Emergence of Resistance to Novel Cephalosporin-β-Lactamase Inhibitor Combinations through the Modification of the Pseudomonas aeruginosa MexCD-OprJ Efflux Pump.

Abstract

A ceftolozane-tazobactam- and ceftazime-avibactam-resistant Pseudomonas aeruginosa isolate was recovered after treatment (including azithromycin, meropenem, and ceftolozane-tazobactam) from a patient that had developed ventilator-associated pneumonia after COVID-19 infection. Whole-genome sequencing revealed that the strain, belonging to ST274, had acquired a nonsense mutation leading to truncated carbapenem porin OprD (W277X), a 7-bp deletion (nt213Δ7) in NfxB (negative regulator of the efflux pump MexCD-OprJ), and two missense mutations (Q178R and S133G) located within the first large periplasmic loop of MexD. Through the construction of mexD mutants and complementation assays with wild-type nfxB, it was evidenced that resistance to the novel cephalosporin-β-lactamase inhibitor combinations was caused by the modification of MexD substrate specificity.

• Authors: María A Gomis-Font, Cristina Pitart, Ester Del Barrio-Tofiño, Yuliya Zboromyrska, Sara Cortes-Lara, Xavier Mulet, Francesc Marco, Jordi Vila, Carla López-Causapé, Antonio Oliver
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 65 Issue 8 Pg. e0008921 (07 16 2021) ISSN: 1098-6596 [Electronic] United States
• PMID: 34060900 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Cephalosporins
• beta-Lactamase Inhibitors
• Cephalosporinase

Topics

• Anti-Bacterial Agents (pharmacology, therapeutic use)
• COVID-19
• Cephalosporinase
• Cephalosporins (pharmacology)
• Humans
• Microbial Sensitivity Tests
• Pseudomonas
• Pseudomonas Infections (drug therapy)
• Pseudomonas aeruginosa (genetics)
• SARS-CoV-2
• beta-Lactamase Inhibitors (pharmacology)