Infections Caused by KPC-producing Klebsiella Pneumoniae: Differences in Therapy and Mortality in a Multicentre Study

J Antimicrob Chemother. 2015 Jul;70(7):2133-43. doi: 10.1093/jac/dkv086. Epub 2015 Apr 21.

Abstract

Objectives: Infections caused by Klebsiella pneumoniae (Kp) carbapenemase (KPC)-producing strains of Kp have become a significant threat in recent years. To assess their outcomes and identify risk factors for 14 day mortality, we conducted a 4 year (2010-13) retrospective cohort study in five large Italian teaching hospitals.

Methods: The cohort included 661 adults with bloodstream infections (BSIs; n = 447) or non-bacteraemic infections (lower respiratory tract, intra-abdominal structure, urinary tract or other sites) caused by a KPC-Kp isolate. All had received ≥48 h of therapy (empirical and/or non-empirical) with at least one drug to which the isolate was susceptible.

Results: Most deaths occurred within 2 weeks of infection onset (14 day mortality: 225/661, 34.1%). Logistic regression analysis identified BSI (OR, 2.09; 95% CI, 1.34-3.29), presentation with septic shock (OR, 2.45; 95% CI, 1.47-4.08), inadequate empirical antimicrobial therapy (OR, 1.48; 95% CI, 1.01-2.18), chronic renal failure (OR, 2.27; 95% CI, 1.44-3.58), high APACHE III score (OR, 1.05; 95% CI, 1.04-1.07) and colistin-resistant isolates (OR, 2.18; 95% CI, 1.37-3.46) as independent predictors of 14 day mortality. Combination therapy with at least two drugs displaying in vitro activity against the isolate was associated with lower mortality (OR, 0.52; 95% CI, 0.35-0.77), in particular in patients with BSIs, lung infections or high APACHE III scores and/or septic shock at infection onset. Combinations that included meropenem were associated with significantly higher survival rates when the KPC-Kp isolate had a meropenem MIC of ≤8 mg/L.

Conclusions: KPC-Kp infections are associated with high mortality. Treatment with two or more drugs displaying activity against the isolate improves survival, mainly in patients who are critically ill.

Keywords: carbapenem resistance; carbapenemases; colistin resistance; combination therapy; inadequate empirical therapy; meropenem MICs; treatment.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Bacterial Proteins / metabolism*
  • Female
  • Hospitals, Teaching
  • Humans
  • Italy / epidemiology
  • Klebsiella Infections / drug therapy*
  • Klebsiella Infections / epidemiology
  • Klebsiella Infections / microbiology
  • Klebsiella Infections / mortality*
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology*
  • Klebsiella pneumoniae / isolation & purification
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Survival Analysis
  • Treatment Outcome
  • Young Adult
  • beta-Lactamases / metabolism*

Substances

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