Exploring Aztreonam in Combination with Ceftazidime-Avibactam or Meropenem-Vaborbactam as Potential Treatments for Metallo- and Serine-β-Lactamase-Producing Enterobacteriaceae
| Autor: | Eric Wenzler, David A Butler, Myung Gull Lee, Mark Biagi, Shitalben R. Patel, T Wu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Klebsiella pneumoniae
Avibactam medicine.medical_treatment Ceftazidime Aztreonam Biology Meropenem Microbiology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine polycyclic compounds medicine Pharmacology (medical) 030212 general & internal medicine Pharmacology 0303 health sciences 030306 microbiology biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Ceftazidime/avibactam Enterobacteriaceae Infectious Diseases chemistry Beta-lactamase bacteria medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 63 |
| ISSN: | 1098-6596 0066-4804 |
| Popis: | Objective: 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. Methods: 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. 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 β-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 β-lactamases. Confirmation of these findings in future in vitro and in vivo models is warranted. |
| Databáze: | OpenAIRE |
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