Effect of prolonged fluconazole treatment on Candida albicans in diffusion chambers implanted into mice. Antimicrob Agents Chemother 2002 Oct;46(10):3175-9
Date
09/18/2002Pubmed ID
12234841Pubmed Central ID
PMC128792DOI
10.1128/AAC.46.10.3175-3179.2002Scopus ID
2-s2.0-0036783675 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Fluconazole is an azole agent with primarily fungistatic activity in standard in vitro susceptibility tests. The present study was undertaken to develop a diffusion chamber model system in mice in order to study the in vivo effects of prolonged fluconazole treatment on Candida albicans. Chambers containing 100 C. albicans yeast cells were implanted subcutaneously on the flanks of C57BL/6 mice and were then retrieved 6 or 14 weeks later (after fluconazole treatment for 4 or 12 weeks, respectively). Leukocyte counts demonstrated that implantation of the chambers did elicit an inflammatory response but that only small numbers of inflammatory cells were able to enter the chamber interior. Treatment with fluconazole at 10 mg/kg of body weight/day for 12 weeks not only reduced the numbers of viable organisms within the chambers compared to those in untreated mice (mean +/- standard deviation of log(10) CFU of 0.7 +/- 1.2 versus 2.3 +/- 2.0; P < 0.001 by the Bonferroni test) but also increased the numbers of chambers that became sterile over the treatment period (14 of 16 versus 6 of 19; P = 0.0009 by the chi-square test). However, treatment for only 4 weeks had minimal effects on the numbers of chamber CFU, and none of the chambers became sterile during this period. Distribution of retrieved organisms between interior fluid and the chamber filters was approximately equal in all the treatment groups. This model system appears to be useful for evaluating the effects of antifungal drugs over prolonged periods in vivo. Its use in the present study demonstrates that fluconazole can increase the rate of sterilization of C. albicans foci that are protected from the host's inflammatory response.
Author List
Sohnle PG, Hahn BLMESH terms used to index this publication - Major topics in bold
AnimalsAntifungal Agents
Candida albicans
Candidiasis
Colony Count, Microbial
Diffusion Chambers, Culture
Disease Models, Animal
Fluconazole
Humans
Leukocyte Count
Male
Mice
Mice, Inbred C57BL
Microbial Sensitivity Tests
Micropore Filters
Time Factors
