Mortality in KPC-producing Klebsiella pneumoniae bloodstream infections: a changing landscape

J Antimicrob Chemother. 2023 Oct 3;78(10):2505-2514. doi: 10.1093/jac/dkad262.

Abstract

Objectives: To assess the impact of carbapenem resistance on mortality in Klebsiella pneumoniae bloodstream infection (BSI) in the era of novel β-lactam/β-lactamase inhibitor combinations.

Material and methods: Retrospective study of patients with K. pneumoniae BSI between January and August 2020 in 16 centres (CARBANEW study within the MULTI-SITA project).

Results: Overall, 426 patients were included: 107/426 (25%) had carbapenem-resistant K. pneumoniae (CR-Kp) BSI and 319/426 (75%) had carbapenem-susceptible K. pneumoniae (CS-Kp) BSI. Crude cumulative 30 day mortality was 33.8% and 20.7% in patients with, respectively, CR-Kp BSI and CS-Kp BSI (P = 0.027). Carbapenemase production or carbapenemase-encoding genes were detected in 84/98 tested CR-Kp isolates (85.7%), mainly KPC (78/84; 92.9%). Ceftazidime/avibactam was the most frequently used appropriate therapy for CR-Kp BSI (80/107; 74.7%). In multivariable analyses, variables showing an unfavourable association with mortality after correction for multiple testing were age-adjusted Charlson comorbidity index (HR 1.20; 95% CI 1.10-1.31, P < 0.001) and Pitt score (HR 1.33; 95% CI 1.15-1.55, P < 0.001), but not carbapenem resistance (HR 1.28, 95% CI 0.74-2.22, P = 0.410). In a propensity score-matched analysis, there was no difference in mortality between patients appropriately treated with ceftazidime/avibactam for CR-Kp BSI and patients appropriately treated with other agents (mainly meropenem monotherapy or piperacillin/tazobactam monotherapy) for CS-Kp BSI (HR 1.07; 95% CI 0.50-2.29, P = 0.866).

Conclusions: Our results suggest that the increased mortality in CR-Kp BSI compared with CS-Kp BSI is not (or no longer) dependent on the type of therapy in areas where ceftazidime/avibactam-susceptible KPC-producing isolates are the most prevalent type of CR-Kp.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azabicyclo Compounds / pharmacology
  • Azabicyclo Compounds / therapeutic use
  • Bacteremia* / drug therapy
  • Bacterial Proteins / genetics
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Ceftazidime / pharmacology
  • Disease Susceptibility
  • Drug Combinations
  • Humans
  • Klebsiella Infections* / drug therapy
  • Klebsiella Infections* / epidemiology
  • Klebsiella pneumoniae
  • Retrospective Studies
  • Sepsis* / drug therapy
  • beta-Lactamase Inhibitors / therapeutic use
  • beta-Lactamases / genetics

Substances

  • Ceftazidime
  • avibactam
  • Azabicyclo Compounds
  • beta-Lactamases
  • Bacterial Proteins
  • Carbapenems
  • beta-Lactamase Inhibitors
  • Drug Combinations
  • Anti-Bacterial Agents