[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
Searching for the Optimal Treatment for Metallo- and Serine-β-Lactamase Producing Enterobacteriaceae: Aztreonam in Combination with Ceftazidime-avibactam or Meropenem-vaborbactam
M Biagi, T Wu, M Lee, S Patel, D Butler, E Wenzler
Metallo-β-lactamase (MBL)-producing Enterobacteriaceae, particularly those that co-harbor serine β-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.
8 clinical Enterobacteriaceae strains (4 Escherichia coli and 4 Klebsiella pneumoniae) co-producing NDM and at least one serine β-lactamase were used for all experiments. Drugs were tested alone, in dual β-lactam combinations, and in triple drug combinations against all strains.
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 β-lactam combination was synergistic against any strain.
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 β-lactamases. Confirmation of these findings in future in vitro and in vivo models is warranted.
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Keywords: Antibiotics; Drugs Resistance; Beta-lactams; NDM; Aztreonam; Meropenem; Vaborbactam; Ceftazidime; Avibactam; Enterobacteriaceae.