Prevention of infection due to Pneumocystis carinii

Pneumocystis carinii remains an important pathogen for the broad spectrum of immunocompromised individuals, despite significant advances in antimicrobial therapy. The recognition of P. carinii pneumonia in oncology patients and malnourished children led to epidemiologic and therapeutic studies of the disease in the 1970s by the Centers for Disease Control and Prevention, which was the source of the only therapeutic agent available at the time, pentamidine methanesulfonate (99, 139). The combination of pyrimethamine and sulfadiazine (105) had some therapeutic efficacy in small groups of patients in the 1960s (142). The combination of trimethoprim (TMP) and sulfamethoxazole (SMZ) (58) (subsequently in fixed combination as TMP-SMX or co-trimoxazole) was subsequently shown to be effective for the prophylaxis and the treatment of mild to moderate infections in animal models and patients and successfully reduced the occurrence of and the morbidity from this infection (56-58, 76). Early clinical trials have been reviewed by Hughes (54). These agents remained the standards for therapy after the recognition of the role of Pneumocystis infection in the human immunodeficiency virus (HIV)-infected population. The inability of many patients to tolerate prophylaxis or treatment with either TMP-SMX or pentamidine initiated a search for new agents for the prevention and treatment of Pneumocystis infection in immunocompromised hosts. This effort has resulted in the development of a variety of newer therapeutic options. Antimicrobial resistance in P. carinii appears to be uncommon clinically; however, standardized techniques for the growth of human-derived organisms in vitro or in animal hosts are not generally available for use for susceptibility testing (discussed below).