Pneumocystis carinii pneumonia
Noah Lechtzin, M.D., M.H.S.
- PCP less common in Africa than US or Europe (3-10% of individuals hospitalized with fever in Africa) & less common than pulmonary TB or bacterial pneumonia in Africa
- Sx: fever, progressive dyspnea on exertion, dry cough
- Differential diagnosis: TB, bacterial pneumonia, KS
- Multiple diagnoses more likely in Zambia; consider empiric treatment if Sx consistent with PCP even if another process has also been diagnosed (e.g. TB)
- Diagnostic capacity limited in Zambia, thus empiric therapy should be relied on
Zambia Information Author: Christopher Hoffmann, MD, MPH
Pneumocystis jiroveci or jirovecii (formerly P. carinii), a fungal organism previously classified as a protozoan
- Ubiquitous organism, respiratory transmission.
- Active cases due to both reactivation of old and acquisition of new infection (N Engl J Med 2004;350:2487).
- Incidence peaked 1987-1988, with subsequent decrease due to prophylaxis and HAART.
- Occurs when CD4 <200; risk increases with decreasing CD4 count.
- Hx: gradual/subacute onset of cough (usually non-productive), dyspnea, fever in most pts. Chills, fatigue, chest pain, weight loss less common.
- PE: fever, normal lung exam in ~50%. May have crackles and/or rhonchi.
- Extrapulmonary involvement rare but can occur.
- Hypoxemia and low DLCO common. Oxygen saturation may be normal at rest, but decreases with exercise
- CXR: diffuse interstitial and/or alveolar infiltrates. 25% are normal with early disease.
- CXR findings variable: Can have lobar infiltrates, nodules, masses, dense infiltrates, blebs, spontaneous pneumothorax and possibly pleural effusions.
- Induced sputum diagnostic in 60%; BAL diagnostic in >90%.
- Elevated LDH common but nonspecific.
- Molecular based diagnostic tests on sputum or oral washings hold promise
- Definitive Dx (by sputum or BAL) preferred over presumptive Dx, as presentation similar for other OIs, toxicity common during 3-week treatment course, and adjunctive corticosteroids may exacerbate other conditions.
- Preferred: TMP-SMX 5 mg/kg (of TMP component) q8h x21 days.
- Alternative: clindamycin 600 mg q8h & primaquine 15-30 mg once-daily.
- Alternative: dapsone 100 mg once-daily & TMP 5 mg/kg q8h x 21 days (mild-to-moderate PCP only).
- Alternative: atovaquone 750 mg three times a day x 21 days (mild-to-moderate PCP only).
- Alternative: pentamidine 4 mg/kg/day IV (high rate of side effects: ARF, hypotension, pancreatitis, hypo- and hyperglycemia, and electrolyte abnormalities).
- Alternative: trimetrexate 45 mg/m2/day IV & leucovorin 20mg/m2 IV (moderate-to-severe PCP). Not as effective as regimen 2. Side effects include myelosuppression, hepatic and renal toxicity.
- Regimens 1-4 can be given orally. Side effects including rash, anemia, hyperkalemia are common. Check G6PD before using dapsone.
- Resistance to TMP-SMX described, but not clearly correlated with treatment outcome. Approach to pts failing TMP-SMX controversial.
- If PaO2 <70 mm Hg or A-a gradient > 35 mm Hg add corticosteroids: prednisone 40 mg PO twice-daily x5d, then 40 mg once-daily x5d, then 20 mg once-daily x11d (or IV equivalent).
- Indications: CD4 <200 or history of thrush. Consider for CD4% <14 or history of AIDS-defining illness.
TMP-SMX, 1 SS or 1 DS tab once-daily. Alternative is 1 DS tab 3 x/wk. (1 DS once-daily preferred for toxo-seropositives with CD4<100).
- Alternative: dapsone 100 mg once-daily.
- Alternative: pentamidine 300 mg in 6 mL sterile water aerosolized monthly.
- Alternative: Atovaquone suspension 750 mg twice-daily or 1500 mg once-daily.
- Discontinue if CD4 >200 x >3 mos on HAART.
- Need for isolation of pts from other immunosuppressed pts controversial.
||Less effective than TMP-SMX but has fewer adverse reactions. Expensive compared to other oral alternatives. Absorption variable if diarrhea. For mild-to-moderate cases only. Also effective (at treatment doses) for prophylaxis, but very expensive.
||Effective when combined with primaquine in mild-to-moderate disease and can be given orally. Some trials using clinda/primaquine had pts with PO2 <70.
||Used as single agent only for prophylaxis; effective for mild-to-moderate PCP when combined with TMP, with fewer side effects than TMP-SMX.
||Best 2nd line agent for severe PCP in pts who cannot tolerate TMP-SMX. Azotemia, hypo- and hyperglycemia common. Aerosolized form should not be used to treat active infection but is alternative agent for prophylaxis.
||Effective when combined with clindamycin in mild-to-moderate disease and can be given orally. Some trials using clinda/primaquine had pts with PO2 <70.
Trimethoprim + Sulfamethoxazole
||1st line agent for treatment and prophylaxis of PCP. Can be given PO or IV. Adverse reactions common.
|Trimetrexate ||Less effective than clindamycin & primaquine and has low success rate in TMP-SMX failures.