Comparative efficacy of delafloxacin for complicated and acute bacterial skin and skin structure infections: results from a network meta-analysis

Abstract

Background Delafloxacin is a novel fluoroquinolone with broad antibacterial activity against pathogens causing acute bacterial skin and skin structure infections (ABSSSI). This network meta-analysis (NMA) was conducted to evaluate the relative efficacy of delafloxacin versus other comparators used for managing patients with ABSSSI. Methods A systematic literature review was conducted to identify randomised controlled trials (RCTs) evaluating adults (≥ 18 years) with ABSSSI, complicated SSSI (cSSSI), complicated skin and soft tissue infections (cSSTI) or severe cellulitis with pathogen of gram-positive, gram-negative, or mixed aetiology. OVID MEDLINE®, Embase, Epub Ahead of Print, Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews were searched from inception through 12 April 2019. A feasibility assessment was conducted, followed by an NMA, which was run in a Bayesian framework. The interventions included in the NMA encompassed monotherapy or combination therapies of amoxicillin/clavulanate, ampicillin/sulbactam, ceftaroline, ceftobiprole, dalbavancin, daptomycin, delafloxacin, fusidic acid, iclaprim, linezolid, omadacycline, oxacillin + dicloxacillin, standard therapy, tedizolid, telavancin, tigecycline, vancomycin, vancomycin + aztreonam and vancomycin + linezolid. Results A feasibility assessment was performed and evidence networks were established for composite clinical response (n = 34 studies), early clinical response (n = 16 studies) and microbiological response (n = 14 studies) in the overall study population, composite clinical response (n = 4 studies) in obese subpopulation and for composite clinical response (n = 18 studies) and microbiological response (n = 14 studies) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infection. Delafloxacin performed significantly better than fusidic acid, iclaprim, vancomycin, and ceftobiprole for composite clinical response. Delafloxacin was comparable to dalbavancin, daptomycin, fusidic acid, iclaprim, linezolid, omadacycline, tedizolid, vancomycin, vancomycin + aztreonam and vancomycin + linezolid in the analysis of early clinical response, whereas for microbiological response, delafloxacin was comparable to all interventions. In the obese subpopulation, the results favoured delafloxacin in comparison to vancomycin, whilst the results were comparable with other interventions among the MRSA subpopulation. Conclusions Delafloxacin is a promising new antibiotic for ABSSSI demonstrating greater improvement (composite clinical response) compared to ceftobiprole, fusidic acid, iclaprim, telavancin and vancomycin and comparable effectiveness versus standard of care for all outcomes considered in the study.

Ceftaroline Fosamil for the Empiric Treatment of Hospitalized Adults with cSSTI: An Economic Analysis from the Perspective of the Spanish National Health System

“…The risk ratios derived from Vlachaki et al 36 are relatively comparable with the current analysis inputs for CFT vs vancomycin (1.00 vs 1.00), linezolid (0.94 vs 1.04), daptomycin (0.94 vs 1.00) and tedizolid (1.05 vs 1.04). Similarly to McCool et al 35 comparison, it is important to highlight that using Vlachaki et al 36 estimates would have resulted in a more favorable analysis for CFT vs linezolid and vancomycin.…”

“…30 Two alternative NMA studies available in the literature were not used, for the clinical cure rate inputs, either because only considering CFT Phase 2 trial in the network of evidence 35 or because the study was not available at the time of this analysis. 36 Nevertheless, a comparison with the current analysis inputs ( Table 1 ) and the two alternative NMAs identified is provided. McCool et al 35 odds ratios of each comparator considered vs tedizolid for clinical response at test-of-cure were extracted (from Table 2 of the publication) and converted in risk ratios vs CFT using tedizolid clinical cure rate of 87% as anchor (same cure rate for tedizolid as in the current analysis – see Table 1 ).…”

“…However, it is important to highlight that using McCool et al 35 estimates would have resulted in a more favorable analysis for CFT vs vancomycin, linezolid and daptomycin, with only tedizolid risk ratio being lower (1.00) than what used in the current analysis (1.05). A similar comparison was performed based on Vlachaki et al 2021 NMA results, 36 with the odds ratios of each comparator vs delafloxacin for composite clinical response extracted (from Figure 3 of the publication) and converted in risk ratios vs CFT using delafloxacin clinical cure rate of 87.2% as anchor (from delafloxacin Phase III trial 37 ). The risk ratios derived from Vlachaki et al 36 are relatively comparable with the current analysis inputs for CFT vs vancomycin (1.00 vs 1.00), linezolid (0.94 vs 1.04), daptomycin (0.94 vs 1.00) and tedizolid (1.05 vs 1.04).…”

“…A similar comparison was performed based on Vlachaki et al 2021 NMA results, 36 with the odds ratios of each comparator vs delafloxacin for composite clinical response extracted (from Figure 3 of the publication) and converted in risk ratios vs CFT using delafloxacin clinical cure rate of 87.2% as anchor (from delafloxacin Phase III trial 37 ). The risk ratios derived from Vlachaki et al 36 are relatively comparable with the current analysis inputs for CFT vs vancomycin (1.00 vs 1.00), linezolid (0.94 vs 1.04), daptomycin (0.94 vs 1.00) and tedizolid (1.05 vs 1.04). Similarly to McCool et al 35 comparison, it is important to highlight that using Vlachaki et al 36 estimates would have resulted in a more favorable analysis for CFT vs linezolid and vancomycin.…”

“…The statistical distributions used for sensitivity analysis are summarized in Tables 1 and 2 , with the beta distribution used for probabilities, and relative risks assumed to be log-normally distributed. 36 The hospitalization and treatment monitoring costs were varied in DSA by ±25%.…”