Omadacycline for Acute Bacterial Skin and Skin Structure Infections

Abstract

Background: Within the last decade, methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent cause of purulent skin and soft tissue infections. New therapeutic options are being investigated for these infections.

Methods: We report an integrated analysis of 2 randomized, controlled studies involving omadacycline, a novel aminomethylcycline, and linezolid for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Omadacycline in Acute Skin and Skin Structure Infections Study 1 (OASIS-1) initiated patients on intravenous omadacycline or linezolid, with the option to transition to an oral formulation after day 3. OASIS-2 was an oral-only study of omadacycline versus linezolid.

Results: In total, 691 patients received omadacycline and 689 patients received linezolid. Infection types included wound infection in 46.8% of patients, cellulitis/erysipelas in 30.5%, and major abscess in 22.7%. Pathogens were identified in 73.2% of patients. S. aureus was detected in 74.7% and MRSA in 32.4% of patients in whom a pathogen was identified. Omadacycline was noninferior to linezolid using the Food and Drug Administration primary endpoint of early clinical response (86.2% vs 83.9%; difference 2.3, 95% confidence interval -1.5 to 6.2) and using the European Medicines Agency primary endpoint of investigator-assessed clinical response at the posttreatment evaluation. Clinical responses were similar across different infection types and infections caused by different pathogens. Treatment-emergent adverse events, mostly described as mild or moderate, were reported by 51.1% of patients receiving omadacycline and 41.2% of those receiving linezolid.

Conclusions: Omadacycline was effective and safe in ABSSSI.

Clinical trials registration: NCT02378480 and NCT02877927.

Keywords: MRSA; acute bacterial skin and skin structure infections; omadacycline; skin infection; tetracyclines.

Figure 1.

Disposition of patients enrolled in OASIS-1 and OASIS-2. Abbreviations: CE, clinically evaluable; ITT, intent-to-treat; ME, microbiologically evaluable; micro-mITT, all mITT patients with ≥1 causative pathogen; mITT, modified ITT; OASIS, Omadacycline in Acute Skin and Skin Structure Infections Study.

Figure 2.

Forest plots for US Food and Drug Administration and European Medicines Agency endpoints in different analysis populations show that omadacycline had statistically similar outcomes to linezolid. Abbreviations: CE, clinically evaluable; CI, confidence interval; ECR, early clinical response; ME, microbiologically evaluable; micro-mITT, all mITT patients with ≥1 causative pathogen; mITT, modified intent-to-treat; PTE, posttreatment evaluation.

Figure 3.

Reduction in lesion size from baseline to posttreatment evaluation in mITT population: A, OASIS-1 intravenous to oral study; B, OASIS-2 oral-only study; and C, combined data from OASIS-1 and OASIS-2. In all graphs, omadacycline shows a similar trend to linezolid in lesion size over the study duration. Error bars represent the standard error. Lines are offset horizontally to better visualize the data points. Abbreviations: EOT, end of treatment; mITT, modified intent-to-treat; OASIS, Omadacycline in Acute Skin and Skin Structure Infections Study; PTE, posttreatment evaluation; SE, standard error.