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Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia.

ABSTRACT: Limited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteremia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis of the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteremia, published until August 2012, were identified from the MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and SCOPUS databases. All comparative studies on patients older than 18 years of age that provided mortality data were considered eligible for this systematic review and meta-analysis. ?he primary outcome of the meta-analysis was 30-day all-cause mortality. Ten retrospective studies including 967 patients were identified. Patients treated with daptomycin had significantly higher 30-day all-cause mortality (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.08 to 2.40) and infection-related mortality (OR, 3.61; 95% CI, 1.42 to 9.20) rates than patients treated with linezolid. When data from all 10 studies were combined, overall mortality was also significantly increased among patients treated with daptomycin (OR, 1.41; 95% CI, 1.06 to 1.89). These findings were confirmed when odds ratios adjusted for potential confounders were pooled. Relapse rates among patients treated with daptomycin were also higher (OR, 2.51; 95% CI, 0.94 to 6.72), although this difference did not reach statistical significance. Adverse event rates were not significantly different between the two groups. Notwithstanding the absence of randomized prospective data, available evidence suggests that mortality rates may be higher with daptomycin than with linezolid among patients treated for VRE bacteremia.

SUBMITTER: Balli EP

PROVIDER: S-EPMC3910884 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia.

Balli Eleni P EP Venetis Chris A CA Miyakis Spiros S

Antimicrobial agents and chemotherapy 20131118 2

Limited therapeutic options exist for the treatment of vancomycin-resistant Enterococcus (VRE) bacteremia; the most commonly used are daptomycin and linezolid. We attempted a systematic review and meta-analysis of the comparative efficacy of those two agents. Studies comparing daptomycin to linezolid treatment for VRE bacteremia, published until August 2012, were identified from the MEDLINE, EMBASE, CENTRAL, ISI Web of Science, and SCOPUS databases. All comparative studies on patients older than ...[more]

PMID: 24247127

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Project description:BackgroundLinezolid, which has bacteriostatic activity, is approved for the treatment of vancomycin-resistant enterococci (VRE) infections. Meanwhile, daptomycin exerts bactericidal activity against VRE, but is not approved for the treatment of VRE bacteremia. Only a few studies with small sample sizes have compared the effectiveness of these drugs for treatment of VRE bacteremia.MethodsPubMed, EMBASE, and the Cochrane Library were searched for studies of VRE bacteremia treatment published before January 1, 2014. All studies reporting daptomycin and linezolid treatment outcomes simultaneously were included. The endpoints were mortality and microbiological cure. The adjusted odds ratios (aORs) of mortality in daptomycin- and linezolid-treated patients were extracted if available. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for all outcomes using a random-effects model.ResultsThirteen studies (532 patients receiving daptomycin, 656 patients receiving linezolid) met the selection criteria. All studies had retrospective cohort designs and relatively small sample sizes. Eight studies compared the aORs of mortality in daptomycin- and linezolid-treated patients. Four studies were published as conference papers and there was significant heterogeneity among these studies (I2 = 63%, p = 0.04). Daptomycin use was not associated with better microbiological cure (daptomycin vs. linezolid, OR: 0.67, 95% CI: 0.42-1.06, p = 0.09). However, mortality was higher in patients receiving daptomycin (OR: 1.43, 95% CI: 1.09-1.86, p = 0.009). Subgroup analysis of studies that reported aORs indicated that daptomycin was associated with higher mortality (OR: 1.59, 95% CI: 1.02-2.50, p = 0.04). There was no evidence of publication bias, but all enrolled studies were retrospective, had small sample sizes, and had substantial limitations.ConclusionsAlthough limited data is available, the current meta-analysis shows that linezolid treatment for VRE bacteremia was associated with a lower mortality than daptomycin treatment. However, the results should be interpreted cautiously because of limitations inherent to retrospective studies and the high heterogeneity among studies. A large randomized trial is needed to confirm the present results.

Project description:The genomic evolution in vivo in persistent infection was critical information for understanding how methicillin-resistant Staphylococcus aureus (MRSA) was adapted to host environments with high antibiotic selective pressure. Thirty-two successive MRSA blood isolates with incremental non-susceptibility to vancomycin (VISA), daptomycin (DRSA), and/or linezolid (LRSA) were isolated from a patient failing multiple courses of antimicrobial therapy during 1,356 days of bacteremia. Whole genome sequencing (WGS) for all consecutive isolates were conducted to characterize the evolutionary pathways, resistance-associated mutations and their temporal relationship with antimicrobial treatment. The WGS-based phylogeny categorized the isogenic strains into three major clades, I (22 isolates), II (7 isolates), and III (3 isolates), respectively, harboring a median (range) of 7 (1-30), 62 (53-65), and 118 (100-130) non-synonymous mutations when compared to the very first isolate. Clade I strains were further grouped into early and late subclades, which, respectively, shared the most recent common ancestor with Clade III strains at day 393.7 and Clade II strain at day 662.5. Clade I and Clade III strains were characterized, respectively, with high rates of VISA (9/22, 40.9%) and VISA-and-DRSA phenotype (2/3, 66.7%). Linezolid-resistance including VISA-DRSA-and-LRSA phenotype was exclusively identified in Clade II strains after eight courses of linezolid treatment. The LRSA displayed a small colony variant phenotype and were associated with G2576T mutations in domain V region of 23S rRNA. Substantial loss of mobile elements or alleles mediating resistance or virulence were identified during the evolution of multi-resistance. However, the gene loss might not be correlated to the development of VISA, DRSA, or LRSA phenotype. In conclusion, MRSA in persistent bacteremia was adapted to harsh host environment through multiple pathways involving both resistance-associated mutations and extensive gene loss.

Dataset Information

Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia.

Publications

Systematic review and meta-analysis of linezolid versus daptomycin for treatment of vancomycin-resistant enterococcal bacteremia.

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