The relative contribution of efflux and target gene mutations to fluoroquinolone resistance in recent clinical isolates of Pseudomonas aeruginosa.

European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology
S A DunhamA A Miller

Abstract

The clinical utility of fluoroquinolones (FQs) for the treatment of Pseudomonas aeruginosa (PA) and other serious Gram-negative infections is currently decreasing due to the rapid emergence of resistance. Because previous studies have shown that efflux is a common mechanism contributing to FQ resistance in PA, one suggested approach to extend the longevity of this class of drugs is combination therapy with an efflux pump inhibitor (EPI). In order to determine the viability of this approach, it is necessary to understand the relative contribution of efflux- vs. target-mediated mechanisms of FQ resistance in the clinic. A set of 26 recent PA clinical isolates were characterized for antibiotic resistance profiles, efflux pump expression, topoisomerase mutations, and FQ susceptibility with and without an EPI. The contribution of OprM to the overall antibiotic resistance was assessed in a subset of these strains. Our results suggest that the co-administration of an EPI with FQs or other antibiotics currently in use would not be sufficient to combat the complexity of resistance mechanisms now present in many clinical isolates.

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Citations

Nov 24, 2011·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Diana F FlorescuAndre C Kalil
Jan 1, 2013·Antimicrobial Agents and Chemotherapy·Sebastian BruchmannSusanne Häussler
Jun 15, 2011·Trends in Microbiology·Elena B M BreidensteinRobert E W Hancock
Jun 29, 2011·FEMS Microbiology Reviews·Hiroshi Nikaido, Jean-Marie Pagès
Jan 4, 2019·Journal of Medical Microbiology·Attika RehmanIain L Lamont
Jul 22, 2019·Journal of Burn Care & Research : Official Publication of the American Burn Association·Siamak HeidarzadehAzad Khaledi
May 4, 2021·Frontiers in Cellular and Infection Microbiology·R Frèdi LangendonkJoanne L Fothergill

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