Efficacy and safety of optional parenteral antimicrobial therapy for complicated skin and soft tissue infections: A systematic review and Bayesian network meta-analysis

Background: Skin and soft tissue infections (SSTIs) carry significant economic burden, as well as morbidity and mortality, especially when caused by methicillin-resistant Staphylococcus aureus. This study aims to investigate the efficacy and safety of optional antimicrobial therapy for the treatment of complicated SSTIs (cSSTIs). Methods: We searched PubMed, Medline (Via Ovid SP), Embase (Via Ovid SP), and the Cochrane Central Register of Controlled Trials from their inception to March 22, 2021 for randomized controlled trials (RCTs) that studied the use of optional antimicrobial therapy for cSSTIs. Citations' screening, study selection, data extraction, and risk of bias assessment were independently performed by 2 authors. The primary outcomes were clinical and microbiological treatment success, and adverse events (AEs) were also assessed. Results: A total of 48 trials covering 24,381 patients assessing 20 types of antimicrobial treatment modalities were included. Overall, omadacycline was associated with the highest beneficial effect on clinical and microbiological treatment success and with the largest rank probability based on surface under the cumulative ranking curve values, avarofloxacin was closely followed. Both had, however, omadacycline was related to moderately safety profiles. Lefamulin ranked as the best option was associated with the lowest risk of severe AEs. Subgroup analysis showed similar results. The quality of primary outcomes was moderate to low. Conclusions: The use of omadacycline was associated with higher rates of clinical and microbiological treatment success for the treatment of cSSTIs, with a relative low risk of AEs. Due to the limitations of the included RCTs, high-quality and well-designed RCTs are needed to further confirm the results.