New options for bloodstream infections caused by colistin- or ceftazidime/avibactam-resistant Klebsiella pneumoniae

Concerns regarding carbapenem-resistant Klebsiella pneumoniae (CR-Kp), especially in bloodstream infections (BSIs), are continuing to increase worldwide. Several novel agents with activity against BSI CR-Kp have been approved or are in late-stage clinical development. In this study, the antibacterial effects of ceftazidime/avibactam (CZA), aztreonam/avibactam (AZA), meropenem/vaborbactam (MEV), imipenemcilastatin/relebactam (ICR) and eravacycline (ERV) against three colistin-resistant CR-Kp (COLR-Kp) and four CZA-resistant CR-Kp (CZAR-Kp) were tested by time-kill assay. Klebsiella pneumoniae ATCC (R) BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-beta-lactamase genes. The results revealed that ERV resulted in re-growth of seven tested isolates. CZA and MEV showed a bactericidal effect against isolates harbouring blaKPC-2. ICR reduced the population of six isolates to >5 log10 CFU/mL compared with the initial count. AZA showed a bactericidal effect (>5 log10 CFU/mL) against seven isolates and a bacteriostatic effect (<3 log10 CFU/mL) against one CZAR-Kp isolate. Therefore, AZA and ICR are effective therapeutic candidates for COLR-Kp and CZAR-Kp isolates. (C) 2021 The Author(s). Published by Elsevier Ltd.

Automated summary

This study evaluated the antibacterial effects of several agents against carbapenem-resistant Klebsiella pneumoniae, finding that eravacycline, ceftazidime/avibactam, and meropenem/vaborbactam showed bactericidal effects against isolates carrying blaKPC-2, while aztreonam/avibactam and imipenemcilastatin/relebactam demonstrated therapeutic potential against the tested isolates.