title: Effect of Continuous and Sequential Therapy among Veterans Receiving Daptomycin or Linezolid for Vancomycin-Resistant Enterococcus faecium Bacteremia.
abstract: Vancomycin-resistantEnterococcus faeciumbloodstream infections (VREF-BSI) cause significant mortality, highlighting the need to optimize their treatment. We compared the effectiveness and safety of daptomycin (DAP) and linezolid (LZD) as continuous or sequential therapy for VREF-BSI in a national, retrospective, propensity score (PS)-matched cohort study of hospitalized Veterans Affairs patients (2004 to 2014). We compared clinical outcomes and adverse events among patients treated with continuous LZD, continuous DAP, or sequential LZD followed by DAP (LZD-to-DAP). Secondarily, we analyzed the impact of infectious diseases (ID) consultation and source of VREF-BSI. A total of 2,630 patients were included in the effectiveness analysis (LZD [n= 1,348], DAP [n= 1,055], LZD-to-DAP [n= 227]). LZD was associated with increased 30-day mortality versus DAP (risk ratio [RR], 1.11; 95% confidence interval [CI], 1.01 to 1.22;P= 0.042). After PS matching, this relationship persisted (RR, 1.13; 95% CI, 1.02 to 1.26;P= 0.015). LZD-to-DAP switchers had lower mortality than those remaining on LZD (RR, 1.29; 95% CI, 1.03 to 1.63;P= 0.021), suggesting a benefit may still be derived with sequential therapy. LZD-treated patients experienced more adverse events, including a ≥50% reduction in platelets (RR, 1.07; 95% CI, 1.03 to 1.11;P= 0.001). DAP was associated with lower mortality than was LZD in patients with endocarditis (RR, 1.20; 95% CI, 1.02 to 1.41;P= 0.024); however, there was no statistically significant association between treatment group and mortality with regard to other sources of infection. Therefore, source of infection appears to be important in selection of patients most likely to benefit from DAP over LZD.
authors.affiliation: Department of Pharmacy, Barnes-Jewish Hospital, St. Louis, Missouri, USA nicholas.britt@bjc.org.|Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Britt
authors.affiliation: Pharmacy Service, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.
authors.forename: Emily M
authors.initials: EM
authors.lastname: Potter
authors.affiliation: Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York, USA.
authors.forename: Nimish
authors.initials: N
authors.lastname: Patel
authors.affiliation: Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, Kansas, USA.|Department of Pharmacy Practice, University of Kansas School of Pharmacy, Lawrence, Kansas, USA.
authors.forename: Molly E
authors.initials: ME
authors.lastname: Steed
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy*; D017576:Daptomycin / Q000009:adverse effects / Q000627:therapeutic use*; D016984:Enterococcus faecium / Q000187:drug effects*; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D000069349:Linezolid / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D012189:Retrospective Studies; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology; D065507:Vancomycin-Resistant Enterococci / Q000187:drug effects*; D014728:Veterans
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin; D000069349:Linezolid; D017576:Daptomycin
keywords: Enterococcus; antimicrobial resistance; bloodstream infection; daptomycin; linezolid; transplant infectious diseases; vancomycin resistance