PA Infectious Disease Bootcamp

Domain 1 · Systemic Infections — Highest PANCE Weight

Sepsis, CAP, UTI & Meningitis

Tier 1

Topic 1

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.

Tier 1

Topic 2

Community-Acquired Pneumonia (CAP)

PSI vs CURB-65 · Antibiotic Selection · 3-Day Course · No Anaerobes in Aspiration

★★★ PANCE PriorityMany Traps

Core Recognition & Severity

Classic: Fever + productive cough + dyspnea + pleuritic chest pain + focal CXR consolidation
Most common bacterial pathogen: S. pneumoniae (~15%). Viruses most commonly detected (~40%).
Atypical organisms: Mycoplasma, Chlamydophila, Legionella — gradual onset, dry cough, extrapulmonary features
Legionella pearls: Severe CAP + hyponatremia + diarrhea + water system exposure → urine Legionella antigen
PSI preferred over CURB-65 (ATS/IDSA) — identifies more low-risk patients safe for outpatient treatment

Empiric Antibiotic Selection

Setting	First-Line	Alternative	Board Key
Outpatient, no comorbidities	Amoxicillin 1g TID OR doxycycline 100mg BID	Macrolide if local resistance <25%	Macrolide monotherapy NOT recommended (resistance >30%)
Outpatient, with comorbidities	Amox-clav + macrolide or doxy	Respiratory FQ (levofloxacin)	FQ only if β-lactam/macrolide not tolerated
Inpatient, nonsevere	Ceftriaxone + azithromycin	Respiratory FQ monotherapy	Combination preferred
Inpatient, severe/ICU	β-lactam + macrolide or β-lactam + FQ	+ anti-MRSA/pseudomonal only if risk factors	Hydrocortisone 200mg/day IV for severe CAP reduces mortality (CAPE COD trial)

Duration: 3 days if stability criteria met by day 3. 5 days if met by day 5. ≥7 days for MRSA or Pseudomonas.

⚑ Board Traps — CAP

Fluoroquinolones NOT first-line for CAP — reserve for β-lactam/macrolide intolerance
Macrolide resistance >30% — azithromycin monotherapy NOT recommended empirically
Do NOT add anaerobic coverage (metronidazole/clindamycin) for aspiration pneumonia — associated with 5–6% higher mortality (ATS/IDSA 2019)
Steroids only in SEVERE CAP — hydrocortisone 200mg/day (CAPE COD trial). Not for nonsevere.
3-day course sufficient if clinical stability criteria met by day 3

★ Memory Trick

Inpatient CAP: "C+A = Ceftriaxone + Azithromycin" — the standard combo "FQs are the backup, not the opening move" "Aspiration ≠ anaerobes — stop the metronidazole reflex (it kills)" "CAPE COD steroids = severe CAP only"

Tier 1

Topic 3

UTI — Cystitis & Pyelonephritis

Nitrofurantoin Limitation · ASB Rules · Cystitis vs Pyelo Drug Choices

★★★ PANCE PriorityNitrofurantoin Trap

Cystitis vs Pyelonephritis

	Cystitis	Pyelonephritis
Symptoms	Dysuria, frequency, urgency, suprapubic pain. NO fever.	Cystitis symptoms + fever, rigors, CVA tenderness, N/V
First-Line Rx	Nitrofurantoin 100mg BID × 5d; TMP-SMX × 3d; Fosfomycin 3g × 1	Fluoroquinolone × 5–7d (outpatient) or IV ceftriaxone (inpatient)
Nitrofurantoin OK?	YES — high urine concentration	NO — inadequate renal tissue levels
Culture required?	Not for uncomplicated	Always obtain before starting antibiotics

Asymptomatic Bacteriuria — Treat ONLY These Two

⚑ Treat ASB ONLY In:

Pregnancy — risk of pyelonephritis and preterm labor. Screen at 12–16 weeks.
Before urologic procedures — risk of bacteremia post-instrumentation
Do NOT treat ASB in: Elderly, diabetics, catheterized patients, nursing home residents — no benefit, increases antibiotic resistance and C. diff

⚑ Board Traps — UTI

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 are ASB — treat only if symptomatic. Remove catheter if possible.

★ 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"

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. Test-of-cure culture 1 week after treatment. Avoid nitrofurantoin near term (≥36 weeks) due to neonatal hemolytic anemia risk.

Tier 1

Topic 4

Bacterial Meningitis

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

★★★ PANCE PriorityDexa Timing Trap

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"

Domain 2 · Organ-Specific Infections

Endocarditis, STIs & C. difficile

Tier 1

Topic 5

Infective Endocarditis

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

★★ High Yield2023 Duke Updated

2023 Duke-ISCVID Criteria

Definite IE: 2 major criteria, OR 1 major + 3 minor, OR 5 minor criteria

2023 Updates to Major Criteria

Positive blood cultures: typical organisms from ≥2 separate cultures or persistently positive (>12h)
Endocardial involvement: echo — vegetation, abscess, new valvular regurgitation, new dehiscence
NEW 2023: Cardiac CT or 18F-FDG PET/CT showing periannular complications
NEW 2023: Intraoperative inspection confirming 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"

Tier 1

Topic 6

Sexually Transmitted Infections (STIs)

CDC 2021 · Doxy > Azithro · Ceftriaxone Monotherapy · Syphilis Stages & Serology

★★★ PANCE PriorityCDC 2021Many Traps

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

Syphilis Serology — Critical Distinction

Test Type	Tests	Use	Board Key
Non-treponemal (quantitative)	RPR, VDRL	Screening + monitoring treatment response (titers fall with effective treatment)	Can be false-positive: pregnancy, lupus, viral infections
Treponemal (confirmatory)	FTA-ABS, TP-PA	Confirmatory. Remain POSITIVE FOR LIFE even after cure.	Do NOT use to monitor treatment response — positive forever

⚑ Board Traps — STIs

Doxycycline PREFERRED over azithromycin for chlamydia — azithromycin has lower cure rates for rectal chlamydia
Gonorrhea = ceftriaxone MONOTHERAPY — azithromycin co-treatment no longer recommended
Penicillin ONLY for syphilis in pregnancy — doxycycline contraindicated; desensitize if allergic
Jarisch-Herxheimer reaction: Fever + myalgias within 24h of syphilis treatment → supportive care only. Do NOT stop antibiotics.
Neurosyphilis can occur at ANY stage — not just tertiary
RPR/VDRL = use for monitoring. FTA-ABS = stays positive forever.

★ Memory Trick

Chlamydia: "Doxy > Azithro — Doxy wins in 2021" Gonorrhea: "Ceftriaxone ALONE — no azithro partner anymore" Syphilis in pregnancy: "Only Penicillin. Period. Desensitize if allergic." Serology: "RPR/VDRL = Quantitative (monitor). FTA-ABS = Forever positive (confirm)." Jarisch-Herxheimer: "Feels worse before better — keep the antibiotics going"

Tier 1

Topic 7

Clostridioides difficile Infection (CDI)

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

★★★ PANCE PriorityMetronidazole Trap

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.

Domain 3 · HIV & Opportunistic Infections

HIV/AIDS — CD4-Based Clinical Framework

Tier 1

Topic 8

HIV/AIDS & Opportunistic Infections

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

★★★ PANCE PriorityMany Traps

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 Threshold	OI	Prophylaxis	Board Key
<200	PCP (Pneumocystis jirovecii)	TMP-SMX DS daily — FIRST-LINE	Most important OI prophylaxis drug
<100	Toxoplasma (if seropositive)	TMP-SMX DS daily — covers BOTH PCP AND Toxo	One drug = two OIs covered
<100	Cryptococcus (if CrAg+)	Fluconazole 200mg daily	Screen with serum CrAg in high-prevalence areas
<150 (endemic)	Histoplasmosis	Itraconazole 200mg daily	Ohio/Mississippi valleys only
Any CD4	LTBI	INH × 9mo or rifampin × 4mo + pyridoxine	Screen all HIV patients with TST/IGRA
Any CD4	MAC	NO LONGER routinely recommended if ART started immediately (2024 update)	Major guideline change

OI Presentations — High-Yield Patterns

OI	CD4	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"

Domain 4 · Skin, Soft Tissue & Vector-Borne

SSTI & Lyme Disease

Tier 1

Topic 9

Skin & Soft Tissue Infections

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

★★ High YieldMRSA Coverage Trap

Classification & Treatment (IDSA 2014)

Type	Organism	Treatment	Board Key
Mild nonpurulent cellulitis	β-hemolytic Streptococcus (NOT MRSA)	Oral cephalexin or dicloxacillin × 5 days	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	IV vancomycin + pip-tazo. Surgical consult if necrotizing features.	SIRS + hypotension/sepsis
Purulent SSTI (abscess)	S. aureus / MRSA	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 — Do Not Miss

⚑ NF = Surgical Emergency

Classic triad: Pain out of proportion to exam + rapid progression + systemic toxicity
Physical: Skin discoloration → bullae → necrosis → crepitus (gas in tissues on CT)
Treatment: IMMEDIATE surgical debridement + IV vancomycin + pip-tazo. Antibiotics alone are NOT curative.
Type I (polymicrobial): Mixed aerobic/anaerobic; trunk/perineum (Fournier gangrene)
Type II (Group A Strep): Extremities; often with TSS

⚑ Board Traps — SSTI

Nonpurulent cellulitis = Streptococcus, NOT MRSA — routine MRSA coverage not needed
Purulent SSTI: I&D is primary treatment — antibiotics alone insufficient
5 days sufficient for uncomplicated cellulitis
Pseudocellulitis misdiagnosis rate ~30% — consider stasis dermatitis, DVT, gout
NF: "pain out of proportion" + rapid spread = operate NOW

★ 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 10

Lyme Disease — Complete (Rebuilt from Truncated Source)

3 Stages · Treatment Table · Two-Tier Serology · Tick Prophylaxis · Coinfections

★★ High YieldSerology Trap

Three Stages — Clinical Recognition

Stage	Timing	Key Manifestations	Treatment
Stage 1 — Early Localized	Days–weeks after bite	Erythema migrans (EM): Bull's-eye rash ≥5cm, expanding annular erythema with central clearing. Pathognomonic — no serology needed in endemic area. ± fever, fatigue, myalgias.	Doxycycline 100mg BID × 10–21d (adults). Amoxicillin 500mg TID × 14–21d (pregnancy, children <8yr).
Stage 2 — Early Disseminated	Weeks–months	Cardiac: AV block (1st, 2nd, 3rd degree; PR prolongation is hallmark). Neuro: Facial nerve palsy (BILATERAL = Lyme until proven otherwise), meningitis, radiculopathy. Multiple EM lesions.	Oral doxy for uncomplicated. IV ceftriaxone 2g daily × 14–28d for complete heart block, meningitis, neurologic Lyme.
Stage 3 — Late Disseminated	Months–years	Lyme arthritis: Intermittent/persistent monoarthritis or oligoarthritis; KNEE most common. "Hot swollen knee" in endemic area = Lyme. Neurologic: Encephalopathy, peripheral neuropathy.	Doxycycline 100mg BID × 28d (arthritis). IV ceftriaxone for severe neurologic Lyme. Refractory arthritis → anti-inflammatory or DMARD.

Serology — Two-Tier Testing

Step 1: ELISA (EIA) — sensitive screening. If negative AND EM present in endemic area → treat clinically (serology can be negative early Stage 1).
Step 2 (if ELISA positive/equivocal): Western blot — IgM for early (<4 weeks); IgG for later disease
Serology NOT needed for EM diagnosis — classic bull's-eye in endemic area = treat
Post-treatment Lyme syndrome: Persistent symptoms >6 months after adequate treatment. Positive serology persists for years — does NOT mean active infection. Extended antibiotics are NOT recommended (no benefit per RCTs, potential harm).

Tick Prophylaxis

Single dose doxycycline 200mg PO within 72h of deer tick bite — if: Ixodes scapularis tick, attached ≥36 hours, endemic area, no doxy contraindication
Prevention: DEET repellent, permethrin-treated clothing, daily tick checks, prompt removal

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

⚑ Board Traps — Lyme Disease

Bilateral facial palsy = Lyme disease until proven otherwise — only common cause of bilateral Bell palsy
EM is pathognomonic — do NOT wait for serology in endemic area
3rd-degree AV block = temporary pacing + IV ceftriaxone — resolves completely with treatment
Doxycycline CONTRAINDICATED in children <8 years and pregnancy — use amoxicillin
Post-treatment Lyme: positive serology persists for years — NOT ongoing infection. Extended antibiotics are NOT beneficial.
Tick must be attached ≥36 hours to transmit Borrelia

★ Memory Trick

Lyme stages: "Skin → Heart+Nerves → Joints" (Stage 1 → 2 → 3) "Bull's-eye = treat NOW, no serology needed in endemic area" Stage 2: "PR prolongation is the cardiac hallmark. 3rd degree = pacemaker + IV ceftriaxone" Bilateral Bell palsy: "Two-sided = Lyme. One-sided = many causes." Prophylaxis: "Single dose doxy if tick attached ≥36 hours" Coinfections: "Same tick, same time: Babesia + Anaplasma + Ehrlichia"

Domain 5 · Gap Topics Added ★

Influenza, COVID-19 & Fungal Infections

Tier 1

Topic 11 ★ Gap Added

Influenza

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

★★ High YieldGap TopicTiming Trap

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 12 ★ Gap Added

COVID-19 (SARS-CoV-2)

Paxlovid · Ritonavir CYP3A4 Interactions · Dexamethasone Indication · Molnupiravir Pregnancy

★★ High YieldGap TopicPaxlovid Interactions

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"

Tier 2

Topic 13 ★ Gap Added

Fungal Infections

Invasive Candida · Aspergillus Halo Sign · Coccidioidomycosis · Histoplasmosis · Antifungal Selection

★★ High YieldGap Topic

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.
Invasive Aspergillosis	Prolonged neutropenia, stem cell transplant, high-dose corticosteroids	Fever + non-responding pneumonia + CT "halo sign" (GGO surrounding nodule = early finding) or air-crescent sign (late)	CT chest: halo sign. BAL galactomannan. Serum galactomannan.	Voriconazole FIRST-LINE. Isavuconazole (alternative). Liposomal amphotericin B if azole-intolerant.
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

Echinocandins (caspofungin, micafungin, anidulafungin): First-line for invasive candidiasis. Low toxicity. Not useful for Aspergillus, Cryptococcus, endemic fungi.
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

Blueprint Gap Topics · Added 2025

Rheumatic Fever · EBV/Mononucleosis · VZV & HSV · Giardiasis & Amebiasis · Measles · Mumps · Rubella

Topics present on the 2025 NCCPA PANCE Blueprint not covered in prior modules — now fully integrated

Acute Rheumatic Fever

Jones Criteria · Post-Streptococcal · Carditis · Sydenham Chorea · Secondary Prophylaxis · Penicillin

Why the PANCE Tests This

Rheumatic fever is the most important non-suppurative complication of Group A Streptococcal (GAS) pharyngitis. Jones criteria is the classic PANCE question template, and secondary prophylaxis duration is tested annually across multiple prep resources.

Pathophysiology

GAS pharyngitis → untreated or inadequately treated → molecular mimicry (antibodies cross-react with cardiac, joint, basal ganglia tissue) → rheumatic fever 2–4 weeks after pharyngitis. NOT a direct infection of affected tissues.

Jones Criteria — Diagnosis

Diagnosis: 2 Major OR 1 Major + 2 Minor + Evidence of preceding GAS infection

Evidence of GAS: Positive strep throat culture, rapid antigen test, or elevated ASO titer (or anti-DNase B)

Major Criteria — "JONES"

Joints: Migratory polyarthritis (most common, 70–75%) — large joints, hot/swollen/tender, responds to aspirin
O (heart): Carditis (50–70%) — pancarditis; mitral regurgitation most common valve lesion
Nodules: Subcutaneous nodules (rare, <10%) — firm, painless over bony prominences
Erythema marginatum (10–20%): pink-red rash with central clearing + raised margins; trunk and proximal extremities; transient
Sydenham chorea (10–30%): involuntary, purposeless, rapid movements; "milkmaid's grip"; emotional lability; can appear weeks-months after pharyngitis

Minor Criteria

Fever (>38.5°C)
Elevated ESR or CRP
Prolonged PR interval on EKG
Arthralgia (only if arthritis NOT used as major)

Treatment

Acute Treatment

Eradicate GAS: Amoxicillin × 10 days OR benzathine PCN G IM × 1
Arthritis: aspirin (high-dose) — dramatic response is diagnostic clue
Carditis with heart failure: corticosteroids
Chorea: resolves spontaneously. Valproic acid or carbamazepine if severe

Secondary Prophylaxis ⭐ Most Tested

Benzathine PCN G 1.2 MU IM q4 weeks (preferred over oral for compliance)
No carditis: 5 years or until age 21 (whichever longer)
Carditis, no residual disease: 10 years or until age 21
Carditis + persistent valvular disease: 10 years or until age 40 (sometimes lifelong)
Purpose: prevent recurrent GAS pharyngitis → recurrent ARF → progressive valve damage
⚑ Each recurrence damages heart valves further — prophylaxis is critical

Board Traps

ARF does NOT follow GAS skin infection (impetigo) — only GAS pharyngitis. (Impetigo can cause PSGN, not ARF)
Migratory arthritis means pain moves FROM one joint TO another (not additive). Responds dramatically to aspirin
Sydenham chorea can be the SOLE presentation of ARF — no other criteria needed if post-GAS evidence present
Prolonged PR interval = carditis minor criterion (AV node conduction delay — not permanent heart block)

EBV & Infectious Mononucleosis

Monospot · Posterior LAD · Splenomegaly · Amoxicillin Rash · Atypical Lymphocytes · Complications · No Contact Sports

Presentation

Classic Triad + Key Features

Classic triad: Fever + pharyngitis (often with exudate) + posterior cervical lymphadenopathy
Extreme fatigue/malaise — often incapacitating, may last weeks
Splenomegaly (50–70%): risk of splenic rupture with trauma or contact sports
Hepatomegaly + mild transaminase elevation (80%)
Periorbital edema (Hoagland sign): bilateral — classic but not universal
Palatal petechiae (50%): at junction of hard/soft palate — not pathognomonic but suggestive
Age: adolescents and young adults (15–25). Younger children often asymptomatic

Diagnosis

Monospot Test (Heterophile Antibody)

Rapid agglutination test — quick and cheap
Sensitivity: 85% (false negative in first week and in young children)
False positive: lupus, lymphoma, hepatitis, CMV
If monospot negative but clinical suspicion high → EBV-specific antibodies (VCA IgM)

CBC Findings

Lymphocytosis: >50% lymphocytes or absolute >4500/μL
Atypical lymphocytes (Downey cells): large, irregular, reactive T cells — >10% is classic
Mild thrombocytopenia common
Mild transaminase elevation (hepatitis component)

The Amoxicillin Rash — Most Tested Board Fact

⚑ Amoxicillin Rash in EBV ≠ Penicillin Allergy

70–100% of EBV patients who receive amoxicillin or ampicillin develop a diffuse maculopapular rash
Mechanism: pharmacologic/immune complex reaction — NOT IgE-mediated allergy
This is NOT a penicillin allergy — do NOT label patient as penicillin allergic
Rash also with amoxicillin-clavulanate in EBV
⚑ Classic board question: "patient prescribed amoxicillin for sore throat develops rash — what is the diagnosis?" = EBV, not drug allergy
Real teaching: ALWAYS do monospot before prescribing amoxicillin for pharyngitis

Management & Complications

Treatment

Supportive: rest, hydration, antipyretics/analgesics
No antivirals (acyclovir has no proven benefit)
No contact sports or vigorous activity for ≥3–4 weeks (splenic rupture risk)
Splenomegaly: most resolves by 4–6 weeks. Return to sports: when spleen not palpable + imaging clearance
Corticosteroids: only for airway obstruction (severe tonsillar enlargement) or immune thrombocytopenia

Complications

Splenic rupture (most dangerous acute complication) — spontaneous or traumatic
Airway obstruction from massive tonsillar enlargement
Autoimmune hemolytic anemia (cold agglutinins — IgM against I antigen)
EBV-associated malignancies: Burkitt lymphoma (c-myc translocation), nasopharyngeal carcinoma, CNS lymphoma (immunocompromised), Hodgkin lymphoma
Chronic active EBV: rare, immunocompromised patients

Varicella-Zoster Virus (VZV) & Herpes Simplex Virus (HSV)

Chickenpox vs Shingles · Postherpetic Neuralgia · Ramsay Hunt · HSV Encephalitis · Neonatal HSV · Acyclovir Timing

VZV — Primary Infection (Varicella/Chickenpox)

Chickenpox — Classic Presentation

Highly contagious — respiratory droplets and direct contact
Incubation: 14–21 days
Rash: pruritic vesicles on erythematous base ("dewdrops on rose petals") → pustules → crusting
Key feature: lesions in multiple stages simultaneously (pathognomonic)
Centripetal distribution: trunk → face → extremities (spares palms/soles)
Prodrome: low-grade fever, malaise 1–2 days before rash
Contagious: from 1–2 days before rash until ALL lesions crusted

Treatment

Healthy children: supportive (antihistamines for itch, calamine lotion)
Acyclovir: adolescents/adults (more severe disease), immunocompromised, newborns
⚑ ASPIRIN CONTRAINDICATED in children with varicella → Reye syndrome (hepatic encephalopathy)
Post-exposure prophylaxis: varicella vaccine within 3–5 days; VZIG within 96h for immunocompromised

Complications

Secondary bacterial infection (S. aureus, GAS): most common complication
Varicella pneumonia: adults > children. Bilateral infiltrates. Treat with acyclovir
Encephalitis: cerebellar ataxia (most common CNS complication in children)
Congenital varicella syndrome: limb hypoplasia, skin scarring, microcephaly (1st/2nd trimester exposure)

VZV — Reactivation (Herpes Zoster / Shingles)

Shingles — Dermatomal Reactivation

VZV remains latent in dorsal root ganglia → reactivates with ↓ cell-mediated immunity
Risk: age >50, immunocompromised, stress
Prodrome: dermatomal pain/burning/itching → vesicular rash in same dermatome, unilateral, does NOT cross midline
Antiviral timing: within 72h of rash onset → faster healing + ↓ PHN risk
Acyclovir, valacyclovir (preferred — better bioavailability), famciclovir

Postherpetic Neuralgia (PHN)

Pain persisting >90 days after rash resolution
Most common complication of zoster
Treatment: gabapentin (first-line), pregabalin, TCAs, lidocaine patch, capsaicin cream
Prevention: early antiviral treatment + vaccination (Shingrix)

Special Syndromes

Ramsay Hunt syndrome: VZV in geniculate ganglion → CN VII palsy + ear vesicles + hearing loss. Acyclovir + prednisone
Zoster ophthalmicus: V1 trigeminal (forehead + tip of nose = Hutchinson's sign) → risk of ocular involvement → urgent ophthalmology
Vaccine: Shingrix (recombinant, 2-dose) — recommended age ≥50, >90% efficacy. Preferred over Zostavax

HSV — Herpes Simplex Virus

HSV-1 vs HSV-2

HSV-1: primarily oral (herpes labialis — "cold sores"), also genital (increasing)
HSV-2: primarily genital (herpes genitalis), also neonatal
Both can cause encephalitis, meningitis, esophagitis (immunocompromised)
Latency in sensory ganglia: HSV-1 in trigeminal; HSV-2 in sacral ganglia
Diagnosis: PCR (most sensitive), viral culture, Tzanck smear (multinucleated giant cells — not specific)

HSV Encephalitis ⭐ Most Tested

Most common cause of fatal encephalitis in the US (predominantly HSV-1)
Temporal lobe involvement: fever + altered mental status + temporal lobe seizures + personality change
MRI: temporal lobe hyperintensity (T2/FLAIR)
CSF: lymphocytic pleocytosis, elevated protein, normal glucose, PCR for HSV = diagnostic
Treatment: IV acyclovir × 14–21 days. Start empirically — do NOT wait for PCR results
Mortality: ~70% untreated → <20% with early acyclovir

Neonatal Herpes

Transmission: primarily intrapartum contact with active genital HSV lesions
Presentation in newborn: skin/eye/mouth (SEM), CNS, disseminated disease
Prevention: C-section for active genital lesions at time of delivery (primary outbreak or visible lesions)
Suppressive therapy: acyclovir from 36 weeks gestation if history of genital HSV
Treatment of neonatal HSV: IV acyclovir × 14–21 days

Giardiasis & Amebiasis

Fecal-Oral · Steatorrhea · Trophozoites vs Cysts · Antigen Testing · Metronidazole · Hepatic Abscess

Giardia lamblia

Giardiasis — Most Common Intestinal Parasitic Infection in the US

Transmission: fecal-oral — contaminated water (hikers, campers, streams), daycare centers, developing countries
Trophozoites infect duodenum/jejunum → malabsorption
Presentation: watery to fatty (steatorrhea) diarrhea, bloating, flatulence, abdominal cramps, nausea — NO fever, NO blood
Chronic: malabsorption, weight loss, lactose intolerance (temporary)
Immunocompromised (IgA deficiency, X-linked agammaglobulinemia): severe/chronic giardiasis

Diagnosis

Stool antigen test (ELISA or immunochromatographic): first-line — high sensitivity (>90%)
Stool O&P (ova and parasites): trophozoites or cysts; 3 samples increase sensitivity
String test (Entero-test): swallowed capsule collects duodenal contents — rarely used

Treatment

Metronidazole 250mg TID × 5–7 days (first-line)
Tinidazole: single dose (2g) — better tolerated, high compliance
Nitazoxanide: alternative, also covers Cryptosporidium
Avoid alcohol with metronidazole (disulfiram-like reaction)

Entamoeba histolytica (Amebiasis)

Amebiasis — Bloody Diarrhea + Hepatic Abscess

Transmission: fecal-oral — developing countries, travelers, MSM, institutionalized persons
Intestinal amebiasis: dysentery with bloody, mucoid diarrhea ("currant jelly" stools), tenesmus, fever. "Flask-shaped" ulcers on colonoscopy
Amebic liver abscess: most common extraintestinal complication. RUQ pain + fever + elevated ALP. Single abscess in right lobe (most common). "Anchovy paste" appearance
Diagnosis: stool O&P + serum amebic antibodies. Abdominal US/CT for liver abscess

Treatment

Intestinal disease: metronidazole × 5–10 days + luminal agent (paromomycin or iodoquinol) to eradicate cysts
Liver abscess: metronidazole IV/oral × 5–10 days. Drainage only if large (>10cm), risk of rupture, or no response

Giardia vs Entamoeba

Giardia: watery/fatty, NO blood, NO fever, duodenum/jejunum
Entamoeba: bloody/mucoid, fever, colon + liver
Both: fecal-oral, metronidazole treatment, stool O&P diagnosis

Measles, Mumps & Rubella

Koplik Spots · Cephalocaudal Rash · Orchitis · Congenital Rubella · MMR Vaccine · SSPE

Measles (Rubeola)

Measles — The 3 C's + Prodrome

Prodrome (3–4 days): 3 C's — Coryza, Cough, Conjunctivitis + high fever
Koplik spots: white-gray spots on buccal mucosa (opposite lower molars) — pathognomonic, appear 1–2 days BEFORE rash
Rash: maculopapular, starts at hairline/forehead → cephalocaudal spread (head to feet), confluent on face
Highly contagious: airborne; can remain infectious in air for 2 hours after infected person leaves
Contagious: 4 days before to 4 days after rash onset

Complications

Pneumonia: most common cause of death in children (giant cell pneumonia)
Otitis media: most common complication overall
Encephalitis: 1:1000 cases → permanent disability
SSPE (subacute sclerosing panencephalitis): fatal progressive CNS degeneration, 7–10 years after infection
Measles in pregnancy: premature labor, spontaneous abortion

Treatment & Prevention

Supportive. Vitamin A supplementation reduces mortality (WHO recommendation)
Post-exposure: MMR vaccine within 72h OR IVIG within 6 days (immunocompromised/pregnant)
MMR vaccine: 2 doses (12–15 months, 4–6 years)

Mumps

Mumps — Parotitis + Orchitis

Transmission: respiratory droplets
Classic: painful parotid gland swelling (bilateral parotitis) — "chipmunk cheeks"
Orchitis: most common complication in post-pubertal males (20–30%). Unilateral usually. Can cause testicular atrophy → infertility (rare)
Oophoritis in females (rare)
Aseptic meningitis: most common CNS complication
Sensorineural hearing loss: rare but permanent
Pancreatitis: elevated lipase; associated but not common
Diagnosis: serum mumps IgM antibody or PCR of saliva/CSF
Treatment: supportive. Scrotal support + analgesics for orchitis

Rubella (German Measles)

Acquired Rubella (Postnatal)

Mild disease: low-grade fever + maculopapular rash (starts face, spreads caudally, fades by day 3 — "3-day measles")
Posterior auricular and suboccipital lymphadenopathy (classic)
Arthritis (especially in adult women)
Rarely severe in children — benign

Congenital Rubella Syndrome ⭐

Most dangerous in 1st trimester (organogenesis)
Classic triad: cataracts + cardiac defects (PDA, pulmonary stenosis) + sensorineural hearing loss
Also: microcephaly, blueberry muffin rash (extramedullary hematopoiesis), thrombocytopenia, intellectual disability
Prevention: MMR vaccine (contraindicated in pregnancy — avoid pregnancy for 28 days post-vaccine)
Screen: rubella IgG before pregnancy. Non-immune → vaccinate before conception

Rapid Review — MMR Distinctions

Measles: Koplik spots (pathognomonic) → cephalocaudal rash → complications: pneumonia, SSPE, encephalitis
Mumps: parotitis → orchitis (males), aseptic meningitis. No specific treatment
Rubella: mild acquired disease BUT devastating in pregnancy → congenital triad (cataracts + cardiac + deafness)
MMR vaccine: live attenuated — CONTRAINDICATED in pregnancy, immunocompromised (except HIV with CD4 >200), egg allergy (caution only)
Roseola (HHV-6): fever resolves → rash appears (rose-pink, blanching). Infantile — common febrile seizure cause
Fifth disease (erythema infectiosum, parvovirus B19): slapped-cheek rash + lacy reticular rash on body. Aplastic crisis in sickle cell + hydrops fetalis in pregnancy

Module D · Must-Know Differentials

High-Yield Differentials & Distinguishing Features

The following 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

Skin & Soft Tissue Infections — Cellulitis vs Abscess vs Necrotizing Fasciitis

Purulent vs Non-Purulent · MRSA Decision · Necrotizing Fasciitis Recognition · Surgical Emergency

★★★ PANCE PriorityNecrotizing Fasciitis Cannot Miss

The IDSA Framework — Purulent vs Non-Purulent

Type	Organism	Treatment	MRSA Coverage?
Non-purulent cellulitis (no pus, no abscess)	β-hemolytic Streptococci (Groups A, B, C, G)	Oral cephalexin or dicloxacillin × 5 days. IV if systemic toxicity, rapidly spreading, or immunocompromised.	NOT needed — not MRSA disease
Purulent cellulitis / Abscess	S. aureus (MRSA predominates in community)	I&D is definitive for abscess. Add TMP-SMX or doxycycline for moderate purulent cellulitis or abscess with systemic signs.	YES — CA-MRSA is the presumed organism
Severe cellulitis / SSTI with systemic toxicity	Polymicrobial, MRSA, or streptococcal	IV vancomycin (for MRSA) ± piperacillin-tazobactam (for polymicrobial). Hospital admission.	YES — empiric MRSA coverage required
Necrotizing Fasciitis	Type I: polymicrobial (Bacteroides + Streptococcus + coliforms). Type II: GAS alone (more aggressive).	IMMEDIATE surgical debridement + IV broad-spectrum antibiotics (pip-tazo + vancomycin ± clindamycin for toxin suppression)	SURGICAL EMERGENCY — mortality >30% if delayed

Necrotizing Fasciitis — The Clinical Recognition Challenge

Classic presentation: Severe pain out of proportion to skin findings, rapidly spreading erythema, woody hard induration, fever, systemic toxicity
The pain out of proportion sign: Early NF may look like benign cellulitis on the surface while deep fascia is necrotic. Pain dramatically exceeding the visible wound = NF until proven otherwise.
"Dishwater fluid" on surgical exploration: Gray-brown watery discharge with no frank pus = pathognomonic for polymicrobial necrotizing fasciitis
Gas in tissues on CT: Crepitus on exam or gas seen on CT = anaerobic organisms in the fascia = surgical emergency. Do NOT delay surgery for additional imaging if clinical diagnosis is clear.
LRINEC score (Lab Risk Indicator for Necrotizing Fasciitis): CRP + WBC + Hgb + Na + Cr + glucose — score ≥8 = high risk. Useful adjunct but does NOT replace clinical judgment.

⚑ Board Traps — SSTI

Non-purulent cellulitis does NOT need MRSA coverage — this is the most commonly missed SSTI principle. Non-purulent = streptococcal = beta-lactam is adequate. Routine empiric MRSA coverage for all cellulitis is incorrect.
Antibiotics alone are NOT sufficient for necrotizing fasciitis — surgery is the only cure. No antibiotic regimen can sterilize necrotic tissue. Delay in surgical debridement increases mortality dramatically.
Abscess treatment is incision and drainage — antibiotics alone fail for loculated purulent collections. I&D is the definitive treatment; antibiotics are adjunctive for surrounding cellulitis or systemic signs.
TMP-SMX does NOT adequately cover β-hemolytic streptococci — adequate CA-MRSA coverage but poor strep coverage. For non-purulent cellulitis, use cephalexin, not TMP-SMX.

Tier 1

Differential D-4

Urethral Discharge & STI Differential

Gonorrhea vs Chlamydia vs NGU vs Trichomonas · Treatment Selection · Partner Management

★★★ PANCE Priority

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

Differential D-5

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 (or dapsone/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-6

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-7

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 · Molnupiravir Pregnancy · 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.

Fast Review

10 Rapid-Fire ID Clinical Pearls

1
Sepsis-3 = SOFA ≥2 (organ dysfunction), NOT SIRS. Norepinephrine is first-line vasopressor — NOT dopamine. Vasopressin second-line. Peripheral vasopressor initiation is acceptable. Antibiotics within 1 hour. Balanced crystalloids preferred over NS.
2
Nitrofurantoin and fosfomycin = cystitis ONLY. Neither achieves adequate renal tissue concentrations — never for pyelonephritis. Fluoroquinolones are first-line for pyelo. Treat ASB ONLY in pregnancy and pre-urologic procedures.
3
Meningitis: ADD AMPICILLIN for patients >50, neonates, pregnant, immunocompromised. Cephalosporins have ZERO Listeria coverage. Dexamethasone BEFORE or WITH first antibiotic dose. Never delay antibiotics for CT or LP.
4
S. bovis/gallolyticus endocarditis = colonoscopy mandatory (~60% colorectal neoplasia). Osler = painful (immune complex). Janeway = painless (septic emboli). S. aureus is now #1 overall IE organism.
5
STI 2021 triple update: Chlamydia = doxycycline > azithromycin. Gonorrhea = ceftriaxone MONOTHERAPY (no azithromycin). Syphilis in pregnancy = penicillin ONLY (desensitize if allergic). Jarisch-Herxheimer = supportive care only.
6
C. diff: metronidazole NO LONGER first-line. Vancomycin or fidaxomicin for all initial CDI. Metro IV only in fulminant + ileus (with oral/rectal vanco). FMT >85% cure for recurrent CDI. Soap and water — alcohol gel doesn't kill spores.
7
HIV ring-enhancing lesions: SINGLE = CNS lymphoma (EBV). MULTIPLE = Toxoplasmosis. TMP-SMX covers BOTH PCP AND Toxo below CD4 <100. Cryptococcal meningitis: ALWAYS measure opening pressure. MAC prophylaxis no longer routine if ART started immediately.
8
Bilateral Bell palsy = Lyme disease until proven otherwise. EM rash = treat without serology in endemic area. AV block in Lyme Stage 2: 3rd degree = IV ceftriaxone + temporary pacing. Post-treatment Lyme serology stays positive for years — positive test ≠ active infection.
9
Influenza: oseltamivir within 48h for max benefit — but treat high-risk patients regardless of duration. Negative rapid test ≠ no flu (sensitivity ~70%). Zanamivir CONTRAINDICATED in asthma/COPD. Aspirin + flu in children = Reye syndrome.
10
Paxlovid (ritonavir) = potent CYP3A4 inhibitor. Hold CYP3A4-metabolized statins (atorvastatin, simvastatin). Adjust rivaroxaban/apixaban. Tacrolimus levels spike dramatically. Dexamethasone for COVID ONLY if O₂ requirement — not for mild outpatient disease.

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 20 ID Board Traps

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

20 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.

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 Disease
Bootcamp Syllabus

Full syllabus locked

Infectious DiseaseBootcamp Syllabus

Full syllabus locked

Infectious Disease
Bootcamp Syllabus