Daptomycin for the treatment of vancomycin-resistant enterococcal bloodstream infection

• Main Authors: Yu-Chung Chuang, 莊祐中
• Other Authors: 張上淳
• Format: Others
• Language: en_US
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/8u9dvn

博士 === 國立臺灣大學 === 臨床醫學研究所 === 106 === Linezolid, which has bacteriostatic activity, is approved for the treatment of vancomycin-resistant enterococci (VRE) infections. Daptomycin exerts bactericidal activity against VRE, but is not approved for the treatment of VRE bloodstream infection (BSI). We hypothesize that daptomycin can be used as an effective antimicrobial agent for the treatment of VRE-BSI, and that daptomycin dose and beta-lactam combination therapy may affect the outcome of daptomycin treated VRE-BSI. We therefore performed a systematic review and meta-analysis followed by a prospective observational cohort study in 2010–2015. PubMed, EMBASE, and the Cochrane Library were searched for studies on the treatment of VRE-BSI published prior to January 1, 2014. Thirteen studies (532 patients receiving daptomycin, 656 patients receiving linezolid) met the selection criteria. Mortality was higher in patients receiving daptomycin treatment (odds ratio [OR], 1.43; 95% confidence interval [CI], 1.09–1.86; P=.009). Subgroup analysis of eight studies that reported adjusted odds ratios (aORs) indicated that daptomycin treatment was associated with a higher mortality rate (OR, 1.59; 95% CI, 1.02–2.50; P=.04). We included 112 patients treated with daptomycin for VRE-BSI, with evaluable clinical outcomes. The best outcomes were associated with a daptomycin dose of ≥9 mg/kg compared with doses of <7 mg/kg (aOR, 10.57; 95% CI, 2.25–49.62; P=.003) and 7–9 mg/kg (aOR, 5.01; 95% CI, 1.14–21.98; P=.03). We included 212 patients treated with daptomycin or linezolid for VRE-BSI (daptomycin, n=141; linezolid, n=71). Logistic regression showed that linezolid (aOR, 0.36; 95% CI, 0.17–0.79; P=.01) and high-dose daptomycin (≥9 mg/kg) (aOR, 0.26; 95% CI, 0.09–0.74; P=.01) independently predicted lower mortality compared with low-dose daptomycin (6–9 mg/kg). Linezolid was not superior to high-dose daptomycin in terms of mortality (aOR, 1.40; 95% CI, 0.45–4.37; P=.57). We included 114 patients who received daptomycin for VRE-BSI to evaluate the effect of beta-lactam antibiotic (BLA) combinations. Of these, 87 (76.3%) received daptomycin+BLA. Patients receiving high-dose daptomycin+BLA independently had better survival than those receiving low-dose daptomycin alone (adjusted hazard ratio [aHR]=5.16), low-dose daptomycin+BLA (aHR=5.39), and high-dose daptomycin alone (aHR=19.01) (P<.05 for all comparisons). We included 108 patients with VRE-BSI for real-time quantitative polymerase chain reaction analysis of in vivo bacterial load. Slower early bacterial clearance (aOR, 3.21; 95% CI, 1.03–10.02; P=.045) independently predicted mortality. Compared with the bacterial clearance of low-dose daptomycin, linezolid and high-dose daptomycin produced rapid bacterial clearance (log10 copies/mL/day; −0.04 vs. −0.41; P<.001, and −0.04 vs. −0.56; P = .043; respectively). The current meta-analysis shows that linezolid treatment for VRE-BSI was associated with a lower mortality than daptomycin treatment. This result should be interpreted cautiously, however, because of limitations inherent to retrospective studies of small sample size and the high heterogeneity among the studies. High-dose daptomycin (≥9 mg/kg) was associated with lower mortality in patients with VRE-BSI. Despite having a lower mortality compared with low-dose daptomycin, linezolid conferred no survival benefit compared with high-dose daptomycin. High-dose daptomycin and BLA combination therapy might improve survival. High-dose-daptomycin and linezolid use were associated with rapid bacterial clearance compared with low-dose daptomycin. Our results thus suggest that high-dose daptomycin and BLA combination therapy might be an appropriate regimen for the treatment of VRE-BSI.