Drug resistance in Pneumocystis carinii: an emerging problem

Abstract

Pneumocystis carinii pneumonia (PCP) is a frequent opportunistic infection in AIDS patients. Large numbers of HIV-infected individuals take prophylactic medications to prevent this illness. The development of drug resistance, while expected, cannot be monitored by classical means, since the organism cannot be cultivated in vitro. Two drug target genes, dihydropteroate synthase (DHPS) and cytochrome b, have been cloned and sequenced from human-derived P. carinii. Mutations leading to amino acid substitutions in the active sites of both proteins have been detected in patients receiving prophylaxis with sulfonamides and sulfones (DHPS inhibitors) and with atovaquone (cytochrome b inhibitor), suggesting that drug resistance may indeed be developing.