Prophylaxis of Pneumocystis carinii pneumonia: too much of a good thing?

Background. Azithromycin in combination with sulphonamides is active against Pneumocystis carinii (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 combination for prevention of disseminated Mycobacterium avium infection. Patients had CD4-cell counts less than 100⁄ L at entry and received PCP prophylaxis according to the standard practice of their clinician. Analysis was by intention to treat. Findings. Patients receiving azithromycin, either alone (n=233) or in combination with rifabutin (n= 224), had a 45% lower risk of developing PCP than those receiving rifabutin alone (n=236; p= 0.008). Compared with rifabutin alone, hazard ratio for azithromycin was 0.54 (95% CI 0.32–0.94), for azithromycin plus rifabutin was 0.55 (0.32–0.94), and for regimens containing azithromycin was 0.55 (0.35–0.86). The most common side-effects involved the gastrointestinal tract with dose-limiting toxicities, and were mainly seen in patients receiving combination therapy. Interpretation. Azithromycin as prophylaxis for M avium complex disease provides additional protection against P carinii over and above that of standard PCP prophylaxis. Use of azithromycin is beneficial only as primary prophylaxis. (Lancet 1999;354:891–5)