Poster (Painel)
| 1606-1 | A strategy for treatment optimization of C. albicans infections using micafungin as an antifungal drug in an in vitro infection model | | Autores: | IZOLAN, J.S. (UFRGS - Universidade Federal do Rio Grande do SulUFRGS - Universidade Federal do Rio Grande do SulUFRGS - Universidade Federal do Rio Grande do SulUFRGS - Universidade Federal do Rio Grande do Sul) ; LAUREANO, J.V. (UFRGS - Universidade Federal do Rio Grande do SulUFRGS - Universidade Federal do Rio Grande do Sul) ; ARAUJO, B.V. (UFRGS - Universidade Federal do Rio Grande do SulUFRGS - Universidade Federal do Rio Grande do SulUFRGS - Universidade Federal do Rio Grande do Sul) |
Resumo INTRODUCTION: Micafungin can be considered the first line therapy for the treatment of candidemia and invasive candidiasis in neonates, children, adults and elderly. Its fungicidal action is dose dependent, with excellent efficacy in vitro against most Candida species, including species resistant to amphotericin B, to different azoles and not sensitive to other echinocandins. In the clinical isolates of fungal infections, Candida is the most prevalent and the species albicans is the most commom. Therefore, the aim of this study was mathematically determine the relationship between the effect of different doses of micafungin as a function of the time. MATERIALS AND METHODS: For this purpose, an in vitro model of C. albicans infection was used where the plasma concentration of micafungin in healthy humans were simulated. The in vitro model consists in a culture flask containing RPMI culture medium and a C. albicans suspension standardized for 105 CFU/mL. The dosages simulated were 25, 50, 75 and 150 mg as an infusion of 1 hour and the half-life was simulated by sequential dilutions made every hour during 14h. Fungal growth was determined by counting the number of colonies in Sabouraud agar. The mathematical modeling was conducted with Scientist software v.2.01 ® (MicroMath®, Salt Lake, Utah, USA) using the sigmoidal Emax model, literature data for the pharmacokinetics of micafungin and the pharmacodynamics data obtained in the in vitro model described above. The Emax model chosen was able to adequately describe the curves of inhibition of fungal growth (or fungal death) as a function of time. RESULTS AND DISCUSSION: Micafungin showed a good fungicidal effect with a MIC of 0.125 µg/mL for C. albicans, the mean EC50 (concentration required for half of maximum effect ) obtained for doses 25, 50, 75 and 150 mg were 1.23, 1.6, 1.5 and 1.7 µg/mL, respectively, and kmax (maximum fungicide effect) were 2.1, 1.5, 2.0, and 3.0 h-1. CONCLUSION: The data show effectiveness in the four proposed therapies and better effect for the dose of 150 mg. ACKNOWLEADGMENTS: FAPERGS process # 111656-1. |