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 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 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, CI 0.52-1.18; and OR 1.06, CI 0.85-1.33, respectively). Head-to-head comparisons showed no difference in clinical response between oritavancin and dalbavancin (OR 1.36; CI 0.85-2.18), oritavancin and telavancin (OR 0.98; CI 0.72-1.31) or dalbavancin and telavancin (OR 0.72; CI 0.45-1.13). Telavancin had a higher incidence of overall adverse events compared to standard care (OR 1.33; CI 1.10-1.61). Compared to telavancin, there were fewer overall adverse events with dalbavancin (OR 0.58; CI 0.45-0.76) and oritavancin (OR 0.71; 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 $1,442 to $4,803 per cSSTI, while the use of oritavancin could save $3,571 to $6,932 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.

New Molecular Tools for Regulation and Improvement of A40926 Glycopeptide Antibiotic Production in Nonomuraea gerenzanensis ATCC 39727

“…In conclusion, only a few GPAs are used in clinical practice and those produced by semi-synthesis from natural products, such as dalbavancin derived from A40926, are still quite expensive. Dalbavancin is the first antibiotic designated as a Qualified Infection Diseases Product by the FDA because of its potency, extended dosing interval, and unique dose regimen, but its cost largely exceeds that of first-generation GPAs and consequently its use in hospitals is still limited (Chiasson and White, 2016;Agarwal et al, 2018). Improving A40926-producing strains might lead to a decrease in the cost of dalbavancin.…”

Do Patients with Cellulitis Need to be Hospitalized? A Systematic Review and Meta-analysis of Mortality Rates of Inpatients with Cellulitis

“…30 Lastly, several antibiotics are now available for SSTI that have long half-lives allowing onceweekly outpatient administration. [31][32][33] Another significance of the low pooled mortality rate for cellulitis relates to antibiotic stewardship. Current guidelines recommend relatively narrow spectrum antibiotics for most patients with cellulitis, targeting the most common organisms which are β-hemolytic streptococci and methicillinsusceptible Staphylococcus aureus.…”

Network meta-analysis and pharmacoeconomic evaluation of antibiotics for the treatment of patients infected with complicated skin and soft structure infection and hospital-acquired or ventilator-associated penumonia

“…Linezolid, daptomycin, tigecycline, new glycopeptides such as telavancin and ceftaroline have been approved to treat MRSA infections. While meta-analyses [12–15] which have compared the efficacy and safety of vancomycin with linezolid or other antibiotics has been published; the results of these studies are not consistent and definitive conclusions cannot be drawn.…”