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

• Published in: Journal of antimicrobial chemotherapy 2015-07, Vol.70 (7), p.2133-2143
• Main Authors: Tumbarello, Mario, Trecarichi, Enrico Maria, De Rosa, Francesco Giuseppe, Giannella, Maddalena, Giacobbe, Daniele Roberto, Bassetti, Matteo, Losito, Angela Raffaella, Bartoletti, Michele, Del Bono, Valerio, Corcione, Silvia, Maiuro, Giuseppe, Tedeschi, Sara, Celani, Luigi, Cardellino, Chiara Simona, Spanu, Teresa, Marchese, Anna, Ambretti, Simone, Cauda, Roberto, Viscoli, Claudio, Viale, Pierluigi
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Bacteria; Bacterial infections; Bacterial Proteins - secretion; beta-Lactamases - secretion; Female; Hospitals, Teaching; Humans; Italy - epidemiology; Klebsiella Infections - drug therapy; Klebsiella Infections - epidemiology; Klebsiella Infections - microbiology; Klebsiella Infections - mortality; Klebsiella pneumoniae; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - enzymology; Klebsiella pneumoniae - isolation & purification; Male; Medical treatment; Microbial Sensitivity Tests; Middle Aged; Mortality; Regression analysis; Retrospective Studies; Risk Factors; Survival Analysis; Treatment Outcome; Young Adult
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkv086

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. 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. 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. 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.