Ceftazidime-avibactam, meropenen-vaborbactam, and imipenem-relebactam in combination with aztreonam against multidrug-resistant, metallo-β-lactamase-producing Klebsiella pneumoniae

Abstract

The spread of multidrug-resistant (MDR), metallo-β-lactamase (MBL)-producing Klebsiella pneumoniae represents a major therapeutic challenge. The newly introduced β-lactam-β-lactamase inhibitors (BLBLIs), ceftazidime/avibactam (CAZ/AVI), meropenem/vaborbactam (M/V), and imipenem/relebactam (I/R) are inactive against MBLs. The aim of this study was to evaluate the in vitro efficacy of aztreonam (ATM) in combination with CAZ/AVI, M/V, and I/R against 40 MDR, MBL-producing, and serine-β-lactamases co-producing Klebsiella pneumoniae using the Etest method. Synergy was defined as a fractional inhibitory concentration index ≤0.5. All isolates were resistant to ATM, CAZ/AVI, and I/R and 38/40 (95%) were resistant to M/V. Synergy was observed in 97.5% in the combinations CAZ/AVI-ATM, and I/R-ATM and in 72.5% in the combination M/V-ATM. Further clinical studies are required to confirm the efficacy of these antimicrobial combinations.