Emergence of Vancomycin Resistance after Treatment of Enterococcus: Risk Factors for Subsequent Pathogen Resistance

Background: Vancomycin-resistant Enterococcus (VRE) is a leading cause of nosocomial infections that carries an increased risk of mortality when compared to vancomycin-sensitive Enterococcus (VSE). Data on the frequency of conversion between VSE and VRE in patients are scarce. Among patients presenting with VSE infections, little is known about the subsequent risk of conversion to VRE in the initial treatment period. Methods: A descriptive analysis of VSE to VRE conversion and a retrospective case-control study were performed examining cases of VSE that had subsequent cultures positive for VRE within 90 days within a quaternary healthcare system. Cases were obtained from June 2013 through December 2018. Controls were patients who had VSE culture followed by another VSE culture and were matched by organism (E. faecalis or E. faecium), time between cultures, and initial culture site. Age, gender, healthcare, antibiotic, Clostridiodes difficile, proton pump inhibitor (PPI) exposure, and H2 blocker exposures, and prior VRE infection or colonization were abstracted from the electronic medical record. A univariate analysis with the Fisher exact test was performed with significance considered for P < .05. Results: In total, 8,913 cases of E. faecalis and 2,322 cases of E. faecium were included in the study. Of 8,913 cases of E. faecalis, 51 of 8,503 (0.6%) cultured VRE after VSE, and 47 of 403 (11.7%) cultured VSE after initial VRE. Of E. faecium, 51 of 783 (6.5%) cultured VRE after VSE, and 76 of 1,532 (5.0%) cultured VSE after initial VRE. In total, 76 cases were matched with 99 controls. Patients converting from VSE to VRE were more likely to have prior admission to an intensive care unit (P = .0207), prior positive swab or culture for VRE (P = .0114), previous C. difficile infection (P = .0155), prior vancomycin (P = .0022) and cefepime (P = .0089) exposure. Patients receiving vancomycin after initial VSE culture were more likely to have subsequent cultures positive for VRE (P = .0053). There was no difference in age (P = .966) or male sex (P = .7588). Conclusions: Conversion from VSE to VRE is common, and E. faecium is more likely to become resistant than E. faecalis. Reversion to a vancomycin-sensitive phenotype is also common, and E. faecalis is more likely to show subsequent sensitivity than E. faecium. Previous admission to an intensive care unit, prior colonization or infection with VRE, prior C. difficile infection, and exposure to vancomycin and cefepime are risk factors for emergence of VRE after treatment for vancomycin-sensitive Enterococcus. Funding: None Disclosures: None