Emergence of KPC-31, a KPC-3 Variant Associated with Ceftazidime-Avibactam Resistance, in an Extensively...

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• Carbapenemase-producing Enterobacterales (CPE) are a significant global health threat.
• Pseudomonas aeruginosa is an opportunistic pathogen frequently associated with healthcare-associated infections.
• The emergence of resistance to advanced antibiotics like ceftazidime-avibactam is a growing concern.

Purpose of the Study:

• To characterize a ceftazidime-avibactam-resistant KPC-producing Pseudomonas aeruginosa strain.
• To investigate the genetic basis of resistance in the identified strain.
• To evaluate the performance of common carbapenemase detection assays.

Main Methods:

• Isolation and identification of Pseudomonas aeruginosa from a clinical sample.
• Whole-genome sequencing (WGS) for genetic analysis.
• Antimicrobial susceptibility testing.
• Evaluation of carbapenemase detection assays.

Main Results:

• A ceftazidime-avibactam-resistant KPC-producing Pseudomonas aeruginosa strain was isolated in Argentina.
• WGS revealed a D179Y substitution in KPC-3 (KPC-31) integrated into the chromosome.
• The strain belonged to the high-risk ST235/O11 clone.
• Standard carbapenemase detection assays failed to identify this KPC-producing isolate.

Conclusions:

• A novel ceftazidime-avibactam-resistant KPC-producing P. aeruginosa strain, belonging to the ST235/O11 clone, was identified.
• The D179Y substitution in KPC-3 contributes to resistance.
• Current diagnostic assays may not reliably detect all KPC-producing strains, necessitating improved detection methods.