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. N. O'Donnell,
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
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