Rapid diagnostics and ceftazidime/avibactam for KPC-producing Klebsiella pneumoniae bloodstream infections: impact on mortality and role of combination therapy

Eur J Clin Microbiol Infect Dis. 2023 Apr;42(4):431-439. doi: 10.1007/s10096-023-04577-x. Epub 2023 Feb 20.

Abstract

This study was aimed at investigating risk factors for mortality in patients suffering from KPC-producing Klebsiella pneumoniae (KPC-Kp) bloodstream infections (BSIs), evaluating the impact of rapid diagnostics and ceftazidime/avibactam use. This observational retrospective study (January 2017-May 2021) included all patients with a KPC-Kp BSI. Uni-multivariable analyses were carried out to evaluate the effect of clinical variables on both in-hospital death (IHD) and 30-day all-cause mortality, and the role of the combination of ceftazidime/avibactam plus polymyxin. One hundred and ninety-six patients met the study's inclusion criteria. Older age, having undergone renal replacement therapy during the 30 days preceding the KPC-Kp BSI onset, having an INCREMENT-CPE score ≥ 8, and having suffered from a superimposed and/or following KPC-Kp BSI treatment candidemia were found to be the main factors associated with both mortality rates. Among protective factors, the centrality of ceftazidime/avibactam in monotherapy (IHD: OR: 0.34; CI 95%: 0.11-1.00-30-day all-cause mortality: OR: 0.18; CI 95%: 0.04-0.77) or combination (IHD: OR: 0.51; CI 95%: 0.22-1.19-30-day all-cause mortality: OR: 0.62; CI 95%: 0.21-1.84) emerged and became even more evident once the effect of ceftazidime/avibactam plus polymyxin was removed. Rapid diagnostics may be useful to adopt more effective strategies for the treatment of KPC-Kp BSI patients and implement infection control measures, even if not associated with higher patient survival. Ceftazidime/avibactam, even when used alone, represents an important option against KPC-Kp, while combined use with polymyxin might not have altered its efficacy. Patient comorbidities, severity of BSI, and complications such as candidemia were confirmed to have a significant burden on survival.

Keywords: Bloodstream infection; Carbapenemase; Ceftazidime-avibactam; KPC; Klebsiella pneumoniae; Rapid diagnostic test; Sepsis.

Publication types

  • Observational Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins
  • Candidemia* / drug therapy
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Drug Combinations
  • Hospital Mortality
  • Humans
  • Klebsiella Infections* / diagnosis
  • Klebsiella Infections* / drug therapy
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae
  • Microbial Sensitivity Tests
  • Polymyxins / pharmacology
  • Polymyxins / therapeutic use
  • Rapid Diagnostic Tests
  • Retrospective Studies
  • beta-Lactamases

Substances

  • Ceftazidime
  • Anti-Bacterial Agents
  • avibactam
  • beta-Lactamases
  • Drug Combinations
  • Polymyxins
  • Bacterial Proteins