Prevention of Infection Due to Pneumocystis carinii

Abstract

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 combina- tion 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 suc- cessfully 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 ther- apy after the recognition of the role of Pneumocystis infection in the human immunodeficiency virus (HIV)-infected popula- tion. 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 ef- fort has resulted in the development of a variety of newer therapeutic options. Antimicrobial resistance in P. carinii ap- pears to be uncommon clinically; however, standardized tech- niques for the growth of human-derived organisms in vitro or in animal hosts are not generally available for use for suscep- tibility testing (discussed below). The routine use of prophylaxis for P. carinii has been suc- cessful in improving the survival of persistently immunocom- promised individuals, resulting in an increase in the relative frequency in these hosts of other infections including infections caused by mycobacteria, fungi, and viruses (49, 50, 57, 70, 76, 141). Approaches to the prevention and treatment of Pneumo- cystis infection are changing with the increased use of anti- Pneumocystis prophylaxis in both AIDS and non-AIDS immu- nocompromised hosts and by improvements in antiviral therapies for HIV. The long-term impact of the newer antiviral therapies on the incidence of opportunistic infection in AIDS remains to be established. The specific therapy selected for an individual may be adjusted to reflect the nature of the individ- ual’s predisposing immune deficit(s), the ability of patients to tolerate specific agents, the geographic location of the patient, and the medical institution (31, 54, 109, 133, 138).