Management of Pneumocystis jiroveci pneumonia in children receiving chemotherapy

Sadhna M Shankar, Joseph J Nania
Paediatric Drugs 2007, 9 (5): 301-9
Pneumocystis jiroveci (formerly carinii) pneumonia (PCP) is a serious opportunistic infection in children and adolescents with cancer. It was the most common cause of death among children receiving chemotherapy prior to the inclusion of PCP prophylaxis as part of standard care for children with leukemia. The incidence of PCP has decreased significantly since initiation of prophylaxis; however, breakthrough cases continue to occur. Hematologic malignancies, brain tumors necessitating prolonged corticosteroid therapy, hematopoietic stem cell transplantation, prolonged neutropenia, and lymphopenia are the most important risk factors for PCP in children not infected with HIV. Of children with leukemia, 15-20% may develop PCP in the absence of prophylaxis. Infection with P. jiroveci occurs early in life in most individuals. However, clinically apparent disease occurs almost exclusively in immunocompromised persons. Dyspnea, cough, hypoxia, and fever are the most common presenting symptoms of PCP. Chest radiography and high-resolution CT scans of the chest demonstrate a characteristic ground-glass pattern. Induced sputum analysis and bronchoalveolar lavage are the diagnostic procedures of choice. Gomori's methenamine-silver stain, Geimsa or Wright's stain, and monoclonal immunofluorescent antibody stains are most commonly used to make a diagnosis. However, identification of P. jiroveci DNA using polymerase chain reaction assays in bronchoalveolar lavage fluid is more sensitive. Trimethoprim-sulfamethoxazole (TMP-SMZ; cotrimoxazole) is the recommended drug for the treatment of PCP. Patients who are intolerant of TMP-SMZ or who have not responded to treatment after 5-7 days of therapy with TMP-SMZ should be treated with pentamidine. A short course of corticosteroids is recommended for moderate to severe cases of PCP within the first 72 hours after diagnosis. Mutations in the dihydropteroate synthetase gene may confer resistance to TMP-SMZ; however, the clinical relevance of these mutations is not well established. TMP-SMZ is the most commonly used agent for prophylaxis. Myelosuppression is the most important adverse effect of TMP-SMZ and the most frequent cause for choosing alternative prophylactic agents in children undergoing chemotherapy. Alternative agents for chemoprophylaxis include dapsone, aerosolized pentamidine, and atovaquone. Alternative prophylactic agents must be used in patients developing myelosuppression secondary to TMP-SMZ or dapsone.

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