis)

Doxycycline First-Line 2021 · NAAT Gold Standard · Neonatal Timing · LGV Serovars

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Obligate intracellular bacterium. Serovars D–K cause urogenital disease; serovars L1–L3 cause lymphogranuloma venereum (LGV)
Most common reportable bacterial STI in the US
Infects columnar epithelium of cervix, urethra, rectum, and pharynx
Biphasic life cycle: elementary body (infectious, extracellular) → reticulate body (replicative, intracellular)

Clinical Presentation

The majority of infections are asymptomatic — this is why screening, not symptoms, drives detection
Women: mucopurulent cervicitis, urethritis, dysuria, abnormal discharge → may ascend to PID → tubal factor infertility, ectopic pregnancy
Men: urethritis (dysuria, clear-to-white discharge), epididymitis
Neonates: conjunctivitis at days 5–14; pneumonia at 1–3 months (afebrile, staccato cough)
Reactive arthritis (formerly Reiter): urethritis + conjunctivitis + arthritis — "can't see, can't pee, can't climb a tree"
LGV: painless genital ulcer → painful inguinal buboes; proctocolitis in MSM

Diagnosis

NAAT is the gold standard — sensitivity and specificity both >97%
Women: vaginal swab preferred (endocervical swab, first-catch urine, or liquid Pap acceptable)
Men: first-catch urine preferred
Extragenital: rectal and pharyngeal NAAT at sites of exposure
Test of cure for rectal chlamydia treated with azithromycin; retest all patients at 3 months for reinfection

Management

First-line: doxycycline 100 mg PO BID × 7 days (2021 CDC — replaced single-dose azithromycin)
Alternatives: azithromycin 1 g PO × 1 (no longer first-line); levofloxacin 500 mg PO daily × 7 days
Pregnancy: azithromycin 1 g PO × 1 — doxycycline is contraindicated. Test of cure 3–4 weeks after treatment
LGV: doxycycline 100 mg PO BID × 21 days
Expedited partner therapy: doxycycline × 7 days or azithromycin 1 g × 1
Reportable. Treat all sexual partners from the prior 60 days

⚑ Board Traps — Chlamydia

Doxycycline, not azithromycin, is first-line since 2021 — a stem offering single-dose azithromycin for uncomplicated genital chlamydia is testing the old guideline
Pregnancy flips the answer back to azithromycin — doxycycline is contraindicated
Neonatal conjunctivitis timing is the discriminator: days 2–5 = gonococcal; days 5–14 = chlamydial
Erythromycin eye ointment prophylaxis does NOT prevent chlamydial conjunctivitis — it only prevents gonococcal disease
LGV needs 21 days, not 7 — duration is the tested variable

★ Memory Trick

"Doxy for 7, Azithro if expecting" Neonatal eye timing: Gonorrhea comes early (days 2–5), Chlamydia comes late (days 5–14) — alphabetical order matches chronological order LGV = "Long Genital Verdict" — 21 days

Tier 1

Module 2

Gonorrhea (Neisseria gonorrhoeae)

Ceftriaxone 500 mg Monotherapy · Azithromycin Dropped · DGI Triad · Pharyngeal Test of Cure

★★★ PANCE PriorityCDC 2021

Etiology & Pathophysiology

Gram-negative intracellular diplococcus
Infects columnar and transitional epithelium: urethra, cervix, rectum, pharynx, conjunctiva
Pili and Opa proteins mediate attachment and immune evasion; antigenic variation permits repeat infection — there is no protective immunity

Clinical Presentation

Men: purulent urethral discharge and dysuria — symptomatic in roughly 90%
Women: asymptomatic in up to half; cervicitis, discharge, dysuria; may ascend to PID
Pharyngeal: usually asymptomatic — an important reservoir and the hardest site to eradicate
Rectal: proctitis with discharge, pain, tenesmus; often asymptomatic
Disseminated gonococcal infection (DGI): triad of polyarthralgia + tenosynovitis + dermatitis (painless pustular or vesiculopustular lesions); may progress to monoarticular septic arthritis
Neonates: ophthalmia neonatorum at days 2–5 — purulent conjunctivitis; prevented by erythromycin ointment

Diagnosis

NAAT preferred at all sites — urogenital, pharyngeal, rectal
Culture is required when susceptibility testing is needed — treatment failures and suspected resistance
Test of cure by NAAT at 7–14 days for ALL pharyngeal infections
Grows on Thayer-Martin (chocolate agar + antibiotics) or Martin-Lewis medium
Oxidase-positive; ferments glucose only — meningococcus ferments glucose and maltose

Management (2021 CDC)

First-line: ceftriaxone 500 mg IM × 1 (1 g if ≥150 kg) — monotherapy when chlamydia has been excluded
If chlamydia is not excluded, add doxycycline 100 mg PO BID × 7 days
Alternative (non-pharyngeal only): cefixime 800 mg PO × 1 — unreliable for pharyngeal disease
Cephalosporin allergy: gentamicin 240 mg IM + azithromycin 2 g PO
DGI: ceftriaxone 1 g IV/IM q24h; step down to oral after clinical improvement
Expedited partner therapy: cefixime 800 mg PO × 1

⚑ Board Traps — Gonorrhea

Azithromycin was REMOVED from dual therapy — ceftriaxone alone is now correct when chlamydia is excluded. Answer choices still offering "ceftriaxone + azithromycin" are testing the obsolete regimen
The dose doubled to 500 mg IM — 250 mg is the old answer
Cefixime does not clear the pharynx — if the site is pharyngeal, oral therapy is wrong
DGI dermatitis is painless — painful lesions point elsewhere
Fitz-Hugh-Curtis syndrome = perihepatitis from PID with violin-string adhesions — RUQ pain in a young woman with cervicitis is not cholecystitis

★ Memory Trick

"500 IM, once, alone" — the 2021 gonorrhea regimen in four words Gonococcus ferments Glucose only; Meningococcus adds Maltose DGI triad: joints, tendons, skin — and the skin lesions do not hurt

Tier 1

Module 3

Syphilis (Treponema pallidum)

Stage-Driven Dosing · Nontreponemal vs Treponemal · Neurosyphilis at Any Stage · Pregnancy = Penicillin Only

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Spirochete that cannot be cultured in vitro — diagnosis is always serologic or by direct visualization
Transmission: sexual contact, transplacental, rarely transfusion
Obliterative endarteritis is the hallmark pathology, affecting the vasa vasorum — this explains the aortitis of tertiary disease

The Four Stages

Stage	Timing	Key Features
Primary	10–90 days	Painless chancre — clean base, raised indurated border — at the inoculation site; painless regional lymphadenopathy
Secondary	4–10 weeks	Diffuse maculopapular rash including palms and soles; condylomata lata (moist, flat, gray-white); mucous patches; generalized lymphadenopathy; constitutional symptoms
Early latent	< 1 year	Positive serology, no clinical findings
Late latent	> 1 year	Positive serology, no clinical findings, or duration unknown
Tertiary	Years–decades	Gummas; cardiovascular syphilis (aortitis, ascending aortic aneurysm); neurosyphilis

Neurosyphilis is NOT confined to tertiary disease — it can occur at any stage, including primary.

Neurosyphilis, Ocular and Congenital Disease

Early neurosyphilis: meningitis, cranial nerve palsies (CN VII and VIII), ocular syphilis (uveitis, optic neuritis), otosyphilis
Late neurosyphilis: tabes dorsalis (posterior column degeneration → lightning pains, Charcot joints, Argyll Robertson pupils) and general paresis (dementia, personality change)
Argyll Robertson pupil accommodates but does not react to light — small, irregular, bilateral
Congenital, early (<2 years): rhinitis ("snuffles"), hepatosplenomegaly, rash, osteochondritis
Congenital, late (>2 years): Hutchinson teeth, mulberry molars, interstitial keratitis, saddle nose, saber shins

Diagnosis

Traditional algorithm: nontreponemal test (RPR or VDRL) → confirm with treponemal test (FTA-ABS or TP-PA)
Reverse algorithm: treponemal EIA/CIA → confirm with nontreponemal → if discordant, TP-PA
Nontreponemal tests are quantitative and used to monitor treatment — a 4-fold decline in titer is the response criterion
Treponemal tests stay positive for life and can never be used to judge cure
Darkfield microscopy of chancre exudate — not valid on oral or rectal lesions (commensal spirochetes)
Neurosyphilis: CSF VDRL is specific but insensitive; look also for CSF pleocytosis and elevated protein
False-positive nontreponemal tests: SLE, antiphospholipid syndrome, pregnancy, IV drug use, viral illness

Management

Primary, secondary, early latent: benzathine penicillin G 2.4 million units IM × 1
Late latent or tertiary (non-neuro): benzathine penicillin G 2.4 million units IM weekly × 3
Neurosyphilis, ocular, or otic: aqueous crystalline penicillin G 3–4 million units IV q4h × 10–14 days
Penicillin allergy, not pregnant: doxycycline 100 mg PO BID × 14 days (early) or × 28 days (late)
Pregnancy: penicillin is the ONLY acceptable treatment — desensitize if allergic
Jarisch-Herxheimer reaction: fever, myalgia, headache within 24 hours of the first dose — expected endotoxin release, self-limited, not an allergy and not a reason to stop

⚑ Board Traps — Syphilis

Treponemal titers cannot monitor cure — if a stem asks how to follow response, the answer is RPR or VDRL
Pregnancy plus penicillin allergy = desensitization, never doxycycline (teratogenic) and never azithromycin (resistance and treatment failures)
Ocular or otic syphilis is treated as neurosyphilis — IV penicillin, not IM
Jarisch-Herxheimer is mistaken for anaphylaxis in the classic distractor. It occurs hours later, involves fever and rigors, and treatment continues
A negative darkfield from an oral lesion proves nothing — oral commensal spirochetes make the test invalid there

★ Memory Trick

Benzathine is for Benign stages (primary, secondary, latent, tertiary non-neuro). Aqueous penicillin goes where water goes — into the CSF "1 shot, 3 shots, 14 days" = early → late latent → neuro Lata is flat (syphilis); acuminata is aloft (HPV)

Tier 1

Module 4

Genital Herpes (HSV-1 and HSV-2)

PCR over Tzanck · Episodic vs Suppressive · Sacral Latency · 36-Week Prophylaxis

★★★ PANCE Priority

Etiology & Pathophysiology

HSV-2 remains the most common cause of genital herpes; HSV-1 is increasingly implicated, especially in younger patients
Double-stranded DNA virus establishing latency in the sacral (S2–S4) dorsal root ganglia
Reactivation triggers: stress, immunosuppression, UV exposure, menses

Clinical Presentation

Primary outbreak is the most severe: grouped vesicles on an erythematous base → painful shallow ulcers; bilateral tender inguinal lymphadenopathy; fever, malaise, myalgia
Recurrences are milder, shorter, and unilateral, with a prodrome of tingling or burning
Roughly 70% of infections are asymptomatic — most transmission occurs from unrecognized shedding
Complications: aseptic meningitis (Mollaret meningitis with recurrence), urinary retention, sacral radiculopathy
Neonatal herpes: acquired at delivery — skin-eye-mouth disease, CNS disease, or disseminated (highest mortality)
Variants: herpes gladiatorum (wrestlers), herpetic whitlow (finger), eczema herpeticum (atopic dermatitis)

Diagnosis

Active lesions: PCR of vesicle fluid is preferred (viral culture acceptable but less sensitive)
No lesions: glycoprotein G–based type-specific IgG serology distinguishes HSV-1 from HSV-2
USPSTF recommends AGAINST screening asymptomatic adolescents and adults
Tzanck smear shows multinucleated giant cells — fast, insensitive, and cannot distinguish HSV from VZV

Management

There is no cure — antivirals shorten episodes and reduce transmission
First episode: valacyclovir 1 g PO BID × 7–10 days, or acyclovir 400 mg PO TID × 7–10 days
Recurrence: valacyclovir 500 mg PO BID × 3 days, or 1 g PO daily × 5 days
Suppression (≥6 outbreaks/year): valacyclovir 500 mg–1 g PO daily — reduces transmission to partners by roughly half
Severe or immunocompromised: acyclovir 5–10 mg/kg IV q8h
Pregnancy: suppressive acyclovir or valacyclovir from 36 weeks; cesarean delivery if active lesions or prodrome at labor

⚑ Board Traps — HSV

Do not order serology to diagnose an active ulcer — PCR of the lesion is the answer
Tzanck cannot separate HSV from VZV — if the question hinges on which virus, it must be PCR
Suppression starts at 36 weeks, not at diagnosis, and cesarean is driven by lesions at delivery, not by history
Recurrent erythema multiforme is most often HSV-driven — treat the herpes, not the rash
HSV encephalitis is usually HSV-1 and targets the temporal lobe — a different disease from genital HSV-2

★ Memory Trick

Sacral ganglia for the south end; trigeminal for the face "36 and fix" — suppressive therapy at 36 weeks Primary = bilateral nodes and big symptoms; recurrence = unilateral and underwhelming

Tier 1

Module 5

Human Papillomavirus (HPV)

E6/E7 Oncogenesis · Koilocytes · Gardasil 9 Schedules · Warts vs Dysplasia

★★★ PANCE Priority

Etiology & Pathophysiology

Double-stranded DNA virus; more than 200 types
Low-risk types 6 and 11: anogenital warts (condylomata acuminata), recurrent respiratory papillomatosis
High-risk types 16, 18, 31, 33, 45: cervical, anal, oropharyngeal, vulvar, vaginal, and penile cancer
E6 degrades p53; E7 inactivates Rb → loss of both major tumor suppressor pathways → unchecked proliferation
Most infections clear spontaneously within 1–2 years

Clinical Presentation

Condylomata acuminata: flesh-colored, cauliflower-like papules and plaques on anogenital surfaces
Cervical dysplasia: detected on cytology — koilocytes show a perinuclear halo with nuclear enlargement
Laryngeal papillomatosis: hoarseness in a child, acquired at vaginal delivery from types 6 or 11

Diagnosis

Typical warts are a visual diagnosis — no biopsy needed
Cervical screening: cytology with HPV co-testing, or primary HPV testing
Biopsy if atypical, pigmented, fixed, ulcerated, or unresponsive to treatment
Acetowhite test: acetic acid turns affected epithelium white

Management

Patient-applied: imiquimod 5% cream; podofilox 0.5% solution
Provider-applied: cryotherapy, trichloroacetic acid 80–90%, surgical excision, electrocautery
Cervical dysplasia: LEEP, cone biopsy, or ablation depending on grade
Gardasil 9 covers types 6, 11, 16, 18, 31, 33, 45, 52, 58
Routine vaccination at age 11–12 (may start at 9); catch-up through 26; shared decision-making 27–45
2-dose schedule if the series starts before age 15; 3-dose if 15 or older or immunocompromised
Digital anorectal exam is recommended for anal cancer screening in persons with HIV

⚑ Board Traps — HPV

Treating warts does not treat HPV infection or reduce cancer risk — and vaccination is not therapeutic for existing lesions
Dose count depends on age at first dose, not on total age — under 15 gets two doses
Condylomata acuminata (HPV, raised and cauliflower) vs condylomata lata (syphilis, flat and moist) is a recurring single-best-answer pair
Vaccination does not replace cervical screening — screening continues on schedule
E6 → p53 and E7 → Rb is asked directly; do not transpose them

★ Memory Trick

E6 → p53 (6 and 53 both have the "5-3" pairing to memorize together); E7 → Rb — "7 wrecks the Retinoblastoma brake" 6 and 11 are the warts; 16 and 18 are the malignancies "Under 15, two shots; 15 and up, three"

Tier 1

Module 6

Trichomoniasis (Trichomonas vaginalis)

Only Protozoal STI · NAAT over Wet Mount · 7 Days in Women · Safe in Pregnancy

★★ PANCE PriorityCDC 2021

Etiology & Pathophysiology

Flagellated protozoan — the most common non-viral STI worldwide and the only protozoal STI
Infects squamous epithelium of vagina, urethra, and Skene glands
No cyst form — cannot survive in the environment, so transmission requires direct contact

Clinical Presentation

Women: malodorous frothy yellow-green discharge, vulvovaginal pruritus and irritation, strawberry cervix (punctate hemorrhages), pH >4.5
Men: usually asymptomatic; occasionally urethritis or prostatitis
Roughly 70% are asymptomatic
Associated with increased HIV transmission, preterm birth, and low birth weight

Diagnosis

NAAT has the highest sensitivity and is preferred
Wet mount shows motile trichomonads but is only 50–60% sensitive — a negative wet mount does not exclude infection
Point-of-care rapid antigen testing is available
Culture (InPouch) was the historical gold standard, now superseded by NAAT

Management (2021 CDC)

Women: metronidazole 500 mg PO BID × 7 days — superior to single-dose therapy in women
Men: metronidazole 2 g PO × 1
Pregnancy: metronidazole 500 mg PO BID × 7 days — safe in all trimesters
Allergy or resistance: tinidazole 2 g PO × 1
Avoid alcohol during therapy and for 72 hours after — disulfiram-like reaction
Retest at 3 months given high reinfection rates

⚑ Board Traps — Trichomoniasis

The dose differs by sex — 7 days for women, single 2 g dose for men. This changed in 2021 and is heavily tested
Metronidazole is safe in pregnancy — the old teratogenicity concern is a distractor
A negative wet mount does not rule out trichomoniasis; order NAAT
Strawberry cervix is pathognomonic but seen in only about 2% — its absence means nothing
Partners are treated, unlike bacterial vaginosis

★ Memory Trick

"Women get a week, men get a wallop" — 7 days vs 2 g once Frothy and flagellated and from a partner

Tier 1

Module 7

Bacterial Vaginosis

Amsel Criteria · Clue Cells · No Inflammation · No Partner Treatment

★★★ PANCE Priority

Etiology & Pathophysiology

Polymicrobial dysbiosis — loss of protective Lactobacillus with overgrowth of Gardnerella vaginalis, Atopobium, Mobiluncus, Prevotella, Mycoplasma hominis
Not classically an STI, but strongly associated with sexual activity
Increases acquisition of STIs including HIV

Clinical Presentation

Thin, gray-white, homogeneous discharge with a fishy odor, worse after intercourse
Vulvar irritation is uncommon — this absence of inflammation is what separates BV from candidiasis and trichomoniasis
Frequently asymptomatic

Diagnosis — Amsel Criteria (3 of 4)

Thin, homogeneous gray-white discharge
Vaginal pH >4.5
Positive whiff test — fishy amine odor on addition of KOH
Clue cells on wet mount — epithelial cells studded with adherent bacteria
Nugent score (Gram stain) is the research gold standard

Management

First-line: metronidazole 500 mg PO BID × 7 days, or metronidazole 0.75% vaginal gel × 5 days
Alternative: clindamycin 300 mg PO BID × 7 days, or clindamycin 2% cream × 7 days
Pregnancy: treat symptomatic disease with oral metronidazole; do not screen asymptomatic pregnant patients
Recurrence: consider suppressive metronidazole gel twice weekly for 4–6 months
Partner treatment is not routinely recommended

⚑ Board Traps — Bacterial Vaginosis

No vulvar inflammation — itching and erythema push you toward Candida or Trichomonas instead
pH is the fastest discriminator: BV and Trichomonas run >4.5; Candida stays <4.5
Do not treat the partner — this is the opposite of trichomoniasis
Clue cells, not clue symptoms — three of four Amsel criteria are required
Asymptomatic pregnant patients are not screened, though symptomatic ones are treated

★ Memory Trick

Clue cells solve the clue-less discharge Whiff = fish BV is a dysbiosis, not an infection of a partner — so no partner therapy

Tier 1

Module 8

Pelvic Inflammatory Disease (PID)

Minimum Clinical Criteria · Metronidazole Added 2021 · Keep the IUD · Fitz-Hugh-Curtis

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Ascending polymicrobial infection from cervix and vagina to endometrium, tubes, ovaries, and peritoneum
Most often N. gonorrhoeae and C. trachomatis; also anaerobes, group B streptococcus, enteric Gram-negatives, and M. genitalium
The leading preventable cause of infertility and ectopic pregnancy

Clinical Presentation

Lower abdominal or pelvic pain, abnormal discharge, abnormal uterine bleeding, dyspareunia
Cervical motion tenderness (chandelier sign), uterine tenderness, adnexal tenderness
Fever is present in only a minority — its absence does not exclude PID
Complications: tubo-ovarian abscess, Fitz-Hugh-Curtis perihepatitis (violin-string adhesions), chronic pelvic pain, ectopic pregnancy, infertility

Diagnosis

Clinical diagnosis. Minimum criteria: pelvic or lower abdominal pain PLUS cervical motion, uterine, or adnexal tenderness
Supportive: temperature >38.3°C, mucopurulent cervical discharge, abundant WBCs on wet mount, elevated ESR or CRP, positive NAAT for gonorrhea or chlamydia
Laparoscopy is the gold standard but is not used routinely
Transvaginal ultrasound if tubo-ovarian abscess is suspected

Management (2021 CDC)

Outpatient: ceftriaxone 500 mg IM × 1 + doxycycline 100 mg PO BID × 14 days + metronidazole 500 mg PO BID × 14 days
Inpatient indications: tubo-ovarian abscess, pregnancy, surgical emergency not excluded, failure of oral therapy, inability to tolerate oral intake
Inpatient: cefotetan 2 g IV q12h + doxycycline, or cefoxitin 2 g IV q6h + doxycycline
Transition to oral therapy after 24–48 hours of clinical improvement
An IUD does NOT need to be removed — it may stay in place with close follow-up

⚑ Board Traps — PID

Metronidazole is now routinely included (2021) — regimens without anaerobic coverage are the old answer
Do not remove the IUD — this is the single most commonly missed management point
Treat on minimum criteria alone. Waiting for fever, leukocytosis, or NAAT results costs fertility
RUQ pain in a young woman with cervicitis is Fitz-Hugh-Curtis, not biliary disease
A negative pelvic ultrasound does not exclude PID — imaging is for abscess, not for diagnosis

★ Memory Trick

"Ceftriaxone + Doxy + Metro" — the 2021 outpatient triple Chandelier sign: the pain makes her reach for the ceiling Low threshold, high stakes — overtreating costs a course of doxycycline; undertreating costs a fallopian tube

Tier 1

Module 9

HIV / AIDS — Virology, Diagnosis and ART

4th-Generation Testing · Acute Retroviral Syndrome · ART for All · PrEP and PEP

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

HIV-1 (most common) and HIV-2 — retroviruses carrying reverse transcriptase
Targets CD4+ T lymphocytes, macrophages, and dendritic cells via gp120 binding to CD4 plus a coreceptor (CCR5 or CXCR4)
Progressive CD4 depletion → immunodeficiency → opportunistic infection and malignancy
AIDS is defined by CD4 <200 cells/mm³ OR the presence of an AIDS-defining illness — either one is sufficient

Clinical Presentation

Acute retroviral syndrome (2–4 weeks post-exposure): a mononucleosis-like illness — fever, pharyngitis, lymphadenopathy, maculopapular rash, myalgia, oral ulcers
Clinical latency lasting years with progressive CD4 decline
AIDS-defining illnesses: PCP, cerebral toxoplasmosis, CMV retinitis, Kaposi sarcoma, primary CNS lymphoma, disseminated MAC, cryptococcal meningitis, esophageal candidiasis, PML

Diagnosis

Screening: 4th-generation antigen/antibody combination immunoassay detecting HIV-1/2 antibody plus p24 antigen. Screen everyone aged 15–65 at least once
Confirmation: HIV-1/HIV-2 differentiation immunoassay
Suspected acute HIV: order HIV RNA viral load — p24 antigen and RNA are detectable before antibodies appear
CD4 count and viral load are used for staging and monitoring, not for diagnosis

Management

ART for every person with HIV regardless of CD4 count, started as soon as possible
Preferred initial regimens are INSTI-based: bictegravir/emtricitabine/tenofovir alafenamide, or dolutegravir-based combinations
PrEP: emtricitabine/tenofovir DF or emtricitabine/tenofovir alafenamide daily PO; cabotegravir IM every 2 months
PEP: start within 72 hours — a 28-day three-drug course
Opportunistic infection prophylaxis is CD4-driven — see Module 30

⚑ Board Traps — HIV

Suspected acute HIV requires an RNA viral load, not a repeat antibody test — the antibody window is why the 4th-generation assay includes p24
Monospot-negative mononucleosis should trigger HIV testing along with CMV and Toxoplasma
ART is started regardless of CD4 — there is no longer a threshold to wait for
Esophageal candidiasis is AIDS-defining at any CD4 count; oropharyngeal thrush alone is not
PEP has a 72-hour window and runs 28 days — both numbers are tested

★ Memory Trick

gp120 grabs CD4; the coreceptor decides the door (CCR5 early, CXCR4 late) 4th generation catches 4 things: HIV-1 Ab, HIV-2 Ab, and p24 antigen — which is why it closes the window to about 2 weeks Treat everyone, test everyone once

Tier 1

Module 10

Hepatitis B (HBV)

Serologic Patterns · Window Period · Immune-Mediated Injury · Universal Adult Screening

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Partially double-stranded DNA virus (Hepadnavirus) — the only DNA virus among the hepatitis viruses
Transmitted sexually, parenterally, and perinatally
Hepatocyte injury is immune-mediated, not directly cytopathic — which is why immunosuppressed patients have less inflammation but more virus
May progress to chronic hepatitis → cirrhosis → hepatocellular carcinoma

Clinical Presentation

Acute: often asymptomatic; prodrome of fatigue, anorexia, and nausea → jaundice, RUQ pain, hepatomegaly
Chronic (HBsAg positive >6 months): usually silent until complications appear
Extrahepatic: polyarteritis nodosa, membranous nephropathy, serum sickness–like syndrome

Serologic Markers — What Each One Means

Marker	Interpretation
HBsAg	Active infection — acute or chronic
Anti-HBs	Immunity — from vaccine or from recovery
Anti-HBc IgM	Acute infection — the only marker positive in the window period
Anti-HBc IgG	Past or chronic infection — never produced by vaccination
HBeAg	High replication and high infectivity
Anti-HBe	Lower replication and lower infectivity
HBV DNA	Quantitative viral load — guides treatment

Window period: HBsAg negative, anti-HBs negative, anti-HBc IgM POSITIVE. Vaccinated: anti-HBs only. Recovered: anti-HBs plus anti-HBc IgG.

Management

Acute: supportive care — more than 95% of infected adults clear spontaneously
Chronic: tenofovir or entecavir are the first-line nucleos(t)ide analogs; pegylated interferon-alfa is an alternative
Vaccination: recombinant HBsAg vaccine, 3-dose series or 2-dose Heplisav-B; check post-vaccination titers in high-risk groups
Screen all adults at least once (2023 CDC), plus all pregnant patients at the first prenatal visit, persons with HIV, people who inject drugs, and MSM

⚑ Board Traps — Hepatitis B

Anti-HBc IgG distinguishes natural infection from vaccination — vaccine gives anti-HBs alone
The window period is diagnosed by anti-HBc IgM when both surface markers are negative
HBV is the classic cause of polyarteritis nodosa
Perinatal infection becomes chronic in about 90% of neonates versus about 5% of adults — the age-dependent inversion is the tested point
Immune-mediated damage explains why ALT rises as the immune system attacks, not as the virus replicates

★ Memory Trick

s for safe (anti-HBs = immunity); c for caught it (anti-HBc = real infection) e for extremely infectious (HBeAg) Window = only the core IgM is home

Tier 2

Module 11

Additional High-Yield STIs

M. genitalium · Chancroid · Granuloma Inguinale · Molluscum Contagiosum

★★ PANCE Priority

Mycoplasma genitalium

The smallest free-living bacterium and it lacks a cell wall — therefore intrinsically resistant to all beta-lactams
Causes persistent or recurrent urethritis and cervicitis; a probable contributor to PID
Test by NAAT only in symptomatic patients with persistent urethritis or cervicitis
Macrolide-sensitive: doxycycline × 7 days → azithromycin 1 g day 1, then 500 mg daily days 2–4
Macrolide-resistant or resistance unknown: doxycycline × 7 days → moxifloxacin 400 mg daily × 7 days

Chancroid (Haemophilus ducreyi)

Painful genital ulcer with ragged, undermined borders plus painful inguinal buboes
Diagnosis is clinical; culture requires special media and has low sensitivity; PCR where available
Treatment: azithromycin 1 g PO × 1, or ceftriaxone 250 mg IM × 1

Granuloma Inguinale / Donovanosis (Klebsiella granulomatis)

Painless, slowly progressive, beefy-red highly vascular ulcers that bleed easily
Donovan bodies — intracytoplasmic inclusions within macrophages on biopsy — are pathognomonic
Regional swelling is from pseudobuboes (subcutaneous granulation), not true lymphadenopathy
Treatment: azithromycin 1 g PO weekly or 500 mg PO daily for at least 3 weeks, continued until fully healed

Molluscum Contagiosum

Poxvirus producing firm, dome-shaped, umbilicated papules with a central dimple
Clinical diagnosis; histology shows Henderson-Patterson (molluscum) bodies
Self-limited in immunocompetent patients; cryotherapy or curettage if treatment is desired
Widespread or giant lesions signal advanced immunosuppression — in an adult with HIV this warrants CD4 assessment, and the differential includes disseminated Cryptococcus

⚑ Board Traps — The Other Genital Ulcers

Painful ulcer plus painful nodes = chancroid. Painless ulcer plus painless nodes = syphilis. This pairing is the single highest-yield discriminator
LGV is the exception that breaks the pattern: painless ulcer with painful buboes
Beta-lactams cannot treat M. genitalium — no cell wall means no target
Pseudobuboes are not lymph nodes — granuloma inguinale spares the nodes
Umbilicated papules in advanced HIV are not automatically molluscum — disseminated cryptococcosis looks identical and is lethal

★ Memory Trick

Ducreyi is dubious and painful; pallidum is placid and painless Donovan bodies for Donovanosis No wall → no beta-lactam (Mycoplasma)

Section II · Modules 12–16

Tick-Borne Diseases

Five modules organized by vector and region. The two diseases that do NOT respond to doxycycline are flagged explicitly — that single distinction accounts for most missed questions in this block.

Tier 1

Module 12

Lyme Disease (Borrelia burgdorferi)

EM Needs No Serology · Bilateral CN VII · PR Prolongation and AV Block · 36-Hour Rule · Coinfections

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Spirochete transmitted by Ixodes scapularis (deer tick / black-legged tick)
Endemic in the Northeast and upper Midwest, plus Europe and Asia
The tick must be attached 36–48 hours to transmit — this single fact drives the prophylaxis decision
The most common tick-borne disease in the United States

Clinical Presentation by Stage

Early localized (days to weeks): erythema migrans — expanding annular lesion with central clearing ("bull's-eye"); present in 70–80%; favors groin, axilla, and popliteal fossa
Early disseminated (weeks to months): multiple EM lesions; facial nerve palsy, classically bilateral; Lyme carditis with AV block ranging from first-degree to complete heart block; meningitis; radiculopathy
Late disseminated (months to years): migratory oligoarthritis of large joints, especially the knee; encephalopathy; peripheral neuropathy

Diagnosis

Erythema migrans in an endemic area is a clinical diagnosis — do NOT order serology. Antibodies have not developed yet, so a negative test is falsely reassuring
All other stages: two-tier serologic testing — step 1 ELISA (sensitive), step 2 Western blot (IgM early, IgG late) or a second ELISA
Neuroborreliosis CSF: lymphocytic pleocytosis, elevated protein, intrathecal antibody production
Do not test the tick the patient brings in

Management

Early localized or early disseminated without neurologic or cardiac involvement: doxycycline 100 mg PO BID × 10–21 days — preferred because it also covers Anaplasma co-infection
Alternatives: amoxicillin 500 mg PO TID or cefuroxime 500 mg PO BID × 14–21 days
High-degree AV block or neuroborreliosis: ceftriaxone 2 g IV daily × 14–28 days
Lyme arthritis: oral doxycycline or amoxicillin × 28 days; ceftriaxone IV if refractory
Prophylaxis — single dose doxycycline 200 mg only if ALL four are met: Ixodes tick, attached ≥36 hours, within 72 hours of removal, endemic area

⚑ Board Traps — Lyme Disease

Ordering serology for erythema migrans is the classic wrong answer — treat on sight in an endemic area
Bilateral facial nerve palsy in summer is Lyme until proven otherwise
Post-treatment serology stays positive — it is not a test of cure and a positive titer does not mean active infection
"Chronic Lyme disease" treated with prolonged antibiotics is not evidence-based — prolonged IV therapy causes real harm
Prophylaxis requires all four criteria. A tick attached 12 hours does not qualify, and neither does an unidentified tick

★ Memory Trick

Doxy covers two ticks at once — Lyme and Anaplasma ride the same Ixodes 36 hours to transmit, 72 hours to prevent Heart block or brain → go IV (ceftriaxone)

Stage Details, Prophylaxis and Prevention

Erythema migrans size: the lesion must reach ≥5 cm to meet the surveillance definition — a small red papule at the bite site within 24–48 hours is a hypersensitivity reaction, not EM
Lyme carditis: PR prolongation is the cardiac hallmark, progressing through first-, second-, and third-degree block. Third-degree block needs temporary pacing plus IV ceftriaxone — and it resolves completely with treatment, so a permanent pacemaker is not indicated
Doxycycline is contraindicated in pregnancy and in children under 8 — use amoxicillin 500 mg TID instead. Cefuroxime 500 mg BID is the second alternative
Post-treatment Lyme disease syndrome: fatigue, arthralgia, and cognitive complaints persisting beyond 6 months after adequate therapy. Serology stays positive for years — this is not ongoing infection, and extended antibiotics do not help
Antibiotic-refractory Lyme arthritis: a swollen knee that persists after a full oral course plus IV ceftriaxone is immune-mediated, not persistent infection. Manage with NSAIDs, intra-articular steroids, or a DMARD such as hydroxychloroquine or methotrexate — not more antibiotics
Prevention: DEET repellent, permethrin-treated clothing, daily tick checks, and prompt removal — the 36-hour transmission window is what makes daily checks effective

Common Coinfections (Same Ixodes Tick)

Babesiosis: Hemolytic anemia; "Maltese cross" (tetrad) on blood smear; treat with atovaquone + azithromycin
Anaplasmosis (HGA): Fever, leukopenia, thrombocytopenia, elevated LFTs; treat with doxycycline
Ehrlichiosis (HME): Similar to anaplasmosis; treat with doxycycline

Tier 1

Module 13

Rocky Mountain Spotted Fever (Rickettsia rickettsii)

Centripetal Rash · Treat Before Confirming · Doxycycline at Every Age · Spotless Variant

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Obligate intracellular bacterium transmitted by Dermacentor variabilis (dog tick) and D. andersoni (wood tick)
Tropism for vascular endothelium → vasculitis → increased permeability → petechiae, edema, and end-organ damage
The most lethal tick-borne disease in the United States
Despite the name, most cases occur in the southeastern and south-central US — North Carolina, Oklahoma, Arkansas, Tennessee, Missouri

Clinical Presentation

Classic triad: fever, headache, rash
Rash appears day 3–5, starting on wrists, forearms, and ankles, then spreading centrally to the trunk; macular → petechial → may become purpuric
Progression to DIC, shock, renal failure, encephalitis, and pulmonary edema
"Rocky Mountain spotless fever" — the rash is absent early in many patients and never appears in about 10%. Waiting for it is fatal

Diagnosis

Clinical suspicion is the diagnosis. Treat empirically.
Serology by indirect immunofluorescence is the confirmatory gold standard, but antibodies do not appear until week 2 — too late to guide therapy
Skin biopsy of a petechial lesion with immunofluorescence can confirm early
Supporting labs: thrombocytopenia, hyponatremia, elevated transaminases

Management

Doxycycline 100 mg PO or IV BID — the treatment of choice at ALL ages, including young children and pregnant patients
Duration: minimum 3 days after defervescence, typically 7–14 days total
Do NOT wait for confirmatory serology. Empiric treatment drops mortality from 20–25% to under 5%
Chloramphenicol is the historical alternative but performs worse and carries marrow toxicity

⚑ Board Traps — RMSF

Withholding doxycycline from a child is the most dangerous distractor on this topic. Short courses do not stain teeth, and RMSF kills
The rash moves centripetally — inward from wrists and ankles to the trunk — the opposite direction of most exanthems
Do not delay treatment for serology; antibodies lag the illness by two weeks
Absence of rash does not exclude RMSF
Hyponatremia plus thrombocytopenia plus fever after outdoor exposure is the lab triad that should trigger empiric therapy

★ Memory Trick

Centripetal = toward the center: wrists and ankles first, trunk second Treat first, confirm later — the only tick-borne disease where hesitation is measured in mortality Rocky Mountain is a misnomer — think Carolina, not Colorado

Tier 2

Module 14

Ehrlichiosis and Anaplasmosis

Morulae in Monocytes vs Granulocytes · Same Labs · Doxycycline for Both

★★ PANCE Priority

The Two Diseases Side by Side

Feature	Ehrlichiosis	Anaplasmosis
Organism	Ehrlichia chaffeensis	Anaplasma phagocytophilum
Vector	Lone Star tick (Amblyomma americanum)	*Ixodes scapularis* — the same tick as Lyme
Region	Southeastern, south-central, mid-Atlantic	Northeastern and upper Midwest
Target cell	Monocytes	Granulocytes / neutrophils
Rash	Up to 30%, more common in children	Rare
Co-infection	Uncommon	Lyme and babesiosis — shared Ixodes vector
Treatment	Doxycycline 100 mg PO BID	Doxycycline 100 mg PO BID

Clinical Presentation

Fever, headache, myalgia, and malaise — a nonspecific febrile illness after outdoor exposure
The lab signature is shared: leukopenia + thrombocytopenia + elevated transaminases
Anaplasmosis is rash-rare; if a rash is present with anaplasmosis, suspect concurrent Lyme

Diagnosis

Peripheral smear for morulae — mulberry-like intracytoplasmic inclusions; monocytes in ehrlichiosis, granulocytes in anaplasmosis
PCR is the most sensitive acute test
Serology by IFA confirms retrospectively with paired titers
Smear sensitivity is low — a negative smear does not exclude either disease

Management

Doxycycline 100 mg PO BID for both, continued at least 3 days after fever resolves
Treat empirically on clinical suspicion — the same principle as RMSF
Rifampin is the alternative in true doxycycline intolerance or pregnancy for anaplasmosis

⚑ Board Traps — Ehrlichia and Anaplasma

The cell type is the whole question. Monocytes point to Ehrlichia; granulocytes point to Anaplasma
Fever with leukopenia and thrombocytopenia after a tick bite is not viral — this triad should prompt doxycycline
Anaplasmosis shares the Lyme tick, so a patient with erythema migrans plus cytopenias may have both
A rash argues against anaplasmosis and toward RMSF, ehrlichiosis, or concurrent Lyme

★ Memory Trick

Ehrlichia → Monocytes ("Ehrlichia Meets Monos") Anaplasma → grAnulocytes — the A carries through Same tick as Lyme → same drug as Lyme (doxycycline)

Tier 2

Module 15

Babesiosis (Babesia microti)

Maltese Cross · Hemolytic Anemia · Asplenia Risk · Not Doxycycline

★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Intraerythrocytic protozoan transmitted by Ixodes scapularis
Also transmitted by blood transfusion — the most common transfusion-transmitted parasitic infection in the US
Endemic in the Northeast and upper Midwest
Severe disease in asplenic, elderly, and immunocompromised patients — the spleen is the primary clearance organ

Clinical Presentation

Mild: flu-like illness with fever, fatigue, myalgia, and chills
Severe: hemolytic anemia — jaundice, dark urine, elevated LDH and indirect bilirubin, low haptoglobin — plus hepatosplenomegaly, ARDS, and renal failure
Rash is uncommon. If a rash is present, look for Lyme co-infection

Diagnosis

Peripheral smear: intraerythrocytic ring forms and the pathognomonic "Maltese cross" tetrad — this is what separates Babesia from Plasmodium
PCR is highly sensitive and useful at low parasitemia
Serology by IFA for B. microti may miss other species
Quantify percent parasitemia — it drives the treatment decision

Management

Mild to moderate: atovaquone 750 mg PO BID + azithromycin 500–1000 mg on day 1, then 250 mg daily × 7–10 days
Severe (parasitemia >10%, significant hemolysis, or organ failure): clindamycin IV + quinine PO × 7–10 days
Consider exchange transfusion for parasitemia >10% or severe hemolysis
Asplenic or immunocompromised: treat at least 6 weeks, including 2 weeks after parasite clearance

⚑ Board Traps — Babesiosis

Doxycycline does NOT treat babesiosis. This is the exception to the "all tick-borne disease gets doxycycline" rule
Maltese cross distinguishes Babesia from malaria — Plasmodium does not form tetrads, and no travel history is needed for Babesia
Asplenia converts a mild illness into a fatal one — splenectomy history changes the whole management arc
Same tick as Lyme, so a patient failing doxycycline for presumed Lyme with worsening anemia may have babesiosis
Hemolytic anemia is the tell — no other Ixodes-borne disease produces it

★ Memory Trick

Babesia = Babesia Bursts Blood cells (hemolysis) Maltese cross for the Malaria Mimic Atovaquone + Azithromycin = the two A's for the one exception to doxycycline

Tier 2

Module 16

Other Tick-Borne Diseases

Tularemia · Colorado Tick Fever · Tick Paralysis · Powassan Virus

★ PANCE Priority

Tularemia (Francisella tularensis)

Transmitted by Dermacentor ticks and by direct contact with rabbits or rodents
Ulceroglandular form is most common: an ulcer at the bite site with painful regional lymphadenopathy
Pneumonic form is a recognized bioterrorism concern
Diagnosis is serologic; culture requires biosafety level 3 — alert the laboratory before sending specimens
Treatment: streptomycin or gentamicin first-line; doxycycline or ciprofloxacin are alternatives with higher relapse rates

Colorado Tick Fever

Coltivirus transmitted by Dermacentor andersoni (wood tick)
Western US mountain regions above 4,000 feet
"Saddleback" biphasic fever — fever, brief defervescence, then fever again
Diagnosis by RT-PCR; viral inclusions can be seen within erythrocytes
Treatment is supportive. Defer blood donation for 6 months given prolonged viremia in RBCs

Tick Paralysis

Not an infection — a neurotoxin in tick saliva blocks presynaptic acetylcholine release
Ascending flaccid paralysis that mimics Guillain-Barré syndrome, often with normal CSF
Finding and removing the tick produces rapid resolution — this is both the diagnosis and the cure
Classically a child with a tick hidden in the scalp or behind an ear

Powassan Virus

Ixodes-transmitted flavivirus of the northeastern US and Great Lakes
Meningoencephalitis with seizures and focal deficits
Transmission can occur within 15 minutes of attachment — unlike the 36-hour requirement for Lyme, so prophylaxis timing rules do not apply
Treatment is supportive; roughly 10% mortality with frequent neurologic sequelae

⚑ Board Traps — The Remaining Tick-Borne Diseases

Tularemia is the second exception to doxycycline — aminoglycosides are first-line
Always examine the scalp in a child with ascending paralysis. Tick paralysis is reversible; Guillain-Barré is not, and the CSF distinguishes them
Powassan transmits in minutes, not hours — a short attachment time does not reassure you here
Notify the lab when tularemia is suspected — unwarned culture handling has caused laboratory-acquired infection
Biphasic fever after a mountain hiking trip points to Colorado tick fever, not relapsing malaria

★ Memory Trick

Tularemia = Tubes of aminoglycoside (not doxy) Saddleback fever rides up, down, and up again Paralysis? Part the hair.

Section III · Modules 17–28

Opportunistic Infections in Advanced HIV

Twelve modules ordered by the CD4 threshold at which each becomes possible. Read alongside the CD4 ladder in Module 30 — nearly every board question in this domain is anchored to a count.

Tier 1

Module 17

Pneumocystis Pneumonia (PCP)

CD4 <200 · Ground-Glass + LDH · Steroid Threshold · Check G6PD

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Pneumocystis jirovecii — an atypical fungus, previously misclassified as a protozoan (which is why it still responds to TMP-SMX rather than to standard antifungals)
Risk begins at CD4 <200 cells/mm³; also immunosuppressive therapy, especially corticosteroids, and transplant recipients
Airborne acquisition or reactivation of latent infection

Clinical Presentation

Gradual onset over weeks — progressive dyspnea, dry nonproductive cough, fever
Hypoxemia out of proportion to examination and imaging; desaturation with exertion is an early sign
Bilateral diffuse interstitial or ground-glass opacities; the chest radiograph may be normal early, so CT is more sensitive
Pneumothorax is a recognized complication, arising from subpleural cysts

Diagnosis

Induced sputum or bronchoalveolar lavage with silver (GMS) stain or direct fluorescent antibody
Elevated serum LDH — nonspecific but tracks severity
Elevated serum (1→3) beta-D-glucan — sensitive for fungi but not specific
Respiratory PCR is highly sensitive but may detect colonization rather than disease

Management

First-line: TMP-SMX, trimethoprim 15–20 mg/kg/day in 3–4 divided doses — 21 days in HIV, 14 days in non-HIV
Adjunctive corticosteroids if PaO₂ <70 mmHg or A-a gradient ≥35: prednisone 40 mg BID × 5 days → 40 mg daily × 5 days → 20 mg daily × 11 days. Start within 72 hours of antimicrobial therapy
Alternatives: IV pentamidine; atovaquone (mild disease); dapsone plus trimethoprim; clindamycin plus primaquine
Prophylaxis: TMP-SMX DS daily or three times weekly, started when CD4 <200 or with oropharyngeal candidiasis
Discontinue prophylaxis when CD4 >200 for at least 3 months on ART

⚑ Board Traps — PCP

Steroids go in only for moderate-severe disease (PaO₂ <70 or A-a gradient ≥35). Giving them to a well-oxygenated patient is wrong, and withholding them from a hypoxic one increases mortality
Steroids are started with or before antibiotics, not after clinical decline
A normal chest radiograph does not exclude PCP — get the CT
Check G6PD before dapsone or primaquine — hemolytic anemia is the consequence of skipping it
Aerosolized pentamidine does not cover Toxoplasma, so a sulfa-allergic patient on it still needs toxoplasmosis consideration
The most common AIDS-defining opportunistic infection — if the stem gives CD4 <200 with dyspnea, start here

★ Memory Trick

Ground-glass + high LDH + CD4 under 200 = PCP, every time 70 and 35 are the steroid numbers — PaO₂ below 70, gradient above 35 Dapsone and primaquine both need a G6PD check first

Tier 1

Module 18

Toxoplasmosis (Toxoplasma gondii)

CD4 <100 · Multiple Ring-Enhancing Lesions · Empiric Therapy · Leucovorin Rescue

★★★ PANCE Priority

Etiology & Pathophysiology

Obligate intracellular protozoan; the cat is the definitive host
Acquired by ingesting oocysts (cat feces, contaminated food or water) or tissue cysts (undercooked meat), or transplacentally
Reactivation risk at CD4 <100 cells/mm³ — cerebral disease in AIDS is nearly always reactivation of latent infection, which is why IgG serostatus matters

Clinical Presentation

Immunocompetent: usually asymptomatic; may cause cervical lymphadenopathy or a mononucleosis-like illness
Cerebral toxoplasmosis in AIDS: headache, confusion, fever, focal neurologic deficits, seizures
Imaging: MULTIPLE ring-enhancing lesions favoring the basal ganglia and corticomedullary junction
Congenital triad: chorioretinitis, hydrocephalus, and diffuse intracranial calcifications
Ocular disease is the most common cause of posterior uveitis in immunocompetent adults

Diagnosis

Cerebral disease is diagnosed presumptively: compatible imaging + positive Toxoplasma IgG → treat empirically and reassess in 2 weeks
Brain biopsy is reserved for non-responders
Serology: IgG indicates prior exposure (and therefore reactivation risk); IgM suggests acute infection
CSF PCR is supportive when lumbar puncture is safe

Management

Pyrimethamine + sulfadiazine + leucovorin for a minimum of 6 weeks
Leucovorin (folinic acid) prevents pyrimethamine-induced marrow suppression — it is not optional and it does not reduce efficacy
Alternatives: TMP-SMX; pyrimethamine plus clindamycin (for sulfa allergy)
Prophylaxis: TMP-SMX DS daily when CD4 <100 AND Toxoplasma IgG positive
Discontinue when CD4 >200 for at least 3 months on ART
Congenital: pyrimethamine + sulfadiazine + leucovorin for 12 months

Ring-Enhancing Lesions in AIDS — The Discriminator

Feature	Cerebral Toxoplasmosis	Primary CNS Lymphoma
Number	Multiple	Single
Location	Basal ganglia, corticomedullary junction	Periventricular
Serology / CSF	Toxoplasma IgG positive	CSF EBV DNA positive
Empiric therapy	Responds within 2 weeks	No response → proceed to biopsy
CD4	< 100	< 50

⚑ Board Traps — Toxoplasmosis

Do not biopsy first. The correct next step for multiple ring-enhancing lesions with positive IgG is empiric therapy
Omitting leucovorin is the classic pharmacology error — pyrimethamine is a dihydrofolate reductase inhibitor
Negative Toxoplasma IgG makes cerebral toxoplasmosis very unlikely and should redirect you to lymphoma
TMP-SMX covers both PCP and Toxoplasma — one drug, two prophylaxis indications
Prophylaxis requires BOTH criteria: CD4 <100 and positive IgG

★ Memory Trick

Toxo = Two or more; Lymphoma = Lone lesion Leucovorin rescues the marrow, not the parasite Cats, cysts, and CD4 under 100

Tier 1

Module 19

Cytomegalovirus (CMV)

CD4 <50 · Pizza-Pie Retina · Owl's Eye Inclusions · Most Common Congenital Infection

★★★ PANCE Priority

Etiology & Pathophysiology

Herpesvirus HHV-5, double-stranded DNA; establishes lifelong latency
Transmitted in saliva, urine, sexual contact, breast milk, blood, and transplanted organs
Disease risk at CD4 <50 cells/mm³, and in transplant recipients

Clinical Presentation

Immunocompetent: a heterophile-NEGATIVE mononucleosis syndrome, self-limited
CMV retinitis (most common in AIDS): painless progressive vision loss and floaters; fundoscopy shows the "pizza pie" appearance — hemorrhages plus yellow-white exudates
CMV colitis: diarrhea, abdominal pain, bloody stools; "punched-out" ulcers on colonoscopy
CMV esophagitis: large, shallow, linear ulcers — versus Candida (white plaques) and HSV (small deep ulcers)
CMV encephalitis and polyradiculopathy also occur
Congenital CMV is the most common congenital infection. Sensorineural hearing loss is the most common sequela; also periventricular calcifications, petechial "blueberry muffin" rash, hepatosplenomegaly, microcephaly, chorioretinitis

Diagnosis

CMV retinitis is a clinical diagnosis by dilated fundoscopic examination — do not delay for laboratory confirmation
Tissue disease: biopsy showing "owl's eye" intranuclear inclusion bodies is pathognomonic
Quantitative CMV DNA PCR on serum or CSF
pp65 antigenemia assay; serology distinguishes prior exposure from acute infection

Management

First-line: ganciclovir IV (induction 5 mg/kg BID × 14–21 days, then maintenance) or oral valganciclovir
Retinitis: intravitreal ganciclovir or foscarnet injection plus systemic therapy
Alternatives: foscarnet (ganciclovir resistance or marrow suppression); cidofovir
Toxicities: ganciclovir causes myelosuppression and neutropenia; foscarnet causes nephrotoxicity with hypocalcemia and hypomagnesemia
No routine primary prophylaxis — the intervention is ART to raise CD4 above 100

⚑ Board Traps — CMV

Monospot-negative mononucleosis is CMV, acute HIV, or Toxoplasma — not EBV
Owl's eye = CMV; Cowdry type A = HSV or VZV. Do not swap them
Congenital CMV gives PERIVENTRICULAR calcifications; congenital toxoplasmosis gives DIFFUSE scattered calcifications
Vision loss in a patient with CD4 <50 is an ophthalmologic emergency — examine the retina rather than ordering serology
Match the toxicity to the drug: marrow for ganciclovir, kidney and electrolytes for foscarnet

★ Memory Trick

CMV = See My Vision at CD4 under 50 Pizza pie retina: cheese (exudate) and tomato sauce (hemorrhage) Ganciclovir hits the margan — marrow; Foscarnet hits the nephros — kidney

Tier 2

Module 20

Mycobacterium avium Complex (MAC / MAI)

CD4 <50 · Fever + Anemia + Alk Phos · AFB Blood Cultures · Rifabutin over Rifampin

★★ PANCE PriorityProphylaxis Updated

Etiology & Pathophysiology

Nontuberculous mycobacteria — M. avium and M. intracellulare — ubiquitous in water and soil
NOT transmitted person to person, so no isolation is required. This is the key contrast with M. tuberculosis
Disseminated disease risk at CD4 <50 cells/mm³ — the lowest threshold of any opportunistic infection

Clinical Presentation

Disseminated MAC: high fevers, drenching night sweats, weight loss, chronic diarrhea, abdominal pain
Hepatosplenomegaly and diffuse lymphadenopathy
Labs: severe anemia, elevated alkaline phosphatase, elevated LDH — this triad in advanced HIV is the classic board signature
Pulmonary MAC in the immunocompetent host is a different disease and is now taught in Pulmonary Module 19 — Nontuberculous Mycobacteria. Disseminated MAC below, at CD4 <50, is the HIV illness

Diagnosis

Mycobacterial (AFB) blood cultures are the gold standard for disseminated disease — routine blood cultures will not grow it, so the test must be requested specifically
Bone marrow biopsy: noncaseating granulomas containing acid-fast bacilli
Sputum culture for pulmonary disease, with repeated positive samples required to distinguish disease from colonization

Management

Disseminated disease: clarithromycin 500 mg PO BID (or azithromycin 500 mg daily) + ethambutol 15 mg/kg/day, with or without rifabutin
Rifabutin is preferred over rifampin in HIV — substantially fewer interactions with antiretrovirals, though it remains a CYP3A4 substrate and inducer
Rule out active tuberculosis before starting rifabutin — adding a single rifamycin to undiagnosed TB selects for resistance
Monitor for ethambutol optic neuritis — baseline and periodic visual acuity and color vision testing
Primary prophylaxis is no longer routinely recommended when ART is started promptly. Where ART will be delayed, azithromycin 1200 mg weekly at CD4 <50 remains the historical regimen
Discontinue secondary prophylaxis when CD4 >100 for at least 3 months on ART with treated disease

⚑ Board Traps — MAC

Routine MAC prophylaxis has been dropped for patients starting ART immediately — a stem offering weekly azithromycin to a newly diagnosed patient going straight onto ART is testing the obsolete recommendation
MAC is not contagious. Airborne isolation is the wrong answer
Order AFB blood cultures specifically — standard cultures will be reported as no growth
Rifabutin, not rifampin, in a patient on ART
Ethambutol is the eye drug in both MAC and TB regimens — a new visual complaint means stop it
Disseminated MAC and pulmonary MAC are separate illnesses. Disseminated disease belongs to advanced HIV at CD4 <50; the nodular bronchiectatic and fibrocavitary pulmonary forms occur in immunocompetent hosts and are covered in the Pulmonary syllabus.

★ Memory Trick

MAC at 50 — the lowest CD4 threshold, sharing the floor with CMV Fever + anemia + alk phos in advanced HIV = MAC Rifa-BUT-in — use it but only after excluding TB

Tier 1

Module 21

Cryptococcal Meningitis (Cryptococcus neoformans)

CD4 <100 · CrAg · Opening Pressure · Delay ART for IRIS

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Encapsulated yeast found in soil and pigeon droppings
Inhaled → pulmonary infection → hematogenous dissemination to the CNS
Risk at CD4 <100 cells/mm³; also transplant recipients and patients on high-dose corticosteroids
The polysaccharide capsule is the major virulence factor — it inhibits phagocytosis and it is what the antigen test detects

Clinical Presentation

Subacute meningitis: headache is the most common symptom, with fever, altered mental status, and often subtle or absent neck stiffness
Elevated intracranial pressure: papilledema, cranial nerve palsies, nausea and vomiting
Disseminated disease: umbilicated skin papules resembling molluscum contagiosum
Pulmonary disease: cough, dyspnea, nodules or infiltrates
The presentation is indolent, so patients often present after weeks of headache

Diagnosis

Serum and CSF cryptococcal antigen (CrAg): sensitivity and specificity both above 95% — the single best test
ALWAYS measure the CSF opening pressure, often above 25 cm H₂O
CSF: lymphocytic pleocytosis (which may be minimal in AIDS because there are few lymphocytes to recruit), low glucose, elevated protein
India ink: encapsulated yeast with narrow-based budding — roughly 60–80% sensitive
Culture on Sabouraud agar, growing in 3–7 days

Management

Induction: liposomal amphotericin B + flucytosine IV for at least 2 weeks
Consolidation: fluconazole 400 mg PO daily × 8 weeks
Maintenance: fluconazole 200 mg PO daily for at least 12 months; discontinue when CD4 >100 for 3 months with an undetectable viral load
Elevated intracranial pressure is managed with SERIAL therapeutic lumbar punctures, targeting an opening pressure below 20 cm H₂O; ventriculoperitoneal shunt if refractory
Delay ART initiation by 4–6 weeks to reduce the risk of immune reconstitution inflammatory syndrome

⚑ Board Traps — Cryptococcal Meningitis

Elevated intracranial pressure, not the fungus, is the leading cause of death. The correct intervention is serial lumbar puncture — not mannitol, not steroids, not acetazolamide
Do NOT start ART immediately. This is the one opportunistic infection where ART is deliberately deferred, and "start ART today" is the trap
Minimal CSF pleocytosis does not exclude the diagnosis in advanced AIDS
Neck stiffness is frequently absent — a normal neck examination does not rule this out
Narrow-based budding is Cryptococcus; broad-based budding is Blastomyces
Umbilicated papules in advanced HIV may be disseminated Cryptococcus, not molluscum

★ Memory Trick

Crypto = Cap and Pressure — the capsule makes the diagnosis, the pressure kills the patient Tap it, tap it again — serial LPs Narrow-based = Neoformans; Broad-based = Blastomyces

Tier 1

Module 22

Candidiasis (Candida species)

Thrush vs Esophagitis · AIDS-Defining at Any CD4 · pH <4.5 · Echinocandins for Invasive Candidiasis

★★★ PANCE Priority

Etiology & Pathophysiology

C. albicans is most common; also C. glabrata, C. tropicalis, C. krusei, and the emerging multidrug-resistant C. auris
A normal commensal of the gastrointestinal tract, oral mucosa, and vagina — disease reflects host change, not new acquisition
Risk factors: HIV, diabetes, antibiotics, corticosteroids, and other immunosuppression

Clinical Presentation

Oropharyngeal (thrush): white curd-like plaques on buccal mucosa, palate, and tongue that scrape off leaving an erythematous base; may be the first sign of HIV
Esophageal candidiasis is AIDS-defining: odynophagia, dysphagia, retrosternal chest pain; endoscopy shows white plaques and exudates
Vulvovaginal: thick white "cottage cheese" discharge, vulvar pruritus, erythema, dysuria, vaginal pH below 4.5
Invasive candidiasis: candidemia, endocarditis, and endophthalmitis — in ICU patients with central lines, total parenteral nutrition, and broad-spectrum antibiotics

Diagnosis

Oropharyngeal: clinical; KOH preparation shows pseudohyphae and budding yeast if confirmation is needed
Esophageal: in a patient with HIV, thrush plus odynophagia is treated empirically with fluconazole. Endoscopy is reserved for non-responders
Vulvovaginal: KOH with pseudohyphae plus pH below 4.5 — the normal pH is what separates it from bacterial vaginosis and trichomoniasis
Invasive: blood cultures, (1→3) beta-D-glucan, T2Candida panel. Every patient with candidemia needs a dilated ophthalmologic examination

Management

Oropharyngeal: fluconazole 200 mg PO once, then 100 mg daily × 7–14 days; topical nystatin or clotrimazole troches for mild disease
Esophageal: fluconazole 200–400 mg PO or IV daily × 14–21 days — systemic therapy is required, never topical
Vulvovaginal, uncomplicated: fluconazole 150 mg PO × 1, or a topical azole × 3–7 days
Vulvovaginal, recurrent (≥4 per year): fluconazole 150 mg PO weekly × 6 months
Invasive: an echinocandin (micafungin, caspofungin, anidulafungin) is first-line, with step-down to fluconazole once susceptibility is known and the patient is stable
C. auris: often pan-resistant — echinocandins preferred, with strict contact precautions

⚑ Board Traps — Candidiasis

Esophageal candidiasis is AIDS-defining regardless of CD4 count. Oropharyngeal thrush alone is not
Topical therapy cannot treat esophageal disease — nystatin swish-and-swallow is the wrong answer
Do not scope first. In HIV with thrush and odynophagia, treat empirically and scope only if there is no response
Vaginal candidiasis has a NORMAL pH below 4.5 — an elevated pH points to bacterial vaginosis or trichomoniasis
C. krusei is intrinsically fluconazole-resistant, so fluconazole step-down requires species identification
Candidemia is never a contaminant. It requires treatment, line removal, and an eye examination

★ Memory Trick

Plaques that scrape = Candida; plaques that do not scrape = oral hairy leukoplakia (EBV) Esophagus = AIDS-defining; mouth = not Candida keeps the pH normal — it is the only one of the three vaginitides that does

Invasive Fungal Infection — Pattern Recognition Beyond Candida

Invasive candidiasis alongside the moulds and endemic mycoses, with the imaging sign, antigen test, and first-line antifungal for each. Invasive aspergillosis appears only here — it is the one invasive fungal infection without its own module.

High-Yield Pattern Recognition

Organism	Epidemiology	Classic Presentation	Dx	Treatment
Candida (mucosal)	Antibiotics, corticosteroids, DM, dentures, immunocompromised	Oral thrush: white plaques (scrape off → raw surface). Esophageal: odynophagia + dysphagia.	Clinical (oral); EGD (esophageal)	Oral: nystatin. Esophageal: fluconazole × 14–21d.
Invasive Candidiasis	ICU, TPN, broad-spectrum ABx, central venous catheter, abdominal surgery	Fever unresponsive to antibiotics in ICU. Can cause endophthalmitis.	Blood cultures (50% sensitive). β-D-glucan. Fundoscopic exam mandatory in ALL candidemic patients.	Echinocandin FIRST-LINE (caspofungin, micafungin). Fluconazole if stable + susceptible. Remove CVC.
Coccidioidomycosis	Southwest US (AZ, CA, TX). Soil/dust exposure.	Primary "Valley Fever": flu-like + cough + erythema nodosum/multiforme. Disseminated (immunocompromised): meningitis, bone/joint.	Serology (IgM early, IgG late). Sputum culture.	Mild: fluconazole. Severe: amphotericin B → fluconazole. Meningitis: LIFELONG fluconazole (100% relapse if stopped).
Histoplasmosis	Ohio/Mississippi river valleys; bird/bat droppings; caves. CD4 <150 = prophylaxis with itraconazole.	Mimics TB. Progressive disseminated (immunocompromised): fever, weight loss, hepatosplenomegaly, oral ulcers, pancytopenia.	Urine histoplasma antigen (BEST for acute disseminated). Serology.	Mild: itraconazole. Moderate-severe: amphotericin B → itraconazole.

Antifungal Drug Selection — Quick Reference

Azoles (fluconazole, voriconazole, itraconazole, posaconazole): Broad fungistatic activity. Multiple CYP drug interactions (tacrolimus, warfarin, statins).
Amphotericin B (liposomal preferred): Broadest spectrum — reserved for severe/refractory. Major toxicities: nephrotoxicity, infusion reactions, hypokalemia, hypomagnesemia.

⚑ Board Traps — Fungal Infections

Echinocandin first-line for invasive candidiasis — not fluconazole empirically (Candida resistance concerns)
CT "halo sign" = early invasive aspergillosis in neutropenic patient — start voriconazole empirically
Coccidioidomycosis meningitis = LIFELONG fluconazole — 100% relapse rate if stopped
Histoplasma urine antigen is best for acute disseminated disease — more sensitive than serology in acute illness
Fundoscopic exam mandatory in ALL candidemic patients — Candida endophthalmitis causes blindness
Azoles are potent CYP inhibitors — check all drug interactions before prescribing

📚 Invasive aspergillosis and ABPA are taught in the Pulmonary syllabus — see Pulmonary Module 18 — Pulmonary Fungal Infections for the halo sign, galactomannan, and voriconazole.

Tier 1

Module 23

Tuberculosis in HIV — What Changes

TST ≥5 mm in HIV · Atypical Radiograph · ART Timing · Rifabutin Substitution · IRIS

★★★ PANCE PriorityMany Traps

📚 Tuberculosis is now taught in full in the Pulmonary syllabus. The organism, TST and IGRA cutoffs, latent-versus-active decision-making, RIPE therapy, drug toxicities, extrapulmonary forms, and public health reporting are all worked in Pulmonary Module 8 — Tuberculosis. This module keeps only what is specific to the patient with HIV.

TB in the Patient with HIV — What Changes

HIV is the single strongest risk factor for progression from latent infection to active disease — roughly a 10% annual risk versus a 10% lifetime risk in the immunocompetent host
The TST cutoff drops to ≥5 mm in HIV, because the most immunosuppressed patients mount the weakest reaction. Screen every patient with HIV at diagnosis, by TST or IGRA, at any CD4 count
A negative TST or IGRA does not exclude active TB — anergy causes false negatives in up to a quarter of active cases, and the rate is higher at low CD4
The chest radiograph misleads in advanced HIV: lower lobe disease, absent cavitation, miliary pattern, or a normal film. Extrapulmonary and disseminated TB are far more common
ART timing: start antiretrovirals within 2 weeks if CD4 <50, and within 8 weeks if CD4 ≥50 — earlier than that raises IRIS risk, later raises mortality
Watch for IRIS — paradoxical worsening of TB after ART begins. Continue both treatments; add corticosteroids for severe cases
Substitute rifabutin for rifampin with most antiretroviral regimens. Rifampin is a potent CYP450 inducer and collapses antiretroviral levels
Latent TB is treated at any CD4 count — it is the one prophylaxis indication with no threshold. Exclude active disease first

⚑ Board Traps — TB with HIV

5 mm is the cutoff in HIV — applying the 10 or 15 mm threshold to a patient with HIV is the classic false negative.
A normal chest film does not exclude TB in advanced HIV. If the suspicion is real, get sputum for AFB smear, culture, and NAAT.
Rifabutin, not rifampin, in a patient on antiretrovirals.
Do not delay ART to finish TB therapy — the windows are 2 weeks and 8 weeks by CD4, not "after TB treatment completes."
Worsening after starting ART is usually IRIS, not treatment failure — do not stop either regimen.

★ Memory Trick

"Five for HIV" — the smallest cutoff for the weakest immune response "Two and eight" — ART within 2 weeks if CD4 under 50, within 8 weeks if 50 or above Rifa-BUT-in — use it when the patient is on ART Worse after ART = IRIS, not failure

Tier 1

Module 24

Herpes Zoster and Varicella in the Immunocompromised

Hutchinson Sign · Ramsay Hunt · Dissemination Criteria · Shingrix

★★★ PANCE PriorityMany Traps

Etiology & Pathophysiology

Varicella-zoster virus (HHV-3) establishes latency in the dorsal root and cranial nerve ganglia
Reactivation produces herpes zoster in a dermatomal distribution
Both incidence and severity rise with immunosuppression — HIV, transplantation, chemotherapy, and advancing age

Clinical Presentation

Classic zoster: painful grouped vesicles in a single dermatome that does NOT cross the midline; thoracic dermatomes are most common
Prodrome of pain, burning, or itching precedes the rash by days — and can mimic angina, cholecystitis, or renal colic depending on the dermatome
Herpes zoster ophthalmicus: V1 involvement. Hutchinson sign — vesicles on the tip or side of the nose, indicating nasociliary nerve involvement and high risk of ocular disease. Urgent ophthalmology referral.
Ramsay Hunt syndrome (herpes zoster oticus): reactivation in the geniculate ganglion of the facial nerve → vesicles in the external auditory canal or on the auricle + ipsilateral facial nerve palsy, often with CN VIII involvement causing sensorineural hearing loss and vertigo
Immunocompromised: multidermatomal or disseminated disease (more than 20 vesicles outside the primary and adjacent dermatomes), plus visceral involvement — pneumonia, hepatitis, encephalitis
Post-herpetic neuralgia: pain persisting beyond 90 days; risk rises sharply with age

Diagnosis

Typical dermatomal zoster is a clinical diagnosis
PCR of vesicle fluid is the preferred confirmatory test when the presentation is atypical or disseminated
Direct fluorescent antibody or viral culture are alternatives
Tzanck smear shows multinucleated giant cells but cannot distinguish VZV from HSV

Management

Immunocompetent: valacyclovir 1 g PO TID × 7 days, ideally started within 72 hours of rash onset; or acyclovir 800 mg PO five times daily × 7 days
Immunocompromised, disseminated, or visceral disease: acyclovir 10 mg/kg IV q8h
Post-herpetic neuralgia: gabapentin, pregabalin, tricyclic antidepressants, capsaicin, lidocaine patches
Prevention: Shingrix, recombinant adjuvanted vaccine, 2 doses — recommended at age 50 and above, and for immunocompromised adults 19 and above. Efficacy above 90%

⚑ Board Traps — VZV

Hutchinson sign is an ophthalmologic emergency — nose-tip vesicles mean the eye is at risk even before visual symptoms appear
Ramsay Hunt is a facial nerve (CN VII) syndrome from the geniculate ganglion — ear vesicles plus facial palsy. It is not a trigeminal syndrome, and it is distinguished from Bell palsy by the vesicles
Immunocompromised patients get IV acyclovir, not oral valacyclovir
The 72-hour window is a target, not a cutoff — still treat immunocompromised or ophthalmic disease presenting later
Shingrix is a recombinant, non-live vaccine, so it is safe in immunocompromised patients; live Zostavax is no longer available in the US
Disseminated zoster in an immunocompromised patient looks like varicella — and warrants airborne plus contact precautions

★ Memory Trick

Hutchinson's nose → call the eye doctor Ramsay Hunt: ear vesicles + facial droop — Bell palsy with a rash is never Bell palsy Over 20 vesicles off-dermatome = disseminated

Tier 2

Module 25

Histoplasmosis (Histoplasma capsulatum)

Ohio and Mississippi Valleys · Intracellular Yeast · Urine Antigen · Mimics TB

★★ PANCE Priority

Etiology & Pathophysiology

Dimorphic fungus: mold in the environment at 25°C, yeast at body temperature
Endemic to the Ohio and Mississippi River valleys; associated with bird and bat droppings — caves, chicken coops, demolition sites
Inhaled → phagocytosed by macrophages → survives and replicates intracellularly → may disseminate
Disseminated disease risk at CD4 <150 cells/mm³

Clinical Presentation

Acute pulmonary: flu-like illness, self-limited in immunocompetent hosts
Chronic pulmonary: mimics tuberculosis with upper lobe cavitary disease
Disseminated histoplasmosis is AIDS-defining: fever, weight loss, hepatosplenomegaly, pancytopenia, mucocutaneous ulcers of the palate and tongue, and adrenal insufficiency
Mediastinal lymphadenopathy, with mediastinal fibrosis as a late complication

Diagnosis

Urine and serum Histoplasma antigen is the most sensitive test for disseminated disease — note that it cross-reacts with Blastomyces
Peripheral smear or bone marrow biopsy: small yeast INSIDE macrophages
Serology by complement fixation and immunodiffusion (H and M bands) — less useful in immunosuppression
Culture is definitive but slow at 2–4 weeks and requires biosafety level 3
Methenamine silver or PAS staining on tissue

Management

Mild to moderate: itraconazole 200 mg PO TID × 3 days, then BID × 12 months
Severe or disseminated: liposomal amphotericin B × 1–2 weeks, then step down to itraconazole × 12 months
Prophylaxis: itraconazole 200 mg daily if CD4 <150 in an endemic area — less commonly needed now that ART is started promptly
Monitor itraconazole levels — absorption is erratic and requires gastric acid

⚑ Board Traps — Histoplasmosis

Small yeast inside macrophages is Histoplasma; large encapsulated extracellular yeast is Cryptococcus
Pancytopenia plus hepatosplenomegaly plus oral ulcers in advanced HIV is disseminated histoplasmosis, not lymphoma
Adrenal insufficiency is a classic and easily missed complication — check for hyponatremia and hyperkalemia
The urine antigen cross-reacts with Blastomyces, so geography and morphology still matter
Itraconazole needs an acidic stomach — proton pump inhibitors cause treatment failure

★ Memory Trick

Histo hides Inside macrophages Ohio and Mississippi, birds and bats Mimics TB on film, mimics lymphoma on labs

📚 The chronic cavitary pulmonary form of histoplasmosis is taught in Pulmonary Module 18 — Pulmonary Fungal Infections. This module covers it as an opportunistic infection, anchored to the CD4 threshold.

Tier 2

Module 26

Coccidioidomycosis (Coccidioides immitis / posadasii)

Valley Fever · Spherules with Endospores · Erythema Nodosum · Lifelong Fluconazole for Meningitis

★★ PANCE Priority

Etiology & Pathophysiology

Dimorphic fungus: mold in soil producing arthroconidia that are inhaled and convert to spherules containing endospores in tissue
Endemic to the southwestern US — Arizona and California's San Joaquin Valley — and northern Mexico. Hence "Valley Fever"
Higher risk of dissemination: immunocompromise, pregnancy (especially third trimester), and patients of Filipino and African ancestry; also diabetes

Clinical Presentation

Acute pulmonary Valley Fever: flu-like illness with cough, chest pain, and fever — often mistaken for community-acquired pneumonia that fails antibiotics
Erythema nodosum or erythema multiforme ("desert rheumatism") indicates a robust immune response and therefore a BETTER prognosis
Chronic pulmonary: thin-walled cavities
Disseminated disease: verrucous skin lesions and ulcers, bone and joint involvement, and basilar meningitis with CSF eosinophilia

Diagnosis

Serology: IgM by tube precipitin for acute disease; IgG by complement fixation, where TITERS CORRELATE WITH DISEASE SEVERITY and are followed serially
Tissue biopsy showing spherules filled with endospores is pathognomonic
Culture grows on Sabouraud agar but is highly infectious to laboratory staff — biosafety level 3, and the laboratory must be warned
CSF: complement-fixing antibodies plus eosinophilic pleocytosis

Management

Mild pulmonary disease in an immunocompetent host: observation — most cases resolve without antifungals
Moderate to severe pulmonary: fluconazole or itraconazole
Disseminated, non-meningeal: amphotericin B, then step down to an azole
Meningeal disease: high-dose fluconazole, LIFELONG — azoles penetrate CSF and relapse is the rule if therapy stops
Pregnancy: amphotericin B, because azoles are teratogenic

⚑ Board Traps — Coccidioidomycosis

Erythema nodosum is a GOOD prognostic sign here — students reflexively read rash as severity
Coccidioidal meningitis requires lifelong fluconazole; stopping therapy causes relapse. There is no "complete the course" answer
Pregnancy flips the drug to amphotericin B — fluconazole is teratogenic
Eosinophils in the CSF should make you think fungal, specifically Coccidioides
Most mild pulmonary disease needs no antifungal — treating everyone is a distractor
Warn the microbiology laboratory — the mold form is a genuine occupational hazard

★ Memory Trick

Spherules with endospores — a fungal ball packed with seeds Rash = good news in Valley Fever Meningitis = fluconazole forever

📚 The pulmonary presentation of coccidioidomycosis is taught in Pulmonary Module 18 — Pulmonary Fungal Infections. This module covers it as an opportunistic infection, anchored to the CD4 threshold.

Tier 2

Module 27

Progressive Multifocal Leukoencephalopathy (PML)

JC Virus · Non-Enhancing White Matter · No Mass Effect · Natalizumab Warning

★★ PANCE Priority

Etiology & Pathophysiology

JC virus, a polyomavirus, is ubiquitous — most adults are already seropositive, so PML reflects reactivation, not acquisition
Reactivation with severe immunosuppression: CD4 <200, and with natalizumab or rituximab
Lytic infection of oligodendrocytes → demyelination of white matter — which explains the absence of inflammation, enhancement, and mass effect

Clinical Presentation

Subacute, progressive, focal neurologic deficits: hemiparesis, visual field loss (homonymous hemianopia), cognitive decline, aphasia, ataxia
NO fever, NO mass effect, NO contrast enhancement — the negatives are the diagnosis
Rapidly progressive and often fatal without immune reconstitution

Diagnosis

MRI: asymmetric, NON-enhancing white matter lesions without mass effect or edema; T2/FLAIR hyperintense, typically subcortical
CSF JC virus PCR — roughly 70–90% sensitive and highly specific
Brain biopsy is definitive: demyelination with bizarre astrocytes and intranuclear inclusions within oligodendrocytes

Management

There is no specific antiviral for JC virus
The treatment is immune reconstitution — initiate or optimize ART
Natalizumab-associated PML: stop the drug and use plasma exchange to remove it
Watch for IRIS — paradoxical worsening after ART initiation, which may require corticosteroids
Prognosis remains poor; median survival is roughly 6 months without immune recovery

⚑ Board Traps — PML

Non-enhancing lesions without mass effect separate PML from toxoplasmosis and lymphoma, both of which enhance
There is no antiviral to give. A stem offering ganciclovir, acyclovir, or cidofovir is testing whether you know the answer is ART
Natalizumab carries an FDA boxed warning for PML — new neurologic deficits in a multiple sclerosis patient on natalizumab is the classic non-HIV presentation
Afebrile is the rule — fever should redirect you toward an infectious mass lesion
Worsening after starting ART may be IRIS, not treatment failure

★ Memory Trick

PML = Plain, Motionless Lesions — no enhancement, no mass effect, no fever JC virus, Just CD4 — the only therapy is raising the CD4 Natalizumab → watch the white matter

Tier 2

Module 28

Kaposi Sarcoma

HHV-8 · Violaceous Lesions · Visceral Involvement · ART as Cornerstone

★★ PANCE Priority

Etiology & Pathophysiology

Human herpesvirus 8 (HHV-8, also called KSHV) is a necessary cause of every form of Kaposi sarcoma
A vascular neoplasm of endothelial origin
Four epidemiologic types: AIDS-related (most common), classic (elderly men of Mediterranean or Ashkenazi descent), endemic (sub-Saharan Africa), and iatrogenic (post-transplant)

Clinical Presentation

Skin: violaceous, purple-red, NON-blanching macules, papules, plaques, or nodules, typically painless and anywhere on the body
Oral involvement, especially the palate, is common and may be the presenting site
Visceral disease: gastrointestinal tract (bleeding, obstruction) and pulmonary involvement (nodules, effusions, respiratory failure)
Lymphedema from lymphatic obstruction

Diagnosis

Skin biopsy: spindle-shaped cells with vascular slits, extravasated erythrocytes, and HHV-8 immunostaining (LANA-1)
Chest radiography or CT if pulmonary involvement is suspected
Endoscopy for gastrointestinal symptoms — lesions bleed, so biopsy is often deferred

Management

ART initiation or optimization is the cornerstone of AIDS-related disease — many lesions regress with immune recovery alone
Limited cutaneous disease: intralesional vinblastine, radiation, cryotherapy, or topical alitretinoin
Disseminated or visceral disease: liposomal doxorubicin is first-line; paclitaxel is an alternative
Monitor for KS-IRIS — paradoxical worsening after ART initiation

⚑ Board Traps — Kaposi Sarcoma

Violaceous, non-blanching lesions in a patient with HIV are Kaposi sarcoma until proven otherwise — bacillary angiomatosis is the main mimic and is treated with erythromycin or doxycycline
ART alone can produce regression; chemotherapy is not the first answer for limited cutaneous disease
HHV-8 causes all four types, not only the AIDS-related form
HHV-8 also causes primary effusion lymphoma and multicentric Castleman disease
Kaposi sarcoma is not strictly CD4-dependent — it can appear at relatively preserved counts

★ Memory Trick

8 is for Kaposi — HHV-8 Purple, painless, non-blanching Start ART; the lesions may leave on their own

Section IV · Modules 29–33

High-Yield Comparison Tables

Five side-by-side tables for the differentials that generate the most single-best-answer questions: genital ulcers, the CD4 ladder, tick-borne disease, vaginal discharge, and esophageal lesions in HIV.

Tier 1

Module 29

STI Comparison Tables — Ulcers, Discharge and CDC 2021 Treatment

Genital Ulcers · Urethral & Vaginal Discharge · CDC 2021 First-Line Treatment · The LGV Exception

★★★ PANCE PriorityMany Traps

How This Table Is Tested

Nearly every genital ulcer question resolves on two variables: is the ulcer painful, and are the nodes painful? Learn the pairing first, then the exceptions. Syphilis is painless-painless. Chancroid is painful-painful. LGV breaks the pattern with a painless ulcer and painful buboes.

The Five Genital Ulcers

Disease	Pathogen	Ulcer	Pain	Lymphadenopathy	Diagnosis	Treatment
Syphilis (primary)	T. pallidum	Clean base, indurated border	Painless	Painless, bilateral	Darkfield; RPR/VDRL then FTA-ABS	Benzathine penicillin G IM
Herpes	HSV-1, HSV-2	Grouped vesicles → shallow ulcers	Painful	Painful, bilateral	PCR of vesicle fluid	Valacyclovir or acyclovir
Chancroid	H. ducreyi	Ragged, undermined edges	Painful	Painful, unilateral buboes	Clinical; culture on special media	Azithromycin or ceftriaxone
LGV	C. trachomatis L1–L3	Small, transient papule or ulcer	Painless	Painful, unilateral buboes	Serology; NAAT	Doxycycline × 21 days
Granuloma inguinale	K. granulomatis	Beefy-red, highly vascular	Painless	Pseudobuboes — not true nodes	Donovan bodies on biopsy	Azithromycin × 3+ weeks

⚑ Board Traps — Genital Ulcers

Penicillin is the ONLY acceptable syphilis treatment in pregnancy — doxycycline is contraindicated and a penicillin-allergic pregnant patient must be desensitized, never switched.
Nontreponemal titers (RPR/VDRL) monitor treatment; treponemal tests (FTA-ABS, TP-PA) stay positive for life and can never judge cure. A fourfold decline defines response.
LGV is the pattern-breaker — painless ulcer, painful nodes. It is the single most useful exception to memorize
Chancroid buboes are unilateral; syphilitic nodes are bilateral
Granuloma inguinale spares the lymph nodes entirely — the swelling is subcutaneous granulation tissue
Darkfield is invalid on oral and rectal lesions because of commensal spirochetes
Ulcers frequently coexist. A patient with any genital ulcer needs testing for syphilis, HSV, and HIV

★ Memory Trick

Painful ulcer + painful node = chancroid (Ducreyi is dubious) Painless + painless = syphilis (pallidum is placid) LGV = Lymph nodes Go Very tender while the ulcer stays quiet

CDC 2021 Treatment Summary

STI	First-Line Treatment	Key Change / Board Trap
Chlamydia	Doxycycline 100mg BID × 7 days	Doxy NOW PREFERRED over azithromycin — better efficacy, especially rectal chlamydia
Gonorrhea	Ceftriaxone 500mg IM × 1 (1g if ≥150kg)	Azithromycin co-treatment NO LONGER recommended — ceftriaxone MONOTHERAPY
Syphilis — Primary/Secondary/Early Latent	Benzathine penicillin G 2.4 MU IM × 1	Penicillin ONLY in pregnancy — if allergic, desensitize
Syphilis — Late Latent/Unknown Duration	Benzathine penicillin G 2.4 MU IM weekly × 3 (total 7.2 MU)	3 weekly doses
Neurosyphilis	IV aqueous crystalline penicillin G × 10–14 days	Can occur at ANY stage — evaluate for ocular/otic/neuro symptoms in all syphilis
PID	Ceftriaxone 500mg IM + doxycycline × 14d + metronidazole × 14d	Metro NOW routinely added for anaerobic coverage (2021 update)
Trichomoniasis	Women: Metro 500mg BID × 7d \| Men: 2g × 1	7-day course preferred for women
Genital herpes (1st episode)	Acyclovir 400mg TID × 7–10d	Valacyclovir 1g BID is an alternative

Urethral & Vaginal Discharge — Full Organism Differential

Gonorrhea vs chlamydia vs non-gonococcal urethritis vs trichomoniasis — presentation, diagnosis, CDC 2021 treatment, and partner management side by side.

STI Presentation and Treatment Comparison

Organism	Presentation	Diagnosis	Treatment (CDC 2021)	Board Key
Neisseria gonorrhoeae	Purulent urethral/cervical discharge, dysuria. Men: purulent green/yellow discharge. Women: often asymptomatic.	NAAT (most sensitive). Gram stain: intracellular diplococci.	Ceftriaxone 500mg IM × 1 (1g if ≥150kg). MONOTHERAPY — no azithromycin added.	No fluoroquinolones (widespread resistance). Always test + treat for chlamydia co-infection if not excluded by NAAT.
Chlamydia trachomatis	Often asymptomatic (#1 reported STI in US). Mucopurulent discharge, dysuria, cervicitis, PID.	NAAT.	Doxycycline 100mg BID × 7 days (preferred over azithromycin — lower recurrence rate per 2021 update).	Doxycycline now preferred over azithromycin for chlamydia. Major CDC 2021 update boards test directly.
Non-gonococcal urethritis (NGU)	Mild discharge, dysuria, usually less purulent than GC	NAAT negative for GC/chlamydia. May be Mycoplasma genitalium, Ureaplasma.	Doxycycline 100mg BID × 7 days.	If recurrent/persistent NGU: test for Mycoplasma genitalium → treat with moxifloxacin if positive.
Trichomonas vaginalis	Women: frothy yellow-green vaginal discharge + "strawberry cervix" + pruritus. Men: often asymptomatic.	NAAT or wet prep (motile trichomonads).	Metronidazole 2g PO × 1 (or 500mg BID × 7d for recurrent). Treat BOTH partners simultaneously.	Concurrent treatment of sex partner is mandatory — very high re-infection rate without partner treatment.
Bacterial Vaginosis (BV)	Thin gray-white discharge + fishy odor (worse after sex). Clue cells on wet prep. Whiff test positive.	Amsel criteria (3 of 4) or Nugent score.	Metronidazole 500mg BID × 7 days OR vaginal metronidazole gel × 5 days.	BV is NOT an STI — it's a disruption of normal flora. Male partner treatment does NOT reduce recurrence (unlike trichomonas).

⚑ Board Traps — STIs

Gonorrhea: ceftriaxone MONOTHERAPY (no azithromycin co-treatment) — CDC 2021 changed from dual therapy. Azithromycin-resistant gonorrhea has increased. Monotherapy is now standard. If chlamydia cannot be excluded, add doxycycline separately.
Chlamydia: doxycycline now preferred over azithromycin — CDC 2021 update. Azithromycin has lower cure rates for rectal chlamydia and more treatment failures.
Syphilis in pregnancy: penicillin ONLY, no exceptions — doxycycline is contraindicated in pregnancy. Azithromycin has ~30% failure rate. Even with penicillin allergy, desensitization is mandatory.
BV partner treatment does NOT help — unlike trichomonas, treating the male partner does not reduce BV recurrence. This is the opposite of trichomonas management.
Disseminated gonococcal infection (DGI): Young sexually active adult + migratory polyarthralgia + tenosynovitis + skin lesions (pustular on erythematous base) = DGI. NAAT and cultures of all sites. IV ceftriaxone × 7 days.

Tier 1

Module 30

Opportunistic Infections by CD4 Count

The Master Threshold Table · Prophylaxis Triggers · Stop Rules

★★★ PANCE PriorityMany Traps

Why This Is the Highest-Yield Table in the Chapter

HIV questions on the PANCE are frequently CD4-anchored: the stem gives a count and a syndrome, and the answer follows from the threshold. Learn the descending ladder as a single sequence rather than as isolated facts.

The CD4 Ladder — What Becomes Possible at Each Threshold

CD4 (cells/mm³)	Infections and Malignancies That Become Likely	Prophylaxis
< 500	Kaposi sarcoma, oral hairy leukoplakia, recurrent bacterial pneumonia, tuberculosis reactivation	ART — started at any CD4
< 200	PCP, coccidioidomycosis	TMP-SMX DS daily
< 150	Disseminated histoplasmosis	Itraconazole, endemic areas only
< 100	Cerebral toxoplasmosis, cryptococcosis	TMP-SMX (only if Toxoplasma IgG positive); no routine cryptococcal prophylaxis
< 50	MAC, CMV retinitis, PML, primary CNS lymphoma	None routinely if ART starts promptly

Discontinue PCP and Toxoplasma prophylaxis when CD4 stays above 200 for at least 3 months on ART.

The Stop Rules — Equally Testable

PCP prophylaxis: stop when CD4 >200 for ≥3 months on ART
Toxoplasma prophylaxis: stop when CD4 >200 for ≥3 months on ART
MAC and cryptococcal secondary prophylaxis: stop when CD4 >100 for ≥3 months with treated disease
CMV: no primary prophylaxis exists — the intervention is ART
Latent TB is screened and treated at ANY CD4 count — it is the one indication with no threshold

⚑ Board Traps — CD4 Thresholds

Routine MAC prophylaxis has been dropped for patients starting ART promptly. Weekly azithromycin is the historical answer, not the current one
Toxoplasma prophylaxis requires positive IgG in addition to CD4 <100 — a seronegative patient does not need it
TMP-SMX covers PCP and Toxoplasma simultaneously — one drug clears two indications, which is why it is the single most important prophylactic agent in HIV care
Esophageal candidiasis and tuberculosis are AIDS-defining at ANY CD4, so a normal count does not exclude AIDS
Prophylaxis is stopped on sustained CD4 recovery, not on viral suppression alone

★ Memory Trick

Descending ladder: 200 PCP → 150 Histo → 100 Toxo and Crypto → 50 MAC, CMV, PML, Lymphoma One drug, two bugs: TMP-SMX for PCP and Toxoplasma Everything stops at 200 for 3 months except MAC and Crypto, which stop at 100 for 3 months

Tier 1

Module 31

Tick-Borne Disease — Side-by-Side Comparison

Vector · Region · Smear Finding · The Two Non-Doxycycline Exceptions

★★★ PANCE Priority

The Six Tick-Borne Diseases

Disease	Pathogen	Vector	Region	Key Finding	Rash	Treatment
Lyme	B. burgdorferi	Ixodes scapularis	Northeast, upper Midwest	Erythema migrans	Bull's-eye	Doxycycline
RMSF	R. rickettsii	Dermacentor	Southeast, south-central	Vasculitis; hyponatremia	Wrists/ankles → trunk	Doxycycline
Ehrlichiosis	E. chaffeensis	Lone Star tick	Southeast, south-central	Morulae in monocytes	Up to 30%	Doxycycline
Anaplasmosis	A. phagocytophilum	Ixodes scapularis	Northeast, upper Midwest	Morulae in granulocytes	Rare	Doxycycline
Babesiosis	B. microti	Ixodes scapularis	Northeast, upper Midwest	Maltese cross; hemolysis	None	Atovaquone + azithromycin
Tularemia	F. tularensis	Dermacentor; rabbits	Widespread	Ulceroglandular	Variable	Streptomycin or gentamicin

⚑ Board Traps — Tick-Borne Disease

Doxycycline treats every tick-borne disease in this table EXCEPT babesiosis and tularemia. The commonly repeated "doxycycline for all tick-borne illness" shortcut has two exceptions, not one
The Ixodes tick carries three diseases — Lyme, anaplasmosis, and babesiosis — so co-infection is expected and a patient failing doxycycline may have babesiosis
Rash direction distinguishes RMSF: centripetal, from wrists and ankles inward
Morulae cell type is the whole question: monocytes for Ehrlichia, granulocytes for Anaplasma
Hemolytic anemia points only to babesiosis among the Ixodes-borne infections

★ Memory Trick

One tick, three diseases: Ixodes = Lyme, Anaplasma, Babesia ("LAB") Two exceptions to doxycycline: Babesia and Tularemia Dermacentor carries the Deadly one (RMSF)

Tier 1

Module 32

Vaginal Discharge — Side-by-Side Comparison

pH as the First Discriminator · Wet Mount Findings · Partner Treatment

★★★ PANCE Priority

The Three Vaginitides

Feature	Bacterial Vaginosis	Vulvovaginal Candidiasis	Trichomoniasis
Discharge	Thin, gray-white, homogeneous	Thick, white, cottage-cheese	Frothy, yellow-green
Odor	Fishy — whiff test positive	None	Malodorous
pH	> 4.5	< 4.5 — normal	> 4.5
Wet mount	Clue cells	KOH: pseudohyphae and budding yeast	Motile trichomonads
Inflammation	Minimal — no vulvar irritation	Prominent pruritus and erythema	Variable; strawberry cervix
Treatment	Metronidazole	Fluconazole or topical azole	Metronidazole
Treat partner?	No	No	Yes

⚑ Board Traps — Vaginal Discharge

Candidiasis is the only one with a normal pH. If the stem gives pH <4.5, yeast is the answer
Only trichomoniasis requires partner treatment — it is the only true STI of the three
Absence of vulvar inflammation points to bacterial vaginosis
Metronidazole is safe in pregnancy for both bacterial vaginosis and trichomoniasis
Trichomoniasis dosing differs by sex: 7 days for women, single 2 g dose for men

★ Memory Trick

Check the pH first — it splits the three in one step Clue cells, Cottage cheese, Corkscrew swimmers — BV, Candida, Trichomonas Only Trich brings a partner

Tier 1

Module 33

Esophageal Ulcer and Lesion Differential in HIV

Plaques vs Large Shallow vs Small Deep · Inclusion Bodies · When to Scope

★★ PANCE Priority

Four Causes, Four Appearances

Pathogen	Endoscopic Appearance	Diagnosis	Treatment
Candida	White plaques and pseudomembranes	Clinical in HIV; endoscopy only if refractory	Fluconazole
CMV	Large, shallow, linear ulcers	Biopsy: owl's eye inclusions	Ganciclovir or valganciclovir
HSV	Small, deep, well-circumscribed ulcers	Biopsy: Cowdry type A inclusions, multinucleated giant cells	Acyclovir or valacyclovir
Aphthous (idiopathic)	Large, deep ulcers of the mid-to-distal esophagus	Diagnosis of exclusion	Corticosteroids; thalidomide

The Diagnostic Sequence

Step 1: thrush plus odynophagia in a patient with HIV → treat empirically with fluconazole. Do not scope first
Step 2: no response after 3–7 days → upper endoscopy with biopsy to look for CMV, HSV, or aphthous ulceration
Step 3: match the inclusion body — owl's eye is CMV, Cowdry type A is HSV
Fluconazole-refractory candidiasis also raises the possibility of a non-albicans species such as C. krusei

⚑ Board Traps — Esophageal Disease in HIV

Endoscopy is not the first step when thrush and odynophagia coexist — empiric fluconazole is
Large and shallow is CMV; small and deep is HSV. The size-depth pairing is the discriminator and it is asked directly
Owl's eye is CMV; Cowdry type A is HSV or VZV
Esophageal candidiasis is AIDS-defining; oropharyngeal thrush is not
Topical antifungals never treat esophageal disease

★ Memory Trick

CMV = Crater, wide and shallow; HSV = Hole, small and deep Owl's eye watches for CMV; Cowdry for HSV Treat, then scope

Section V · Modules 34–35

Screening and Prevention

Who to screen, how often, and which vaccine at which age — including the 2023 shift to universal adult hepatitis B screening and the HPV dose count that depends on age at first dose.

Tier 1

Module 34

STI and Viral Hepatitis Screening Recommendations

USPSTF and CDC · Who, When, How Often · Universal Adult Hepatitis Screening

★★★ PANCE PriorityUpdated 2023

Bacterial STIs

Chlamydia and gonorrhea: all sexually active women under 25 annually; older women with risk factors; MSM at all sites of contact at least annually; all persons with HIV annually
Syphilis: all pregnant patients at the first prenatal visit; MSM at least annually; anyone at increased risk. Repeat in the third trimester and at delivery in high-prevalence settings

HIV

All persons aged 15–65 at least once, regardless of risk
All pregnant patients, with repeat testing in the third trimester if at high risk
At least annually in persons at ongoing risk; every 3 months for patients on PrEP

Viral Hepatitis

Hepatitis B: universal screening of all adults at least once (2023 CDC), plus all pregnant patients, persons with HIV, people who inject drugs, MSM, and persons from endemic regions
Hepatitis C: all adults aged 18–79 at least once (USPSTF), and all pregnant patients with every pregnancy

HPV and Cervical Cancer Screening

Ages 21–29: cytology alone every 3 years
Ages 30–65: cytology plus HPV co-testing every 5 years, primary HPV testing every 5 years, or cytology alone every 3 years
Persons with HIV: more frequent cervical screening, plus digital anorectal examination for anal cancer

⚑ Board Traps — Screening

HIV screening is universal, not risk-based — everyone 15 to 65 at least once
Hepatitis B screening became universal for adults in 2023; risk-based-only screening is the outdated answer
Hepatitis C is screened every pregnancy, not once per lifetime, in pregnant patients
Extragenital screening in MSM requires swabbing the sites of exposure — urine NAAT alone misses pharyngeal and rectal infection
Screening does not stop after HPV vaccination

★ Memory Trick

25 for chlamydia, 15–65 for HIV, 18–79 for hepatitis C Every pregnancy: HIV, syphilis, hepatitis B, hepatitis C MSM: annually, and at every site of contact

Tier 1

Module 35

Immunization Summary for Infectious Disease

HPV · Hepatitis A and B · Shingrix · Meningococcal · Mpox

★★★ PANCE Priority

Vaccines Most Often Tested on the PANCE

Vaccine	Who and When	Board Key
HPV (Gardasil 9)	Routine at 11–12 (may start at 9); catch-up through 26; shared decision 27–45	2 doses if started before 15; 3 doses if 15 or older or immunocompromised
Hepatitis B	Universal infant series; all unvaccinated adults through 59; age 60+ with risk factors	3-dose series, or 2-dose Heplisav-B
Hepatitis A	2-dose series — MSM, people who inject drugs, chronic liver disease, travel to endemic areas	Also given for post-exposure prophylaxis
Zoster (Shingrix)	2 doses at age 50 and above; immunocompromised adults 19 and above	Recombinant, not live — safe in immunocompromised patients. Efficacy above 90%
Meningococcal	MenACWY at 11–12 with a booster at 16; MenB at 16–23 by shared decision or in outbreaks	Asplenia, complement deficiency, and college dormitories raise priority
Mpox (JYNNEOS)	At-risk populations including MSM and persons with HIV	Non-replicating; safe in immunocompromised patients

⚑ Board Traps — Immunization

HPV dose count depends on age at the FIRST dose, not current age — under 15 gets two doses
Shingrix is recombinant and therefore safe in immunocompromised patients. Live Zostavax is no longer available in the US and is the outdated answer
Hepatitis B vaccination is now recommended for all adults through 59 regardless of risk
Vaccination is not therapeutic — giving HPV vaccine does not treat existing warts or dysplasia
Live vaccines are contraindicated at CD4 <200; Shingrix, hepatitis B, and JYNNEOS are not live and remain acceptable

★ Memory Trick

Under 15 → 2 shots; 15 and up → 3 shots (HPV) Shingrix is recombinant — the x marks "not live" 50 for the general population, 19 if immunocompromised (zoster)

Section VI · Fast Review

30 Rapid-Fire Pearls — Systematic Review

One-line discriminators drawn from all 35 modules above. Use these as a final pass, not as a first pass.

1
Painless chancre = syphilis; painful chancre = chancroid. Painless ulcer with PAINFUL buboes = LGV, the pattern-breaker.
2
Condylomata lata (flat, moist) = syphilis; condylomata acuminata (raised, cauliflower) = HPV.
3
Strawberry cervix = trichomoniasis. Chandelier sign (cervical motion tenderness) = PID.
4
Clue cells = BV; pseudohyphae = Candida; motile trichomonads = Trichomonas. Candida is the only one with a normal pH below 4.5.
5
Koilocytes = HPV; Cowdry type A = HSV/VZV; owl's eye = CMV; Donovan bodies = granuloma inguinale; morulae = Ehrlichia or Anaplasma.
6
Erythema migrans is a clinical diagnosis — treat without serology in an endemic area. Post-treatment serology stays positive and is never a test of cure.
7
Centripetal rash from wrists and ankles toward the trunk = RMSF. Treat empirically with doxycycline at any age; do not wait for serology.
8
Morulae in monocytes = Ehrlichia; morulae in granulocytes = Anaplasma. Both give leukopenia, thrombocytopenia, and elevated transaminases.
9
Maltese cross tetrad in RBCs = Babesia — and babesiosis is one of only TWO tick-borne diseases doxycycline does not treat. Tularemia is the other, requiring an aminoglycoside.
10
Ring-enhancing lesions in HIV: MULTIPLE in the basal ganglia = toxoplasmosis (treat empirically); SINGLE and periventricular with CSF EBV DNA = primary CNS lymphoma.
11
Non-enhancing white matter lesions with no mass effect and no fever = PML (JC virus). There is no antiviral — the treatment is ART.
12
Pizza-pie retina at CD4 below 50 = CMV retinitis. Painless vision loss in advanced HIV is an ophthalmologic emergency.
13
Bilateral diffuse ground-glass opacities + elevated LDH + CD4 below 200 = PCP. Add steroids only if PaO₂ is below 70 or the A-a gradient is 35 or more.
14
India ink with narrow-based budding = Cryptococcus (broad-based budding = Blastomyces). Elevated opening pressure kills — the answer is serial lumbar punctures, and ART is deliberately delayed 4–6 weeks.
15
Small yeast inside macrophages = Histoplasma; spherules with endospores = Coccidioides. In Valley Fever, erythema nodosum signals a GOOD prognosis.
16
CD4 below 50 with fever, severe anemia, and elevated alkaline phosphatase = disseminated MAC. MAC is not contagious, so no isolation, and routine prophylaxis is no longer given when ART starts promptly.
17
The CD4 ladder: 200 PCP → 150 histoplasmosis → 100 toxoplasmosis and cryptococcosis → 50 MAC, CMV, PML, and CNS lymphoma. TMP-SMX covers PCP and Toxoplasma together.
18
Esophageal candidiasis is AIDS-defining at any CD4; oropharyngeal thrush is not. Treat empirically with systemic fluconazole and scope only non-responders.
19
Esophageal ulcers in HIV: white plaques = Candida; large and shallow = CMV; small and deep = HSV.
20
Violaceous non-blanching lesions in HIV = Kaposi sarcoma (HHV-8). ART alone can produce regression.
21
Argyll Robertson pupil = neurosyphilis — accommodates but does not react to light. Ocular and otic syphilis are treated as neurosyphilis with IV penicillin.
22
Nontreponemal titers (RPR/VDRL) monitor treatment; treponemal tests stay positive for life. A 4-fold decline defines response.
23
Jarisch-Herxheimer reaction: fever and rigors within 24 hours of treating syphilis. Expected endotoxin release — not an allergy and not a reason to stop.
24
Pregnant with syphilis and a penicillin allergy: desensitize, then give penicillin. There is no acceptable alternative.
25
Neonatal conjunctivitis: days 2–5 = gonococcal; days 5–14 = chlamydial. Erythromycin ointment prophylaxis prevents only the gonococcal form.
26
Gonorrhea is ceftriaxone 500 mg IM once, as monotherapy when chlamydia is excluded — azithromycin was removed from dual therapy. Chlamydia is doxycycline for 7 days, except in pregnancy where it is azithromycin.
27
Heterophile-negative mononucleosis → consider acute HIV, CMV, or toxoplasmosis. Suspected acute HIV requires an RNA viral load, not a repeat antibody test.
28
Ethambutol is the eye, isoniazid is the nerve, pyrazinamide is the joint, rifampin turns fluids orange. Use rifabutin instead of rifampin in patients on ART.
29
Hutchinson sign (vesicles on the nose tip) means the eye is at risk — urgent ophthalmology. Ramsay Hunt is ear vesicles plus facial palsy from the geniculate ganglion of CN VII.
30
An IUD does not need removal in PID, and metronidazole is now part of the routine regimen.

Part 1 · The Core Six

Core PANCE Infectious Disease Topics

The six topics that carry the most weight on the PANCE and PANRE. Work these first, in this order — each opens with pre-read questions, then the full topic card.

Tier 1

Topic 1

UTI — Cystitis & Pyelonephritis

2025 IDSA Reclassification · Nitrofurantoin Limitation · ASB Rules · Duration of Therapy · Pregnancy

2025 IDSA Reclassification — What "Complicated" Actually Means

The 2025 IDSA guidelines changed how UTI is classified. Diabetes, immunocompromise, and benign prostatic hyperplasia alone do NOT make a UTI "complicated" if the infection appears confined to the bladder — both men and women can now have uncomplicated UTI.

Complicated UTI = infection extending beyond the bladder: pyelonephritis, febrile/bacteremic UTI, or CAUTI
Signs of complicated UTI: fever, chills, rigors, hemodynamic instability, flank pain, CVA tenderness

🚨 Classic Trap: A diabetic woman with isolated dysuria and no systemic signs has UNCOMPLICATED cystitis under the 2025 reclassification — don't reflexively label her "complicated" based on her diabetes alone.

Microbiology

Organism	Frequency	Key Notes
E. coli	75–90%	Most common cause of both uncomplicated and complicated UTI
Klebsiella pneumoniae	6–8%	Second most common Gram-negative
S. saprophyticus	5–6%	#2 cause in young sexually active women — classic board question
Proteus mirabilis	2–5%	Urease-producing → alkaline urine → struvite (staghorn) stones
Enterococcus	~5%	Intrinsically resistant to cephalosporins
Pseudomonas	<5%	More common in catheterized/healthcare-associated UTI

🩺 PANCE Pearl: S. saprophyticus is coagulase-negative and novobiocin-RESISTANT — this distinguishes it from S. epidermidis, which is novobiocin-sensitive. A classic board differentiator.

Cystitis vs Pyelonephritis

	Cystitis	Pyelonephritis
Symptoms	Dysuria, frequency, urgency, suprapubic pain. NO fever.	Cystitis symptoms + fever, rigors, CVA tenderness, N/V
Culture required?	NOT mandatory in non-pregnant women with typical symptoms	ALWAYS obtain — confirmatory test is ≥10,000 CFU/mL of a uropathogen
First-line Rx	Nitrofurantoin, TMP-SMX, fosfomycin, or pivmecillinam	Fluoroquinolone (outpatient) or IV ceftriaxone/cefepime/pip-tazo (inpatient)
Nitrofurantoin OK?	YES — high urine concentration	NO — inadequate renal tissue levels

🩺 PANCE Pearl: Urine culture is recommended for recurrent UTI, treatment failure, atypical presentation, men, and age ≥65 — even in suspected cystitis.

Urinalysis Interpretation

Nitrites: high specificity (~95%) but low sensitivity (~50%) — only produced by Gram-negative Enterobacteriaceae. NOT produced by Enterococcus, Staphylococcus, or Pseudomonas
Leukocyte esterase: sensitive but less specific
Pyuria alone ≠ UTI — common in elderly with incontinence and in catheterized patients
A negative dipstick does NOT rule out UTI in a patient with high pretest probability

🚨 Classic Trap: Sterile pyuria differential — TB of the urinary tract, interstitial nephritis, nephrolithiasis, urethritis (Chlamydia), recently treated UTI, bladder cancer. Don't assume "no growth + WBCs" means lab error.

Imaging — When (and When NOT) to Order It

Uncomplicated pyelonephritis responding to therapy does NOT need imaging. Order CT abdomen/pelvis only for:

Sepsis or septic shock
Known or suspected urolithiasis
Urine pH ≥7.0 (suggests urease-producing organism/obstruction)
New GFR decrease to ≤40 mL/min (suggests obstruction)
Failure to improve after 48–72 hours of appropriate therapy

CT with contrast detects abscess/gas; CT without contrast detects stones; ultrasound is preferred in pregnancy and is more sensitive for hydronephrosis.

🚨 Classic Trap: Do NOT order imaging for uncomplicated pyelonephritis that is improving on therapy — this is a frequently tested unnecessary-testing trap.

Treatment — Uncomplicated Cystitis (First-Line)

Agent	Dose	Duration	Key Notes
Nitrofurantoin	100mg BID	5 days	Take with food; avoid if CrCl <30 (label says <60); NEVER for pyelonephritis
TMP-SMX	160/800mg BID	3 days	Only if local resistance <20%; avoid if recent use
Fosfomycin	3g	1 dose	Convenient but may be less effective than multi-day regimens
Pivmecillinam	400mg TID	3 days	Recently FDA-approved in the US for uncomplicated UTI in women

🚨 Classic Trap: Do NOT use amoxicillin or ampicillin empirically — E. coli resistance rates exceed 40%. Fluoroquinolones are NOT first-line for uncomplicated cystitis (reserved for pyelonephritis/invasive infection).

Treatment — Acute Pyelonephritis

Outpatient (uncomplicated): Ciprofloxacin 500mg BID × 5–7d, or levofloxacin 750mg daily × 5d, or TMP-SMX × 7–14d (ONLY if susceptibility confirmed)
If local fluoroquinolone resistance >10%: give one dose of long-acting parenteral antibiotic (ceftriaxone 1g IV/IM or an aminoglycoside) BEFORE starting oral therapy
Inpatient, no sepsis: ceftriaxone, cefepime, piperacillin-tazobactam, or a fluoroquinolone
Inpatient with sepsis or ESBL/MDR risk: carbapenems (meropenem, ertapenem), novel beta-lactam/beta-lactamase inhibitors, or cefiderocol

🚨 Classic Trap: TMP-SMX should NOT be used empirically for pyelonephritis — resistance rates approach 20% in many US regions. Use only after susceptibility is confirmed.

Duration of Therapy — 2025 IDSA

Syndrome	Duration
Uncomplicated cystitis (women)	3–5 days (agent-dependent)
Uncomplicated cystitis (men)	7 days
Pyelonephritis (fluoroquinolone)	5–7 days
Pyelonephritis (non-fluoroquinolone)	7 days
Gram-negative bacteremia, urinary source	7 days if afebrile/stable/source controlled
CAUTI	7 days (up to 10–14 if slow response)

🩺 PANCE Pearl: Shorter courses (5–7 days) are as effective as longer courses (10–14 days) per meta-analysis — this is a major 2025 update. Men with complicated UTI may still benefit from 10–14 days given occult prostatitis risk.

Special Populations

Pregnancy: screen ALL patients with urine culture early in prenatal care; treat ASB if ≥10⁵ CFU/mL. Safe: nitrofurantoin, cephalexin, amoxicillin-clavulanate, fosfomycin. AVOID amoxicillin/ampicillin alone (resistance) and fluoroquinolones (teratogenic). Nitrofurantoin contraindicated at term (38–42 wks — neonatal hemolytic anemia); TMP-SMX avoided in 1st trimester (neural tube defects) and last 8 weeks (kernicterus). Pyelonephritis in pregnancy → ADMIT for IV antibiotics.
CAUTI: bacteriuria ≥10³ CFU/mL + symptoms + catheter within 48h. Do NOT treat asymptomatic bacteriuria or obtain cultures in asymptomatic catheterized patients. Management = remove/exchange catheter + systemic antibiotics.
Men: UTI is uncommon before age 60 — always obtain culture. Consider occult prostatitis in febrile UTI without flank pain.

⚑ Asymptomatic Bacteriuria — Treat ONLY These Two

Pregnancy — reduces risk of pyelonephritis, preterm birth, low birth weight
Before endourological procedures with mucosal trauma (TURP, cystoscopy with biopsy)
Do NOT treat ASB in: elderly, diabetics, catheterized patients, spinal cord injury, pre-op (non-urologic), renal transplant >1 month post-transplant, or delirium alone without urinary/systemic symptoms

🚨 Classic Trap: Treating ASB in the elderly does NOT reduce mortality, does NOT prevent symptomatic UTI, and INCREASES C. diff risk and antimicrobial resistance. Delirium alone in an elderly patient with bacteriuria should prompt evaluation for OTHER causes of delirium — not reflexive antibiotics.

Recurrent UTI & Prevention

Defined as ≥3 UTIs/year or ≥2 in 6 months. Evidence-based preventive measures:

Adequate fluid intake (≥1.5 L/day)
Cranberry products (modest benefit)
Methenamine hippurate (effective for prevention)
Vaginal estrogen in postmenopausal women
Antibiotic prophylaxis (continuous low-dose or post-coital) for refractory cases

🩺 PANCE Pearl: "Honeymoon cystitis" — UTI associated with intercourse — responds well to post-coital prophylaxis with a single dose of TMP-SMX or nitrofurantoin.

High-Yield Severe Pyelonephritis Variants

Emphysematous pyelonephritis: gas-forming infection, most common in diabetics. CT shows gas in renal parenchyma. Medical emergency — IV antibiotics ± drainage ± nephrectomy.
Xanthogranulomatous pyelonephritis: chronic destructive granulomatous process, often with Proteus or E. coli and staghorn calculi. CT shows "bear paw sign." Treatment = nephrectomy.
Renal cortical abscess (carbuncle): usually hematogenous spread of S. aureus. Perinephric abscess: usually ascending UTI with Gram-negatives. Both may require drainage.

⚑ Board Traps — UTI Summary

Nitrofurantoin = CYSTITIS ONLY — does not penetrate renal tissue. Never for pyelonephritis.
Fosfomycin = CYSTITIS ONLY — same limitation
Fluoroquinolones = FIRST-LINE for pyelonephritis — but NOT for uncomplicated cystitis
TMP-SMX resistance >20% in many US regions — do NOT use empirically for pyelo
CAUTI: Most represent ASB — treat only if symptomatic. Remove catheter if possible.
Proteus mirabilis → urease → alkaline urine (pH >7) → struvite (staghorn) stones
Do NOT treat cloudy or malodorous urine in the absence of symptoms

★ Memory Trick

Nitrofurantoin: "Stays in the URINE — perfect for cystitis, NEVER for pyelo (can't reach kidneys)" FQs: "Tissue penetration = pyelo drug" ASB: "Treat only the PREGNANT and PRE-PROCEDURAL — no one else" Nitrofurantoin long-term: can cause pulmonary fibrosis (chronic use) or acute hypersensitivity pneumonitis, plus hepatotoxicity and peripheral neuropathy.

Clinical Vignette

A 28-year-old pregnant woman at 14 weeks has a urine culture showing 100,000 CFU/mL E. coli. She has no dysuria or fever. What is the most appropriate management?

Answer: Treat — asymptomatic bacteriuria in pregnancy is one of only two indications to treat ASB. Use nitrofurantoin 100mg BID × 5 days or cephalexin. Avoid nitrofurantoin near term (38–42 weeks) due to neonatal hemolytic anemia risk.

Tier 1

Topic 2

HIV/AIDS & Opportunistic Infections

👁 Free Preview

CD4 Thresholds · PCP / Toxo / Crypto / CMV / MAC · IRIS · TMP-SMX Dual Coverage

Diagnosis & Screening

USPSTF: Screen all persons aged 15–65 at least once; all pregnant persons every pregnancy
Diagnostic algorithm: 4th-gen Ag/Ab combo → confirmatory HIV-1/HIV-2 differentiation immunoassay → if indeterminate → HIV-1 RNA (NAT)
Acute HIV: p24 antigen positive before antibodies → mononucleosis-like illness 2–4 weeks post-exposure

OI Prophylaxis by CD4 Count

CD4 Count (cells/mm³)	Opportunistic Infection	Prophylaxis	Board Key
< 200	PCP (Pneumocystis jirovecii)	TMP-SMX DS daily — FIRST-LINE	The single most important OI prophylaxis drug
< 150	Histoplasmosis	Itraconazole 200 mg daily	Endemic areas only — Ohio and Mississippi River valleys
< 100	Toxoplasma (if IgG seropositive)	TMP-SMX DS daily — covers BOTH PCP and Toxoplasma	One drug, two OIs covered
< 100	Cryptococcus (if serum CrAg+)	Fluconazole 200 mg daily	Screen with serum CrAg in high-prevalence settings
< 50	MAC	None if ART is started promptly	Routine MAC prophylaxis is no longer recommended when ART begins immediately
Any count	Latent TB (LTBI)	3HP or 4R preferred; 9H is the alternative — always add pyridoxine with INH	Screen every HIV patient with TST or IGRA at diagnosis

OI Presentations — High-Yield Patterns

OI	CD4 (cells/mm³)	Classic Presentation	Key Dx	Treatment
PCP	< 200	Bilateral diffuse GGO on CT; elevated LDH; hypoxia worsens with exertion; dry cough; CXR may be NORMAL early	Sputum or BAL silver stain/DFA	TMP-SMX high dose × 21d. Add prednisone if PaO₂ <70 or A-a gradient >35.
Toxoplasmosis	< 100	Multiple ring-enhancing lesions on MRI; headache; focal deficits	MRI + toxo serology. Empiric treatment.	Pyrimethamine + sulfadiazine + leucovorin
Crypto meningitis	< 100	Headache, fever, elevated opening pressure on LP; India ink positive	ALWAYS measure opening pressure. CrAg serum + CSF.	Amphotericin B + flucytosine (induction × 2wk) → fluconazole maintenance
CMV retinitis	< 50	"Pizza pie" fundoscopy (hemorrhages + exudates). Vision loss.	Ophthalmologic exam	Valganciclovir PO or ganciclovir IV
MAC	< 50	Fever, night sweats, weight loss, diarrhea, elevated alk phos	Mycobacterial blood cultures	Azithromycin + ethambutol
CNS Lymphoma	< 50	SINGLE ring-enhancing lesion; EBV-associated	CSF EBV DNA; biopsy if no toxo response	Radiation ± chemo; poor prognosis

⚑ Board Traps — HIV/OIs

TMP-SMX = DUAL prophylaxis for PCP AND Toxoplasma — below CD4 <100, one drug covers both OIs
Single ring-enhancing = CNS lymphoma (EBV). Multiple = Toxoplasmosis.
PCP: CXR may be NORMAL early — CT is more sensitive. Elevated LDH + bilateral GGO = classic.
Crypto meningitis: ALWAYS measure opening pressure — elevated ICP (>25 cm H₂O) causes vision loss and death. Therapeutic LPs mandatory.
IRIS: Paradoxical worsening of OI symptoms weeks after starting ART — recovering immune system attacks existing infection.
MAC prophylaxis NO LONGER routinely recommended if ART started immediately (2024)
PCP corticosteroids: Required if PaO₂ <70 or A-a gradient >35 — reduces mortality ~50%

★ Memory Trick

CD4 <200: PCP → TMP-SMX CD4 <100: Add Toxo (TMP-SMX covers both) → "two-for-one" CD4 <50: CMV + MAC + CNS lymphoma → "the deadly fifty" "Single ring = Lymphoma (EBV). Multiple rings = Toxo." "Crypto: ALWAYS check the pressure — elevated ICP kills faster than the fungus"

Before you beginSexually Transmitted Infections1 question

Answer this one before you read the topic. Getting it wrong is expected and useful — attempting a question first is what makes the material below stick. The explanation unlocks only after you submit.

Question 1 of 1 · High Yield · Syphilis · Staging Drives Duration

A 30-year-old woman presents with a single painless, firm, indurated genital ulcer with a clean base that she first noticed about 3 weeks ago. There is mild non-tender inguinal adenopathy. She has no rash, no mucous patches, and no neurologic or ocular symptoms. RPR is reactive at 1:32 and FTA-ABS is positive. She has no drug allergies and is not pregnant. What stage does this represent, and what is the correct treatment?

ASecondary syphilis — benzathine penicillin G 2.4 million units IM weekly × 3 doses BNeurosyphilis — IV aqueous crystalline penicillin G every 4 hours × 10–14 days CLatent syphilis of unknown duration — doxycycline 100 mg orally BID × 28 days DPrimary syphilis — benzathine penicillin G 2.4 million units IM weekly × 3 doses EPrimary syphilis — benzathine penicillin G 2.4 million units IM as a single dose

Click to Reveal Answer

Correct answer: E — Primary syphilis — benzathine penicillin G 2.4 million units IM as a single dose

A solitary painless, indurated, clean-based ulcer is the chancre of primary syphilis. Reactive nontreponemal (RPR) plus confirmatory treponemal (FTA-ABS) testing establishes the diagnosis; the stage is determined by the clinical findings, not by the titer. The single most testable point in syphilis is that staging drives duration, not drug: primary, secondary, and early latent syphilis all receive one intramuscular dose of benzathine penicillin G 2.4 million units. The weekly × 3 regimen belongs to late latent disease and latent syphilis of unknown duration. Follow-up is with quantitative nontreponemal titers at 6 and 12 months, where a fourfold (two-dilution) decline — here 1:32 down to 1:8 — defines an adequate serologic response.

Why the other choices are wrong

Secondary syphilis — benzathine penicillin G 2.4 million units IM weekly × 3 doses — Incorrect on both counts. Secondary syphilis presents with a diffuse non-pruritic copper-colored maculopapular rash involving the palms and soles, condylomata lata, mucous patches, and generalized lymphadenopathy — not with a chancre. And even when secondary disease is present, the treatment remains a single dose.
Neurosyphilis — IV aqueous crystalline penicillin G every 4 hours × 10–14 days — Incorrect. Neurosyphilis requires neurologic, ocular, or otic findings to justify lumbar puncture and IV therapy. This patient has none. Reflexively escalating to IV penicillin exposes the patient to a central line and 10–14 days of inpatient or infusion therapy for no benefit.
Latent syphilis of unknown duration — doxycycline 100 mg orally BID × 28 days — Incorrect. Latent syphilis is by definition seroreactivity without clinical findings; this patient has an active lesion, so she cannot be latent. Doxycycline 100 mg BID (14 days for early disease, 28 days for late latent) is only an alternative for the non-pregnant penicillin-allergic patient — never the preferred agent when penicillin can be given.
Primary syphilis — benzathine penicillin G 2.4 million units IM weekly × 3 doses — Incorrect, and the highest-yield distractor on this topic. The stage is identified correctly, but the duration is wrong. Three weekly doses are reserved for late latent syphilis or latent syphilis of unknown duration, where the organism burden is low and replication is slow. Over-treating primary syphilis is not the tested error; the tested error is applying the weekly regimen to early disease and thereby signaling that you have not learned which regimen maps to which stage.

Board pearlPainless indurated ulcer = chancre = primary syphilis. Herpes is the painful one; syphilis is the painless one, and that single adjective decides the question. Memorize the duration map: primary, secondary, and early latent all get ONE dose of benzathine penicillin G 2.4 million units IM — late latent and unknown duration get three weekly doses — neurosyphilis gets IV aqueous penicillin G for 10–14 days. In pregnancy, penicillin is the only acceptable therapy; a penicillin-allergic pregnant patient must be desensitized, never switched to doxycycline (teratogenic) or azithromycin (resistance and treatment failure). Expect the Jarisch-Herxheimer reaction — fever, chills, myalgias, and headache within 24 hours of the first dose — and recognize it as expected endotoxin release, not an allergy and not a reason to stop treatment.

Covered below under Module 3 — Syphilis

Tier 1

Topic 3

Infective Endocarditis

2023 Duke Criteria · Organisms by Context · Osler vs Janeway · Surgical Indications

Duke Criteria — PANCE Version (Classic)

Definite IE: 2 Major OR 1 Major + 3 Minor OR 5 Minor criteria

Major Criteria:

Positive blood cultures: typical organism (S. aureus, viridans Strep, HACEK) from ≥2 separate cultures
Evidence of endocardial involvement: vegetation on echo OR new valvular regurgitation

Minor Criteria:

Predisposing condition (valve disease, IVDU)
Fever ≥38°C
Vascular phenomena (emboli, Janeway lesions, mycotic aneurysm)
Immunologic phenomena (Osler nodes, Roth spots, RF positive)
Positive blood cultures not meeting major criteria

🩺 PANCE Pearl: Osler nodes = painful (immune complex) · Janeway lesions = painless (septic emboli). "Osler HURTS, Janeway DOESN'T." Both are peripheral signs of IE.

Organisms by Clinical Context

Organism	Classic Association	Board Key
S. aureus	IVDU (tricuspid), acute IE, prosthetic valves	#1 cause overall. IVDU → right-sided tricuspid valve. High mortality.
Viridans streptococci	Native valve subacute, dental procedures	Subacute course. Penicillin-susceptible.
S. bovis/gallolyticus	Colon lesions, elderly	MANDATORY colonoscopy — ~60% colorectal neoplasia association
Enterococcus	GI/GU procedures	Synergistic therapy: ampicillin + gentamicin OR ampicillin + ceftriaxone
HACEK organisms	Culture-negative IE (slow-growing gram-negatives)	Treat with ceftriaxone. Prolonged incubation needed for cultures.
S. epidermidis (CoNS)	Prosthetic valve <60 days	Early prosthetic (<60d) = CoNS. Late (>60d) = same as native valve.

Peripheral Signs — Osler vs Janeway

Finding	Pain?	Mechanism	Location
Osler nodes	PAINFUL — "Ouch-sler"	Immune complex deposition	Finger/toe pulp
Janeway lesions	PAINLESS	Septic microemboli	Palms and soles
Roth spots	—	Retinal hemorrhages with white center	Fundoscopic exam
Splinter hemorrhages	—	Septic microemboli in nail capillaries	Subungual

Surgical Indications (Class I)

Heart failure from valvular dysfunction
Uncontrolled infection despite ≥5–7 days appropriate antibiotics
Abscess, pseudoaneurysm, or fistula formation
Large mobile vegetations >10mm with embolic events
Fungal IE — large vegetations, refractory to antifungals alone

⚑ Board Traps — Endocarditis

S. bovis/gallolyticus IE = colonoscopy always (~60% colon neoplasia)
Blood cultures × 3 sets BEFORE antibiotics
Osler = Ouch (painful). Janeway = painless (palms/soles).
Prophylaxis: Only for highest-risk patients (prosthetic valves, prior IE, unrepaired cyanotic CHD) undergoing dental procedures with gingival manipulation. NOT for GI/GU procedures.
S. aureus is now #1 overall IE organism — surpassed viridans strep due to IVDU increase

★ Memory Trick

Osler vs Janeway: "Osler = Ouch (painful, immune). Janeway = Just painless (palms/soles, embolic)" S. bovis: "Bovis has a colonoscopy ticket — always" HACEK: "Culture-negative slow growers — treat with ceftriaxone" "CoNS (<60d prosthetic) → CoNS same (>60d) → native valve organisms"

Before you beginBacterial Meningitis1 question

Question 1 of 1 · High Yield · Bacterial Meningitis — Dexamethasone Timing

A 19-year-old college student has fever, severe headache, neck stiffness, photophobia, confusion, and non-blanching petechiae, consistent with bacterial meningitis. Before a CT scanner is available, in what sequence should interventions occur, and why does dexamethasone timing relative to antibiotics matter?

ABlood cultures, dexamethasone, then antibiotics BAntibiotics first, then dexamethasone once the LP confirms the diagnosis COmit dexamethasone — no benefit in adult bacterial meningitis DCT head before any treatment, even if this delays antibiotics ELumbar puncture and CSF analysis before starting any antibiotics

Click to Reveal Answer

Correct answer: A — Blood cultures, dexamethasone, then antibiotics

The correct sequence for suspected bacterial meningitis with this presentation is: (1) blood cultures x2 immediately, (2) dexamethasone 0.15 mg/kg IV, (3) ceftriaxone plus vancomycin — all completed within 30 minutes. The critical timing concept is that dexamethasone must be given BEFORE or WITH (never after) the first antibiotic dose. The mechanism: antibiotics cause bacterial cell wall lysis, which releases inflammatory mediators and cytokines that drive much of the morbidity in bacterial meningitis (including hearing loss and neurologic sequelae). Dexamethasone given before/with antibiotics blunts this inflammatory cascade; given afterward, it provides little to no benefit since the inflammatory response has already been triggered.

Why the other choices are wrong

Antibiotics first, then dexamethasone once the LP confirms the diagnosis — Incorrect. This sequence eliminates the benefit of dexamethasone, since its protective effect against the inflammatory cytokine cascade depends on administration before or simultaneous with the first antibiotic dose — giving it after antibiotics (and after bacterial lysis has already triggered the inflammatory response) provides minimal benefit.
Omit dexamethasone — no benefit in adult bacterial meningitis — Incorrect. Dexamethasone has demonstrated benefit in adult bacterial meningitis, particularly for pneumococcal meningitis, in reducing neurologic complications including hearing loss — it should be included in the treatment protocol, given before or with the first antibiotic dose.
CT head before any treatment, even if this delays antibiotics — Incorrect — and potentially fatal. Treatment (antibiotics, dexamethasone) should never be delayed for CT imaging in suspected bacterial meningitis with this presentation — CT is only needed before lumbar puncture if there are specific signs of mass effect (papilledema, focal neurologic deficits, severely altered mental status), and even then, antibiotics should be started before the CT, not after.
Lumbar puncture and CSF analysis before starting any antibiotics — Incorrect — and dangerous. While LP provides valuable diagnostic information, antibiotics (along with dexamethasone) should never be delayed for LP in suspected bacterial meningitis with this severity of presentation — if LP cannot be performed immediately (e.g., due to need for CT first), antibiotics and dexamethasone should still be given promptly without waiting.

Board pearlDexamethasone must precede or accompany the first antibiotic dose — never follow it. Antibiotics lyse the organism and release inflammatory cell-wall products; steroids given afterwards have missed the surge they exist to blunt. The benefit is clearest in pneumococcal meningitis, reducing hearing loss and mortality. CT before LP is required only for focal deficit, papilloedema, seizure, immunocompromise, or altered consciousness — and even then the antibiotic goes in first.

Covered below under Topic 4 — Bacterial Meningitis

Tier 1

Topic 4

Bacterial Meningitis

Age-Based Coverage · CSF Patterns · Dexamethasone Timing · Never Delay ABx

Age-Based Empiric Coverage

Age Group	Key Organisms	Empiric Therapy	Board Key
Neonates (0–28d)	Group B Strep, E. coli, Listeria	Ampicillin + cefotaxime (or gentamicin)	GBS #1 neonates
Children/Adults (1mo–50yr)	S. pneumoniae (#1), N. meningitidis	Vancomycin + ceftriaxone	Vanco covers pen-resistant pneumococcus
Adults >50 / Immunocompromised / Pregnant	S. pneumoniae, N. meningitidis, Listeria	Vancomycin + ceftriaxone + AMPICILLIN	Cephalosporins have ZERO Listeria coverage — ampicillin is essential

CSF Pattern Recognition

Parameter	Bacterial	Viral (Aseptic)	Fungal/TB
Opening Pressure	Elevated (>20 cm H₂O)	Normal or mildly elevated	Elevated
WBC / Cell type	>1000, neutrophil predominant	10–500, lymphocyte predominant	10–500, lymphocyte
Glucose	LOW (<40 mg/dL)	Normal	LOW
Protein	HIGH (>250 mg/dL)	Normal/mildly elevated	HIGH

Key Management Rules

Antibiotics within 1 hour — delay >6h increases mortality from 6% to 45%
Dexamethasone BEFORE or WITH first antibiotic dose — reduces mortality in pneumococcal meningitis. No benefit if given after antibiotics.
CT needed first? (focal deficits, papilledema, immunocompromised) → draw blood cultures + give dexa + start antibiotics FIRST, then CT, then LP
N. meningitidis contacts: Rifampin, ciprofloxacin, or IM ceftriaxone × 1 dose
Waterhouse-Friderichsen: Meningococcal septicemia → bilateral adrenal hemorrhage → DIC + purpura fulminans + adrenal crisis + shock

⚑ Board Traps — Meningitis

NEVER delay antibiotics for CT or LP — blood cultures + dexa + antibiotics FIRST if CT needed
Dexamethasone BEFORE or WITH first dose — post-antibiotic dexa provides zero benefit
ADD AMPICILLIN for >50, neonates, pregnant, immunocompromised — cephalosporins do NOT cover Listeria
S. pneumoniae = #1 adult meningitis — vancomycin added for resistant strains

★ Memory Trick

Coverage: "Adults = Vanc + Ceftriaxone. Over 50 = Add Ampicillin (Listeria)" "Cephalosporins can't touch Listeria — only ampicillin works" Dexa timing: "BEFORE or WITH — not after. The first dose is the only chance." CSF: "Bacterial = Bugs (neutrophils) + Bad glucose + Big protein"

Part 2 · Extended Coverage · Access Locked

Additional PANCE Infectious Disease Topics

Everything beyond the core six — still fully tested, still fully worked. Included with bootcamp enrollment.

Before you beginSepsis & Community-Acquired Pneumonia1 question

Question 1 of 1 · High Yield · Septic Shock — Surviving Sepsis Hour-1 Bundle

A 68-year-old nursing home patient arrives obtunded with BP 74/44, HR 128, T 39.4°C, RR 28, and lactate 5.2 mmol/L, meeting criteria for septic shock. A colleague suggests obtaining a CT scan before starting antibiotics to identify the infection source first. What is the correct sequence according to the 2021 Surviving Sepsis Campaign Hour-1 Bundle?

A30 mL/kg crystalloid is a strict requirement before anything else BBlood cultures are no longer required before antibiotics CStart vasopressors immediately, before any fluid resuscitation DAntibiotics within 1 hour, with CT imaging performed afterward ECT imaging first to identify and drain the source before antibiotics

Click to Reveal Answer

Correct answer: D — Antibiotics within 1 hour, with CT imaging performed afterward

The Surviving Sepsis Campaign Hour-1 Bundle mandates that broad-spectrum antibiotics be administered within 1 hour of septic shock recognition — this should not be delayed for imaging studies to identify the source. The correct sequence is: obtain lactate, draw blood cultures x2, administer broad-spectrum antibiotics, give fluid resuscitation (30 mL/kg crystalloid for hypotension or lactate ≥4, though this fluid volume recommendation was downgraded from mandatory to suggested in 2021), and start vasopressors if needed to maintain MAP ≥65 if fluids are inadequate. Source-identifying imaging like CT should be obtained after these immediate life-saving interventions, not before.

Why the other choices are wrong

30 mL/kg crystalloid is a strict requirement before anything else — Incorrect. While fluid resuscitation remains important, the 2021 SSC update specifically DOWNGRADED the 30 mL/kg fluid recommendation from a strict mandate to a suggestion, recognizing that fluid overload can also harm septic patients — this fluid volume should be individualized, not treated as an absolute mandatory first step before other bundle elements.
Blood cultures are no longer required before antibiotics — Incorrect. Blood cultures (x2, from different sites) remain a core component of the Hour-1 Bundle and should be obtained promptly — ideally before antibiotics when this doesn't meaningfully delay administration, since cultures guide subsequent antimicrobial de-escalation.
Start vasopressors immediately, before any fluid resuscitation — Incorrect. The standard approach still generally involves initial fluid resuscitation, with vasopressors added if the patient remains hypotensive despite fluids (to maintain MAP ≥65) — though both fluids and vasopressors should be considered together rather than treating vasopressors as the absolute first step before any fluid administration.
CT imaging first to identify and drain the source before antibiotics — Incorrect — and dangerous. This significantly delays antibiotic administration, which is time-critical in septic shock — each hour of delayed appropriate antibiotics is associated with increased mortality. Antibiotics should never be delayed for source-identifying imaging in septic shock.

Board pearlNothing delays the antibiotic — not a CT, not the lumbar puncture, not a specialist call. The Hour-1 bundle order is lactate, two blood cultures, broad-spectrum antibiotics, then 30 mL/kg crystalloid for hypotension or lactate at or above 4, with vasopressors added if the MAP stays under 65. Cultures go before antibiotics only because they take seconds; if drawing them would delay therapy, give the antibiotic. Remember Sepsis-3: sepsis is infection plus organ dysfunction, and septic shock adds a pressor requirement with lactate above 2.

Covered below under Topic 5 — Sepsis & Septic Shock

Tier 1

Topic 5

Sepsis & Septic Shock

Sepsis-3 · SSC 2021 Hour-1 Bundle · Norepinephrine First · Lactate Clearance

★★★ PANCE PrioritySSC 2021

Why the PANCE Tests This

Sepsis is the #1 cause of ICU mortality in the US. Boards test: Sepsis-3 definition (SOFA-based, NOT SIRS), vasopressor selection, the Hour-1 Bundle, and fluid strategy. Multiple questions per exam.

Definitions — Sepsis-3 (2016)

Sepsis: Life-threatening organ dysfunction from dysregulated host response to infection. SOFA score increase ≥2 points.
Septic shock: Sepsis + vasopressors needed for MAP ≥65 mmHg + serum lactate >2 mmol/L despite adequate fluids. Mortality >40%.
qSOFA: AMS + SBP ≤100 + RR ≥22. Screening tool ONLY — NOT diagnostic. SSC 2021 recommends AGAINST using qSOFA alone for screening.

SSC 2021 Hour-1 Bundle

The 5-Step Bundle — All Within Hour 1

1. Measure lactate — re-measure if >2 mmol/L. Lactate >4 = high-risk.
2. Blood cultures × 2 sets from separate sites BEFORE antibiotics
3. Broad-spectrum antibiotics within 1 hour — every hour of delay increases mortality ~7%
4. 30 mL/kg IV crystalloid within 3h for hypotension or lactate ≥4 (downgraded to WEAK recommendation 2021)
5. Vasopressors if MAP <65 during or after fluids — start peripherally, do NOT wait for central access

Vasopressor Hierarchy

Line	Agent	Notes	Board Key
First-line	Norepinephrine	Titrate to MAP ≥65	NOT dopamine — higher arrhythmia risk with dopamine
Second-line	Vasopressin 0.03 units/min	Add when NE ≥0.25–0.5 mcg/kg/min	NE-sparing; fixed dose
Third-line	Epinephrine	Refractory shock	Can cause lactic acidosis (β2)
Adjunct	Hydrocortisone 200 mg/day CI	Vasopressor-refractory septic shock	Weak recommendation; improves shock reversal

Balanced crystalloids (LR) preferred over NS — reduces AKI (SMART trial)
Peripheral vasopressor start is acceptable — SSC 2021 endorses peripheral initiation

⚑ Board Traps — Sepsis

Sepsis-3 = ORGAN DYSFUNCTION (SOFA ≥2), NOT just SIRS — fever + tachycardia + leukocytosis alone is no longer "sepsis"
qSOFA is NOT a diagnostic criterion — SSC 2021 recommends against using it alone for screening
Norepinephrine is FIRST-LINE — NOT dopamine. Dopamine: higher arrhythmia risk, worse outcomes in cardiogenic shock subgroup.
Antibiotics within 1 hour — blood cultures first but do NOT delay antibiotics waiting for results
30 mL/kg crystalloid was downgraded to WEAK recommendation in 2021 — use dynamic measures (passive leg raise, pulse pressure variation) to guide further fluids
Do NOT delay vasopressors for central access — start peripherally now

★ Memory Trick

Hour-1 Bundle: "LACTATE" — Lactate measure + Antibiotics + Cultures (blood) before ABx + Target MAP 65 + End with vasopressors "SIRS is DEAD — Sepsis-3 needs SOFA ≥2" Vasopressor order: "NE → Vaso → Epi" — Never Very Easy to manage refractory shock

Clinical Vignette

A 72-year-old diabetic presents with fever, confusion, BP 78/48, lactate 5.2 mmol/L. Blood cultures drawn. Dopamine is started peripherally by the covering team.

Answer: Two errors — (1) norepinephrine is first-line, NOT dopamine; (2) peripheral initiation is acceptable and correct (not an error). Broad-spectrum antibiotics should have been started simultaneously. LR 30 mL/kg bolus should accompany. Hydrocortisone 200 mg/day if vasopressor-refractory.

📚 Now taught in the Pulmonary syllabus. Community-acquired pneumonia is worked in full in Pulmonary Module 3, which owns this topic to avoid teaching it twice across the two syllabi.

Tier 1

Topic 6

Clostridioides difficile Infection (CDI)

Metronidazole No Longer First-Line · Vancomycin/Fidaxomicin · FMT · Soap & Water

Diagnosis

Test only symptomatic patients: ≥3 unformed stools/24h, NOT on laxatives
Two-step algorithm: GDH EIA + Toxin A/B EIA → if discordant → NAAT (PCR) as tiebreaker
Do NOT test asymptomatic patients — colonization without symptoms needs no treatment
Do NOT use as test-of-cure — stool can remain positive 4–6 weeks after resolution

Treatment by Severity

Episode/Severity	Definition	Treatment
Initial, Nonsevere	WBC ≤15K, Cr <1.5	Vancomycin 125mg PO QID × 10d OR Fidaxomicin 200mg BID × 10d
Initial, Severe	WBC >15K or Cr ≥1.5	Vancomycin 125mg PO QID × 10d OR Fidaxomicin 200mg BID × 10d
Fulminant	Hypotension, ileus, toxic megacolon	Vancomycin 500mg PO QID + Metronidazole 500mg IV TID ± Vancomycin per rectum (if ileus)
1st Recurrence	—	Vancomycin taper/pulse OR Fidaxomicin (preferred — fewer recurrences)
2nd+ Recurrence	—	FMT — >85% cure rate. FDA-approved: Rebyota (fecal), Vowst (oral spores)

⚑ Board Traps — C. difficile

Metronidazole is NO LONGER first-line for CDI — vancomycin or fidaxomicin for all initial episodes
Metronidazole IV only in FULMINANT CDI with ileus — always combined with oral/rectal vancomycin, NEVER alone
Fidaxomicin has fewer recurrences — preferred when cost permits
Soap and water ONLY during C. diff outbreaks — alcohol sanitizer does NOT kill spores
Stop the inciting antibiotic ASAP — continuing it increases recurrence
Do NOT test asymptomatic patients — colonization ≠ infection

★ Memory Trick

CDI treatment: "Vanco or Fidaxo — Metronidazole is RETIRED from first-line" "Metro IV only in FULMINANT (ileus) — always WITH oral/rectal vanco, never alone" FMT: "85% cure for recurrent C. diff — the gold standard" "SOAP AND WATER for C. diff — alcohol gel doesn't kill spores"

Clinical Vignette

A 74-year-old on piperacillin-tazobactam develops 6 watery stools/day. C. diff toxin positive, WBC 22K, Cr 1.8. No ileus, no hypotension.

Answer: Severe CDI (WBC >15K + Cr ≥1.5). Treat with vancomycin 125mg PO QID × 10 days OR fidaxomicin. NOT metronidazole. Stop pip-tazo if possible. No ileus → no IV metronidazole or rectal vanco needed. Soap-and-water handwashing. Contact precautions.

Tier 1

Topic 7

Skin & Soft Tissue Infections

Cellulitis · Abscess I&D · MRSA Coverage Rules · Erysipelas · Necrotizing Fasciitis · LRINEC · Dishwater Fluid

Classification & Treatment (IDSA 2014)

Type	Organism	Treatment	Board Key
Mild nonpurulent cellulitis	β-hemolytic Streptococcus — groups A, B, C, G (NOT MRSA)	Oral cephalexin or dicloxacillin × 5 days. Go IV if systemic toxicity, rapid spread, or immunocompromised.	Routine MRSA coverage NOT needed
Moderate cellulitis	β-hemolytic Strep	IV cefazolin or ceftriaxone	Upgrade if 1–2 SIRS criteria
Severe cellulitis	Mixed, MRSA possible	Admit. IV vancomycin + pip-tazo. Surgical consult if necrotizing features.	SIRS + hypotension/sepsis
Purulent SSTI (abscess)	S. aureus — CA-MRSA is the presumed organism	I&D is PRIMARY treatment. Add TMP-SMX/doxy only if surrounding cellulitis or SIRS.	Antibiotics alone = insufficient
Erysipelas	Group A Strep	Penicillin VK or amoxicillin (IV PCN G if severe)	Sharply demarcated, raised, bright red borders

Necrotizing Fasciitis — Recognition and Surgical Emergency

Classic triad: pain out of proportion to exam + rapid progression + systemic toxicity, with woody, hard induration of the involved tissue
The pain-out-of-proportion sign: early NF can look like benign cellulitis on the surface while the deep fascia is already necrotic. Pain dramatically exceeding the visible findings is NF until proven otherwise.
Physical progression: skin discoloration → bullae → necrosis → crepitus (gas in tissues)
"Dishwater fluid" at exploration: gray-brown watery discharge with no frank pus is pathognomonic for polymicrobial necrotizing fasciitis
Gas on CT or crepitus on exam means anaerobes in the fascia — a surgical emergency. Do NOT delay surgery for further imaging when the clinical diagnosis is already clear.
LRINEC score (Laboratory Risk Indicator for Necrotizing Fasciitis — CRP, WBC, hemoglobin, sodium, creatinine, glucose): ≥8 = high risk. A useful adjunct that does not replace clinical judgment — a low score never rules NF out.
Type I (polymicrobial): Bacteroides + streptococci + coliforms; mixed aerobic/anaerobic; trunk and perineum (Fournier gangrene)
Type II (group A Streptococcus, often alone): extremities, more aggressive, frequently with toxic shock syndrome
Treatment: IMMEDIATE surgical debridement + IV vancomycin + piperacillin-tazobactam, plus clindamycin for exotoxin suppression in suspected group A strep. Antibiotics alone are never curative.
Mortality exceeds 30% when debridement is delayed — no antibiotic regimen can sterilize necrotic tissue

⚑ Board Traps — SSTI

Nonpurulent cellulitis is streptococcal, NOT MRSA — routine empiric MRSA coverage is not needed. This is the most commonly missed SSTI principle.
TMP-SMX does NOT adequately cover β-hemolytic streptococci. It covers CA-MRSA well and strep poorly, so for nonpurulent cellulitis the answer is cephalexin, not TMP-SMX.
Purulent SSTI: incision and drainage (I&D) is the definitive treatment — antibiotics alone fail against a loculated collection, and are adjunctive only for surrounding cellulitis or systemic signs.
Antibiotics alone never cure necrotizing fasciitis — surgery is the only cure, and every hour of delay raises mortality.
Five days is sufficient for uncomplicated cellulitis — longer courses are a distractor.
Pseudocellulitis is misdiagnosed roughly 30% of the time — consider stasis dermatitis, DVT, gout, and contact dermatitis before escalating antibiotics.
"Pain out of proportion" plus rapid spread means operate NOW — not another dose, not another scan.

★ Memory Trick

Nonpurulent cellulitis = Strep → cephalexin (NOT vancomycin) Purulent (abscess) = MRSA possible → I&D FIRST Erysipelas: "Sharp borders + Group A Strep + Penicillin" NF: "Pain out of proportion = danger out of proportion = OPERATE NOW"

Tier 1

Topic 8 ★ Gap Added

Influenza

Oseltamivir Timing · High-Risk Groups · Zanamivir Contraindication · Reye Syndrome

Core Recognition

Classic: Abrupt onset fever (38.5–40°C) + myalgias + headache + dry cough + malaise — "hit by a truck" feeling
vs. Common cold: Flu = sudden onset, high fever, prominent myalgias. Cold = gradual, mild/no fever, nasal congestion predominant.
Diagnosis: Rapid influenza diagnostic test (RIDT) — fast but low sensitivity (~70%). RT-PCR is gold standard. Treat empirically if high clinical suspicion even if RIDT negative.
Complications: Primary influenza pneumonia; secondary bacterial pneumonia (S. pneumoniae, MRSA, H. influenzae); myocarditis; encephalitis

High-Risk Groups for Complications

Age ≥65 or <5 years (especially <2)
Pregnancy (up to 2 weeks postpartum)
Chronic conditions: pulmonary (COPD, asthma), cardiovascular, renal, hepatic, DM
Immunocompromised; Obesity (BMI ≥40); Long-term care facility residents

Antiviral Treatment

Drug	Route/Duration	Board Key
Oseltamivir (Tamiflu)	75mg BID × 5 days PO	First-line for most patients. Safe in pregnancy. Adjust for renal impairment.
Zanamivir (Relenza)	2 inhalations BID × 5 days (inhaled)	CONTRAINDICATED in asthma/COPD — risk of severe bronchospasm
Baloxavir marboxil (Xofluza)	Single oral dose (weight-based)	Alternative for uncomplicated flu in low-risk outpatients
IV peramivir	600mg IV × 1 dose	For hospitalized patients who cannot take oral/inhaled medications

⚑ Antiviral Timing — The Critical Rule

Maximum benefit within 48 hours of symptom onset — reduces duration ~1–2 days
Treat high-risk patients regardless of symptom duration — benefit persists beyond 48h in hospitalized/high-risk
Low-risk patients with symptoms >48h: Antivirals unlikely to benefit — supportive care
Treat confirmed or suspected flu WITHOUT waiting for test results in high-risk patients

Vaccination

Annual influenza vaccination for everyone ≥6 months
Adults ≥65: High-dose (Fluzone HD) or adjuvanted (Fluad) — superior immunogenicity
Live attenuated (FluMist): Preferred for healthy non-pregnant adults 2–49 years. Contraindicated: immunocompromised, pregnant, asthma/severe wheeze, <2yr, >49yr.

⚑ Board Traps — Influenza

Oseltamivir within 48 hours for maximum benefit — but give to high-risk patients regardless of duration
Zanamivir (inhaled) CONTRAINDICATED in asthma and COPD — severe bronchospasm risk
Negative rapid test does NOT rule out influenza — sensitivity ~70%. Treat if suspicious in high-risk patient.
Aspirin/salicylates CONTRAINDICATED in children with influenza — Reye syndrome (hepatic failure + encephalopathy)
Secondary MRSA pneumonia post-influenza: Patient improves then suddenly deteriorates → MRSA pneumonia. Add vancomycin or linezolid.

★ Memory Trick

Tamiflu timing: "48-hour rule — best within 48h. But give anyway in high-risk or hospitalized." Zanamivir: "Inhaled = no asthma, no COPD — bronchospasm risk" "Negative rapid test ≠ no flu — only 70% sensitive. Treat if suspicious." "Aspirin in kids + flu = Reye syndrome — NEVER" Secondary bacterial pneumonia: "Gets better → gets MUCH worse = MRSA. Add vancomycin."

Tier 1

Topic 9 ★ Gap Added

COVID-19 (SARS-CoV-2)

Paxlovid · Ritonavir CYP3A4 Interactions · Dexamethasone Indication · COVID-19 Antivirals

Antiviral Treatment — High-Risk Outpatients

Drug	Mechanism/Duration	Board Key
Nirmatrelvir/ritonavir (Paxlovid)	Protease inhibitor + CYP3A4 inhibitor booster. 5 days PO. Start within 5 days of onset.	Multiple CYP3A4 drug interactions via ritonavir. ~85% reduction in hospitalization/death in high-risk.
Remdesivir	RNA polymerase inhibitor. 3 days IV (outpatient) or 5 days IV (hospitalized non-ventilated)	3-day IV course for high-risk outpatients who cannot take oral medications
Molnupiravir	RNA polymerase inhibitor (mutagenic). 5 days PO.	Less effective than Paxlovid. CONTRAINDICATED in pregnancy — mutagenic potential.
Dexamethasone 6mg/day × ≤10d	Anti-inflammatory	ONLY for hospitalized patients requiring O₂ or ventilatory support (RECOVERY trial). AVOID in non-O₂-requiring outpatients.

Paxlovid Drug Interactions — Critical for PANCE

Ritonavir is a potent CYP3A4 inhibitor — dramatically increases levels of co-administered drugs:

Drug Category	Examples	Action Required
CYP3A4-metabolized statins	Atorvastatin, simvastatin, lovastatin	HOLD during Paxlovid course — risk of myopathy/rhabdomyolysis. OK: rosuvastatin, pravastatin.
DOACs	Rivaroxaban, apixaban, warfarin	Dose adjustment or hold. Increase INR monitoring for warfarin.
Immunosuppressants	Tacrolimus, cyclosporine, sirolimus	Dramatic level increase → toxicity. Urgent dose reduction + level monitoring.
CYP3A4 inducers (reduce Paxlovid efficacy)	Carbamazepine, phenytoin, phenobarbital, rifampin	These LOWER Paxlovid levels → choose alternative antiviral
Cardiac drugs	Amiodarone, dronedarone, ranolazine	Avoid — risk of serious arrhythmias

Severe / Hospitalized COVID-19

Dexamethasone 6mg daily × ≤10 days: All hospitalized patients requiring supplemental O₂ (RECOVERY trial)
Remdesivir 5-day course: For hospitalized patients not yet requiring mechanical ventilation
Baricitinib or tocilizumab: For rapidly increasing O₂ requirements
Therapeutic anticoagulation: Markedly elevated D-dimer = high VTE risk

⚑ Board Traps — COVID-19

Paxlovid drug interactions are a major board topic — hold CYP3A4-metabolized statins. Check tacrolimus in transplant patients. Anticoagulation dose adjustment.
Dexamethasone ONLY for O₂-requiring hospitalized patients — may worsen outcomes in non-hypoxic outpatients
Molnupiravir CONTRAINDICATED in pregnancy — mutagenic
Paxlovid "rebound": Symptom recurrence 2–8 days after completing course — supportive care; re-treatment not routine
Negative rapid antigen test in symptomatic patient: Confirm with PCR if clinical suspicion high
Start Paxlovid within 5 days of symptom onset

★ Memory Trick

Paxlovid: "Start within 5 days — check ALL medications for CYP3A4 interactions" "Hold the CYP3A4 statins (atorvastatin, simvastatin) — ritonavir makes levels skyrocket" Dexamethasone: "Only when they need O₂ — don't use in mild outpatient disease" Molnupiravir in pregnancy: "Mutagenic = NEVER in pregnancy"

Module D · Must-Know Differentials

High-Yield Differentials & Distinguishing Features

These five differentials represent the highest-frequency diagnostic challenges in infectious disease on the PANCE/PANRE. Each framework targets the single pivotal feature that separates one diagnosis from another — the exact decision point boards test.

Tier 1

Differential D-1

Fever + Rash — The Must-Not-Miss Differential

RMSF · Meningococcemia · Viral Exanthem · Drug Reaction · Secondary Syphilis · Toxic Shock

★★★ Most-Tested ID DifferentialMultiple Fatal Diagnosis Traps

The Pivotal Distinguishing Feature Table

Diagnosis	Rash Character	Key Distinguishing Feature	Cannot Miss
Rocky Mountain Spotted Fever (RMSF)	Blanching macules/papules → petechiae → purpura. Starts wrists/ankles → spreads centrally (centripetal). Palms and soles involved.	Tick exposure history (Dermacentor tick). Fever + rash on palms/soles = RMSF until proven otherwise.	Start doxycycline IMMEDIATELY — do NOT wait for confirmatory testing. Delay = death. Even in children.
Meningococcemia (N. meningitidis)	Petechial/purpuric rash — non-blanching. Rapid spread. May progress to purpura fulminans.	Abrupt onset high fever + meningismus + non-blanching petechiae = meningococcemia. College student, complement deficiency, asplenia are risk factors.	Blood cultures + IV ceftriaxone immediately. Rifampin prophylaxis for close contacts. Waterhouse-Friderichsen = bilateral adrenal hemorrhage.
Viral Exanthem (measles, rubella, EBV, enterovirus)	Maculopapular, erythematous, blanching. Spreads cephalocaudally (head to toe) in measles.	Koplik spots (white dots on buccal mucosa) = measles pathognomonic. EBV: posterior cervical lymphadenopathy + splenomegaly + atypical lymphocytes.	Amoxicillin rash in EBV is maculopapular, not urticarial — does NOT mean penicillin allergy.
Drug-Induced Exanthem / SJS / TEN	Maculopapular → urticarial. SJS: targetoid lesions + mucosal involvement + epidermal detachment <10% BSA. TEN: >30% BSA detachment.	Onset 1–3 weeks after starting new drug (allopurinol, sulfonamides, anticonvulsants, NSAIDs). Mucosal involvement = SJS/TEN not simple drug rash.	SJS/TEN: stop the offending drug immediately. Burn unit care. Steroids controversial. Mortality in TEN up to 30%.
Secondary Syphilis	Copper-colored maculopapular rash — characteristically involves palms and soles. Non-pruritic.	Diffuse rash + palms/soles + lymphadenopathy + condyloma lata + 4–10 weeks after primary chancre. RPR/VDRL positive.	Secondary syphilis rash is non-pruritic — if the rash itches, reconsider. Palm/sole involvement is the classic board clue.
Toxic Shock Syndrome (TSS)	Diffuse sunburn-like erythroderma. Desquamation of palms/soles occurs 1–2 weeks later.	Tampon use or wound infection + fever >38.9 + hypotension + diffuse sunburn rash + multi-organ involvement. S. aureus toxin (TSST-1) mediated.	Streptococcal TSS is more severe (higher mortality ~30–60%). Source control (remove tampon, debride wound) is critical.

⚑ Board Traps — Fever + Rash

RMSF: "Rocky Mountain" is a misnomer — most cases occur in the South Atlantic states (North/South Carolina, Oklahoma, Arkansas, Tennessee). Not just the Rocky Mountains. History of tick bite in any endemic area = RMSF until proven otherwise.
Start doxycycline for RMSF before lab confirmation — indirect fluorescent antibody testing takes time. The window period (day 3–5 of illness) is when rash appears. Waiting for confirmation = death. This principle is tested repeatedly.
Amoxicillin rash in EBV is NOT a penicillin allergy — it is a pharmacologic reaction from the immune activation of EBV interacting with the aminopenicillin. The patient is NOT truly allergic and should not have "penicillin allergy" in their chart.
Non-blanching petechiae/purpura = emergent situation — meningococcemia or RMSF. Do not dismiss petechiae as "viral" in a febrile patient. A glass-press test (skin blanching with pressure) distinguishes purpura (non-blanching) from viral rash (blanching).

★ Memory Trick

RMSF: "Palms + Soles + Tick exposure = doxycycline NOW — don't wait" Meningococcemia: "Non-blanching petechiae + sick-looking patient = blood cultures + ceftriaxone" Secondary syphilis: "Copper penny rash on palms and soles = syphilis. Check RPR." "Fever + Rash + Sick = Doxy first, ask questions later"

Tier 1

Differential D-2

Meningitis — CSF Pattern Interpretation

Bacterial vs Viral vs Fungal vs TB · Opening Pressure · Cell Count · Glucose · Protein

★★★ PANCE PriorityLP Sequencing Trap

CSF Pattern Recognition — The Most-Tested Table in ID

Type	Opening Pressure	WBC (cells/μL)	Predominant Cell	Glucose	Protein	Key Feature
Bacterial	↑↑ (>200)	>1000 (100–10,000)	Neutrophils (PMN)	↓↓ (<45 mg/dL or <60% serum)	↑↑ (>100 mg/dL)	Gram stain + culture. Empiric: ceftriaxone + vancomycin + dexamethasone ± ampicillin
Viral (Aseptic)	Normal or mildly ↑	10–500 (usually <300)	Lymphocytes	Normal (≥45)	Normal or mildly ↑ (<100)	Enteroviruses most common. HSV: lymphocytic pleocytosis + RBCs + temporal lobe changes. PCR diagnosis.
Fungal (Cryptococcus)	↑↑↑ (often >300)	5–100 (may be very low in immunosuppressed)	Lymphocytes	↓	↑	India ink positive (60–80%). Cryptococcal antigen (CSF + serum) >99% sensitivity. HIV + CD4 <100.
TB Meningitis	↑	100–500	Lymphocytes (early PMN possible)	↓↓ (very low, can be <20)	↑↑ (>100–500)	Basilar meningitis on MRI. AFB smear low sensitivity. ADA elevated. Treat empirically if suspected.
Lyme Meningitis	Normal or mildly ↑	10–200	Lymphocytes	Normal	Mildly ↑	Lymphocytic pleocytosis + Lyme serology (ELISA → Western blot). Treat with IV ceftriaxone × 14–28 days.

LP Sequencing — The Most Tested Clinical Decision

⚑ The LP Decision Tree — Never Delay Antibiotics

No papilledema + no focal deficits + immunocompetent: Dexamethasone + antibiotics FIRST → LP immediately after (or simultaneously)
Papilledema OR focal deficits OR immunocompromised OR seizure: Blood cultures + dexamethasone + antibiotics → CT head → LP if safe
The golden rule: NEVER delay antibiotics waiting for CT or LP. Mortality increases ~7% for every hour of antibiotic delay in bacterial meningitis.
CSF culture remains positive for 2–4 hours after antibiotic administration — the LP is still valuable even if antibiotics have been given

⚑ Board Traps — Meningitis

Cephalosporins have ZERO Listeria coverage — add ampicillin for age >50, neonates, pregnancy, and immunocompromised. This is the most tested meningitis drug selection fact.
Dexamethasone before or with first antibiotic dose — proven to reduce neurological sequelae in S. pneumoniae meningitis. After the first dose, steroids lose benefit.
Cryptococcal meningitis: very high opening pressure — may need therapeutic LP to reduce ICP (target <20 cmH₂O). Treatment: liposomal amphotericin B + flucytosine induction → fluconazole consolidation/maintenance.
HSV encephalitis: Lymphocytic pleocytosis + RBCs in CSF + temporal lobe involvement on MRI + fever + altered mental status = treat empirically with IV acyclovir before PCR results return.

Tier 1

Differential D-3

Fever in the Immunocompromised Host

HIV CD4 Thresholds · Neutropenic Fever · Transplant Recipient · Steroid-Induced Immunosuppression

★★★ PANCE Priority

HIV — CD4-Guided Differential

CD4 Count	OI Prophylaxis Threshold	Must-Consider Infections	Board Key
<500	No specific prophylaxis; start ART	Bacterial pneumonia, TB reactivation, oral candidiasis, VZV reactivation	Start ART regardless of CD4 — U=U (undetectable = untransmittable)
<200	PCP prophylaxis: TMP-SMX DS daily (/atovaquone/pentamidine)	Pneumocystis jirovecii (PCP) — bilateral GGO, dry cough, LDH elevated	PCP: TMP-SMX is treatment AND prophylaxis. Add prednisone if PaO₂ <70.
<100	Toxoplasma prophylaxis: TMP-SMX DS covers both PCP and Toxo	Toxoplasmosis (multiple ring-enhancing lesions), Cryptococcal meningitis (India ink +, very high OP)	Single ring-enhancing lesion = lymphoma. Multiple = toxo. Empiric toxo treatment × 2 weeks; if no improvement → biopsy.
<50	MAC prophylaxis: azithromycin weekly	CMV retinitis (floaters + visual loss + "pizza pie" fundus), MAC (fever + weight loss + night sweats + elevated ALP), Histoplasma	CMV retinitis: IV ganciclovir (or oral valganciclovir). Irreversible blindness if untreated — urgent ophthalmology.

Neutropenic Fever — The Oncology Emergency

Definition: ANC <500 (or <1000 with predicted fall to <500) + single temperature ≥38.3°C OR ≥38°C sustained × 1 hour
Empiric antibiotic: anti-pseudomonal beta-lactam — cefepime, piperacillin-tazobactam, or meropenem. Within 1 hour of fever.
Add vancomycin ONLY if: hemodynamic instability, suspected CRBSI, pneumonia, skin/soft tissue infection, or known MRSA colonization — NOT routinely
Anti-fungal empiric therapy: Add if fever persists >4–7 days on antibiotics — echinocandin or liposomal amphotericin
G-CSF: Consider in high-risk neutropenic fever to accelerate ANC recovery

⚑ Board Traps — Immunocompromised Fever

TMP-SMX DS covers BOTH PCP prophylaxis AND Toxoplasma prophylaxis — one drug, two benefits. If a patient is on TMP-SMX, they are protected against both. If they cannot tolerate TMP-SMX, they need separate prophylaxis for each.
Single vs multiple ring-enhancing lesions in HIV: Single = CNS lymphoma (EBV-associated). Multiple = toxoplasmosis. Treat empirically for toxo × 2 weeks; if no improvement → brain biopsy for lymphoma. This exact scenario is tested every exam cycle.
CMV retinitis is an emergency — vision loss is irreversible without prompt treatment. Any HIV patient with CD4 <50 reporting visual symptoms (floaters, decreased acuity) needs urgent fundoscopic exam and ganciclovir.
Cryptococcal meningitis: therapeutic lumbar puncture for elevated ICP — the very high opening pressure causes vision loss and death independent of the infection itself. Drain CSF to target OP <20 cmH₂O daily until controlled.

Tier 1

Differential D-4

Infectious Diarrhea — Toxin-Mediated vs Invasive vs C. diff

Incubation Timing · Organism-to-Mechanism Mapping · When to Treat vs Observe · Anti-motility Traps

★★★ PANCE PriorityAnti-motility Agent Traps

Incubation Time → Organism Identification

Incubation	Mechanism	Organism	Key Feature	Treatment
1–6 hours	Preformed toxin	S. aureus (staph toxin), B. cereus (emetic)	Rapid onset vomiting > diarrhea. Often after eating rice (B. cereus) or egg salad/deli meats (S. aureus). No fever.	Supportive only — toxin already formed, antibiotics useless
8–16 hours	Preformed toxin	C. perfringens, B. cereus (diarrheal)	Diarrhea after beef stew, cafeteria food. Mild, self-limited <24h.	Supportive only
1–3 days	Invasive / toxin-producing	Salmonella, Shigella, Campylobacter, ETEC, Vibrio	Fever + bloody diarrhea (Shigella, Campylobacter, Salmonella). ETEC = traveler's diarrhea (watery, no blood). Vibrio after raw oysters.	Shigella: azithromycin or fluoroquinolone. Campylobacter: azithromycin. Salmonella: usually self-limited; treat if immunocompromised or <3 months.
3–5 days	Shiga toxin + invasive	STEC (E. coli O157:H7), EHEC	Bloody diarrhea + HUS (microangiopathic hemolytic anemia + thrombocytopenia + AKI). Children and elderly.	DO NOT give antibiotics — increases Shiga toxin release and HUS risk. Supportive care. No anti-motility agents.
Variable (post-antibiotic)	Toxin A+B mediated	C. difficile	Recent antibiotics + watery diarrhea ± pseudomembranes on colonoscopy. WBC >15K + Cr rise = severe.	Vancomycin PO or fidaxomicin. Stop offending antibiotic. Contact precautions. Soap and water (alcohol gel fails).

Anti-motility Agents — The Board Trap Drug List

⚑ NEVER Give Anti-motility Agents (Loperamide, Diphenoxylate) in These Situations

E. coli O157:H7 / STEC infection — slows toxin clearance → increases HUS risk
Shigella (bloody dysentery) — prolongs illness, increases risk of toxic megacolon
C. difficile colitis — slows toxin clearance, can precipitate toxic megacolon
Febrile dysentery with bloody stool — any invasive bacterial cause. Anti-motility = harmful.
Safe to use: ETEC (watery traveler's diarrhea without blood or fever), viral gastroenteritis

⚑ Board Traps — Infectious Diarrhea

Antibiotics for E. coli O157:H7 increase HUS risk — the most dangerous ID board trap. STEC produces Shiga toxin. Antibiotics trigger toxin release → HUS. Never treat STEC with antibiotics.
Salmonella bacteremia risk: treat non-typhoidal Salmonella only if immunocompromised, <3 months old, or bacteremic — otherwise the illness is self-limited and antibiotics prolong the carrier state.
C. diff: metronidazole is no longer first-line — oral vancomycin or fidaxomicin for all initial episodes. Metro IV only in fulminant CDI with ileus + oral/rectal vancomycin simultaneously.

Tier 1

Differential D-5

Antibiotic Selection — Coverage Gaps & Contraindications

Penicillin Allergy Cross-Reactivity · MRSA Drugs · Anaerobic Coverage · Atypical Coverage · Pregnancy Safety

★★★ Most-Tested ID Pharmacology

Coverage Gaps — The Most Tested Antibiotic Facts

Antibiotic	Does NOT Cover	Board Trap Scenario
Cephalosporins (all generations)	Listeria monocytogenes, Enterococcus, MRSA (except ceftaroline)	Immunocompromised meningitis — add ampicillin for Listeria coverage
Nitrofurantoin	Systemic infection, pyelonephritis, bacteremia, Proteus, Klebsiella (variable)	Patient with pyelo started on nitrofurantoin — inadequate renal tissue levels
Azithromycin (macrolides)	MRSA, gram-negatives (except atypicals)	Gonorrhea treatment — azithromycin no longer recommended; ceftriaxone monotherapy per CDC 2021
Metronidazole	Aerobic organisms, MRSA	Being added to aspiration pneumonia — increases mortality per IDSA 2019 without benefit
TMP-SMX	β-hemolytic Streptococci, Pseudomonas, Enterococcus	Non-purulent cellulitis — TMP-SMX targets MRSA but misses Strep; use cephalexin instead
Fluoroquinolones	MRSA (except some activity), Bacteroides, Enterococcus	Cipro for aspiration pneumonia — no anaerobic or atypical coverage in older formulations
Vancomycin	Gram-negative organisms, VRE (some strains), biofilm (needs higher levels)	VISA/VRSA: use linezolid or daptomycin

Penicillin Allergy — The Most Over-Documented Allergy

~90% of patients labeled "penicillin allergic" are not truly allergic — most reactions are non-allergic side effects (GI intolerance, rash without anaphylaxis).
Cross-reactivity between penicillin and cephalosporins: ~1–2% (much lower than previously thought 10%). Shared R1 side chain determines cross-reactivity, not the beta-lactam ring itself.
Cephalosporins are safe in patients with penicillin allergy UNLESS: prior anaphylaxis to penicillin AND structurally similar cephalosporin (same R1 side chain). Penicillin skin testing remains gold standard for evaluation.
Carbapenems: cross-reactivity with penicillin is very low (<1%) — can generally be used even with penicillin allergy history, especially if not anaphylaxis.

Antibiotic Contraindications in Special Populations

Antibiotic	Contraindicated In	Alternative
Doxycycline / Tetracyclines	Pregnancy (all trimesters), children <8 years	Azithromycin in pregnancy. Amoxicillin for Lyme in kids <8. Exception: no alternative for RMSF — doxycycline is used even in children <8 if RMSF suspected.
Fluoroquinolones	Children (theoretical cartilage damage), pregnancy (relative CI), myasthenia gravis (worsens NMJ block)	Beta-lactams for most pediatric/pregnancy infections. Avoid in MG.
Nitrofurantoin	Pyelonephritis, bacteremia, CrCl <30 (inadequate concentration), term pregnancy (>38 weeks — risk of neonatal hemolytic anemia)	Cephalexin or fosfomycin for UTI in pregnancy at term
Metronidazole	First trimester pregnancy (relative — teratogenicity concern); alcohol use during treatment	Topical metronidazole safer in first trimester. Avoid alcohol during and 48h after treatment.
Aminoglycosides	Pregnancy (ototoxicity/nephrotoxicity), CKD (nephrotoxic)	Use with caution, monitor levels. Avoid if possible in pregnancy.

⚑ Board Traps — Antibiotic Selection

Doxycycline in children <8: ONE exception — RMSF. The risk of dental staining/bone effects from a short doxycycline course is far outweighed by the risk of death from untreated RMSF. Doxycycline is the drug of choice for RMSF in ALL ages.
Nitrofurantoin cannot be used for pyelonephritis — inadequate renal parenchymal levels. This is tested by giving a patient with fever + CVA tenderness + UTI a nitrofurantoin prescription and asking what's wrong.
Cephalosporins do NOT cover Listeria or Enterococcus — frequently tested in meningitis and endocarditis questions. For endocarditis caused by Enterococcus, penicillin/ampicillin + gentamicin is required.

Module E · Comprehensive Board Pearls

Board Pearls — Organized by Domain

These pearls represent the exact clinical decision points most frequently tested on PANCE/PANRE infectious disease questions — the specific facts and paradigm shifts that separate passing from failing candidates.

Tier 1

Board Pearls — Sepsis, CAP & Respiratory Infections

Sepsis-3 · SSC Bundle · CAP Antibiotics · Meningitis Sequence · Influenza

★★★ Highest Yield

Sepsis-3 = SOFA ≥2, NOT SIRS. qSOFA is a screening tool only — do NOT use qSOFA alone to diagnose sepsis per SSC 2021.
Norepinephrine is first-line vasopressor for septic shock — NOT dopamine (higher arrhythmia risk, SOAP II trial). Vasopressin is second-line at 0.03 units/min. Peripheral vasopressor initiation is now acceptable — do not wait for central access.
The 30 mL/kg crystalloid recommendation was downgraded to WEAK in SSC 2021. Use dynamic measures (passive leg raise, pulse pressure variation) to guide further resuscitation. Balanced crystalloids (LR) preferred over normal saline.
CAP inpatient regimen: ceftriaxone + azithromycin. Metronidazole added to aspiration pneumonia increases mortality — no anaerobic coverage in standard CAP. Reserve for lung abscess with putrid sputum.
Meningitis antibiotic sequence: dexamethasone BEFORE or WITH first antibiotic dose. Steroids given after the first dose provide no benefit. Never delay antibiotics for CT or LP.
Ampicillin must be added for Listeria coverage in patients >50 years, neonates, pregnant women, and immunocompromised. Cephalosporins have zero Listeria activity.
Influenza: negative rapid test does NOT exclude influenza — sensitivity only ~70%. Treat high-risk patients with oseltamivir regardless of test result and regardless of symptom duration.
Zanamivir (inhaled) is contraindicated in COPD and asthma — risk of severe bronchospasm. Use oral oseltamivir in all respiratory disease patients.
Reye syndrome: Aspirin + viral illness (influenza, VZV) in children → acute encephalopathy + liver failure. Never give aspirin to children with viral illness.

Tier 1

Board Pearls — STIs, C. diff, HIV & Lyme

CDC 2021 STI Updates · C. diff Paradigm Shifts · HIV CD4 Thresholds · Lyme Staging

★★★ Highest YieldMultiple Guideline Update Traps

Gonorrhea: ceftriaxone MONOTHERAPY — no azithromycin co-treatment (CDC 2021). Azithromycin-resistant gonorrhea increased significantly. If chlamydia not excluded by NAAT, add doxycycline 100mg BID × 7 days separately.
Chlamydia: doxycycline preferred over azithromycin (CDC 2021). Azithromycin has higher rectal chlamydia treatment failure rates. Doxycycline × 7 days is now first-line.
Syphilis in pregnancy: penicillin is the ONLY acceptable treatment. Doxycycline contraindicated. Azithromycin has ~30% failure rate. Desensitization is mandatory even with anaphylaxis history.
Jarisch-Herxheimer reaction: Fever + chills + rigors within 24 hours of penicillin treatment for syphilis (or Lyme, leptospirosis). NOT an allergic reaction. Treat with antipyretics + reassurance. Do NOT stop antibiotics.
C. diff: metronidazole is no longer first-line. Oral vancomycin 125mg QID × 10 days OR fidaxomicin 200mg BID × 10 days for ALL initial CDI episodes. Metro IV only in fulminant CDI with ileus + oral/rectal vancomycin.
C. diff hand hygiene: soap and water required — alcohol gel does NOT kill spores. The most important infection control distinction for C. diff. Tested every exam cycle.
FMT (fecal microbiota transplant) >85% cure rate for recurrent CDI — superior to antibiotics for ≥3 recurrences. Bezlotoxumab (anti-toxin B monoclonal antibody) reduces recurrence in high-risk patients.
HIV CD4 thresholds — memorize all four: <200 = PCP prophylaxis (TMP-SMX). <100 = add Toxo prophylaxis (TMP-SMX covers both). <50 = add MAC prophylaxis (azithromycin weekly) + CMV risk. U=U: start ART immediately regardless of CD4.
Single ring-enhancing lesion in HIV = CNS lymphoma (EBV). Multiple lesions = toxoplasmosis. Empirically treat for toxo × 2 weeks; if no improvement → brain biopsy. Serum Toxoplasma IgG negative = toxo less likely (95% sensitive for prior exposure).
Lyme bilateral facial palsy = Stage 2 early disseminated disease. Treat with oral doxycycline × 14–21 days (not IV unless CNS involvement beyond isolated cranial neuropathy). Positive serology persists for years after treatment — do NOT re-treat based on serology alone.

Tier 1

Board Pearls — Endocarditis, SSTI & Fungal Infections

Duke Criteria · Organism-Patient Pairing · Necrotizing Fasciitis · Invasive Candidiasis · Antifungal Selection

★★★ Highest Yield

S. gallolyticus (bovis) endocarditis = colonoscopy mandatory. ~60% association with colorectal neoplasia. Non-negotiable board fact — appears in every ID exam.
S. aureus endocarditis in IVDU: tricuspid valve. Strep viridans: mitral/aortic (after dental procedure). Gram-negative (HACEK): subacute, large friable vegetations. Enterococcus: GI/GU procedures.
Osler nodes = tender (immune complex deposition). Janeway lesions = painless (septic emboli). Both are peripheral stigmata of endocarditis — the tenderness is the distinguishing feature.
Duke Criteria: 2 major, 1 major + 3 minor, or 5 minor = definite endocarditis. Major criteria: positive blood cultures (standard organisms × 2, or persistent) + positive echocardiogram (vegetation, abscess, or new prosthetic dehiscence).
Non-purulent cellulitis: β-hemolytic strep, treat with cephalexin — NOT TMP-SMX. Purulent/abscess: presumed S. aureus/MRSA, treat with TMP-SMX + I&D.
Necrotizing fasciitis: surgical debridement is the only cure. "Dishwater fluid" + crepitus + pain out of proportion + rapidly spreading = emergent surgery. No antibiotic regimen is sufficient without debridement.
Invasive candidiasis in ICU: echinocandin first-line (caspofungin, micafungin, anidulafungin). Fluconazole acceptable for stable patients with susceptible species. Mandatorily: remove all CVCs and perform fundoscopic exam (endophthalmitis in ~5–10%).
Aspergillus: halo sign on CT (ground-glass halo around pulmonary nodule) in neutropenic/immunocompromised patient. First-line treatment: voriconazole (NOT amphotericin B — inferior per IDSA 2016 guidelines).
Geographic fungi memory map: Ohio/Mississippi valley = Histoplasma. Southwest US desert = Coccidioides. Great Lakes/Pacific Northwest = Blastomyces.
Coccidioidomycosis meningitis: lifelong fluconazole maintenance required — 100% relapse rate if stopped. Unlike most other fungal infections, cannot be "cured" and discontinued.

Tier 1

Board Pearls — COVID-19, Antivirals & ID Pharmacology

Paxlovid CYP3A4 · Dexamethasone Threshold · COVID-19 Antivirals · RIPE Toxicity · Drug Interactions

★★★ Highest Yield

Paxlovid (nirmatrelvir/ritonavir): ritonavir is a potent CYP3A4 inhibitor. Check all medications before prescribing. Critical interactions: rivaroxaban, apixaban (increased bleeding), tacrolimus/cyclosporine (toxic levels), statin toxicity, many others. Always use an interaction checker.
Paxlovid window: must be prescribed within 5 days of symptom onset. Most effective within 3 days. Not beneficial after day 5 of symptoms.
Molnupiravir is contraindicated in pregnancy — mutagenic mechanism (incorporates into viral RNA). Women of childbearing age must use effective contraception during and 4 days after treatment.
Dexamethasone in COVID-19: only for patients requiring supplemental oxygen or ventilation. RECOVERY trial: dexamethasone 6mg daily × 10 days reduces mortality in moderate-severe COVID. Harms patients who do NOT need oxygen.
Remdesivir: 3-day IV course for non-hospitalized high-risk COVID-19 within 7 days of symptom onset. Also used for hospitalized patients not on mechanical ventilation.
RIPE therapy toxicity — memorize all four: Rifampin = orange body fluids (benign) + potent CYP450 inducer (reduces OCP/warfarin/methadone levels). Isoniazid = peripheral neuropathy (give B6/pyridoxine) + hepatotoxicity. Pyrazinamide = hyperuricemia (gout). Ethambutol = optic neuritis (monitor color vision monthly).
Rifampin drug interactions: reduces levels of warfarin, OCPs, methadone, many HIV antiretrovirals, azole antifungals, steroids. Counsel patients on alternative contraception. May precipitate TB treatment failure if interacting drugs not adjusted.
Doxycycline in children <8: use for RMSF regardless of age. The mortality risk of untreated RMSF (high) vastly exceeds the risk of dental staining from a short doxycycline course. This is explicitly stated in CDC guidelines.
Tick prophylaxis after Ixodes bite: single dose doxycycline 200mg within 72 hours if tick attached ≥36 hours, in an endemic area, and patient is not pregnant and is ≥8 years old. Reduces risk of Lyme transmission by ~87%.
Amphotericin B toxicity: infusion-related reactions (fever, rigors, hypotension) + nephrotoxicity. Pre-medicate with acetaminophen + diphenhydramine ± meperidine for rigors. Liposomal formulation has significantly less nephrotoxicity — preferred in most settings.

Clinical Emergency List

10 "Don't Miss" ID Emergencies

1. Septic Shock

MAP <65 + vasopressor requirement + lactate >2 after fluids. Mortality >40%. Start norepinephrine peripherally — do NOT wait for central line. Antibiotics within 1 hour. Blood cultures first but do NOT delay antibiotics. Hydrocortisone 200mg/day if vasopressor-refractory.

2. Bacterial Meningitis

Fever + headache + neck stiffness. Petechiae/purpura = N. meningitidis emergency. Dexamethasone + antibiotics FIRST. Never delay for CT or LP. Blood cultures → dexa → vanc + ceftriaxone (+ ampicillin if >50/immunocompromised) → LP/CT. Hours to permanent damage.

3. Necrotizing Fasciitis

"Pain out of proportion to exam" + rapid skin progression + crepitus. Immediate surgical debridement. CT (gas in fascia) if unclear — do NOT delay surgery for imaging if NF is clinically obvious. Broad-spectrum IV antibiotics (vanc + pip-tazo). Mortality increases 9% per hour of surgical delay.

4. Waterhouse-Friderichsen Syndrome

Meningococcal septicemia → bilateral adrenal hemorrhage → DIC + purpura fulminans + cardiovascular collapse. Treat meningococcal infection + stress-dose corticosteroids (hydrocortisone 100mg IV bolus) immediately. DIC management: FFP, platelets. Prophylaxis for contacts: rifampin, cipro, or IM ceftriaxone × 1 dose.

5. Cryptococcal Meningitis with Elevated ICP

LP opening pressure >25 cm H₂O + cryptococcal meningitis. ALWAYS measure opening pressure. Elevated ICP causes vision loss, hearing loss, and death from herniation. Serial therapeutic LPs (remove 20–30 mL, target OP <20 cm) or lumbar drain. Start amphotericin B + flucytosine immediately.

6. Fulminant C. difficile Colitis

Hypotension + ileus + toxic megacolon (colon >6cm) + WBC >30K. Vancomycin 500mg PO QID + metronidazole 500mg IV TID + vancomycin per rectum (if ileus). Surgical consultation urgently. Colectomy if peritonitis, perforation, or no response in 24–48h. Stop all inciting antibiotics.

7. Invasive Aspergillosis in Neutropenia

Prolonged fever in neutropenic patient + CT "halo sign" (GGO surrounding nodule). Start voriconazole empirically — do NOT wait for culture confirmation. Galactomannan from BAL/serum. G-CSF to recover neutrophil count. Mortality >50% untreated.

8. Severe Lyme Carditis (3rd-Degree AV Block)

Young patient (endemic area) + complete heart block + Lyme serology positive. Temporary transvenous pacemaker for hemodynamic instability + IV ceftriaxone 2g daily × 14–21 days. AV block typically resolves completely — permanent pacemaker rarely needed.

9. Secondary MRSA Pneumonia Post-Influenza

Patient improving from flu → sudden clinical deterioration → new cavitating infiltrates + high fever. Think MRSA post-influenza pneumonia. S. aureus (including MRSA) is the most common secondary pathogen. Add vancomycin or linezolid. High mortality — early recognition is critical.

10. Toxic Shock Syndrome

Staph TSS: Fever + diffuse erythroderma ("sunburn rash") + hypotension + multi-organ failure. Retained tampon, nasal packing, wound. Remove source immediately. IV vancomycin + clindamycin (suppresses toxin production). Streptococcal TSS: Group A Strep, often with NF — surgical debridement + penicillin + clindamycin + IVIG.

Chapter Summary

Top 22 ID Board Traps

The patterns that consistently separate passing from failing on ID questions.

22 Traps · All Domains

Sepsis — Definition

Sepsis-3 = ORGAN DYSFUNCTION (SOFA ≥2), NOT SIRS. qSOFA is a screening tool NOT a diagnostic criterion — SSC 2021 recommends AGAINST using qSOFA alone.

Sepsis — Vasopressor

Norepinephrine is first-line (NOT dopamine). Vasopressin is second-line. Peripheral initiation is acceptable — do NOT wait for central venous access.

CAP — Aspiration

Do NOT add anaerobic coverage for aspiration pneumonia — 5–6% higher mortality (ATS/IDSA 2019). Standard CAP antibiotics are adequate.

UTI — Nitrofurantoin

Nitrofurantoin = CYSTITIS ONLY. Does not achieve adequate renal tissue concentrations. NEVER for pyelonephritis. Same rule applies to fosfomycin.

UTI — ASB

Treat ASB ONLY in pregnancy and before urologic procedures. Do NOT treat in elderly, diabetics, catheterized patients, or nursing home residents.

Meningitis — Listeria

Add AMPICILLIN for Listeria in patients >50, neonates, pregnant, immunocompromised. Cephalosporins have ZERO Listeria activity.

Meningitis — Dexamethasone

Dexamethasone BEFORE or WITH first antibiotic dose — post-antibiotic dexa has NO benefit. Never delay antibiotics for LP or CT.

Endocarditis — S. bovis

S. bovis/gallolyticus IE = mandatory colonoscopy (~60% colorectal neoplasia). Osler = painful (immune). Janeway = painless (septic emboli).

STI — Gonorrhea

Gonorrhea = ceftriaxone MONOTHERAPY — azithromycin co-treatment NO LONGER recommended (CDC 2021). Chlamydia = doxycycline PREFERRED over azithromycin.

STI — Syphilis in Pregnancy

Penicillin ONLY for syphilis in pregnancy. If penicillin-allergic → desensitize and treat. Doxycycline and azithromycin are NOT alternatives in pregnancy.

C. diff — Metronidazole

Metronidazole NO LONGER first-line for CDI. Vancomycin or fidaxomicin for all initial episodes. Metro IV only in fulminant CDI with ileus.

C. diff — Hand Hygiene

Soap and water only for C. diff — alcohol sanitizers do NOT kill spores. This is the key infection control distinction from other pathogens.

HIV — Ring Lesion

Single ring-enhancing lesion = CNS lymphoma (EBV). Multiple = Toxoplasmosis. TMP-SMX provides dual prophylaxis for PCP AND Toxo below CD4 <100.

HIV — MAC Prophylaxis

MAC prophylaxis NO LONGER routinely recommended if ART is started immediately (2024 update). PCP corticosteroids required if PaO₂ <70 or A-a gradient >35.

SSTI — MRSA Coverage

Nonpurulent cellulitis = β-hemolytic Streptococcus, NOT MRSA. Routine MRSA coverage not indicated. Purulent SSTI: I&D is primary treatment — antibiotics alone insufficient.

Lyme — Bilateral Bell Palsy

Bilateral Bell palsy = Lyme disease until proven otherwise. Bull's-eye rash = treat without serology in endemic area. Post-treatment serology stays positive — ≠ active infection.

Influenza — Testing

Negative rapid influenza test does NOT rule out influenza (sensitivity ~70%). Treat high-risk patients regardless of test result or duration. Zanamivir CONTRAINDICATED in asthma/COPD.

COVID — Dexamethasone

Dexamethasone ONLY for O₂-requiring hospitalized patients. Do NOT give to non-hypoxic outpatients — may worsen early disease.

COVID — Paxlovid

Ritonavir (Paxlovid) = potent CYP3A4 inhibitor. Hold atorvastatin/simvastatin. Adjust rivaroxaban/apixaban/warfarin. Tacrolimus levels increase dramatically.

Fungal — Invasive Candida

Echinocandin (caspofungin/micafungin) first-line for invasive candidiasis — not fluconazole empirically. Fundoscopic exam mandatory in ALL candidemic patients.

TB — TST Cutoffs

The TST cutoff depends on the patient: 5 / 10 / 15 mm. ≥5 mm: HIV, recent close contact, fibrotic CXR, immunosuppressed. ≥10 mm: health care workers, recent immigrants, IVDU, children <5, diabetes/ESRD. ≥15 mm: no risk factors. Prior BCG does NOT raise the cutoff — use an IGRA.

TB — Latent vs Active

NEVER treat latent TB before excluding active disease — single-drug therapy against active TB breeds resistance. A positive TST/IGRA is never the endpoint: the next step is ALWAYS chest X-ray + symptom screen. Active TB is reportable to the health department.

Quick-Scan Reference — Numbers That Win Points

SEPSIS ANTIBIOTICS

Within 1 hour
Each hour delay ↑ mortality ~7%

SYPHILIS IN PREGNANCY

Penicillin ONLY
Desensitize if allergic

HIV OI THRESHOLDS

<200 PCP · <100 Toxo
<50 CMV, MAC, CNS lymphoma

C. DIFF SEVERITY

Severe: WBC >15K or Cr ≥1.5
Fulminant: hypotension/ileus

TICK PROPHYLAXIS

Doxy 200mg × 1 dose
If attached ≥36 hours

TAMIFLU TIMING

Best <48h onset
Give anyway if high-risk

PAXLOVID WINDOW

Within 5 days onset
Check ALL CYP3A4 interactions

RIPE THERAPY (TB)

2 months RIPE
+ 4 months RI = 6 months total

⬡ Closing Statement

"Infectious disease on the PANCE tests judgment, not just drug names. The metronidazole that's no longer first-line for C. diff. The nitrofurantoin that stops at the bladder. The dexa that must come before the antibiotic. The ampicillin forgotten in the immunocompromised patient with meningitis. These are not trick questions — they are the exact decisions that separate the clinician who causes harm from the one who prevents it."

— Rajiv Choudhary, MD, MPH

Infectious DiseaseBootcamp Syllabus

Infectious Disease
Bootcamp Syllabus