In vivo impact of the MexAB-OprM efflux system on β-lactam efficacy in an experimental model of Pseudomonas aeruginosa

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• 作者：David Boutoille ; Cé ; dric Jacqueline ; Virginie Le Mabecque ; Gilles Potel ; Jocelyne Caillon
• 关键词：MexA-MexB-OprM ; Pseudomonas aeruginosa ; β ; -Lactams
• 刊名：International Journal of Antimicrobial Agents
• 出版年：2009
• 出版时间：May 2009
• 年：2009
• 卷：33
• 期：5
• 页码：417-420
• 全文大小：122 K

文摘

In this study, the in vivo impact of the MexAB-OprM efflux system on antipseudomonal β-lactam efficacy was investigated. The respective activities of human simulated regimens of ticarcillin (TIC), piperacillin/tazobactam (PIP/TAZ) and ceftazidime (CFZ) on two isogenic mutants of Pseudomonas aeruginosa PAO1, namely PAO4098E overexpressing MexAB-OprM and PAO4098ET which is OprM-depleted, were evaluated in an experimental rabbit endocarditis model. The following human daily doses by intermittent administration or continuous infusion were simulated: 15 g and 18 g for TIC; 12 g and 16 g for PIP/TAZ; and 3 g and 6 g for CFZ. TIC, PIP/TAZ and CFZ exhibited minimum inhibitory concentrations of 64, 8 and 2 μg/mL, respectively, against PAO4098E and 0.5, 0.5 and 1 μg/mL against PAO4098ET. Against PAO4098E, only the high-dose regimens of CFZ were effective, with the most significant effect being achieved by continuous infusion. In contrast, all the tested regimens were effective against PAO4098ET. In the most difficult-to-treat infections due to P. aeruginosa exhibiting the efflux system MexAB-OprM, CFZ at high doses and by continuous infusion should be preferred to TIC and PIP/TAZ.