Carbapenemase -producing Pseudomonas aeruginosa isolates from Turkey: first report of P. aeruginosa high-risk clones with VIM-5– and IMP-7–type carbapenemases in a tertiary hospital

Abstract

We investigated the presence of carbapenemases in carbapenem-resistant Pseudomonas aeruginosa isolates, which were collected over a 14-month period in a Turkish hospital, with in-depth molecular characterization of carbapenemase-producing isolates. Among 45 study isolates; two isolates were identified as carbapenemase producers by both Carba NP and Carbapenem Inactivation Method (CIM) tests, and only one of them gave a positive result in PCR tests for a carbapenemase gene (blaVIM). Whole genome sequencing (WGS) of the two isolates revealed the presence of blaVIM-5 gene in an ST308 isolate while the other one expressed IMP-7 in an ST357 isolate, both STs are considered high-risk clones. The two carbapenemaseproducing isolates were multidrug resistant, as they harbored other resistance determinants, including a variant of the recently described plasmid-encoded fluoroquinolone resistance determinant crpP gene, crpP-2. We report for the first time P. aeruginosa high-risk clones carrying VIM-5-and IMP-7-type carbapenemases with multiple resistance determinants in Turkey.

Understanding the binding conformation of ceftolozane/tazobactam with Metallo‐β‐lactamases VIM‐5 and IMP‐7 of Pseudomonas aeruginosa: A molecular docking and virtual screening process

“…Our results have the resemblance with the in vitro studies carried out by Cekin et al, which revealed that the antimicrobial susceptibility tests on 12 carbapenem‐resistant P . aeruginosa isolates have shown the highest 78% of susceptibility to the piperacillin‐tazobactam antibiotic/inhibitor combination therapy and lowest susceptibility of 9% to the monobactam, aztreonam 4 . The isolates producing VIM‐5 carbapenemase have shown high resistance for ceftolozane/tazobactam combination with the Minimum Inhibitory Concentration (MIC) value of ≥256 μg/ml 4 .…”

“…aeruginosa isolates have shown the highest 78% of susceptibility to the piperacillin‐tazobactam antibiotic/inhibitor combination therapy and lowest susceptibility of 9% to the monobactam, aztreonam 4 . The isolates producing VIM‐5 carbapenemase have shown high resistance for ceftolozane/tazobactam combination with the Minimum Inhibitory Concentration (MIC) value of ≥256 μg/ml 4 . Next, imipenem with the binding energy of −8.82 kcal/mol, 3 H‐bond formations with ARG109 (1.8 Å), TYR134 (2.1 & 2.8 Å), SER154 (2.2 Å), and 2 hydrophobic interactions with LEU155 & PHE167.…”

“…The in vitro susceptibility study on 12 isolates of P . aeruginosa expressing IMP‐7 MBL (3 isolates) reveals the MIC of ≥256 μg/ml for ceftolozane/tazobactam combination, which is highly resistant 4 . The ureidopenicillin antibiotic, piperacillin, and IMP‐7 MBL interacting energy were found to be −7.16 kcal/mol.…”

“…aeruginosa causing infections have been treated with the antibiotics such as beta (β)‐lactams, quinolones, and aminoglycosides. Later the extreme use of such drugs has led to the emergence of resistance 4 . In the current situation, multi‐drug resistant (MDR) P .…”

“…In particular, the production of Verona integrin‐borne Metallo‐β‐lactamse‐5 (VIM‐5) and Imipenemase‐7 (IMP‐7), a class B Metallo‐β‐lactamase (MBL) in P . aeruginosa cause resistance to the ceftolozane/tazobactam combinations 4 . The VIM type β‐lactamases are grouped under the subclass of B1 MBLs, which has two zinc metal ions through which it mediates the catalytic activity.…”