A coup d'état by NDM-producing Klebsiella pneumoniae overthrows the major bacterial population during KPC-directed therapy

Justin R. Lenhard, Amisha P. Rana, Eric Wenzler, Yanqin Huang, Barry N. Kreiswirth, Liang Chen, Zackery P. Bulman

Research output: Contribution to journalArticle

Abstract

The objective of this study was to utilize a co-culture hollow-fiber infection model (HFIM) to characterize the interplay between a small, difficult-to-detect, New Delhi metallo-β-lactamase–producing Klebsiella pneumoniae (NDM-Kp) minor population and a larger K. pneumoniae carbapenemase (KPC)–producing K. pneumoniae population in the presence of KPC-directed antibacterial therapy. Selective plating onto agar with ceftazidime-avibactam was used to track the density of the NDM-Kp population. Susceptibility testing and the Verigene System failed to identify the small initial NDM-Kp population. However, a ceftazidime-avibactam Etest detected resistant colonies that were confirmed to be NDM-Kp. In the HFIM, all of the investigated drug regimens caused regrowth within 24 h and resulted in >109 CFU/mL of NDM-Kp. Our study demonstrates that the HFIM is a powerful tool for studying the population dynamics of multiple pathogens during antimicrobial exposure and also highlights that difficult-to-detect minor populations of drug-resistant bacteria may cause treatment failure without appropriate antibacterial therapy.

Original languageEnglish (US)
Article number115080
JournalDiagnostic Microbiology and Infectious Disease
Volume98
Issue number1
DOIs
StatePublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

Keywords

  • Ceftazidime-avibactam
  • Hollow fiber infection model
  • Klebsiella pneumoniae
  • Polymicrobial
  • Rapid diagnostics

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