• Aoyagi, Kari
• Fisher, Mark
• Yan, Jun
• She, Rosemary
• Li, Rachel
• Spellberg, Brad
• Luna, Phd, Brian
• Cheng, Jiaqi
• Rubio, Jennifer
• Builta, Zac

Abstract

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title/><jats:p>The emergence of plasmid-mediated resistance threatens the efficacy of polymyxins as the last line of defense against pan-drug-resistant infections. However, we have found that using Mueller-Hinton II (MHII), the standard minimum inhibitory concentration (MIC) medium, results in MIC data that are disconnected from<jats:italic>in vivo</jats:italic>treatment outcomes. We found that culturing putative colistin-resistant<jats:italic>Acinetobacter baumannii</jats:italic>clinical isolates, as defined by MICs of &gt;2 mg/L in standard MHII testing conditions, in bicarbonate-containing media reduced MICs to the susceptible range by preventing colistin resistance-conferring lipopolysaccharide modifications from occurring. Furthermore, the lower MICs in bicarbonate-containing media accurately predicted<jats:italic>in vivo</jats:italic>efficacy of a human-simulated dosing strategy of colistin and polymyxin B in a lethal murine infection model for some polymyxin-resistant<jats:italic>A. baumannii</jats:italic>strains. Thus, current polymyxin susceptibility testing methods overestimate the contribution of polymyxin resistance-conferring mutations and incorrectly predict antibiotic activity<jats:italic>in vivo</jats:italic>. Polymyxins may remain a viable therapeutic option against<jats:italic>Acinetobacter baumannii</jats:italic>strains heretofore determined to be “pan-resistant.”</jats:p></jats:sec>

Topics

• size-exclusion chromatography
• susceptibility