Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

• Published in: Clinical infectious diseases Vol. 64; no. 3; pp. 257 - 264
• Main Authors: Tamma, Pranita D., Goodman, Katherine E., Harris, Anthony D., Tekle, Tsigereda, Roberts, Ava, Taiwo, Abimbola, Simner, Patricia J.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.02.2017
• Subjects: Adult; Aged; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; ARTICLES AND COMMENTARIES; Bacteremia - blood; Bacteremia - drug therapy; Bacteremia - mortality; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; beta-Lactam Resistance; beta-Lactamases - genetics; beta-Lactamases - metabolism; Carbapenems - pharmacology; Carbapenems - therapeutic use; Clinical outcomes; Cohort Studies; Comparative analysis; CRE bacteria; Deoxyribonucleic acid; DNA; DNA, Bacterial - genetics; DNA, Bacterial - isolation & purification; Enterobacteriaceae; Enterobacteriaceae - drug effects; Enterobacteriaceae - enzymology; Enterobacteriaceae - pathogenicity; Enterobacteriaceae Infections - blood; Enterobacteriaceae Infections - drug therapy; Enterobacteriaceae Infections - mortality; Female; Genes; Humans; Major; Male; Meropenem; Middle Aged; Mortality; Retrospective Studies; Thienamycins - pharmacology; Thienamycins - therapeutic use; Treatment Outcome; klebsiella pneumoniae carbapenemase; carbapenemases; multidrug-resistant gram-negative; CRE
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciw741

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). Conclusion. 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.