Zambian HIV Guidelines:: Pneumocystis carinii pneumonia

	Zambia HIV National Guidelines
	Introduction HIV Counseling and Testing Sexually Transmitted Infections (STIs) General Principles of Antiretroviral Therapy for Chronic HIV Infection in Adults and Adolescents When to Start ARV Therapy for Chronic HIV Infection in Adults and Adolescents Initial Regimen for ARV Therapy Adherence Baseline evaluation and Monitoring Calculations: Ideal Body Weight, Body Mass Index and Creatinine Clearance ARV Therapy for Individuals with Tuberculosis Co-Infection Adverse Effects and Toxicity Immune Reconstitution Inflammatory Syndrome (IRIS) Changing or Stopping ART Treatment Failure Stopping ARV Therapy Post Exposure Prophylaxis Cotrimoxazole Prophylaxis WHO Staging in Adults and Adolescents Nutrition Care and Support Palliative Care in HIV and AIDS
	Guide Editors
	Editor In Chief Joel E. Gallant, MD, MPH Pharmacology Editor Paul Pham, PharmD, BCPS Zambia Guideline Team Peter Mwaba MMed PhD FRCP Alywn Mwinga MMed Isaac Zulu MMed MPH Velepie Mtonga MMed Albert Mwango MBChB Jabbin Mulwanda MMed FCS

Pneumocystis carinii pneumonia

Noah Lechtzin, M.D., M.H.S.
02-05-2008

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

PATHOGENS

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.

Initial Therapy

Preferred: TMP-SMX 5 mg/kg (of TMP component) q8h x21 days.
Alternative: clindamycin 600 mg q8h & primaquine 15-30 mg qd.
Alternative: dapsone 100 mg qd & TMP 5 mg/kg q8h x 21 days (mild-to-moderate PCP only).
Alternative: atovaquone 750 mg tid 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/m²IV (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.

Adjunctive Therapy

If PaO2 <70 mm Hg or A-a gradient > 35 mm Hg add corticosteroids: prednisone 40 mg PO bid x5d, then 40 mg qd x5d, then 20 mg qd x11d (or IV equivalent).

Prophylaxis

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 qd. Alternative is 1 DS tab 3 x/wk. (1 DS qd preferred for toxo-seropositives with CD4<100).
Alternative: dapsone 100 mg daily.
Alternative: pentamidine 300 mg in 6 mL sterile water aerosolized monthly.
Alternative: Atovaquone suspension 750 mg bid or 1500 mg qd.
Discontinue if CD4 >200 x >3 mos on HAART.

Infection Control

Drug	Recommendations/Comments
Atovaquone	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.
Clindamycin	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.
Dapsone	Used as single agent only for prophylaxis; effective for mild-to-moderate PCP when combined with TMP, with fewer side effects than TMP-SMX.
Pentamidine	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.
Primaquine	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	1stline 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.

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