Production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in Klebsiella pneumoniae infection

Eur J Clin Microbiol Infect Dis. 2023 Dec;42(12):1485-1497. doi: 10.1007/s10096-023-04675-w. Epub 2023 Oct 27.

Abstract

Purpose: To know whether the production of OXA-48 carbapenemase exerts an independent impact on the outcome of Klebsiella pneumoniae infection, once adjusted by clinical syndrome and baseline risk factors.

Methods: We performed a case-cohort study including 117 infectious episodes due to OXA-48-producing K. pneumoniae (OXA-48-Kp) and 117 episodes due to non-OXA-48-producing strains (non-OXA-48-Kp). Both groups were matched (1:1 ratio) by clinical syndrome (source of infection, preceding invasive procedures and indwelling devices, and associated bacteremia) and hospitalization ward at infection onset. Multivariate Cox regression was used to investigate the association between OXA-48-Kp infection and clinical cure by day 14 (primary outcome) and 30-day all-cause mortality (secondary outcome).

Results: Both study groups were well balanced regarding underlying conditions and comorbidity burden. Sepsis or septic shock were more frequent in OXA-48-Kp cases than non-OXA-48-Kp controls (41 [35.0%] vs. 17 [14.5%]; P-value < 0.0001). Clinical cure by day 14 was less commonly achieved in OXA-48-Kp cases (49 [41.9%] vs. 95 [81.2%]; P-value < 0.001), whereas 30-day all-cause mortality was higher (33 [28.2%] vs. 18 [15.4%]; P-value = 0.018). Multivariate analysis confirmed that OXA-48-Kp infection was independently associated with the lack of 14-day clinical cure (adjusted hazard ratio [aHR]: 0.45; 95% confidential interval [95%CI]: 0.29-0.70; P-value < 0.0001). A non-significant association was observed for 30-day all-cause mortality (aHR: 1.65; 95%CI: 0.92-2.94; P-value = 0.093).

Conclusion: Our matched analysis suggests that the production of OXA-48 carbapenemase acts as an independent risk factor for poor outcome in K. pneumoniae infection as compared to episodes due to non-carbapenemase-producing strains.

Keywords: Klebsiella pneumoniae; OXA-48 carbapenemase; Outcomes; Risk factor; Virulence.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Proteins
  • Cohort Studies
  • Humans
  • Klebsiella Infections* / microbiology
  • Klebsiella pneumoniae*
  • Retrospective Studies
  • Risk Factors
  • beta-Lactamases

Substances

  • carbapenemase
  • Anti-Bacterial Agents
  • beta-Lactamases
  • Bacterial Proteins