Morphology: Atypical fungus — cell wall lacks ergosterol (azoles ineffective). Cysts (5–8 μm) and trophic forms in alveoli. GMS / DFA / PCR positive on BAL.
Typical drugs
- #1Trimethoprim-sulfamethoxazole— First-line treatment AND prophylaxis. TMP 15–20 mg/kg/day divided q6–8h × 21 days for treatment.
- #2Pentamidine— IV alternative for severe PCP intolerant to TMP-SMX. Inhaled pentamidine for prophylaxis only (not treatment).
- #3Atovaquone— Mild–moderate PCP and prophylaxis (must take with fatty meal).
- #4Primaquine— Combo with clindamycin — moderate–severe alternative; check G6PD first.
- #5Dapsone— Prophylaxis alternative; check G6PD first.
Empiric therapy when resistant
If TMP-SMX failure: add steroids (if not started), confirm diagnosis, switch to IV pentamidine or primaquine + clindamycin. ID consult.
Resistance mechanisms
Target alteration
DHPS (dihydropteroate synthase) mutations associated with sulfa exposure
Example: Possible reduced TMP-SMX efficacy — clinical impact debated.
Resistance notes
True clinical resistance rare; mutations associated with prior sulfa exposure but clinical impact uncertain.
Pearls
Risk factors: HIV (CD4 <200), solid organ transplant, hematologic malignancy, chronic steroid use (≥20 mg prednisone × ≥4 wk), biologics (rituximab, alemtuzumab), idiopathic CD4 lymphopenia. Adjunctive STEROIDS if PaO2 <70 OR A-a gradient >35 — prednisone 40 mg BID × 5 d, then taper × 21 d (HIV-PCP only; data weaker in non-HIV but commonly extrapolated). Prophylaxis trigger: CD4 <200 in HIV; ≥20 mg prednisone × ≥1 mo + other risks; HSCT / SOT per protocol. Note PCR-positive doesn't always mean disease (colonization).
References
- ATS/IDSA HIV-related Pneumonia Guidelines (2009)
- AST Fungal IDC Guidelines (2019)