title: High rate of colistin resistance among patients with carbapenem-resistant Klebsiella pneumoniae infection accounts for an excess of mortality.
abstract: Carbapenem-resistant Klebsiella pneumoniae (CR-KP) is becoming a common cause of healthcare-associated infection in Italy, with high morbidity and mortality. Prevalent CR-KP clones and resistance mechanisms vary between regions and over time. Therapeutic approaches and their impact on mortality have to be investigated. We performed a prospective study of patients with CR-KP isolation, hospitalized in nine hospitals of Rome, Italy, from December 2010 to May 2011, to describe the molecular epidemiology, antibiotic treatment and risk factors for mortality. Overall, 97 patients (60% male, median age 69 years) were enrolled. Strains producing blaKPC-3 were identified in 89 patients, blaVIM in three patients and blaCTX-M-15 plus porin defects in the remaining five patients. Inter-hospital spread of two major clones, ST512 and ST258, was found. Overall, 36.1% and 20.4% of strains were also resistant to colistin and tigecycline, respectively. Infection was diagnosed in 91 patients who received appropriate antibiotic treatment, combination therapy and removal of the infectious source in 73.6%, 59.3% and 28.5% of cases, respectively. Overall, 23 different antibiotic regimens were prescribed. In-hospital mortality was 25.8%. Multivariate analysis adjusted for appropriate treatment, combination therapy and infectious-source removal, showed that Charlson comorbidity score, intensive-care unit onset of infection, bacteraemia and infection due to a colistin-resistant CR-KP strain were independent risk factors for mortality. The spread of clones producing K. pneumoniae carbapenemases, mainly ST258, is currently the major cause of CR-KP infection in central Italy. We observed a high rate of resistance to colistin that is independently associated with worse outcome.
authors.affiliation: 2nd Division of Infectious Diseases, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy. Electronic address: maddalena.giannella@libero.it.
authors.forename: A
authors.initials: A
authors.lastname: Capone
authors.affiliation: 2nd Division of Infectious Diseases, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Giannella
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanitá, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Fortini
authors.affiliation: Department of Microbiology, University "La Sapienza" Policlinico Umberto I, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Microbiology, Azienda Ospedaliera San Filippo Neri, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Meledandri
authors.affiliation: Department of Microbiology, Azienda Ospedaliera San Filippo Neri, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ballardini
authors.affiliation: Department of Infectious Diseases, University "La Sapienza" Policlinico Umberto I, Rome, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Venditti
authors.affiliation: Department of Microbiology, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Bordi
authors.affiliation: Department of Microbiology, Azienda Ospedaliera Grassi Ostia, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Capozzi
authors.affiliation: Department of Microbiology, Santa Lucia Fundation, Rome, Italy.
authors.forename: M P
authors.initials: MP
authors.lastname: Balice
authors.affiliation: Health-care Infectious Unit, Azienda Ospedaliera San Giovanni Addolorata.
authors.forename: A
authors.initials: A
authors.lastname: Tarasi
authors.affiliation: Microbiology and Heart Surgery ICU, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Parisi
authors.affiliation: Microbiology and Heart Surgery ICU, Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lappa
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanitá, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Carattoli
authors.affiliation: 2nd Division of Infectious Diseases, National Institute for Infectious Diseases "Lazzaro Spallanzani", Rome, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Petrosillo
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003091:Colistin / Q000494:pharmacology* / Q000627:therapeutic use; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D007558:Italy / Q000453:epidemiology; D007710:Klebsiella Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology* / Q000401:mortality*; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents; D003091:Colistin