title: Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia.
abstract: BACKGROUND
  Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative.
  
  
  METHODS
  We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes.
  
  
  RESULTS
  There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were blaKPC(92%), followed by blaNDM(5%) and blaOXA-48-type(3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01-24.81).
  
  
  CONCLUSIONS
  Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Johns Hopkins University School of Medicine, ptamma1@jhmi.edu.
authors.forename: Pranita D
authors.initials: PD
authors.lastname: Tamma
authors.affiliation: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Goodman
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
authors.affiliation: Division of Medical Microbiology, Department of Pathology, Johns Hopkins Hospital, and.
authors.forename: Tsigereda
authors.initials: T
authors.lastname: Tekle
authors.affiliation: Division of Medical Microbiology, Department of Pathology, Johns Hopkins Hospital, and.
authors.forename: Ava
authors.initials: A
authors.lastname: Roberts
authors.affiliation: Division of Medical Microbiology, Department of Pathology, Johns Hopkins Hospital, and.
authors.forename: Abimbola
authors.initials: A
authors.lastname: Taiwo
authors.affiliation: Division of Medical Microbiology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Simner
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016470:Bacteremia / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D004755:Enterobacteriaceae / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D012189:Retrospective Studies; D013845:Thienamycins / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D004269:DNA, Bacterial; D013845:Thienamycins; D001618:beta-Lactamases; C063912:carbapenemase; D000077731:Meropenem
keywords: CRE; carbapenemases; klebsiella pneumoniae carbapenemase; multidrug-resistant gram-negative.