Efficacy of azithromycin in prevention of Pneumocystis carinii pneumonia: a randomised trial

Background Azithromycin in combination with sulphonamides is active against Pneumocystis carinii pneumonia (PCP) in animals. We assessed the clinical efficacy of azithromycin for PCP prophylaxis in human beings. Methods We identified HIV-1-infected patients with PCP during a prospective randomised trial comparing azithromycin, rifabutin, and the two drugs in c ombination for prevention of disseminated Mycobacterim avium infection. Pat ients had CD4-cell counts less than 100/mu L at entry and received PCP prop hylaxis according to the standard practice of their clinician. Analysis was by intention to treat. Findings Patients receiving azithromycin, either alone (n=233) or in combin ation with rifabutin (n=224), had a 45% lower risk of developing PCP than t hose receiving rifabutin alone (n=236; p=0.008). Compared with rifabutin al one, hazard ratio for azithromycin was 0.54 (95% CI 0.32-0.94), for azithro mycin plus rifabutin was 0.55 (0.32-0.94), and for regimens containing azit hromycin was 0.55 (0.35-0.86). The most common side-effects involved the ga strointestinal tract with dose-limiting toxicities, and were mainly seen in patients receiving combination therapy. Interpretation Azithromycin as prophylaxis for M avium complex disease prov ides additional protection against P carinii over and above that of standar d PCP prophylaxis, Use of azithromycin is beneficial only as primary prophy laxis.