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

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.