Abstract
INTRODUCTION: Appropriate oral antibiotic therapy for the treatment of acute bacterial skin and skin structure infections (ABSSSI) is a challenge, as current oral treatment guidelines do not fully cover the most common skin pathogens. Both linezolid and omadacycline are available as intravenous or bioequivalent oral formulations. MATERIALS AND METHODS: This post hoc analysis of the OASIS-1 (ClinicalTrials.gov identifier NCT02378480) and OASIS-2 (ClinicalTrials.gov identifier NCT02877927) phase 3 trials assessed safety and clinical efficacy of intravenous (IV)-start versus oral (PO)-start therapy in patients treated with omadacycline or linezolid for ABSSSI. In OASIS-1, patients were randomized to IV omadacycline or linezolid, with optional switch to oral therapy, while patients in OASIS-2 received oral omadacycline or linezolid. Treatment was provided for 7-14 days in both studies. The primary endpoint was an early clinical response (ECR) at 48 to 72 h, defined as survival and ≥ 20% reduction in lesion size, without rescue antibacterial therapy. RESULTS: A total of 645 IV-start inpatients and 735 PO-start outpatients were assessed. Median age was 47 years for the IV-start group and 44 years for the PO-start group. Most patients had solely gram-positive infections (97% in each group; ECR [85.2% IV-start and 85.0% PO-start]), and the incidence of treatment-emergent adverse events (AEs) was similar between the groups. The most frequent AEs observed were nausea (11.2% [IV-start] versus 18.9% [PO-start]) and subcutaneous abscess (5.6% [IV-start] versus 1.9% [PO-start]). Discontinuation due to AEs was infrequent in both groups (2% [IV-start] versus 1.2% [PO-start]). CONCLUSION: Oral therapy is equally efficacious to IV therapy when omadacycline or linezolid is used to treat ABSSSIs. These data strengthen the evidence for oral omadacycline as a therapeutic option for ABSSSI, particularly for patients who have experienced treatment failure because of the limitations of other therapies. TRIAL REGISTRATION: Clinicaltrials.gov, NCT02378480 and NCT02877927.