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System 07 · ~8% of exam

Infectious Disease

Fever workup by site and host. Sepsis is the drumbeat emergency. Know your empiric antibiotics and when to narrow.

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Chief complaints

BUILD THE DIFFERENTIAL

Vignettes enter through one of these doors. Each complaint lays out the full differential, marks the can't-miss diagnoses, and tells you the next right action for each.

Fever workupSepsisSTIs
CHIEF COMPLAINT · HIGH-YIELD

Fever workup

Source hunt by history, exam, and targeted testing. Host matters, immunocompromised differs.

Approach

Always: full exam (skin, joints, lines, lungs, abdomen, GU, CNS), urinalysis, blood cultures, CBC, CXR. Travel history, exposures, sick contacts. Immunocompromised broaden to fungal, viral, atypical.

The differential
Diagnosis Key features / clues Next step
Sepsis SIRS + suspected infection. Hypotension, tachycardia, altered mental status, organ dysfunction. Sepsis bundle within 1 hour: cultures, lactate, broad antibiotics, 30 mL/kg crystalloid if lactate ≥ 4 or hypotension
Neutropenic fever ANC < 500 with fever ≥ 38.3. Recent chemo. Blood cultures × 2, CXR, UA · empiric cefepime or pip-tazo · add vanc if line, mucositis, hypotension
Meningitis Fever + headache + neck stiffness + AMS. Empiric antibiotics first, then LP · CT before LP if focal deficit, AMS, papilledema, immunocompromised
Endocarditis Fever + new murmur or vascular phenomena (Janeway, Osler, Roth, splinter). 3 sets of blood cultures from separate sites, different times · TTE (TEE if high suspicion or prosthetic) · Duke criteria
UTI / pyelonephritis Dysuria, frequency, urgency, suprapubic pain. Pyelo: flank pain, fever. UA · urine culture · antibiotics
Pneumonia Cough, sputum, focal crackles, infiltrate. CXR · sputum · blood cultures · antibiotics per CURB-65
Skin/soft tissue Redness, warmth, tenderness, abscess. Clinical · I&D for abscess · cover MRSA for purulent
⚑ = can't-miss diagnosis · rule out first
Pearls
Pearl
Sepsis 1-hour bundle: blood cultures (before antibiotics if possible), lactate, broad antibiotics within 1 hour, 30 mL/kg crystalloid if hypotensive or lactate ≥ 4, vasopressors (norepi first) if still hypotensive.
Pearl
Fever of unknown origin: > 38.3 for > 3 weeks with no diagnosis after initial evaluation. Big four: infection, malignancy, autoimmune, drug fever.
Pearl
Drug fever is often accompanied by eosinophilia and a relative bradycardia (despite high temp).
CHIEF COMPLAINT · HIGH-YIELD

Sepsis

Life-threatening organ dysfunction from dysregulated host response to infection. Time-sensitive bundle.

Approach

Identify source. Give antibiotics within 1 hour (empiric based on suspected source). Fluids (30 mL/kg if hypotension or lactate ≥ 4). Pressors if not responsive to fluids. Source control (drain abscesses, remove lines, debride).

The differential
Diagnosis Key features / clues Next step
Septic shock Sepsis + persistent hypotension requiring pressors and lactate > 2 despite fluids. Norepinephrine first (target MAP ≥ 65) · add vasopressin · steroids if refractory
Source-specific sepsis Depends on source: lung (pneumonia), urine (UTI), abdomen, skin, CNS, blood (line/endocarditis). Targeted antibiotics + source control
⚑ = can't-miss diagnosis · rule out first
Pearls
Pearl
qSOFA (RR ≥ 22, AMS, SBP ≤ 100) screens for sepsis quickly but has poor sensitivity. NEWS or SIRS criteria can also trigger escalation.
Pearl
Balanced crystalloids (LR, Plasma-Lyte) are preferred over saline in most cases.
Pearl
Lactate clearance is a useful resuscitation target. Serial lactates can guide ongoing fluid/pressor needs.
CHIEF COMPLAINT

STIs

Screen by risk factors. Empiric treatment covers gonorrhea + chlamydia for urethritis or cervicitis.

Approach

Urethritis/cervicitis: NAAT for gonorrhea and chlamydia, treat empirically. GUD: HSV most common, then syphilis. Serology and PCR.

The differential
Diagnosis Key features / clues Next step
Gonorrhea Purulent urethritis or cervicitis. Can disseminate (tenosynovitis, dermatitis, polyarthralgia → septic arthritis). Ceftriaxone 500 mg IM (1 g if ≥ 150 kg) · treat chlamydia empirically unless ruled out
Chlamydia Urethritis (men), cervicitis or asymptomatic (women). LGV with bubos. Doxycycline 100 mg BID × 7 days (azithro if pregnant)
Syphilis Primary: painless chancre. Secondary: rash (palms/soles), condyloma lata, constitutional. Latent. Tertiary: gumma, CV, neuro. RPR/VDRL, then FTA-ABS. Benzathine PCN G 2.4 million U IM (single for early, weekly × 3 for late). Neurosyphilis: IV PCN × 10–14 days
HSV Painful vesicular lesions, recurrent. PCR · acyclovir, valacyclovir, or famciclovir
HIV Acute: fever, rash, lymphadenopathy, pharyngitis (mono-like). Chronic: opportunistic infections. 4th-gen antigen/antibody · viral load · CD4 count · start ART
Trichomoniasis Frothy yellow-green discharge, strawberry cervix. Metronidazole 2 g single dose (or 500 BID × 7 days) · treat partners
Bacterial vaginosis Thin gray discharge, fishy odor, clue cells, vaginal pH > 4.5. Not technically an STI. Metronidazole or clindamycin
⚑ = can't-miss diagnosis · rule out first
Pearls
Pearl
Jarisch-Herxheimer reaction after penicillin for syphilis: fever, myalgia, headache. Self-limited in hours.
Pearl
Every PID treatment includes coverage for gonorrhea, chlamydia, and anaerobes. Admit if pregnant, failed outpatient, TOA, unable to tolerate PO.
Pearl
HIV acute retroviral syndrome can look like mono. PCR (viral load) is positive before antibodies. Check on high suspicion.
✦

Disease deep dives

DEFINITIVE DX

Once you've identified the likely diagnosis from the chief complaint, these pages give you the presentation, workup, management, and exam pearls in depth.

Sepsis
Organ dysfunction from infection. Early recognition and aggressive treatment save lives.
Infective Endocarditis
Duke criteria. IVDU gets right-sided (tricuspid). Dental procedures can seed. Prosthetic valves are their own category.
HIV
Test every adult at least once. Start ART at diagnosis regardless of CD4. Prophylaxis by CD4.
Tuberculosis
Latent vs active. 4-drug RIPE for 2 months, then 2 drugs for 4 months. Test and treat contacts.
Cellulitis & SSTI
Purulent vs non-purulent drives coverage. Necrotizing fasciitis is a surgical emergency.
DISEASE DEEP DIVE

Sepsis

Organ dysfunction from infection. Early recognition and aggressive treatment save lives.

Presentation

Fever, tachycardia, tachypnea, hypotension, AMS, oliguria. Source-specific features.

Workup
  1. Blood cultures × 2. Before antibiotics if possible, from separate sites.
  2. Lactate. Hypoperfusion marker. Trend.
  3. Source-specific cultures. Urine, sputum, wound, CSF.
  4. Imaging. CXR, abdominal imaging based on suspicion.
Management
  1. Antibiotics within 1 hour. Broad empiric: vancomycin + (pip-tazo OR cefepime OR meropenem). Narrow once cultures return.
  2. IV fluids. 30 mL/kg crystalloid bolus if hypotension or lactate ≥ 4.
  3. Vasopressors. Norepinephrine first (target MAP ≥ 65). Add vasopressin. Epinephrine if refractory.
  4. Steroids. Hydrocortisone 200 mg/day for refractory septic shock on pressors.
  5. Source control. Drain abscesses, remove infected lines, debride necrotic tissue, surgery for perforation.
Pearls
Pearl
Broad empiric antibiotics differ by source. Abdomen: pip-tazo + coverage. Pneumonia: ceftriaxone + azithro (HAP: vanc + pip-tazo). Skin: vancomycin + gram-negative.
Pearl
Do not wait for blood cultures to return to narrow antibiotics if cultures are negative. Use clinical response and alternative diagnoses.
DISEASE DEEP DIVE

Infective Endocarditis

Duke criteria. IVDU gets right-sided (tricuspid). Dental procedures can seed. Prosthetic valves are their own category.

Presentation

Fever, new murmur, constitutional symptoms. Vascular: Janeway lesions, splinter hemorrhages, Roth spots, Osler nodes. Emboli: stroke, renal infarct, splenic infarct.

Workup
  1. Blood cultures × 3. From separate sites, separated by time. Before antibiotics.
  2. Echo. TTE first; TEE if high suspicion, TTE negative, or prosthetic valve. TEE has much higher sensitivity.
  3. Duke criteria. Definite: 2 major, 1 major + 3 minor, or 5 minor. Major: persistent bacteremia with typical organism, endocardial involvement on echo. Minor: fever, predisposition, vascular/immunologic phenomena, microbiological evidence not meeting major.
Management
  1. Empiric antibiotics. Native valve: vancomycin + ceftriaxone. Prosthetic valve: vancomycin + gentamicin + cefepime or rifampin. Tailor to cultures.
  2. Duration. 4–6 weeks IV. Based on organism, native vs prosthetic.
  3. Surgery indications. HF from valve dysfunction, uncontrolled infection, recurrent emboli, prosthetic valve dysfunction, paravalvular abscess, fungal endocarditis.
  4. Prophylaxis. Before dental procedures only for highest-risk: prosthetic valves, prior IE, congenital heart disease (certain types), cardiac transplant with valvulopathy. Amoxicillin 2 g.
Pearls
Pearl
S. aureus is the most common overall and most common in IVDU. Strep viridans in subacute (dental). Enterococcus in GI/GU. HACEK in culture-negative.
Pearl
Tricuspid IE (IVDU): septic pulmonary emboli on CXR, multiple nodular lesions, sometimes cavitary.
Pearl
Culture-negative endocarditis: HACEK, Bartonella, Coxiella, Brucella, fungi, T. whipplei. Serologic testing.
DISEASE DEEP DIVE

HIV

Test every adult at least once. Start ART at diagnosis regardless of CD4. Prophylaxis by CD4.

Presentation

Acute: fever, pharyngitis, lymphadenopathy, rash, mouth ulcers, myalgia (2–4 weeks post-exposure). Chronic: opportunistic infections, constitutional symptoms.

Workup
  1. 4th-generation Ag/Ab. Detects p24 antigen and antibodies. Positive 2–4 weeks after infection.
  2. Confirmation. HIV-1/2 antibody differentiation assay. If discordant, HIV RNA.
  3. Baseline. CD4, viral load, HLA-B*5701 (before abacavir), hep B/C, toxoplasma IgG, STI screen, TB screen, resistance genotype.
Management
  1. ART at diagnosis. Start immediately. Preferred: INSTI-based regimens. Bictegravir/TAF/FTC (single pill). Dolutegravir + TAF/FTC or TDF/3TC.
  2. PCP prophylaxis. CD4 < 200: TMP-SMX.
  3. Toxoplasma prophylaxis. CD4 < 100 and Toxo IgG+: TMP-SMX.
  4. MAC prophylaxis. Rarely needed now with ART. CD4 < 50 if ART delayed: azithromycin.
  5. Monitoring. Viral load and CD4 every 3 months initially. Target undetectable viral load (< 50).
  6. Pre-exposure prophylaxis. Daily TDF/FTC or TAF/FTC for high-risk individuals.
  7. Post-exposure prophylaxis. Within 72 hours. Triple-drug regimen × 28 days.
Pearls
Pearl
U = U: undetectable = untransmissible. Sustained undetectable viral load means no sexual transmission.
Pearl
IRIS (immune reconstitution inflammatory syndrome): paradoxical worsening of opportunistic infection after ART start. Treat the OI, continue ART, steroids if severe.
Pearl
Start ART within 2 weeks of OI treatment in most cases, sooner if CD4 very low. Exception: TB meningitis, cryptococcal meningitis (delay 4–8 weeks).
DISEASE DEEP DIVE

Tuberculosis

Latent vs active. 4-drug RIPE for 2 months, then 2 drugs for 4 months. Test and treat contacts.

Presentation

Active pulmonary: chronic cough, hemoptysis, night sweats, weight loss, fever. Extrapulmonary: any organ. Latent: positive PPD or IGRA without disease.

Workup
  1. PPD or IGRA. Latent screen. IGRA preferred if BCG vaccinated.
  2. Active disease. Sputum AFB × 3 (induction if needed), sputum NAAT, culture (gold standard but slow).
  3. CXR. Upper lobe cavitary in reactivation. Lower or mid lobe in primary. Miliary in disseminated.
Management
  1. Latent TB. Isoniazid 9 months OR rifampin 4 months OR INH + rifapentine weekly × 12 (3HP).
  2. Active TB. RIPE for 2 months (rifampin, isoniazid, pyrazinamide, ethambutol), then RI for 4 months.
  3. DOT. Directly observed therapy recommended.
  4. Resistance. MDR (resistant to rifampin and INH), XDR (additional resistance). Longer, more toxic regimens.
  5. Public health. Report. Contact tracing. Respiratory isolation for smear-positive patients.
Pearls
Pearl
INH side effects: hepatotoxicity, peripheral neuropathy (give B6). Rifampin: orange body fluids, induces CYP450. Pyrazinamide: hyperuricemia, hepatotoxicity. Ethambutol: optic neuritis (monthly vision checks).
Pearl
Baseline LFTs before starting TB treatment. Monitor if high risk or symptoms.
Pearl
Steroids as adjunct: TB meningitis (always), TB pericarditis (sometimes). Reduces mortality.
DISEASE DEEP DIVE

Cellulitis & SSTI

Purulent vs non-purulent drives coverage. Necrotizing fasciitis is a surgical emergency.

Presentation

Erythema, warmth, swelling, tenderness. Fever variable. Necrotizing fasciitis: pain out of proportion, systemic toxicity, crepitus, bullae, skin anesthesia.

Workup
  1. Clinical. No imaging needed for simple cellulitis.
  2. Cultures. From abscess drainage if purulent. Blood cultures if systemic.
  3. Imaging. CT or MRI if deep infection or necrotizing fasciitis suspected.
Management
  1. Non-purulent cellulitis. Strep coverage, cephalexin or cefazolin IV. Amoxicillin also an option.
  2. Purulent (abscess). Incision and drainage (primary). Antibiotics for large, systemic symptoms, immunocompromised, multiple sites. Cover MRSA: TMP-SMX, doxycycline, or clindamycin outpatient; vancomycin or linezolid inpatient.
  3. Necrotizing fasciitis. Emergent surgical debridement. Empiric vancomycin + pip-tazo + clindamycin (toxin suppression). Adjunctive IVIG for streptococcal toxic shock.
Pearls
Pearl
Erysipelas: well-demarcated, raised borders, often facial. Streptococcal.
Pearl
Water exposure cellulitis: Vibrio vulnificus (salt water, especially in liver disease), Aeromonas (fresh water), Mycobacterium marinum (fish tanks).
Pearl
Animal or human bites: pasteurella, staph, strep, anaerobes. Amoxicillin-clavulanate.
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