Searching for the Optimal Treatment for Metallo- and Serine-?-Lactamase Producing Enterobacteriaceae: Aztreonam in Combination with Ceftazidime-avibactam or Meropenem-vaborbactam.

ABSTRACT: Objective: Metallo-?-lactamase (MBL)-producing Enterobacteriaceae, particularly those that co-harbor serine ?-lactamases, are a serious emerging public health threat given their rapid dissemination and the limited number of treatment options. Pre-clinical and anecdotal clinical data support the use of aztreonam in combination with ceftazidime-avibactam against these pathogens, but other aztreonam-based combinations have not been explored. The objective of this study was to evaluate the in vitro activity and compare synergy between aztreonam in combination with ceftazidime-avibactam and meropenem-vaborbactam against serine and MBL-producing Enterobacteriaceae via time-kill analyses. Methods: 8 clinical Enterobacteriaceae strains (4 Escherichia coli and 4 Klebsiella pneumoniae) co-producing NDM and at least one serine ?-lactamase were used for all experiments. Drugs were tested alone, in dual ?-lactam combinations, and in triple drug combinations against all strains. Results: All strains were resistant to ceftazidime-avibactam and meropenem-vaborbactam and 7/8 (87.5%) strains were resistant to aztreonam. Aztreonam combined with ceftazidime-avibactam was synergistic against all 7 aztreonam-resistant strains. Aztreonam combined with meropenem-vaborbactam was synergistic against all aztreonam-resistant strains with the exception of an OXA-232-producing K. pneumoniae strain. Neither triple combination was synergistic against the aztreonam-susceptible strain. Likewise, neither dual ?-lactam combination was synergistic against any strain. Conclusions: These data suggest that aztreonam plus meropenem-vaborbactam has similar activity to aztreonam plus ceftazidime-avibactam against Enterobacteriaceae producing NDM and other non-OXA-48-like serine ?-lactamases. Confirmation of these findings in future in vitro and in vivo models is warranted.

SUBMITTER: Biagi M 

PROVIDER: S-EPMC6879249 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature