Cem ARTAN, Nedret KOÇ, MÜGE OĞUZKAYA ARTAN

The effect of combinations of antimycotics on systemic candidiasis in a mouse model

Amaç: Bu çalışma fare sistemik kandidoz modelinde terbinafin ve terbinafin- amphotericin B ve terbinafin-flukanazol etkinliğinin araştırılması için planlandı. Gereç ve Yöntemler: Enfeksiyon oluşumundan 24 saat sonra amphotericin B (1mg/kg/gün ip), fluconazole (100 mg/kg/gün ip), terbinafin (100 mg/kg/gün oral gavaj) ve terbinafin ile amphotericin B ve terbinafine ile fluconazole'ün aynı dozlarda kombinasyonlarının uygulandığı 10 günlük tedavi başladı, ve böbrek kültürleri yapıldı. Bulgular: Yaşamı sürdürme bakımından kontrol grubu ile terbinafin grubu arasında fark gözlenmedi (p>0.05). Terbinafin tedavisine amphotericin B eklenmesi ile kontrol grubu ile arada anlamlı fark oluştu (p

Sistemik fare kandidoz modelinde antifungal kombinasyonlarının etkinliği

Objective: This study was planned to investigate the therapeutic efficacy of terbinafine and interaction between terbinafine with amphotericin B, and fluconazole on candidiasis in a mouse model. Material and Methods: Treatment with amphotericin B (1mg/kg/day intraperitoneally), fluconazole (100 mg/kg/day ip), terbinafine (100 mg/kg/day by oral gavage) and combinations of terbinafine with amphotericin B and terbinafine with fluconazole at the same doses began 24 h after infection and continued for 10 days, and kidney cultures were performed. Results: No significant improvement in survival was not found between the control and the terbinafine group (p>0.05). With the addition of amphotericin B to terbinafine, significant improvement in survival was found compared with the survival of untreated controls (p<0.0001). When compared with the control group, the kidney culture results of the amphotericin B group were superior to those with two-fold reduction in CFU counts (p<0.05), but the difference between the terbinafine group and the control group was not significant (p>0.05). Terbinafine with amphotericin B and terbinafine with fluconazole combinations, when compared by fungal density reduction with amphotericin B, were less effective and the difference was significant (p<0.0001). Conclusion: Terbinafine had no effect on controlling systemic candidiasis alone and a slight effect in combination with amphotericin B and fluconazole.

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1) Loui A, Banerjee P, Drusano GL, et al. Interaction between fluconazole and amphotericin B in mice with systemic infection due to fluconazole-susceptible or –resistant strains of Candida albicans. Antimicrob Agents Chemother. 1999;43:2841-7.
2) Santangelo R, Paderu P, Delmas G, Chen ZW, Mannino R, Zarif L, et al. Efficacy of oral cochleate-amphotericinB in a mouse model of systemic candidiasis. Antimicrob Agents Chemother. 2000;44:2356-60.
3) Sugar AM, Hitchcock CA, Troke PF, Picard M. Combination therapy of murine invasive candidiasis with fluconazole and amphotericin B. Antimicrob Agents Chemother. 1995;39:598-601.
4) Zarif L, Graybill JR, Perlin D, Najvar L, Bocanegra R, Mannino RJ. Antifungal activity of amphotericin B cochleates against Candida. Antimicrob Agents Chemother. 2000;44:1463-9.
5) Anaissie EJ, Karyotakis NC, Hachem R, Dignani MC, Rex JH, Paetznick V. Correlation between in vitro and in vivo activity of antifungal agents against Candida species. J Infect Dis. 1994;170:384-9.
6) Barchiesi F, Di Francessco LF, Scalise G. In vitro activities of terbinafine in combination with fluconazole and itraconazole against isolates of Candida albicans with reduced suspectibility to azoles. Antimicrob Agents Chemother. 1997;41:1812-4.
7) Koç AN, Evrensel N, Gökahmetoglu S, Oguzkaya M. The in vitro effects of antifungal agents against Candida albicans. Antibiyotik ve Kemoterapi Dergisi. 2000;14:15-20.
8) Barchiesi F, Di Francesco LF, Compagnucci P, Arzeni D, Giacometti A, Scalise G. In vitro interaction of terbinafine with amphotericin B, fluconazole and itraconazole against clinical isolates of Candida albicans. J Antimicrob Chemother. 1998;41:59-65.
9) Cacciapuoti A, Loebenberg D, Corcoran E, Menzel F Jr, Moss EL Jr, Norris C, et al. In vitro and in vivo activities os SCH 56592 (posaconazole), a new triazole antifungal agent, against Aspergillus and Candida. Antimicrob Agents Chemother. 2000;44:2017-22.
10) Abdel-Rahman SM, Nahata MC. Oral terbinafine: a new antifungal agent. Ann Pharmacother. 1997;31:445-56.
11) Balfour JA, Faulds D. Terbinafine a review of its pharmacodynamics and pharmacokinetic properties, and therapeutic potential in superficial mycoses. Drugs. 1992;43:259-84.
12) Perea S, Gonzalez G, Fothergill AW, Sutton DA, Rinaldi MG. In vitro activities of terbinafine in combination with fluconazole, itraconazole, voriconazole, and posaconazole against clinical isolates of Candida glabrata with decreased susceptibility to azoles. J Clin Microbiol. 2002;40:1831-3.
13) Sorensen KN, Sobel RA, Clemons KV, Calderon L, Howell KJ, Irani PR, et al. Comparative efficacies of terbinafine and fluconazole in treatment of experimental coccidioidal meningitis in a rabit model. Antimicrob Agents Chemother. 2000;44:3087-91.
14) Warren NG, Hazen KC. Candida, Cryptococcus, and other yeasts of medical importance, In Manuel of Clinical Microbiology, 7th edn (P.R. Murray, E.J. Baron, M.A. Pfaller, F.C. Tenover, & R.H. Yolken, Eds), pp. 1184-1199. American Society for Microbiology, Washington, DC. 1999.
15) Sugar AM, Liu XP. Interactions of itraconazole with amphotericin B in the treatment of murine invasive candidiasis. J Infect Dis. 1997;177:1660-3.
16) Graybill JR, Najvar LK, Luther MF, Fothergill AW. Treatment of murine disseminated candidiasis with L-743, 872. Antimicrob Agents Chemother. 1997;41:1775-7.
17) Walzer PD, Ashbaugh A. Use of terbinafine in mouse and rat models of Pneumocyctis carinii pneumonia. Antimicrob Agents Chemother. 2002;46:514-6.
18) Ghannoum MA, Elewski B. Successfull treatment of fluconazole- resistant oropharyngeal candidiasis by a combination of fluconazole and terbinafine. Clin Diag Lab Immunol. 1999;6:921-3.
19) National Committee for Clinical Laboratory Standarts. Reference method for broth dilution antifungal susceptibility testing of yeast. 1997. Approved standart. Document M27-A. National Committee for Clinical Laboratory Standarts, Wayne, P.
20) Conti C, Angelici E, Canipari R. Structural changes in rat Pneumocystis carinii surface antigens after terbinafine administration in experimental P. carinii pneumonia. J Antimicrob Chemother. 1999;43:301-4.