Correlation between in vitro and in vivo activity of antifungal agents against Candida species.
The correlation between antifungal susceptibility testing and in vivo response to antifungal therapy was examined in experimental murine candidiasis. In vitro susceptibility testing was done using a microbroth dilution method. Twenty-two Candida albicans, 4 Candida lusitaniae, and 2 Candida krusei isolates were tested against fluconazole, flucytosine, and amphotericin B. In vivo antifungal activity was tested in murine hematogenous candidiasis. Normal CF1 mice were infected with each of the C. albicans strains; immunosuppressed CF1 mice were inoculated with C. lusitaniae or C. krusei. Mice received various doses of antifungal agents, and survival was monitored for 21 days. Kidney fungal burden was examined on day 4. Antifungal therapy significantly prolonged survival and reduced tissue counts in animals infected with organisms susceptible to the agent tested (P < .05). In vitro resistance to a drug predicted its lack of in vivo activity. These results appear to correlate well with outcome of murine hematogenous candidiasis.
Anaissie
E J
EJ
Department of Medical Specialties, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Karyotakis
N C
NC
Hachem
R
R
Dignani
M C
MC
Rex
J H
JH
Paetznick
V
V
D000666:Amphotericin B / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002175:Candida / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D002177:Candidiasis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use; D005437:Flucytosine / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D000666:Amphotericin B; D015725:Fluconazole; D005437:Flucytosine