Determinação das Concentrações de Antimicrobianos Capazes de Prevenir o Surgimento de Mutantes Resistentes de Pseudomonas aeruginosa

• Ano de defesa: 2006
• Autor(a) principal: Gugel, Juliana [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Lactâmicos; Polimixina B; Pseudomonas aeruginosa; Janela para seleção de mutantes resistentes; Fluoroquinolonas
• Link de acesso: http://repositorio.unifesp.br/handle/11600/9325

Pseudomonas aeruginosa is a leading cause of nosocomial infections, giving rise to a wide range of life-threatening conditions. The ability of P. aeruginosa isolates to develop multidrug resistance imposes a serious therapeutic problem. The mutant-prevention concentration (MPC) is a novel strategy designed to minimize the selection of first-step resistant mutants present in large, > or = 1010 CFU/mL, bacterial populations. Objectives: The aim of this study was to evaluate the mutant prevention concentration (MPC) of three fluoroquinolones, four β-lactams and polymyxin B against P. aeruginosa clinical isolates and to determine the correlation between MIC and MPC. In addition, the mutant selection window was determined. Methods: 20 clinical isolates of P. aeruginosa susceptible to fluoroquinolones, β-lactams and polymyxin B have been tested using disk diffusion and MIC values have been determined by agar dilution in accordance with NCCLS/CLSI guidelines. For MPC testing, ≥ 1010 cells were applied to agar plates containing antibiotic and incubated for 48h. The lowest concentration that prevented growth was defined as the MPC. The concentration range between MIC and MPC was designated as the mutant selection window. Results: Among the fluoroquinolones, ciprofloxacin showed lowest MPC90 (2 μg/ml) followed by gatifloxacin (MPC90, 4 μg/ml) and levofloxacin (MPC90, 8 μg/ml). Ciprofloxacin showed serum concentration above the MPC for longer time period than the remaining fluoroquinoles tested. Among the β-lactams agents, ceftazidime, cefepime and imipenem showed MPC90 greater than 256 μg/ml. In contrast, the mutant selection window for meropenem could be determined (MPC90/MIC90, 32) and the serum concentration dosing interval was above the MPC. Polymyxin B MPC values were higher than 32 for all P. aeruginosa isolates. Conclusions: Low correlation between MIC and MPC was observed for all antimicrobial agents tested. Due to the MPC90 and the time relevant drug concentrations are above MPC, ciprofloxacin demonstrated less potential to select resistant mutants when compared to gatifloxacin and levofloxacin. The mutant selection window could not be determined to ceftazidime, cefepime, imipenem and polymyxin B. MPC might be not suitable for those antimicrobial agents that resistance mechanisms could be inducible or adaptive, such as β-lactams and polymyxin B, respectively.