efflux pump, the masked side of ？-lactam resistance in klebsiella pneumoniae clinical isolates射流泵,蒙面的一面内酰胺耐药性肺炎克雷伯菌临床分离株.pdfVIP

Efflux Pump, the Masked Side of ß-Lactam Resistance in Klebsiella pneumoniae Clinical Isolates 1 1 ´ 2 2 ´ ´ 2 Jean-Marie Pages *, Jean-Philippe Lavigne , Veronique Leflon-Guibout , Estelle Marcon , Frederic Bert , 2 ´ ` 2,3 Latifa Noussair , Marie-Helene Nicolas-Chanoine ´ ´ ´ ´ ´ ˆ 1 UMR-MD-1, Facultes de Medecine et de Pharmacie, Universite de la Mediterranee, IFR88, Marseille, France, 2 AP-HP, Hopital Beaujon, Service de Microbiologie, Clichy, ´ ´ France, 3 INSERM U 773, Centre de Recherche Biomedicale Bichat-Beaujon, CRB3, Universite D. Diderot, Paris, France Abstract Background: b-lactamase production and porin decrease are the well-recognized mechanisms of acquired ß-lactam resistance in Klebsiella pneumoniae isolates. However, such mechanisms proved to be absent in K. pneumoniae isolates that are non susceptible to cefoxitin (FOX) and succeptible to amoxicillin+clavulanic acid in our hospital. Assessing the role of efflux pumps in this b-lactam phenotype was the aim of this study. Methodology/Findings: MICs of 9 b-lactams, including cloxacillin (CLX), and other antibiotic families were tested alone and with an efflux pump inhibitor (EPI), then with both CLX (subinhibitory concentrations) and EPI against 11 unique bacteremia K. pneumoniae isolates displaying the unusual phenotype, and 2 ATCC strains. CLX and EPI-dose dependent effects were studied on 4 representatives strains. CLX MICs significantly decreased when tested with E