465. Comparative Efficacy of Double vs. Single Antibiotic Regimens for the Empiric Treatment of MRSA-Induced Acute Bacterial Skin and Skin Structure Infection

Abstract

BackgroundThe initial management of Acute bacterial skin and skin structure infection (ABSSSI) is burdensome. It requires empirical antibiotic therapy that covers both gram-positive and gram-negative bacteria. Vancomycin plus aztreonam are the most commonly used antibiotic combination, nonetheless, they have many limitations which limits their use. Hence, many new single agents with MRSA and gram-negative coverage, oral options, and/or good safety profile have been developed to be a potential alternative such as: ceftaroline, ceftobiprole, tigecycline and the recent FDA approved antibiotic (delafloxacin). In the absence of head-to-head trials comparing these agents, we decided to conduct a network meta-analysis for these therapeutic regimens.MethodsA Bayesian network meta-analysis of randomized clinical trials identified in PubMed/Medline and Embase databases was conducted. We performed both fixed and random effect models for clinical cure as the primary outcome of interest. Additionally, rankograms were generated using the surface under the cumulative ranking curve (SUCRA) to obtain the treatment ranking probabilities in relation to their relative effect.ResultsWe identified 10 eligible studies involving 4,914 patients. The indirect comparison demonstrated that delafloxacin showed no difference in terms of clinical cure compared with ceftaroline (OR, 0.82, 95% Cr.I 0.39–1.8), ceftobiprole (OR, 0.79, 95% Cr.I 0.32–1.9), SOC (OR, 1.2, 95% Cr.I 0.62–2.4) and tigecycline (OR, 1.0, 95% Cr.I 0.45–2.2) in the fixed effect analysis, nor in the random-effect analysis (OR, 0.8, 95% Cr.I 0.26–2.2; OR, 0.78, 95% Cr.I 0.2–3.0; OR, 1.2, 95% Cr.I 0.51–3.1; and OR, 0.96, 95% Cr.I 0.30–3.0), respectively. Furthermore, the ranking probabilities in the fixed-effect and random-effect analysis showed that ceftaroline was ranked the first in terms of clinical cure (SUCRA, 40.02%) followed by ceftobiprole (SUCRA, 22.80%), delafloxacin (SUCRA, 16.60%), SOC (SUCRA, 13.80%), and then tigecycline (SUCRA, 6.70%).ConclusionCeftaroline, ceftbiprole, delafoxacin, SOC and tigecycline are similarly effective. However, delafloxacin provides better convenience. Further comparative studies regarding their safety are needed. Disclosures All authors: No reported disclosures.

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

“…This NMA included RCTs involving adult patients with ABSSSI, cSSSI, cSSTI or severe cellulitis and comprehensively evaluated the relative clinical efficacy of delafloxacin versus interventions used to treat patients with complicated and ABSSSI. In comparison to previously published NMAs, this NMA included a broader range of infections such as ABSSSI, cSSSIs, cSSTI or severe cellulitis, together with a wider array of interventions [ 32 , 33 ].…”

“…tigecycline, vancomycin, linezolid and vancomycin + aztreonam [ 32 ]. In another NMA which included ten RCTs, the indirect comparison of delafloxacin showed similar efficacy in terms of clinical cure with ceftaroline (OR: 0.82; 95% CrI: 0.39 to 1.8), ceftobiprole (OR: 0.79; 95% CrI: 0.32 to 1.9) and tigecycline (OR: 1.0: 95% CrI: 0.45 to 2.2) [ 33 ]. However, the analysis was restricted to the MRSA ABSSSI population and compared the efficacy of delafloxacin with just ceftaroline, ceftobiprole and tigecycline [ 33 ].…”

“…It evaluated the comparative effectiveness of delafloxacin versus 18 interventions in terms of composite clinical response, early clinical response and microbiological response. This NMA also evaluated the efficacy of delafloxacin with relevant comparators for obese patients, which to our knowledge has not been evaluated in previously published NMAs [ 32 , 33 ]. In the present NMA, an assessment of the risk of bias was undertaken for each identified RCT and the variability across studies was validated by the clinical expert.…”

“…Two previous systematic literature reviews (SLRs) and meta-analyses investigating the safety and efficacy of delafloxacin for the treatment of ABSSSI in adult patients demonstrated similar clinical cure rates of delafloxacin versus comparators in the treatment of ABSSSI and MRSA ABSSSI’s [ 32 , 33 ]. However, these studies included publications with ABSSSI populations only and as such, evaluated overall clinical cure or microbiological response for limited number of interventions (i.e.…”