Prevalence and Molecular Characteristics of Ceftazidime-avibactam Resistance among carbapenem-resistant Pseudomonas aeruginosa Clinical Isolates

Resistance against ceftazidime-avibactam (CZA) in carbapenem-resistant Pseudomonas aeruginosa (CRPA) is emerging. This study was aimed at detecting the prevalence and molecular characteristics of CZA-resistant CRPA clinical isolates in Guangdong Province, China. The antimicrobial susceptibility profile of these strains was determined. A subset of sixteen CZA-resistant CRPA isolates was analyzed by whole genome sequencing (WGS). Genetic surroundings of carbapenem resistance genes and pan-genome-wide association analysis were further studied. Of the 250 CRPA isolates, CZA resistance rate was 6.4% (16/250). The minimum inhibitory concentration (MIC) of CZA range was from 0.25 to >256 mg/L. MIC50 and MIC90 were 2/4 and 8/4 mg/L, respectively. Among the sixteen CZA-resistant CRPA strains, 31.3% (5/16) of them carried class B carbapenem resistance genes including blaIMP-4, blaIMP-45 and blaVIM-2, located on IncP-2 megaplasmids or chromosome, respectively. Pan-genome-wide association analysis of accessory genes for CZA-susceptible or -resistant CRPA isolates showed that PA1874, a hypothetical protein containing BapA prefix-like domain, was enriched in CZA-resistant group significantly. Class B carbapenem resistance genes play important roles in CZA resistance. Meanwhile, PA1874 gene may be a novel mechanism involving in CZA resistance. It is necessary to continually monitor CZA-resistant CRPA isolates.