The New England Journal of Medicine
e-mail icon  FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |    Advanced Search
Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe
 
A correction has been published: N Engl J Med 1997;337(21):1557.

Original Article
PreviousPrevious
Volume 337:15-21 July 3, 1997 Number 1
NextNext

Treatment of Cryptococcal Meningitis Associated with the Acquired Immunodeficiency Syndrome
Charles M. van der Horst, M.D., Michael S. Saag, M.D., Gretchen A. Cloud, M.S., Richard J. Hamill, M.D., J. Richard Graybill, M.D., Jack D. Sobel, M.D., Philip C. Johnson, M.D., Carmelita U. Tuazon, M.D., Thomas Kerkering, M.D., Bruce L. Moskovitz, M.D., William G. Powderly, M.D., William E. Dismukes, M.D., for The National Institute of Allergy and Infectious Diseases Mycoses Study Group and AIDS Clinical Trials Group

 Sign up for free e-toc
 

This Article
-Full Text
- PDF

Commentary
-Letters

Tools and Services
-Add to Personal Archive
-Add to Citation Manager
-Notify a Friend
-E-mail When Cited

More Information
-Related Article
by Larsen, R. A.
-PubMed Citation
ABSTRACT

Background Treatment with low-dose amphotericin B (0.4 mg per kilogram of body weight per day) or oral azole therapy in patients with the acquired immunodeficiency syndrome (AIDS) and cryptococcal meningitis has been associated with high mortality and low rates of cerebrospinal fluid sterilization.

Methods In a double-blind multicenter trial we randomly assigned patients with a first episode of AIDS-associated cryptococcal meningitis to treatment with higher-dose amphotericin B (0.7 mg per kilogram per day) with or without flucytosine (100 mg per kilogram per day) for two weeks (step one), followed by eight weeks of treatment with itraconazole (400 mg per day) or fluconazole (400 mg per day) (step two). Treatment was considered successful if cerebrospinal fluid cultures were negative at 2 and 10 weeks or if the patient was clinically stable at 2 weeks and asymptomatic at 10 weeks.

Results At two weeks, the cerebrospinal fluid cultures were negative in 60 percent of the 202 patients receiving amphotericin B plus flucytosine and in 51 percent of the 179 receiving amphotericin B alone (P = 0.06). Elevated intracranial pressure was associated with death in 13 of 14 patients during step one. The clinical outcome did not differ significantly between the two groups. Seventy-two percent of the 151 fluconazole recipients and 60 percent of the 155 itraconazole recipients had negative cultures at 10 weeks (95 percent confidence interval for the difference in percentages, -100 to 21). The proportion of patients who had clinical responses was similar with fluconazole (68 percent) and itraconazole (70 percent). Overall mortality was 5.5 percent in the first two weeks and 3.9 percent in the next eight weeks, with no significant difference between the groups. In a multivariate analysis, the addition of flucytosine during the initial two weeks and treatment with fluconazole for the next eight weeks were independently associated with cerebrospinal fluid sterilization.

Conclusions For the initial treatment of AIDS-associated cryptococcal meningitis, the use of higher-dose amphotericin B plus flucytosine is associated with an increased rate of cerebrospinal fluid sterilization and decreased mortality at two weeks, as compared with regimens used in previous studies. Although consolidation therapy with fluconazole is associated with a higher rate of cerebrospinal fluid sterilization, itraconazole may be a suitable alternative for patients unable to take fluconazole.


Source Information

From the Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill (C.M.H.); the Division of Infectious Diseases, Department of Medicine (M.S.S., W.E.D.), and the Biostatistics Unit, Comprehensive Cancer Center (G.A.C.), University of Alabama School of Medicine at Birmingham, Birmingham; the Section of Infectious Diseases, Veterans Affairs Medical Center and Baylor College of Medicine, Houston (R.J.H.); the University of Texas Health Sciences Center, San Antonio (J.R.G.); the Division of Infectious Diseases, Wayne State University, Detroit (J.D.S.); the Department of Medicine, University of Texas–Houston Medical Center, Houston (P.C.J.); the Department of Medicine, George Washington University, Washington, D.C. (C.U.T.); the Division of Infectious Diseases, Medical College of Virginia, Richmond (T.K.); the Janssen Research Foundation, Titusville, N.J. (B.L.M.); and the Division of Infectious Diseases, Washington University School of Medicine, St. Louis (W.G.P.). Presented in part at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, September 17–20, 1995.

Address reprint requests to Dr. van der Horst at the Division of Infectious Diseases, C.B.# 7030, University of North Carolina, Chapel Hill, NC 27599-7030.

Full Text of this Article


Related Letters:

Treatment of Cryptococcal Meningitis
Larsen R. A., Zingman B. S., Saag M. S., Cloud G. A., van der Horst C.
Extract | Full Text  
N Engl J Med 1997; 337:1557-1558, Nov 20, 1997. Correspondence

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.