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The in vitro activity of imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and cefiderocol was evaluated against both clinical and isogenic enterobacterial isolates producing carbapenemases of the SME, NmcA, FRI, and IMI types. Ceftazidime-avibactam and meropenem-vaborbactam showed the highest activity against all tested isolates; imipenem-relebactam showed only moderate activity.

A multidrug-resistant (carbapenems, aztreonam + avibactam, and cefiderocol) ST167 Escherichia coli clinical isolate recovered from a patient hospitalized in Switzerland produced NDM-35 showing ca. 10-fold increased hydrolytic activity toward cefiderocol compared to NDM-1. The isolate co-produced a CMY-type β-lactamase, exhibited a four amino-acid insertion in PBP3, and possessed a truncated iron transporter CirA protein. Our study identified an association of unrelated resistance mechanisms leading to resistance to virtually all β-lactams in a high-risk E. coli clone.

A multidrug-resistant (carbapenems, aztreonam + avibactam, and cefiderocol) ST167 Escherichia coli clinical isolate recovered from a patient hospitalized in Switzerland produced NDM-35 showing ca. 10-fold increased hydrolytic activity toward cefiderocol compared to NDM-1. The isolate co-produced a CMY-type β-lactamase, exhibited a four amino-acid insertion in PBP3, and possessed a truncated iron transporter CirA protein.

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.

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.

Among the most common metallo-β-lactamases (MBL), the most clinically significant are the New Delhi Metallo-β-lactamases (NDM). NDM enzymes hydrolyze almost all β-lactams except aztreonam and are not inhibited by novel β-lactamase inhibitors such as avibactam (AVI), relebactam, and vaborbactam (1).….