Cefiderocol (FDC) is a recently developed siderophore cephalosporin showing excellent antibacterial activity against Gram-negative bacteria, including Acinetobacter baumannii . By investigating a series of A. baumannii clinical isolates with elevated MICs of FDC, we showed that PER-like β-lactamases and, to a lesser extent, NDM-like β-lactamases, significantly contributed to reduced susceptibility to that antibiotic.

Metallo-β-lactamase (MBL)-producing Escherichia coli isolates resistant to the newly developed β-lactam/β-lactamase inhibitor drug combination aztreonam-avibactam (ATM-AVI) have been reported. Here, we analyzed a series of 118 clinical MBL-producing E. coli isolates of various geographical origins for susceptibility to ATM-AVI. The nature of the PBP3 protein sequence and the occurrence of bla _CMY genes for susceptibility to ATM-AVI were investigated.

The ability of broad-spectrum β-lactamases to reduce the susceptibility to ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam (AZA), and cefiderocol (FDC) was evaluated both in Pseudomonas aeruginosa and in Escherichia coli using isogenic backgrounds. Although metallo-β-lactamases conferred resistance in most cases, except for AZA, several clavulanic-acid-inhibited extended-spectrum β-lactamases (PER, BEL, SHV) had a significant impact on the susceptibility to CZA, C/T, and FDC.

A series of clinical NDM-5-producing Escherichia coli isolates obtained from two surveillance networks for carbapenem-producing Enterobacterales from 2018 to 2019, namely, Switzerland (NARA) and Germany (SurvCARE), were analyzed. The 33 NDM-5-producing E. coli isolates were highly resistant to β-lactams, including novel β-lactam/β-lactamase inhibitor combinations (ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam), and remained susceptible to fosfomycin, colistin, and tigecycline.

Aztreonam/avibactam is one of the last therapeutic options for treating infections caused by NDM-like-producing Enterobacterales. However, PBP3-modified and NDM-producing Escherichia coli strains that co-produce CMY-42 have been shown to be resistant to this drug combination. The aim of our study was to assess the in vitro activity of cefepime/taniborbactam and cefepime/zidebactam against such aztreonam/avibactam-resistant E. coli strains. MIC values of aztreonam, aztreonam/avibactam, cefepime, cefepime/taniborbactam, cefepime/zidebactam and zidebactam alone were determined for 28 clinical aztreonam/avibactam-resistant E. coli isolates. Those isolates produced either NDM-5 (n = 24), NDM-4 (n = 2) or NDM-1 (n = 2), and they all co-produced CMY-42 (n = 28). They all harboured a four amino acid insertion in PBP-3 (Tyr-Arg-Ile-Asn or Tyr-Arg-Ile-Lys). All strains were resistant to aztreonam/avibactam and cefepime, as expected. The resistance rate to cefepime/taniborbactam was 100%, with MIC₅₀ and MIC₉₀ being at 16 mg/L and 64 mg/L, respectively. Conversely, all strains were susceptible to cefepime/zidebactam, with both MIC₅₀ and MIC₉₀ at 0.25 mg/L. Notably, all strains showed low MICs for zidebactam alone, with MIC₅₀ and MIC₉₀ at 0.5 mg/L and 1 mg/L. Our data highlighted the excellent in vitro performance of the newly developed β-lactam/β-lactamase inhibitor combination cefepime/zidebactam against aztreonam/avibactam-resistant E. coli strains, suggesting that this combination could be considered as an efficient therapeutic option in this context. Our study also highlights the cross-resistance between acquired resistance to aztreonam/avibactam and the cefepime/taniborbactam combination.