SGEM#262: Omadacycline – Is it non-inferior to linezolid for skin and soft tissue infections?

Date: July10th, 2019 Reference: O’Riordan W et al. Omadacycline for Acute Bacterial Skin and Skin-Structure Infections. NEJM Feb 2019 Guest Skeptic: Dr. Anand Swaminathan is an assistant professor of Emergency Medicine at the St. Joseph’s Regional Medical Center in Patterson, NJ. He is a deputy editor for EM: RAP and, associate editor for REBEL EM. Case: A 22-year-old woman presents with redness and swelling of her left lower leg from the top of the ankle to about midway up the calf on the medial surface of the leg. Her skin is warm with mild tenderness, no fluctuance and no crepitus. She is well appearing without a fever and she has no prior medical history or allergies. You are about to write her a prescription for cephalexin when you suddenly remember reading about a new antibiotic that recently became available for skin and soft tissue infections called omadacycline Background: We have covered cellulitis and abscesses a number of times on the SGEM (SGEM 13, 131, 156, 164, 209). Often the guest skeptic on these shows is the amazing Physician Assistant, Chip Lange from TOTAL_EM Podcast and the Practical POCUS course. The production and release of new antibiotics is rare and should be celebrated by clinicians. As antibiotic resistance continues to mount, our options narrow and, in turn, our patients suffer. Recently, the NEJM published two articles on a new antibiotic that was recently FDA approved, omadacycline. The articles compared omadacycline to moxifloxacin in the treatment of community acquired pneumonia (CAP) and to linezolid in the treatment of skin and soft tissue infections. Both studies yielded promising results for the new drug which should be cause for excitement. However, significant biases, methodological flaws and poor selection of comparator treatments should temper our excitement. Clinical Question: Is omadacycline non-inferior to linezolid in terms of early clinical response in the treatment of skin and soft tissue infections? Reference: O’Riordan W et al. Omadacycline for Acute Bacterial Skin and Skin-Structure Infections. NEJM Feb 2019 Population: Patients older than 17 years with a skin infection (cellulitis, erysipelas or major abscess) Exclusions: Patients with one or more doses of systemic antibiotics prior to presentation, topical antibacterial agent within 72 hours, infections that would require more than 14 days of treatment, chronic skin lesions, ulcers or wounds and patients with any liver or renal insufficiency or immunocompromise Intervention: Omadacycline 100 mg IV Q12 for two doses then 100 mg Q24 for at least two more days with the option to transition to 300 mg Q24 for 7-14 days total Comparison: Linezolid 600 mg IV Q12 with the option to transition to 600 mg Q12 orally for 7-14 days after at least three days of IV Outcome: Primary: Early clinical response defined as survival with a reduction in lesion size of at least 20% at 48-72 hours after the first dose Secondary: Clinical response post-treatment(at 7-14 days) Authors’ Conclusions: “Omadacycline was noninferior to linezolid for the treatment of acute bacterial skin and skin-structure infections and had a similar safety profile.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. Unsure The patients were adequately randomized. Yes The randomization process was concealed. Yes The patients were analyzed in the groups to which they were randomized. Yes The study patients were recruited consecutively (i.e. no selection bias). Unsure The patients in both groups were similar with respect to prognostic factors. Yes All participants (patients, clinicians, outcome assessors) were unaware of group allocation. Yes All groups were treated equally except for the intervention. Yes Follow-up was complete (i.e. at least 80% for both groups). Yes