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Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis.

ABSTRACT: OBJECTIVES:Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals. METHODS:We performed a systematic review, network meta-analysis and cost analysis to compare the newer glycopeptides to standard care and to each other for the treatment of complicated SSTIs (cSSTI). A search for randomized controlled trials (RCTs) was conducted in Medline, Embase and the Cochrane Central Register of Controlled Trials. We also developed a model to evaluate the costs associated with dalbavancin and oritavancin from the third-party payer perspective. RESULTS:Seven RCTs met the inclusion criteria. Network meta-analyses suggested that the clinical response to telavancin, dalbavancin and oritavancin was similar to standard care (odds ratio (OR) 1.09, 95% confidence interval (CI) 0.90-1.33; OR 0.78, 95% CI 0.52-1.18; and OR 1.06, 95% CI 0.85-1.33, respectively). Head-to-head comparisons showed no difference in clinical response between oritavancin and dalbavancin (OR 1.36; 95% CI 0.85-2.18), oritavancin and telavancin (OR 0.98; 95% CI 0.72-1.31) or dalbavancin and telavancin (OR 0.72; 95% CI 0.45-1.13). Telavancin had a higher incidence of overall adverse events compared to standard care (OR 1.33; 95% CI 1.10-1.61). Compared to telavancin, there were fewer overall adverse events with dalbavancin (OR 0.58; 95% CI 0.45-0.76) and oritavancin (OR 0.71; 95% CI 0.55-0.92). Studies were of high quality overall. Our cost analyses demonstrated that dalbavancin and oritavancin were less costly compared to standard care under baseline assumptions and many scenarios evaluated. The use of dalbavancin could save third-party payers $1442 to $4803 per cSSTI, while the use of oritavancin could save $3571 to $6932 per cSSTI. CONCLUSIONS:Dalbavancin and oritavancin demonstrate efficacy and safety comparable to standard care in well-designed RCTs and result in cost savings when standard care is treatment that covers MRSA.

SUBMITTER: Agarwal R

PROVIDER: S-EPMC5925741 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis.

Agarwal R R Bartsch S M SM Kelly B J BJ Prewitt M M Liu Y Y Chen Y Y Umscheid C A CA

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases 20170904 4

<h4>Objectives</h4>Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Several new MRSA-active antibiotics have been developed, including semisynthetic glycopeptides (telavancin, dalbavancin and oritavancin). Of these, dalbavancin and oritavancin offer extended dosing intervals.<h4>Methods</h4>We performed a systematic review, network meta-analysis and cost ana ...[more]

PMID: 28882727

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Project description:IntroductionMeticillin-resistant staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant infections worldwide. Its prevalence remains high in the Greek hospital setting. Complicated skin and soft tissue infections (cSSTIs) due to MRSA are associated with prolonged hospitalization, additional healthcare costs and significant morbidity. The purpose of this study was to conduct a cost analysis and a budget impact analysis relative to different management scenarios for MRSA-cSSTIs from a hospital perspective.MethodsEqual efficacy was assumed for the pharmacotherapies under evaluation and resource use was elicited via an expert panel of seven local infectious disease specialists. The model was based on a previously published economic model that was adapted for the Greek hospital setting and included a decision tree for the management of hospitalized patients with MRSA-cSSTIs, which simulated costs and outcomes for the duration of hospitalization according to the therapeutic scenario. Inpatient costs consisted of hospitalization, diagnostic/laboratory testing, physician visits and antibiotic treatment.ResultsCurrent economic impact of MRSA-cSSTIs for the inpatient setting in Greek hospitals was estimated at €29,196,218. Total per patient cost according to first-line agent was €2,457, €2,762, €2,850, €3,494 and €3,094 and mean length of stay was 9.2, 12.5, 10.3, 13.0 and 14.0 days for linezolid, vancomycin, daptomycin, tigecycline, and teicoplanin, respectively. An estimated 10,287 MRSA-cSSTI patients are treated annually in Greek hospitals. Thus, increasing the use of linezolid by 11% over a 3-year period (current use 19%; 3 year projection 30%), for the management of MRSA-cSSTIs, could result in 3-year savings of €896,065.ConclusionManagement of MRSA-cSSTI requires intensive resource use; overall healthcare costs differ according to the chosen first-line treatment. In light of considerable budget constraints, development of hospital strategies which facilitate early discharge, such as the introduction of clinical criteria and guidelines for switching from intravenous to oral MRSA-cSSTI therapy, could result in substantial savings for the Greek hospital budget.

Project description:BackgroundThe treatment of complicated skin and soft tissue infections (cSSTI) is challenging and many patients do not receive adequate first-line therapy. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe cSSTI or Community-Acquired Pneumonia in the Hospital Setting) was a retrospective observational study of cSSTI patients in real-life settings in European hospitals. In this analysis, we review characteristics and outcomes of patients with an early response (≤72 hours) compared with those without an early response to treatment. We also compare the results according to two differing definitions of early response, one of which (Definition 1) requires resolution of fever within 72 hours, in line with previous US FDA guidelines.MethodsPatients were adults hospitalized with cSSTIs 2010-2011 and requiring treatment with intravenous antibiotics. Clinical management, clinical outcomes and healthcare resource use were assessed using a descriptive analysis approach.ResultsThe analysis set included 600 patients, of which 363 showed early response with Definition 1 and 417 with Definition 2. Initial treatment modification was frequent, and highest in patients without early response (48.1% with Definition 1). Patients without early response were more likely to have diabetes than those with early response (31.6% vs. 22.9%, respectively) and to suffer from more severe disease (e.g. skin necrosis: 14.8% and 7.7%, respectively), to be infected with difficult-to-treat microorganisms and to have recurrent infections. Furthermore, patients without early response had a higher rate of adverse clinical outcomes (e.g. septic shock) and higher use of healthcare resources. The results obtained with the two definitions for early response were largely similar.ConclusionsThis study highlights the significance of early evaluation of patients in hospitals, in potentially preventing prolonged use of inappropriate or ineffective antibacterial therapy.Trial registrationNCT01293435 .

Project description:ObjectiveDaptomycin, a cyclic lipopeptide that exhibits rapid, concentration-dependent bactericidal activity in vitro against a broad spectrum of Gram-positive pathogens, has now, since 2003, been approved in more than 70 countries and regions to treat skin and soft-tissue infections (SSTIs). The purpose of this meta-analysis was to compare the safety and efficacy of daptomycin with other antibiotics, especially with vancomycin which has long been considered the standard therapy for complicated SSTIs.DesignMeta-analysis of randomised controlled trials (RCTs).Data sourcesWe thoroughly searched PubMed, EMBASE, Cochrane Central to identify relevant RCTs. Six RCTs with a total of 1710 patients were included in this meta-analysis.ResultsThe results demonstrated that the efficacy of daptomycin was at par with or maybe better than other first-line antibiotics for treating SSTIs as shown by the OR for clinical success (OR=1.05, 95% CI 0.84 to 1.31, p=0.65, I(2)=0%); daptomycin versus vancomycin subgroup (OR=1.19, 95% CI 0.77 to 1.83, p=0.43, I(2)=0%); overall microbiological success (OR=1.05, 95% CI 0.61 to 1.79, p=0.86, I(2)=42%); microbiological success of daptomycin versus comparators for Staphylococcus aureus (SA, OR=1.05, 95% CI 0.61 to 2.60, p=0.53, I(2)=47%), for methicillin-resistant S. aureus (OR=0.90, 95% CI 0.77 to 1.06, p=0.20, I(2)=56%). However, daptomycin tended to have a similar treatment-related adverse events (AEs) incidence in comparison with other antibiotics (OR=1.06, 95% CI 0.71 to 1.59, p=0.76, I(2)=41%). The trend showed that daptomycin might cause less discontinuation due to AEs and death compared with other first-line antibiotics (OR=0.71, 95% CI 0.46 to 1.10, p=0.12, I(2)=11%). Significantly more patients in the daptomyicn group had creatine phosphokinase elevation than those in the control group; however, it could be reversed when the therapy ended (OR=1.95, 95% CI 1.04 to 3.65, p=0.04, I(2)=0).ConclusionsThis meta-analysis demonstrated that the safety and efficacy of daptomycin was not inferior to that of other first-line drugs, and daptomycin tended to exhibit superior efficacy when compared with vancomycin or with comparators for SA infections; nevertheless, more high-quality RCTs are needed to draw a more credible conclusion.

Dataset Information

Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis.

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Newer glycopeptide antibiotics for treatment of complicated skin and soft tissue infections: systematic review, network meta-analysis and cost analysis.

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