109 PNEUMOCYSTIS CARINII INFECTION
Harrison’s Manual of Medicine
PNEUMOCYSTIS CARINII INFECTION
Outpatient/Home Care Considerations
Pneumocystis carinii is a eukaryotic organism that causes disease in immunocompromised hosts, particularly those with HIV infection. Although its taxonomy has been controversial, recent molecular studies clearly place the organism among the fungi.
P. carinii has a worldwide distribution. It is transmitted by airborne inhalation; person-to-person transmission has been suggested in some instances. People at risk for pneumocystosis have defects in cellular and humoral immunity; at-risk groups include premature malnourished infants, children with primary immunodeficiency diseases, pts receiving immunosuppressive therapy (especially glucocorticoids) for cancer and organ transplantation, and pts infected with HIV. In HIV infection, the incidence of P. carinii pneumonia (PCP) rises dramatically when the CD4+ cell count falls below 200/µL.
P. carinii Pneumonia Pts with PCP have dyspnea, fever, and nonproductive cough. In HIV-infected pts, the symptoms may be more subtle with insidious onset, and pts are often ill for several weeks. In pts not infected with HIV, symptoms commonly begin after the glucocorticoid dose has been tapered and last ~1–2 weeks. Physical findings include tachypnea, tachycardia, and cyanosis, but lung auscultation reveals few abnormalities. CXR classically demonstrates bilateral diffuse infiltrates, but many other patterns have been associated with PCP, including nodular densities, cavitary lesions, upper lobe infiltrates (particularly in pts receiving aerosolized pentamidine prophylaxis), and pneumothorax. Early in the course, the CXR may be normal. Evaluation of arterial blood gas reveals hypoxia and an increase in alveolar-arterial oxygen gradient. Gallium scan demonstrates increased uptake in the lungs.
Extrapulmonary Infection Infection usually remains confined to the lungs, but extrapulmonary infection has been described. One risk factor for extrapulmonary spread in pts with HIV infection is the administration of aerosolized pentamidine prophylaxis. The organs most frequently involved include lymph nodes, liver, spleen, and bone marrow. Clinical manifestations range from incidental findings at autopsy to specific organ involvement.
As the clinical presentation may vary, the level of suspicion of infection must be high in populations most at risk. The diagnosis is made by demonstration of the organism with stains, including methenamine silver, toluidine blue, and cresyl echt violet. The immunofluorescence and immunoperoxidase staining procedures, based on commercially available monoclonal antibodies, are sensitive and are used in many laboratories. The mainstay of diagnosis is the staining of specimens obtained by fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). In HIV-infected pts, in whom the burden of organisms is high, induced sputum may yield a diagnosis. While this technique is simple and noninvasive, its success has varied at different institutions. Transbronchial and open lung biopsy now are reserved for situations in which BAL is not diagnostic.
Trimethoprim-sulfamethoxazole (TMP-SMZ) is the drug of choice for all forms of pneumocystosis. It is administered PO or IV at a TMP dosage of 15–20 (mg/kg)/d in three or four divided doses. Because TMP-SMZ is poorly tolerated by >50% of pts with HIV infection, resulting in fever, rash, neutropenia, thrombocytopenia, hepatitis, or hyperkalemia, alternative regimens are often required. For the treatment of mild to moderate cases of PCP, alternative regimens include TMP [15 (mg/kg)/d PO] plus dapsone (100 mg/d PO), clindamycin (600 mg q6h IV or 300–450 mg q6h PO) plus primaquine (15–30 mg of base/d PO), or atovaquone alone (750 mg twice daily PO). For the treatment of moderate to severe forms of pneumocystosis, two drugs are available. Pentamidine isethionate—4 (mg/kg)/d given as a single slow IV infusion—is about as effective as TMP-SMZ but exerts some toxic effects in most recipients, including hypotension, dysglycemia, azotemia, and cardiac arrhythmias. Alternatively, trimetrexate is given (45 mg/m2 IV once daily) with folinic acid (20 mg/m2 q6h PO or IV) to prevent bone marrow suppression. Because respiratory decompensation frequently follows initiation of treatment in HIV-infected pts with moderate to severe PCP, glucocorticoids (e.g., prednisone, 40 mg PO bid tapered to 20 mg PO qd over 3 weeks) are given adjunctively to pts with PAO2 values £70 mmHg or an alveolar-arterial oxygen gradient ³35 mmHg and have been shown to improve survival. The use of glucocorticoids has not been studied in PCP unrelated to HIV infection. The duration of therapy is 14 d for non-HIV-infected pts and 21 d for HIV- infected pts.
Pts with HIV infection should receive prophylactic therapy for life after an episode of PCP (secondary prophylaxis). Primary prophylaxis is given to HIV- infected pts with CD4+ cell counts <200/µL, unexplained fever for ³2 weeks, or a history of oropharyngeal candidiasis. The prophylactic regimen of choice is TMP-SMZ (one double-strength tablet qd). Alternative regimens, necessitated by the high rate of adverse reactions to TMP-SMZ in HIV infection, include TMP-SMZ at reduced dose or frequency; dapsone alone; dapsone, pyrimethamine, and leucovorin; or aerosolized pentamidine in a Respirgard II nebulizer. Indications for prophylaxis of PCP in immunocompromised pts without HIV infection are less clear, but prophylaxis should be given to all such pts after recovery from PCP.
Outpatient/Home Care Considerations
Pts with mild PCP who can tolerate oral therapy may be managed as outpatients. Hospitalized pts may be discharged to complete therapy at home when they are able to breathe room air and tolerate oral therapy.
For a more detailed discussion, see Walzer PD: Pneumocystis carinii Infection, Chap. 209, p. 1182, in HPIM-15.