795. Mortality Impact of CLSI Carbapenem Breakpoint Changes in Enterobacteriaceae Bloodstream Infections: a Patient-level Analysis of Published Data
Session: Poster Abstract Session: Treatment of Resistant Infections - Clinical Analyses
Thursday, October 5, 2017
Room: Poster Hall CD
  • Carb_bsi_IDWEEK_092517_final.pdf (390.0 kB)
  • Background: In 2010, the Clinical and Laboratory Standards Institute (CLSI) lowered susceptibility breakpoints for carbapenem agents, though few studies have evaluated the clinical impact of these changes. The objective of this study was to determine if a clinical breakpoint exists for carbapenems in patients with Gram-negative Enterobacteriaceaebloodstream infections (GNBSIs).

    Methods: Patient-level data from 4 publications (Rhodes JN 2016, Biehle LR 2015, Patel TS 2015, Esterly JS 2012) reporting outcomes for GNBSIs treated with carbapenems for ≥48 hours were compiled. Patients with an MIC ≥16 mg/L to both imipenem (IMI) and meropenem (MER) were excluded. Classification and Regression Tree (CART) analyses were used to determine optimal splits for carbapenem MIC with respect to 30-day all-cause mortality. Univariate and multivariate regression analyses were conducted using Stata 14.

    Results: A total of 194 patients were extracted. Klebsiella pneumoniae was the most common pathogen (70.1%) followed by Escherichia coli(15.0%). Primary bacteremia/unknown and urinary tract were the most common sources of GNBSI (31.4% and 25.8%, respectively). MER and IMI MICs were available for 144 patients (74.2%) and 138 patients (71.1%), respectively. Carbapenem agent used was known for 141 patients, of which 94 received MER, 24 received ertapenem, 12 received doripenem, and 11 received IMI. CART analysis identified a significant difference in mortality between patients infected with organisms having MER MICs ≤ 1 mg/L (n = 10/121, 8.3%) versus those with >1 mg/L (n =7/21, 33.3%; p <0.01) regardless of carbapenem used. This breakpoint was also identified in the subgroup of patients with available MER MICs who were treated with MER (n=5/64, 7.8% vs 7/19, 36.8%; p<0.01). In multivariate logistic regression, MER MIC > 1 mg/L was associated with increased odds of 30-day mortality after controlling for ICU admission in the any carbapenem treatment (OR 5.0, 95%CI 1.63-15.6; p<0.01) and MER treated populations (OR 7.16, 1.88-27.3; p<0.01).

    Conclusion: This pooled patient-level analysis of GNBSIs treated with carbapenems represents the largest of its kind to date. A significant increase in mortality was identified in patients with MER non-susceptible isolates as defined by the 2010 CLSI breakpoints.

    J Nicholas O'Donnell, PharmD, MSc, Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, NY, Nathaniel Rhodes, PharmD, MSc, Department of Pharmacy, Northwestern Medicine, Chicago, IL, Lauren R Biehle, PharmD, University of Wyoming, Laramie, WY; Rose Medical Center, Denver, CO, Twisha Patel, PharmD, Michigan Medicine, Ann Arbor, MI, Milena McLaughlin, PharmD, MSc, BCPS-AQ ID, AAHIVP, Northwestern Memorial Hospital, Chicago, IL, John Esterly, PharmD, HCV/HIV, Merck, Chicago, IL and Elizabeth B. Hirsch, PharmD, BCPS, Department of Pharmacy, Beth Israel Deaconess Medical Center, Boston, MA; Northeastern University, Boston, MA


    J. N. O'Donnell, None

    N. Rhodes, None

    L. R. Biehle, None

    T. Patel, Merck: Grant Investigator , Research grant

    M. McLaughlin, None

    J. Esterly, Merck: Employee , Salary

    E. B. Hirsch, Merck: Grant Investigator , Grant recipient
    The Medicines Company: Speaker's Bureau , Speaker honorarium

    Findings in the abstracts are embargoed until 12:01 a.m. PDT, Wednesday Oct. 4th with the exception of research findings presented at the IDWeek press conferences.