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

Author:

Tumbarello Mario1,Trecarichi Enrico Maria1,De Rosa Francesco Giuseppe23,Giannella Maddalena4,Giacobbe Daniele Roberto5,Bassetti Matteo6,Losito Angela Raffaella1,Bartoletti Michele4,Del Bono Valerio5,Corcione Silvia23,Maiuro Giuseppe1,Tedeschi Sara4,Celani Luigi1,Cardellino Chiara Simona23,Spanu Teresa7,Marchese Anna8,Ambretti Simone9,Cauda Roberto1,Viscoli Claudio5,Viale Pierluigi4,

Affiliation:

1. 1  Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy

2. 2  Department of Medical Sciences, University of Turin, Torino, Italy

3. 3  Infectious Diseases at Amedeo di Savoia Hospital, Torino, Italy

4. 4  Clinic of Infectious Diseases, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy

5. 5  Infectious Diseases Division, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy

6. 6  Infectious Diseases Division, Santa Maria Misericordia University Hospital, Udine, Italy

7. 7  Institute of Microbiology, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy

8. 8  Microbiology Unit, University of Genoa (DISC) and IRCCS San Martino-IST, Genoa, Italy

9. 9  Operative Unit of Clinical Microbiology, S. Orsola-Malpighi Hospital, Bologna, Italy

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)

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