Two mechanisms of killing of Pseudomonas aeruginosa by tobramycin assessed at multiple inocula via mechanism-based modeling

Jurgen Bernd Bulitta, Neang S Ly, Cornelia Barbara Landersdorfer, Nicholin Agata Wanigaratne, Tony Velkov, Rajbharan Yadav, Antonio Oliver, Lisandra Lorraine Martin, Beom Soo Shin, Alan Forrest, Brian Tsuji

Research output: Contribution to journalArticleResearchpeer-review

43 Citations (Scopus)

Abstract

Bacterial resistance is among the most serious threats to human health globally, and many bacterial isolates have emerged that are resistant to all antibiotics in monotherapy. Aminoglycosides are often used in combination therapies against severe infections by multidrug-resistant bacteria. However, models quantifying different antibacterial effects of aminoglycosides are lacking. While the mode of aminoglycoside action on protein synthesis has often been studied, their disruptive action on the outer membrane of Gram-negative bacteria remains poorly characterized. Here, we developed a novel quantitative model for these two mechanisms of aminoglycoside action, phenotypic tolerance at high bacterial densities, and adaptive bacterial resistance in response to an aminoglycoside (tobramycin) against three Pseudomonas aeruginosa strains. At low-intermediate tobramycin concentrations (
Original languageEnglish
Pages (from-to)2315 - 2327
Number of pages13
JournalAntimicrobial Agents and Chemotherapy
Volume59
Issue number4
DOIs
Publication statusPublished - 2015

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