Infections in the Immunocompromised Host
A board-focused walkthrough of infections in the immunocompromised host, organized by the failed immune arm (neutropenia, T-cell, humoral/asplenia, complement, CGD) and mapping each exposure clue to its classic organism, diagnosis, and next-best-step management. Emphasizes HIV CD4 thresholds, the transplant timeline, and high-yield decision points like empiric neutropenic-fever antibiotics, PCP steroid criteria, and when to start vs defer ART.
The one question that solves the vignette
The single most useful move on the boards is to ask which arm of the immune system is down — the defect predicts the pathogen.
- Neutropenia (chemotherapy, acute leukemia; ANC <500/µL) invites bacteria — especially Pseudomonas and other gram-negatives — plus molds (Aspergillus, Mucor) and Candida.
- Impaired cell-mediated (T-cell) immunity (HIV, transplant on calcineurin inhibitors, chronic steroids, TNF-α inhibitors) opens the door to intracellular organisms: Pneumocystis, CMV/HSV/VZV, Cryptococcus, endemic fungi, TB/MAC, Listeria, Toxoplasma, and JC virus.
- Humoral / asplenic defects (myeloma, CVID, sickle cell, splenectomy) leave patients defenseless against encapsulated bacteria.
- Terminal complement (C5–C9) deficiency → recurrent Neisseria.
Match the missing defense to the exposure clue and the answer usually falls out.
- Neutropenia (ANC <500): Pseudomonas, enteric GNRs, viridans strep (mucositis), S. aureus; molds Aspergillus/Mucor, Candida
- T-cell defect: PCP, CMV/HSV/VZV, Cryptococcus, Histoplasma/Coccidioides, TB/MAC, Listeria, Toxoplasma, JC virus (PML)
- B-cell / humoral & asplenia: encapsulated — S. pneumoniae, H. influenzae, N. meningitidis; asplenics also Babesia and Capnocytophaga (dog bite)
- Terminal complement (C5–C9): recurrent, often milder Neisseria
- Chronic granulomatous disease (NADPH-oxidase defect): catalase-positive organisms; Dx = dihydrorhodamine (DHR) flow cytometry
- Neutropenic fever is an emergency: cultures, then an empiric antipseudomonal β-lactam within 1 hour
Organism → exposure clue → first-line treatment
| Organism | Classic clue / exposure | First-line treatment |
|---|---|---|
| Pneumocystis jirovecii | HIV CD4 <200; subacute dyspnea, ↑LDH, ground-glass | TMP-SMX; +steroids if PaO₂ ≤70 |
| Cryptococcus neoformans | CD4 <100; headache, ↑ICP; pigeon droppings | (Liposomal) Ampho B + flucytosine → fluconazole |
| CMV | CD4 <50 / transplant; "pizza-pie" retinitis, colitis; owl-eye inclusions | Ganciclovir / valganciclovir (foscarnet if resistant) |
| Toxoplasma gondii | CD4 <100; multiple ring-enhancing basal-ganglia lesions | Pyrimethamine + sulfadiazine + leucovorin |
| Aspergillus | Prolonged neutropenia; halo/air-crescent sign, hemoptysis | Voriconazole |
| Mucorales (Rhizopus) | DKA / deferoxamine; black palate eschar; non-septate hyphae | Debridement + liposomal Ampho B |
| Nocardia | Transplant/steroids; lung + brain abscess; partially acid-fast | TMP-SMX |
| Listeria | Elderly/pregnant/T-cell defect; meningitis; tumbling motility | Ampicillin ± gentamicin |
Vignette: A 58-year-old woman, 10 days after induction chemo for AML, has a single temperature of 38.5°C. She looks well; BP 118/74. ANC is 180/µL.
Diagnosis: Febrile neutropenia (ANC <500 + one temp ≥38.3°C, or ≥38.0°C sustained 1 h).
Next best step:
- Draw two sets of blood cultures (peripheral + line) and basic labs — do not delay therapy for imaging.
- Start empiric antipseudomonal monotherapy now: cefepime, piperacillin-tazobactam, or meropenem — target door-to-antibiotic <60 min.
- Add vancomycin only for a specific reason: hemodynamic instability, suspected line/skin infection, severe mucositis, MRSA colonization, or pneumonia.
- If fever persists >4 days (4–7 d) on broad-spectrum antibiotics → add an empiric antifungal (an echinocandin or liposomal amphotericin B) and get CT chest for invasive mold; use voriconazole if invasive aspergillosis is documented/strongly suspected.
Board trap: never wait for the ANC or culture results before giving antibiotics.
- CD4 <200: Pneumocystis → start TMP-SMX prophylaxis; look for ground-glass, ↑LDH, ↑β-D-glucan
- CD4 <150 (+ endemic area): Histoplasma (itraconazole prophylaxis)
- CD4 <100: Toxoplasma → add prophylaxis if Toxo IgG-positive (TMP-SMX also covers it); rising Cryptococcus risk
- CD4 <50: MAC (disseminated) and CMV end-organ disease — retinitis (dilated fundoscopy for painless vision loss/floaters), colitis, esophagitis
- TMP-SMX is first-line for both prophylaxis and treatment of PCP (and covers Toxo, Nocardia, Listeria)
- Start ART — durable immune recovery is the real fix. Begin within ~2 weeks for most OIs, but defer in cryptococcal meningitis (~4–6 wks) and TB meningitis (~8 wks) to avoid life-threatening CNS IRIS
- Primary MAC prophylaxis is no longer routinely recommended if the patient promptly starts effective ART
- Stop prophylaxis once CD4 stays above threshold on ART (e.g., stop PCP prophylaxis when CD4 >200 for ≥3 months)
Vignette: A 34-year-old man on no medications has 3 weeks of dry cough and worsening exertional dyspnea. Resting exam is near-normal, but SpO₂ falls to 86% while walking. CXR shows diffuse bilateral perihilar infiltrates; LDH is high. HIV screen is positive; CD4 = 90.
Diagnosis: Pneumocystis jirovecii pneumonia (PCP).
Next best step:
- Induced sputum or BAL for GMS/DFA/PCR (the organism can't be cultured); serum β-D-glucan supports it.
- Start high-dose TMP-SMX.
- Check an ABG: if PaO₂ ≤70 mmHg (or A–a gradient ≥35), add adjunctive corticosteroids with/just before antibiotics — steroids reduce mortality in moderate-severe disease.
- Begin ART (~within 2 weeks) and continue TMP-SMX at prophylactic dosing after treatment.
Buzzwords: hypoxia out of proportion to exam, ↑LDH, ground-glass, exertional desaturation.
Vignette: A 52-year-old man with poorly controlled diabetes presents in DKA with facial pain, bloody nasal discharge, and a black eschar on the hard palate; vision is worsening in the right eye.
Diagnosis: Rhino-orbital-cerebral mucormycosis (Rhizopus).
Next best step:
- Urgent surgical debridement + liposomal amphotericin B — angioinvasion is rapid; do not wait.
- Correct the acidosis/DKA; stop deferoxamine if present.
- Biopsy: broad, non-septate (aseptate) hyphae with wide (~90°) branching.
Contrast — invasive aspergillosis: prolonged neutropenia; CT halo → air-crescent sign, hemoptysis; biopsy shows septate, acute-angle (~45°) branching hyphae; serum galactomannan aids diagnosis; treat with voriconazole.
- <1 month (nosocomial): surgical-site/line infections, aspiration, C. difficile, donor-derived; HSV reactivation
- 1–6 months (peak immunosuppression → opportunistic): CMV (most important — fever, cytopenias, colitis), PCP, Aspergillus, Nocardia, Listeria, BK virus (renal-allograft nephropathy), reactivated TB/endemic fungi
- >6 months: community-acquired pathogens (CAP, UTI, respiratory viruses); late CMV/PCP if prophylaxis stopped; EBV → PTLD
- Standard prophylaxis: TMP-SMX (covers PCP, Toxoplasma, Nocardia, Listeria) and valganciclovir (CMV)
Encapsulated organisms (deadly in asplenia and humoral defects) — Please SHiNE my SKiS:
- *P*seudomonas · *S. pneumoniae* · *H. influenzae* type b · *N. meningitidis* · *E. coli*
- *Salmonella* · *Klebsiella* · group B *Strep*
→ S. pneumoniae is the #1 cause of overwhelming post-splenectomy infection (OPSI). Vaccinate (pneumococcal, meningococcal, Hib) before elective splenectomy; peripheral smear shows Howell-Jolly bodies in asplenia.
Chronic granulomatous disease = catalase-positive organisms: *S. aureus, Serratia, Burkholderia cepacia, Nocardia, Aspergillus* (recurrent abscesses/lymphadenitis). Dx = dihydrorhodamine (DHR) flow cytometry (replaced the older nitroblue-tetrazolium test).
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