Document 0032
 DOCN  M9620032
 TI    In vitro evaluation of combination of fluconazole and flucytosine
       against Cryptococcus neoformans var. neoformans.
 DT    9602
 AU    Nguyen MH; Barchiesi F; McGough DA; Yu VL; Rinaldi MG; Department of
       Medicine, University of Pittsburgh Medical Center,; Pennsylvania 15213,
       USA.
 SO    Antimicrob Agents Chemother. 1995 Aug;39(8):1691-5. Unique Identifier :
       AIDSLINE MED/96100733
 AB    Amphotericin B and fluconazole are current acceptable therapies for
       cryptococcal meningitis; however, their effect remains suboptimal. The
       combination of fluconazole and flucytosine has yielded encouraging
       clinical results in human immunodeficiency virus patients with
       cryptococcal meningitis. To investigate the biological basis of this
       finding, we performed in vitro combination testing of fluconazole and
       flucytosine against 50 clinical strains of Cryptococcus neoformans var.
       neoformans. Synergy (fractional inhibitory concentration index of < 1.0)
       was observed in 62% of cases, while antagonism (fractional inhibitory
       concentration index of > 2.0) was not observed. For cases in which
       synergy was not achieved (autonomous or additive effects), the
       beneficial effect of the combination was still seen (i.e., there was
       still a decrease, although not as dramatic, in the MIC of one or both
       drugs when used in combination). The in vitro inhibitory action of
       flucytosine was greatly enhanced by the addition of fluconazole; the
       flucytosine MICs for Cryptococcus isolates were markedly decreased to
       concentrations which were severalfold lower than the achievable
       cerebrospinal fluid flucytosine concentration. On the other hand, the
       addition of flucytosine did not greatly enhance the in vitro activity of
       fluconazole if the initial fluconazole MIC for the isolate was > or = 8
       micrograms/ml. Controlled clinical studies are warranted to further
       elucidate the potential utility of fluconazole-flucytosine combination
       therapy.
 DE    Antifungal Agents/*PHARMACOLOGY  Cryptococcus neoformans/*DRUG EFFECTS
       Drug Combinations  Drug Synergism  Fluconazole/*PHARMACOLOGY
       Flucytosine/*PHARMACOLOGY  Microbial Sensitivity Tests  Support,
       Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).