Cefiderocol Resistance in Klebsiella pneumoniae Is Linked to SHV Extended-Spectrum β-Lactamase Activities and Functional Loss of the Outer Membrane Porin OmpK35

• Published in: Microbiology spectrum Vol. 11; no. 3; p. e0349622
• Main Authors: Moon, Sun Hee, Huang, En
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 15.06.2023
• Subjects: Anti-Bacterial Agents - pharmacology; Antimicrobial Chemotherapy; avibactam; beta-Lactamases - genetics; beta-Lactamases - metabolism; blaSHV; Cefiderocol; Cephalosporins - pharmacology; Escherichia coli - genetics; Escherichia coli - metabolism; Humans; Klebsiella Infections; Klebsiella pneumoniae; Klebsiella pneumoniae - metabolism; Microbial Sensitivity Tests; Porins - genetics; Porins - metabolism; Research Article; resistance; blaSHV; cefiderocol; Klebsiella pneumoniae; resistance; avibactam
• ISSN: 2165-0497; 2165-0497
• DOI: 10.1128/spectrum.03496-22

Klebsiella pneumoniae AR 0047 from the CDC and FDA Antibiotic Resistance Isolate Bank is resistant to cefiderocol, a siderophore-conjugated cephalosporin. Genomics analysis and genetic complementation revealed that a frameshift mutation in contributed to cefiderocol resistance. Heterologous expression of or in Escherichia coli increased the host resistance to cefiderocol. Moreover, avibactam, a β-lactamase inhibitor, enhanced cefiderocol activity against the resistant strain. Therefore, cefiderocol resistance is linked to SHV and the loss of . Understanding cefiderocol resistance mechanisms is essential for providing solutions to treat infections and to prevent resistance development. Cefiderocol resistance in Klebsiella pneumoniae AR 0047 is linked to SHV β-lactamase activities and functional loss of outer membrane porin. The cefiderocol-avibactam combination represents an opportunity to increase potency against cefiderocol-resistant pathogens.