Abstract
Relationships between azole susceptibility and in vivo response to antifungal therapy in a murine model of candidiasis were investigated for Candida albicans isolates sampled from human immunodeficiency virus type 1-positive patients with oropharyngeal candidiasis. The susceptibilities of seven clinical isolates and two reference strains to fluconazole (FCZ) and itraconazole (ITZ) were determined in vitro by the broth microdilution method. Four isolates were resistant to FCZ and ITZ, two were susceptible to both azoles, and three were resistant to FCZ and susceptible to ITZ (dissociated resistance). CD1 mice were inoculated with each isolate and treated with either FCZ or ITZ (drug regimen, 5 mg/kg of body weight twice daily for 5 days). Quantitative cultures of kidneys were performed at the end of the treatment. On the other hand, the survival rates of the mice were followed daily. These two parameters were clearly correlated with in vitro susceptibility. Thus, the phenomenon of a dissociation of resistance to FCZ and ITZ may be found in vivo as well as in vitro.
Full Text
The Full Text of this article is available as a PDF (267.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anaissie E. J., Karyotakis N. C., Hachem R., Dignani M. C., Rex J. H., Paetznick V. Correlation between in vitro and in vivo activity of antifungal agents against Candida species. J Infect Dis. 1994 Aug;170(2):384–389. doi: 10.1093/infdis/170.2.384. [DOI] [PubMed] [Google Scholar]
- Anaissie E., Paetznick V., Bodey G. P. Fluconazole susceptibility testing of Candida albicans: microtiter method that is independent of inoculum size, temperature, and time of reading. Antimicrob Agents Chemother. 1991 Aug;35(8):1641–1646. doi: 10.1128/aac.35.8.1641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barchiesi F., Colombo A. L., McGough D. A., Fothergill A. W., Rinaldi M. G. In vitro activity of itraconazole against fluconazole-susceptible and -resistant Candida albicans isolates from oral cavities of patients infected with human immunodeficiency virus. Antimicrob Agents Chemother. 1994 Jul;38(7):1530–1533. doi: 10.1128/aac.38.7.1530. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bart-Delabesse E., Boiron P., Carlotti A., Dupont B. Candida albicans genotyping in studies with patients with AIDS developing resistance to fluconazole. J Clin Microbiol. 1993 Nov;31(11):2933–2937. doi: 10.1128/jcm.31.11.2933-2937.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Becker J. M., Henry L. K., Jiang W., Koltin Y. Reduced virulence of Candida albicans mutants affected in multidrug resistance. Infect Immun. 1995 Nov;63(11):4515–4518. doi: 10.1128/iai.63.11.4515-4518.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dupont B., Graybill J. R., Armstrong D., Laroche R., Touzé J. E., Wheat L. J. Fungal infections in AIDS patients. J Med Vet Mycol. 1992;30 (Suppl 1):19–28. doi: 10.1080/02681219280000731. [DOI] [PubMed] [Google Scholar]
- Fan-Havard P., Capano D., Smith S. M., Mangia A., Eng R. H. Development of resistance in candida isolates from patients receiving prolonged antifungal therapy. Antimicrob Agents Chemother. 1991 Nov;35(11):2302–2305. doi: 10.1128/aac.35.11.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garcia-Hermoso D., Dromer F., Improvisi L., Provost F., Dupont B. Fluconazole concentrations in saliva from AIDS patients with oropharyngeal candidosis refractory to treatment with fluconazole. Antimicrob Agents Chemother. 1995 Mar;39(3):656–660. doi: 10.1128/AAC.39.3.656. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ghannoum M. A., Spellberg B., Saporito-Irwin S. M., Fonzi W. A. Reduced virulence of Candida albicans PHR1 mutants. Infect Immun. 1995 Nov;63(11):4528–4530. doi: 10.1128/iai.63.11.4528-4530.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Graybill J. R., Najvar L. K., Holmberg J. D., Correa A., Luther M. F. Fluconazole treatment of Candida albicans infection in mice: does in vitro susceptibility predict in vivo response? Antimicrob Agents Chemother. 1995 Oct;39(10):2197–2200. doi: 10.1128/aac.39.10.2197. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imbert-Bernard C., Valentin A., Reynes J., Mallié M., Bastide J. M. Adhérence aux cellules épithéliales buccales de souches de Candida albicans isolées chez des patients VIH+: corrélation avec le sérotype, la sensibilité au fluconazole et la virulence. Pathol Biol (Paris) 1994 Jun;42(6):567–573. [PubMed] [Google Scholar]
- Imbert-Bernard C., Valentin A., Reynes J., Mallié M., Bastide J. M. Relationship between fluconazole sensitivity of Candida albicans isolates from HIV positive patients and serotype, adherence and CD4+ lymphocyte count. Eur J Clin Microbiol Infect Dis. 1994 Sep;13(9):711–716. doi: 10.1007/BF02276053. [DOI] [PubMed] [Google Scholar]
- Le Guennec R., Reynes J., Mallié M., Pujol C., Janbon F., Bastide J. M. Fluconazole- and itraconazole-resistant Candida albicans strains from AIDS patients: multilocus enzyme electrophoresis analysis and antifungal susceptibilities. J Clin Microbiol. 1995 Oct;33(10):2732–2737. doi: 10.1128/jcm.33.10.2732-2737.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ng T. T., Denning D. W. Fluconazole resistance in Candida in patients with AIDS--a therapeutic approach. J Infect. 1993 Mar;26(2):117–125. doi: 10.1016/0163-4453(93)92707-4. [DOI] [PubMed] [Google Scholar]
- Reynes J., Mallie M., Ravisse P., Bastide J. M. Activity of fluconazole against Candida albicans isolates from HIV+ patients in a digestive candidosis turkey model. J Med Vet Mycol. 1992;30(5):363–367. [PubMed] [Google Scholar]
- Stiller R. L., Bennett J. E., Scholer H. J., Wall M., Polak A., Stevens D. A. Correlation of in vitro susceptibility test results with in vivo response: flucytosine therapy in a systemic candidiasis model. J Infect Dis. 1983 Jun;147(6):1070–1077. doi: 10.1093/infdis/147.6.1070. [DOI] [PubMed] [Google Scholar]
- Valentin A., Bernard C., Mallié M., Huerre M., Bastide J. M. Control of Candida albicans vaginitis in mice by short-duration butoconazole treatment in situ. Mycoses. 1993 Nov-Dec;36(11-12):379–384. doi: 10.1111/j.1439-0507.1993.tb00726.x. [DOI] [PubMed] [Google Scholar]
- Van Cutsem J., Van Gerven F., Janssen P. A. Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. Rev Infect Dis. 1987 Jan-Feb;9 (Suppl 1):S15–S32. doi: 10.1093/clinids/9.supplement_1.s15. [DOI] [PubMed] [Google Scholar]
- Vanden Bossche H., Warnock D. W., Dupont B., Kerridge D., Sen Gupta S., Improvisi L., Marichal P., Odds F. C., Provost F., Ronin O. Mechanisms and clinical impact of antifungal drug resistance. J Med Vet Mycol. 1994;32 (Suppl 1):189–202. doi: 10.1080/02681219480000821. [DOI] [PubMed] [Google Scholar]