Aydan ÖZKÜTÜK, Sevin KIRDAR, YAVUZ DOĞAN

Anfoterisin-B ve flukonazolün candida albicans üzerindeki postantifungal etkinliği

Arnfoterisin-B veflukonazol sistemik kandidiyazis sağaltımında en sık kullanılan ilaçlardır. Bu ajanların etkinliğini araştıran birçok çalışma mevcuttur. Ancak antifungal ilaçların etkinliğinde ilacın farmäkokinetik özelliklerinin yanında postantifungal etkisinin de rolü vardır. İlaçların gösterdiği postantifungal etki uygun doz aralıklarının belirlenmesinde önemli olabilir. Bu çalışmada dört klinik Candida albicans izolatına karşı amfoterisin-B ve flukonazolün postantifungal etkinliği araştırılmıştır. Bu amaçla logaritmik üreme fazına getirilmiş olan suşlar ilaçların 1x-8x minimum inhibitor konsantrasyonlarıyla 1.5 saat süre ile karşılaştinlmıştır. Sonuç olarak Candida albicans suşlarına karşı flukonazolün ölçülebilir bir postantifungal etkisi görülmezken, amfoterisin-B'nin 7.5 ile 20 saat arası süren postantifungal etkisi saptanmıştır.

Anahtar Kelimeler:

Amfoterisin B, Candida albicans, Mikrobiyal duyarlılık testleri, Antifungal ajanlar

Postantifungal effects of amphotericin-B and fluconazole against candida albicans

Amphotericin-B and fluconazole are most commonly used drugs in the treatment of systemic candidiasis. Several in vitro procedures have been used to assess to effectiveness of these antifungal agents. However the efficacy of antifungal agents may not only depend on their pharmacokinetic properties but it also depends on the postantifungal effect (PAFE) of these agents. PAFE may be important for determining the reliable dosing intervals. In this study, the PAFE of amphotericin-B and fluconazole was evaluated against four clinical isolates of Candida albicans. Strains in logarithmic growth phase were exposured to the antifungal agents for 1.5 hour in concentrations from 1 to 8 times of the MIC. Fluconazole displayed no measurable postantifungal effect but amphotericin-B displayed a prolonged PAFE from 7.5 to 20 hours against Candida albicans isolates.

Keywords:

Amphotericin B, Candida albicans, Microbial Sensitivity Tests, Antifungal Agents,

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1. Andes D: In vivo pharmacodynamics of antifungal drugs in treatment of candidiasis, Antimicrob Agents Chemother 2003;47(4):1179-86.
2. Chryssanthou E, Cars O, Sjolin J:New automated method for determining postantifungal effect of amphotericin B against Candida species: Effects of concentration, exposure time and area under the curve, Antimicrob Agents Chemother 2002;46(12):4016-8.
3. Craig WA: Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men, Clin Infect Dis 1998;26(1):1-10.
4. Ellepola AN, Samaranayake LP: The in vitro post-antifungal effect of nystatin on Candida species of oral origin, J Oral Pathol Med 1999;28 (3):112-6.
5. Ernst EJ,Klepser ME, Pfaller MA: Postantifungal effects of echinocandin, azole andpolyene antifungal agents againstCandida albicans andCryptococcus neoformans, Antimicrob Agents Chemother 2000;44(4):1108-11.
6. Garcia MT, Llorente MT, Minguez F, Prieto J: Postantifungal effect and effects of sub-mic concentrations on previously treated Candida spp. influence of growth phase, J Infect 2002;45(4):263-7.
7. Garcia MT, Llorente MT,Minguez F, Prieto J: Influence of temperature and concentration on the postantifungal effect and effects of sub-mic concentrations of four antifungal agents on previously treated Candida species, Chemotherapy 2000;46(4):245-52.
8. Gerçeker AA, Saraçoğlu K: Seftazidimin tek başına ve amikasin ile kombinasyon halinde Pseudomonas aeruginosa suçları üzerine oluşturduğu postantibiyotik etkinin araştırılması, ANKEM Derg 2003;17(1):70-4.
9. Groll AH, Piscitelli SC, Walsh TJ: Antifungal pharmacodynamics: Concentration-effect relationships in vitro and in vivo, Pharmacotherapy 2001;21(8):133-48.
10. Klepser ME, Ernst EJ, Lewis RE, Ernst ME, Pfaller MA: Influence of test conditions on antifungal time-kill curve results: proposal for standardized methods, Antimicrob Agents Chemother 1998;42(5):1207-12.
11. MacGowan AP: Role of pharmacokinetics and pharmacodynamics: does the dose matter?, Clin Infect Dis 2001;33(Suppl 3):238-9.
12. National Committee for Clinical Laboratory Standards: Reference Method for Broth Dilution Antifungal Susceptibility Testing of Yeasts,Approved standard. Document M27-A, NCCLS, Wayne, Pa (1997).
13. Shu M, EllepolaAN, Samaranayake LP: Effects of two different growth media on the postantifungal effect induced by polyenes on Candida species, J Clin Microbiol 2001;39(7): 2732-5.
14. Spangler SK, Lin G, Jacobs MR, Appelbaum PC: Postantibiotic effect and postantibiotic submic effect of levofloxacin compared to those of of loxacin, ciprofloxacin, erythromycin, azithromycin and clarithromycin against 20 pneumococci, Antimicrob Agents Chemother 1998;42(5): 1253-5.