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Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study.
Tumbarello, Mario 1,*; Trecarichi, Enrico Maria 1; De Rosa, Francesco Giuseppe 2,3; Giannella, Maddalena 4; Giacobbe, Daniele Roberto 5; Bassetti, Matteo 6; Losito, Angela Raffaella 1; Bartoletti, Michele 4; Del Bono, Valerio 5; Corcione, Silvia 2,3; Maiuro, Giuseppe 1; Tedeschi, Sara 4; Celani, Luigi 1; Cardellino, Chiara Simona 2,3; Spanu, Teresa 7; Marchese, Anna 8; Ambretti, Simone 9; Cauda, Roberto 1; Viscoli, Claudio 5; Viale, Pierluigi 4; on behalf of ISGRI-SITA (Italian Study Group on Resistant Infections of the Societa Italiana Terapia Antinfettiva)
[Article] Journal of Antimicrobial Chemotherapy. 70(7):2133-2143, July 2015.

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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.