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

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

Mario Tumbarello  1 , Enrico Maria Trecarichi  2 , Francesco Giuseppe De Rosa  3 , Maddalena Giannella  4 , Daniele Roberto Giacobbe  5 , Matteo Bassetti  6 , Angela Raffaella Losito  2 , Michele Bartoletti  4 , Valerio Del Bono  5 , Silvia Corcione  3 , Giuseppe Maiuro  2 , Sara Tedeschi  4 , Luigi Celani  2 , Chiara Simona Cardellino  3 , Teresa Spanu  7 , Anna Marchese  8 , Simone Ambretti  9 , Roberto Cauda  2 , Claudio Viscoli  5 , Pierluigi Viale  4 ; ISGRI-SITA (Italian Study Group on Resistant Infections of the Società Italiana Terapia Antinfettiva)
Affiliations
Multicenter Study

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

Mario Tumbarello et al. J Antimicrob Chemother. 2015 Jul.

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.

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