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Antimicrobial Activity of Aztreonam in Combination with Old and New β-Lactamase Inhibitors against MBL and ESBL Co-Producing Gram-Negative Clinical Isolates: Possible Options for the Treatment of Complicated Infections. | LitMetric

AI Article Synopsis

  • Metallo-β-lactamases (MBLs) are challenging bacterial enzymes that inactivate most β-lactam antibiotics, with Aztreonam (ATM) being an exception but still susceptible to other enzymes like ESBL.
  • Researchers tested ATM combined with various β-lactamase inhibitors (BLIs) against clinical isolates of bacteria that produce both MBLs and ESBLs.
  • The combination of ATM and avibactam proved most effective, restoring ATM's effectiveness in several cases, though some bacteria showed resistance, indicating more complex resistance mechanisms at play.

Article Abstract

Metallo-β-lactamases (MBLs) are among the most challenging bacterial enzymes to overcome. Aztreonam (ATM) is the only β-lactam not hydrolyzed by MBLs but is often inactivated by co-produced extended-spectrum β-lactamases (ESBL). We assessed the activity of the combination of ATM with old and new β-lactamases inhibitors (BLIs) against MBL and ESBL co-producing Gram-negative clinical isolates. Six and three non-fermenting bacilli co-producing MBL and ESBL determinants were selected as difficult-to-treat pathogens. ESBLs and MBLs genes were characterized by PCR and sequencing. The activity of ATM in combination with seven different BLIs (clavulanate, sulbactam, tazobactam, vaborbactam, avibactam, relebactam, zidebactam) was assessed by microdilution assay and time-kill curve. ATM plus avibactam was the most effective combination, able to restore ATM susceptibility in four out of nine tested isolates, reaching in some cases a 128-fold reduction of the MIC of ATM. In addition, relebactam and zidebactam showed to be effective, but with lesser reduction of the MIC of ATM. and were not inhibited by any ATM-BLI combination. ATM-BLI combinations demonstrated to be promising against MBL and ESBL co-producers, hence providing multiple options for treatment of related infections. However, no effective combination was found for some non-fermentative bacilli, suggesting the presence of additional resistance mechanisms that complicate the choice of an active therapy.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615000PMC
http://dx.doi.org/10.3390/antibiotics10111341DOI Listing

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