title: Infections caused by KPC-producing Klebsiella pneumoniae: differences in therapy and mortality in a multicentre study.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy tumbarello@rm.unicatt.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Tumbarello
authors.affiliation: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy.
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Trecarichi
authors.affiliation: Department of Medical Sciences, University of Turin, Torino, Italy Infectious Diseases at Amedeo di Savoia Hospital, Torino, Italy.
authors.forename: Francesco Giuseppe
authors.initials: FG
authors.lastname: De Rosa
authors.affiliation: Clinic of Infectious Diseases, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Giannella
authors.affiliation: Infectious Diseases Division, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy.
authors.forename: Daniele Roberto
authors.initials: DR
authors.lastname: Giacobbe
authors.affiliation: Infectious Diseases Division, Santa Maria Misericordia University Hospital, Udine, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bassetti
authors.affiliation: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy.
authors.forename: Angela Raffaella
authors.initials: AR
authors.lastname: Losito
authors.affiliation: Clinic of Infectious Diseases, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Bartoletti
authors.affiliation: Infectious Diseases Division, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Del Bono
authors.affiliation: Department of Medical Sciences, University of Turin, Torino, Italy Infectious Diseases at Amedeo di Savoia Hospital, Torino, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Corcione
authors.affiliation: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maiuro
authors.affiliation: Clinic of Infectious Diseases, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Tedeschi
authors.affiliation: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Celani
authors.affiliation: Department of Medical Sciences, University of Turin, Torino, Italy Infectious Diseases at Amedeo di Savoia Hospital, Torino, Italy.
authors.forename: Chiara Simona
authors.initials: CS
authors.lastname: Cardellino
authors.affiliation: Institute of Microbiology, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Spanu
authors.affiliation: Microbiology Unit, University of Genoa (DISC) and IRCCS San Martino-IST, Genoa, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Marchese
authors.affiliation: Operative Unit of Clinical Microbiology, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Ambretti
authors.affiliation: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Roma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.affiliation: Infectious Diseases Division, University of Genoa (DISSAL) and IRCCS San Martino-IST, Genoa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
authors.affiliation: Clinic of Infectious Diseases, University of Bologna, S. Orsola-Malpighi Hospital, Bologna, Italy.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Viale
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000378:metabolism*; D005260:Female; D006784:Hospitals, Teaching; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology / Q000401:mortality*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000201:enzymology* / Q000302:isolation & purification; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase
keywords: carbapenem resistance; carbapenemases; colistin resistance; combination therapy; inadequate empirical therapy; meropenem MICs; treatment