Abstract

Activities of antifolate, antiviral, and other drugs in an immunosuppressed rat model of Pneumocystis carinii pneumonia. P D Walzer , J Foy , P Steele , C K Kim , M White , R S Klein , B A Otter and C Allegra Cincinnati Veterans Affairs Medical Center, Ohio. ABSTRACT The efficacy of antifolate, antiviral, and other drugs was compared in an experimental model of pneumocystosis. Sulfamethoxazole (SMX) administered alone in doses of greater than or equal to 60 mg/kg/day was highly effective in treatment and prophylaxis. Low (less than or equal to 15 mg/kg/day) doses of SMX showed limited, dose-related anti-Pneumocystis carinii activity in therapy but were more effective in prophylaxis. The dihydrofolate reductase (DHFR) inhibitors trimethoprim (TMP), pyrimethamine, and trimetrexate exhibited little anti-P. carinii activity when administered alone and did not enhance the efficacy of SMX; the effects of the DHFR inhibitors could not be related to the dose or the concentration in serum. These data suggested that the rat model is an excellent system for studying the anti-P. carinii activity of sulfonamides but is of limited value in studying DHFR inhibitors. The antiviral drugs azidothymidine, dideoxyinosine, inosine pranobex (Isoprinosine), amantadine, and acyclovir displayed little or no activity against P. carinii; however, azidothymidine did not impair the efficacy of SMX or TMP-SMX. These results supported the clinical practice of giving antiviral agents together with antifolate drugs to patients infected with human immunodeficiency virus and suggested that the beneficial effects of antiviral agents on the occurrence of pneumocystosis are due mainly to their effects on the virus or the host immune response. In contrast to the antiviral drugs, 9-deazainosine, a nucleoside analog with antiprotozoal properties, demonstrated marked activity against P. carinii which was related to dose and route of administration. These data raised the possibility that anti-P. carinii activity is a general property of purine nucleosides and suggested that further exploration of this class of compounds might lead to clinically useful agents. CiteULike Connotea Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter What's this? « Previous | Next Article » Table of Contents This Article doi: 10.1128/​AAC.36.9.1935 Antimicrob. Agents Chemother. September 1992 vol. 36 no. 9 1935-1942 » Abstract PDF Classifications Research Article Services Email this article to a colleague Similar articles in ASM journals Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of AAC Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Load citing article information Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Walzer, P. D. Articles by Allegra, C. Search for related content PubMed PubMed citation Articles by Walzer, P. D. Articles by Allegra, C. Related Content Load related web page information Social Bookmarking CiteULike Connotea Delicious Digg Facebook Google+ Mendeley Reddit StumbleUpon Twitter What's this? current issue December 2011, volume 55, issue 12 Alert me to new issues of AAC About AAC Subscribers Authors Reviewers Advertisers Inquiries from the Press Permissions & Commercial Reprints ASM Journals Public Access Policy AAC RSS Feeds 1752 N Street N.W. • Washington DC 20036 202.737.3600 • 202.942.9355 fax • journals@asmusa.org Print ISSN: 0066-4804 Online ISSN: 1098-6596 Copyright © 2011 by the American Society for Microbiology. For an alternate route to AAC .asm.org, visit: http://intl- AAC .asm.org | More Info» var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-5821458-3"); pageTracker._trackPageview();