Infectious Diseases Society of America, Incorporated

Background Skin and soft tissue infections (SSTIs) are significant indications for antibiotic treatment. Daptomycin, a novel antibiotic, has been registered and licensed to be used in the treatment of these infections. However, its efficacy and safety remain controversial. Objective The objective of this study was to conduct a systematic review with trial sequential analysis (TSA) to evaluate the efficacy and safety of daptomycin for the treatment of SSTIs and to analyze whether the available sample size has been large enough and is conclusive. Methods PubMed, the Cochrane Library, and EMBASE were searched for published randomized controlled trials (RCTs) that compared daptomycin with other antibiotics in adult patients with SSTIs up to February 2016. Results This meta-analysis included eight randomized controlled trials (n=2,002). There was no difference in either the clinical success rate (intention-to-treat population: relative risk [RR] =1.04, 95% confidence interval [CI] =0.99-1.10, P=0.12; clinically evaluable population: RR =1.00, 95% CI =0.97-1.04, P=0.82) or the microbiological success rate (RR =1.00, 95% CI =0.95-1.06, P=0.92) between the daptomycin and comparator groups for treating SSTIs, which was confirmed by TSA. Compared with vancomycin, daptomycin exhibited no advantage in increasing the clinical success rate (RR =1.03, 95% CI =0.95-1.13, P=0.47), and this was also confirmed by TSA. All-cause mortality, overall treatment-related adverse events, and creatine phosphokinase events were similar between these two groups. Conclusion Daptomycin and comparator drugs are equally efficacious with regard to clinical and microbiological success for patients with SSTIs, and TSA showed that no additional randomized controlled trials are required. Although daptomycin is a good alternative when other antibiotics are contraindicated for patients with SSTIs and it can serve as a first-line treatment for SSTIs, clinicians should be aware of potential adverse events, such as daptomycin-induced acute eosinophilic pneumonia and creatine phosphokinase, when treating patients with daptomycin.

/pdf/efficacy-and-safety-of-daptomycin-for-skin-and-soft-tissue-1rbaglifsv.pdf

Efficacy and safety of daptomycin for skin and soft tissue infections: a systematic review with trial sequential analysis.

Skin and soft structure infections (SSTIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) pose serious health risks and cause significant cost burdens, and a conclusive recommendation about antibiotics has not yet been generated. Therefore, we performed this updated network meta-analysis to determine the preferred drug for the treatment of MRSA-caused SSTIs. We searched PubMed, Embase, and Cochrane Library to identify any potentially eligible randomized controlled trials (RCTs) investigating the comparative efficacy and safety of any two of vancomycin, linezolid, tedizolid, and daptomycin in MRSA-caused SSTIs. All statistical analyses were conducted with RevMan, ADDIS, and STATA software. Twenty eligible RCTs involving 7804 patients were included for the final analysis. Direct meta-analysis suggested that linezolid was superior to vancomycin in improving clinical (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.07–1.99; P = 0.02) and microbiological (OR, 1.89; 95% CI, 1.24–2.86; P = 0.003) success, which were all confirmed by network meta-analyses. No statistical differences were identified regarding other comparisons. Meanwhile, there were no significant differences between any two antibiotics related to safety. Moreover, ranking probabilities indicated that linezolid had the highest probability of being ranked best in terms of clinical and microbiological success. Based on the limited evidence, linezolid may be a preferred antibiotic for the treatment of MRSA-caused SSTIs because it showed superiority in clinical and microbiological success without difference regarding safety.

/pdf/comparative-efficacy-and-safety-of-vancomycin-linezolid-8fytmuf57r.pdf

Comparative Efficacy and Safety of Vancomycin, Linezolid, Tedizolid, and Daptomycin in Treating Patients with Suspected or Proven Complicated Skin and Soft Tissue Infections: An Updated Network Meta-Analysis

Objective:The objective was to conduct a systematic review and network meta-analysis (NMA) of existing treatments for ABSSSI focusing on the novel lipoglycopeptide oritavancin.Methods:EMBASE, MEDLINE, MEDLINE in Process, CENTRAL (Cochrane), and select conferences were searched for randomized controlled trials investigating antimicrobial agents for the treatment of ABSSSI. NMA was used to estimate the odds ratios of the Test-Of-Cure (TOC) and Early Clinical Response (ECR) outcomes for treatments relative to vancomycin in the ITT populations. Sub-group analyses in MRSA and MSSA populations were conducted for TOC; sensitivity analyses investigated the use of the clinically evaluable (CE) populations and the restriction to trials following the recent FDA guidelines for clinical trials.Results:The systematic review identified 52 trials. The most commonly investigated treatments were vancomycin and linezolid; most trials reported TOC, but not ECR. The posterior mean and 95% credible intervals for odds r...

Comparative efficacy of antibiotics for the treatment of acute bacterial skin and skin structure infections (ABSSSI): a systematic review and network meta-analysis.

Objectives A systematic review and meta-analysis based on randomized controlled trials (RCTs) of the efficacy and safety of daptomycin versus comparators. Methods Electronic databases (PubMed, Embase, Cochrane Central Register of Controlled Trials and clinical registered trials) were searched to identify RCTs that assessed the efficacy and safety of daptomycin versus therapy with comparators. Two reviewers independently applied selection criteria, performed a quality assessment and extracted the data. The I(2) statistic was calculated for heterogeneity, and a random-effects or fixed-effects model was used for estimates of risk ratio (RR). The primary outcome assessed was clinical treatment success among the intention-to-treat (ITT) population. Results Thirteen trials fulfilled the inclusion criteria. Daptomycin was as efficacious as comparator regimens among the ITT population (RR = 0.98, 95% CI 0.93-1.03) but had a lower efficacy among the clinically evaluable (CE) population (RR = 0.96, 95% CI 0.93-1.00). Subgroup analyses according to the quality of the trial, the type of antibiotic and the type of infection did not alter the outcomes. No significant difference was identified for all-cause mortality between the daptomycin and comparator groups (RR = 1.17, 95% CI 0.76-1.79) but daptomycin therapy did reduce the duration of treatment. Daptomycin caused a significantly lower incidence of renal impairment, nausea and headache but caused a reversible increase in creatine phosphokinase (CPK). Subgroup analysis indicated that daptomycin was significantly associated with a higher incidence of CPK elevation and fewer renal impairments among the population with a mean age ≤60 years and a dose of daptomycin ≥6 mg/kg/24 h. Conclusions Daptomycin showed efficacy similar to the comparator regimens among the ITT population but lower efficacy among the CE population. Fewer adverse effects in total, but more CPK elevation effects, were observed in patients treated with daptomycin.

Efficacy and safety of daptomycin for the treatment of infectious disease: a meta-analysis based on randomized controlled trials

This is a prospective controlled, single blinded, randomized study comparing the efficacy and side effects of daptomycin and telavancin in patients with lower extremity skin and soft tissue infections (SSTI). Forty patients were enrolled with similar SSTI of the lower extremities and received either daptomycin or telavancin. Clinical cure was determined by resolution of their cellulitis. There did not appear to be any significant difference in clinical outcomes, rapidity of improvement, adverse events nor relapse rates. The duration of treatment was shorter in the telavancin arm than in the daptomycin arm of the study.

/pdf/pilot-study-comparing-daptomycin-and-telavancin-in-the-2ng36t0zod.pdf

Pilot Study Comparing Daptomycin And Telavancin In The Treatment Of Skin And Soft Tissue Infections

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Pilot Study Comparing Daptomycin And Telavancin In The Treatment Of Skin And Soft Tissue Infections