Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study

Mario Tumbarello, Enrico Maria Trecarichi, Francesco Giuseppe De Rosa, Maddalena Giannella, Daniele Roberto Giacobbe, Matteo Bassetti, Angela Raffaella Losito, Michele Bartoletti, Valerio Del Bono, Silvia Corcione, Giuseppe Maiuro, Sara Tedeschi, Luigi Celani, Chiara Simona Cardellino, Teresa Spanu, Anna Marchese, Simone Ambretti, Roberto Cauda, Claudio Viscoli, Pierluigi Viale

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article numberdkv086
Pages (from-to)2133-2143
Number of pages11
JournalJournal of Antimicrobial Chemotherapy
Volume70
Issue number7
DOIs
Publication statusPublished - Dec 6 2014

Keywords

  • Carbapenem resistance
  • Carbapenemases
  • Colistin resistance
  • Combination therapy
  • Inadequate empirical therapy
  • Meropenem MICs
  • Treatment

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Tumbarello, M., Trecarichi, E. M., De Rosa, F. G., Giannella, M., Giacobbe, D. R., Bassetti, M., Losito, A. R., Bartoletti, M., Del Bono, V., Corcione, S., Maiuro, G., Tedeschi, S., Celani, L., Cardellino, C. S., Spanu, T., Marchese, A., Ambretti, S., Cauda, R., Viscoli, C., & Viale, P. (2014). Infections caused by KPC-producing Klebsiella pneumoniae: Differences in therapy and mortality in a multicentre study. Journal of Antimicrobial Chemotherapy, 70(7), 2133-2143. [dkv086]. https://doi.org/10.1093/jac/dkv086