Aerosolized pentamidine prevented Pneumocystis carinii pneumonia in patients with HIV
ACP J Club. 1991 Jan-Feb;114:6. doi:10.7326/ACPJC-1991-114-1-006
Leoung GS, Feigal DW, Montgomery AB, et al. and the San Francisco County Community Consortium. Aerosolized pentamidine for prophylaxis against Pneumocystis carinii pneumonia. The San Francisco Community Prophylaxis Trial. N Engl J Med. 1990;323:769-75.
To evaluate the effectiveness of 3 different doses of aerosolized pentamidine, 30 mg every 2 weeks, 150 mg every 2 weeks, and 300 mg every 4 weeks, in preventing episodes of Pneumocystis carinii pneumonia (PCP) in patients infected with human immunodeficiency virus (HIV).
Randomized, unblinded trial of 18 months' duration.
12 treatment centers in the San Francisco Bay area in the United States.
Patients were excluded if they had severe asthma or an anaphylactic reaction to pentamidine or had used aerosolized pentamidine previously or agents with known efficacy against PCP within the past 2 weeks. 441 patients were randomized, of whom 33 were never treated with the study drug and were not included in the analyses. 6 patients were lost to follow-up.
Patients were prescribed 30 mg of aerosolized pentamidine every 2 weeks (n = 135),150 mg every 2 weeks (n = 134), or 300 mg every 4 weeks (n = 139). The study drug was administered for 35 or 40 minutes in a nebulizer (Marquest, Englewood, Colorado, USA).
Main outcome measure
PCP episodes were defined as occurrences of pneumonitis that were clinically consistent with acute PCP, including occurrences that were not confirmed histologically.
Therapy was discontinued because of adverse effects in 2 of the 135 (1%) patients receiving 30 mg of the study drug, 11 of the 134 (8%) receiving 150 mg, and 10 of the 139 (7%) receiving 300 mg. In an intention-to-treat analysis (n = 408), patients receiving 300 mg of the study drug had 28 episodes of PCP compared with 41 in the 30-mg treatment arm (P = 0.02). This difference was greater only when patients who remained on treatment were counted (P = 0.004). No significant differences occurred in the number of episodes between the 150-mg arm and the 300-mg arm, nor between the 30-mg and 150-mg arms. (Mortality did not differ among the 3 treatment arms (P > 0.5 for comparisons between dosage arms). The most common adverse effects were respiratory (serious cough [36%] or wheezing [11%]).
Aerosolized pentamidine prevented Pneumocystis carinii pneumonia in patients with HIV who were at high risk. The most effective dose was 300 mg every 4 weeks, and it had few adverse effects.
Source of funding: Not stated.
Address for article reprint: Dr. D. W. Feigal, Department of Medicine, University of California at San Diego Medical Center, 225 Dickinson Street H811 E, San Diego, CA 94103, USA.
In 1989, the United States Public Health Service recommended that aerosol pentamidine be used for prophylaxis against Pneumocystis carinii pneumonia in HIV-infected persons. This was based largely on data reported by Leoung and coworkers at the 1988 International Conference on AIDS held in Stockholm. This paper reports the final results obtained.
This study was well designed, and the data clearly showed that participants given 300 mg of aerosolized pentamidine every 4 weeks had significantly fewer episodes of P. carinii pneumonia than those given 30 mg every 2 weeks. The treatment was generally well tolerated. Coughing and wheezing were the principal side effects. However, only 0.3% of the participants discontinued treatment because of severe cough.
During the 18 months of observation, 39% of the participants died; only 10% of the deaths were related to P. carinii pneumonia. Although the participants receiving the 300 mg dose had fewer P. carinii pneumonia episodes, no significant difference existed in survival among the 3 treatment groups.
This study clearly shows the clinical efficacy of aerosolized pentamidine in preventing P. carinii pneumonia. Its use probably increases survival. However, further studies are needed to determine the prevalence of extrapulmonary pneumocystosis after such treatment.
Tom D.Y. Chin, MD
University of Kansas Medical CenterKansas City, Kansas, USA