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Background The 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. Methods A 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. Results We 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%). Conclusion Ceftaroline, 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. [ABSTRACT FROM AUTHOR]