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

Int J Antimicrob Agents. 2021 Dec;58(6):106458. doi: 10.1016/j.ijantimicag.2021.106458. Epub 2021 Oct 25.

Abstract

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), imipenem-cilastatin/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® BAA-1705TM was used as a control strain. Two COLR-Kp isolates carried the blaKPC-2 gene and four CAZR-Kp isolates carried metallo-β-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.

Keywords: Bactericidal effect; Carbapenem-resistant Klebsiella pneumoniae; Eravacycline; β-Lactamase inhibitor.

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Azabicyclo Compounds / pharmacology
  • Aztreonam / pharmacology
  • Bacteremia / drug therapy*
  • Bacteremia / microbiology
  • Boronic Acids / pharmacology
  • Carbapenem-Resistant Enterobacteriaceae / drug effects*
  • Ceftazidime / pharmacology
  • Cilastatin / pharmacology
  • Colistin / pharmacology
  • Drug Combinations
  • Humans
  • Imipenem / pharmacology
  • Klebsiella Infections / drug therapy*
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / genetics
  • Meropenem / pharmacology
  • Microbial Sensitivity Tests
  • Tetracyclines / pharmacology
  • beta-Lactamase Inhibitors / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Azabicyclo Compounds
  • Boronic Acids
  • Drug Combinations
  • Tetracyclines
  • avibactam, ceftazidime drug combination
  • beta-Lactamase Inhibitors
  • imipenem, cilastatin and relebactam
  • eravacycline
  • Cilastatin
  • vaborbactam
  • Imipenem
  • Ceftazidime
  • Meropenem
  • Aztreonam
  • Colistin