|
|
 | |||||||||||||||||||||||||||||||
 | |||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||
Background Both trimethoprim-sulfamethoxazole and pentamidine are effective as treatments for Pneumocystis carinii pneumonia, but adverse effects frequently limit their use. Atovaquone (566C80) is a new hydroxynaphthoquinone with activity against P. carinii.
Methods We conducted a double-blind, multicenter study in patients with the acquired immunodeficiency syndrome and mild or moderately severe P. carinii pneumonia. They were randomly assigned to 21 days of orally administered treatment three times daily with either atovaquone (750 mg) or trimethoprim (320 mg) plus sulfamethoxazole (1600 mg).
Results Of the 322 patients with histologically confirmed P. carinii pneumonia, 160 received atovaquone and 162 received trimethoprim-sulfamethoxazole. Of those who could be evaluated for therapeutic efficacy, 28 of 138 patients given atovaquone (20 percent) and 10 of 146 patients given trimethoprim-sulfamethoxazole (7 percent) did not respond (P = 0.002). Treatment-limiting adverse effects required a change of therapy in 11 patients in the atovaquone group (7 percent) and 33 patients in the trimethoprim-sulfamethoxazole group (20 percent) (P = 0.001). Therapy involving only the initial drug was successful and free of adverse effects in 62 percent of those assigned to atovaquone and 64 percent of those assigned to trimethoprim-sulfamethoxazole.
Within four weeks of the completion of treatment, there were 11 deaths in the atovaquone group (4 due to P. carinii pneumonia) and 1 death in the trimethoprim-sulfamethoxazole group (P = 0.003). Diarrhea at entry was associated with lower plasma drug concentrations (P = 0.009), therapeutic failure (P<0.001), and death (P<0.001) in the atovaquone group but not in the trimethoprim-sulfamethoxazole group.
Conclusions For the treatment of P. carinii pneumonia, atovaquone is less effective than trimethoprim-sulfamethoxazole, but it has fewer treatment-limiting adverse effects.
Source Information
From the Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tenn. (W.H.); the Department of Medicine, Davies Medical Center, San Francisco (G.L.); Los Angeles County Hospital and the University of Southern California, Los Angeles (F.K., F.S.); the University of California, San Diego (S.A.B.); the University of Cincinnati, Cincinnati (P.F.); St. Pierre University Hospital, Brussels, Belgium (N.C.); the Department of Critical Care Medicine, National Institutes of Health, Bethesda, Md. (H.M., J. Falloon); the Department of Medicine, the Regional Medical Center, University of Tennessee, Memphis (D.L.); the Wellesley Hospital, Toronto (C.C.); Georgetown University Medical Center, Washington, D.
(J.L.); San Francisco General Hospital and the University of California, San Francisco (S.S.); the Infectious Diseases Research Consortium of Georgia, Atlanta (J.R.); the Johns Hopkins Hospital, Baltimore (J. Feinberg); the Department of Infectious Diseases and Immunology, Burroughs Wellcome Co., Research Triangle Park, N.(S.L., M.R.); and the California Clinical Trials Group and AIDS Clinical Trials Group, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Additional clinical investigators and study centers are listed in the Appendix.
Address reprint requests to Dr. Hughes at the Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105.
This article has been cited by other articles:
HOME | SUBSCRIBE | SEARCH | CURRENT ISSUE | PAST ISSUES | COLLECTIONS | PRIVACY | TERMS OF USE | HELP | beta.nejm.org Comments and questions? Please contact us. The New England Journal of Medicine is owned, published, and copyrighted © 2009 Massachusetts Medical Society. All rights reserved. |
Previous
