title: Impact of therapy and strain type on outcomes in urinary tract infections caused by carbapenem-resistant Klebsiella pneumoniae.
abstract: OBJECTIVE
  Carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important healthcare-associated pathogen. We evaluated the impact of CRKP strain type and treatment on outcomes of patients with CRKP bacteriuria.
  
  
  METHODS
  Physician-diagnosed CRKP urinary tract infection (UTI)-defined as those patients who received directed treatment for CRKP bacteriuria-was studied in the multicentre, prospective Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRaCKle) cohort. Strain typing by repetitive extragenic palindromic PCR (rep-PCR) was performed. Outcomes were classified as failure, indeterminate or success. Univariate and multivariate ordinal analyses to evaluate the associations between outcome, treatment and strain type were followed by binomial analyses.
  
  
  RESULTS
  One-hundred-and-fifty-seven patients with physician-diagnosed CRKP UTI were included. After adjustment for CDC/National Healthcare Safety Network (NHSN)-defined UTI, critical illness and receipt of more than one active antibiotic, patients treated with aminoglycosides were less likely to fail therapy [adjusted OR (aOR) for failure 0.34, 95% CI 0.15-0.73, P=0.0049]. In contrast, patients treated with tigecycline were more likely to fail therapy (aOR for failure 2.29, 95% CI 1.03-5.13, P=0.0425). Strain type data were analysed for 55 patients. The predominant clades were ST258A (n=18, 33%) and ST258B (n=26, 47%). After adjustment for CDC/NHSN-defined UTI and use of tigecycline and aminoglycosides, infection with strain type ST258A was associated with clinical outcome in ordinal analysis (P=0.0343). In multivariate binomial models, strain type ST258A was associated with clinical failure (aOR for failure 5.82, 95% CI 1.47-28.50, P=0.0113).
  
  
  CONCLUSIONS
  In this nested cohort study of physician-diagnosed CRKP UTI, both choice of treatment and CRKP strain type appeared to impact on clinical outcomes.
authors.affiliation: Division of Infectious Diseases, University of North Carolina, Chapel Hill, NC, USA david_vanduin@med.unc.edu.
authors.forename: David
authors.initials: D
authors.lastname: van Duin
authors.affiliation: Department of Infectious Diseases, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Cober
authors.affiliation: Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Richter
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Federico
authors.initials: F
authors.lastname: Perez
authors.affiliation: Department of Medicine, MetroHealth Medical Center, Cleveland, OH, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kalayjian
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Salata
authors.affiliation: Department of Biostatistics and the Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Evans
authors.affiliation: Division of Infectious Diseases, Duke University, Durham, NC, USA.
authors.forename: Vance G
authors.initials: VG
authors.lastname: Fowler
authors.affiliation: Division of Infectious Diseases, Detroit Medical Center, Wayne State University, Detroit, MI, USA.
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.affiliation: Research Service, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH, USA Division of Infectious Diseases and HIV Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USA Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH, USA Department of Pharmacology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015780:Carbapenems / Q000494:pharmacology*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D011446:Prospective Studies; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems
keywords: MDR; UTIs; aminoglycosides; carbapenem-resistant Enterobacteriaceae; tigecycline