Survival of Patients With Vancomycin-Resistant Enterococcus faecium Bacteremia Treated With Conventional or High Doses of Daptomycin or Linezolid Is Associated With the Rate of Bacterial Clearance

Abstract

OBJECTIVES:\r\nVancomycin-resistant enterococci are important pathogens for healthcare-associated infections. Although linezolid is bacteriostatic and daptomycin is rapidly bactericidal against vancomycin-resistant enterococci in vitro, it is not clear whether they differ in their effect on bacterial clearance in patients with vancomycin-resistant enterococci bloodstream infections.\r\n\r\nDESIGN:\r\nProspective observational study.\r\n\r\nSETTING:\r\nTwo university hospitals and research laboratory.\r\n\r\nPATIENTS:\r\nPatients with vancomycin-resistant enterococci bloodstream infection proven by blood cultures were prospectively enrolled from January 2010 to July 2015.\r\n\r\nINTERVENTIONS:\r\nSequential blood samples were collected. Real-time quantitative polymerase chain reaction was used to monitor bacterial loads.\r\n\r\nMEASUREMENTS AND MAIN RESULTS:\r\nOne hundred eight patients with vancomycin-resistant enterococci bloodstream infection were enrolled. Quantitative polymerase chain reaction assays were performed on 465 blood isolates. We found this method to be closely correlated with colony-forming units and more sensitive than culture. Sixty-three patients (58.3%) received \"conventional dose\" daptomycin (6-9 mg/kg), 15 (13.9%) received high-dose daptomycin (≥ 9 mg/kg), and 30 (27.8%) were treated with linezolid (600 mg every 12 hr) as sole agents. The initial mean bacterial load was 1.03 log10 copies/mL and unrelated to survival. Survivors had a more rapid early bacterial clearance than nonsurvivors (Δ log10 copies/mL/d; -0.16 vs 0.31; p = 0.02). Multivariable logistic regression showed that a slower early bacterial clearance independently predicted increased mortality (odds ratio, 3.21; 95% CI, 1.03-10.02; p = 0.045). Conventional dose daptomycin was associated with a significantly slower rate of bacterial clearance than high-dose daptomycin (Δ log10 copies/mL/d; -0.04 vs -0.41; p < 0.001) and linezolid (-0.04 vs -0.56; p = 0.043).\r\n\r\nCONCLUSIONS:\r\nWe found that survivors of vancomycin-resistant enterococci bloodstream infection had a significantly more rapid early bacterial clearance by quantitative polymerase chain reaction than nonsurvivors. High-dose daptomycin and linezolid were associated with more rapid bacterial clearance than conventional dose daptomycin. These results support recommendations that conventional dose daptomycin not be used for the treatment of patients with vancomycin-resistant enterococci bloodstream infection.