Levofloxacin/imipenem prevents the emergence of high-level resistance among Pseudomonas aeruginosa strains already lacking susceptibility to one or both drugs

The Journal of Antimicrobial Chemotherapy
Philip D ListerMark D Reisbig

Abstract

Previous studies have demonstrated that a combination of levofloxacin with imipenem could prevent the emergence of resistance during the treatment of susceptible Pseudomonas aeruginosa isolates in a two-compartment pharmacodynamic model of infection. In this study, the efficacy of levofloxacin/imipenem was further evaluated against a panel of characterized P. aeruginosa strains that lacked susceptibility to one or both drugs in the combination. Five P. aeruginosa strains with characterized resistance mechanisms were evaluated. Log-phase cultures were inoculated into the peripheral compartment of the in vitro pharmacokinetic model and treated using simulated doses of 750 mg levofloxacin (dosed every 24 h) and 250 mg or 1 g doses of imipenem (dosed every 12 h). Peak levels were adjusted for protein binding. Pharmacodynamic interactions were evaluated by measuring the changes in viable counts over 30 h. To evaluate the emergence of resistance, samples removed at 30 h were plated onto agar containing the drug at 4x MIC, and potential mutants were evaluated for changes in susceptibility. Against strains overexpressing MexAB-OprM, MexCD-OprJ and MexEF-OprN efflux pumps, levofloxacin/imipenem prevented the emergence of resistance and ...Continue Reading

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Citations

Jul 6, 2012·Clinical Microbiology Reviews·Pranita D TammaLisa L Maragakis
Aug 15, 2009·Drugs·Xian-Zhi Li, Hiroshi Nikaido
Jun 15, 2010·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Noyal Mariya JosephSubhash Chandra Parija
Aug 19, 2017·Critical Care Medicine·Andre C Kalil
May 7, 2014·Antimicrobial Agents and Chemotherapy·Vera Lúcia Dias SiqueiraCelso Vataru Nakamura
Jan 4, 2019·Journal of Medical Microbiology·Attika RehmanIain L Lamont
Oct 3, 2006·Expert Review of Anti-infective Therapy·Paolo Grossi, Daniela Dalla Gasperina
Nov 7, 2013·Expert Review of Anti-infective Therapy·Alexandre P ZavasckiCornelia B Landersdorfer
Feb 16, 2013·Expert Review of Anti-infective Therapy·Nicola PetrosilloPierluigi Viale
Apr 9, 2021·Annals of the New York Academy of Sciences·Luke N YaegerLori L Burrows
Apr 16, 2021·International Journal of Antimicrobial Agents·Luigia ScudellerEvelina Tacconelli
Dec 10, 2016·ACS Applied Materials & Interfaces·Subhendu PanditMrinmoy De

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