Background. Tedizolid (TZD) is a novel oxazolidinone with potent activity against a wide range of Gram-positive pathogens, including MRSA, and with a favorable safety profile. In two Phase 3 trials, ESTABLISH-1 and ESTABLISH-2, TZD (200 mg once daily for 6 days) demonstrated noninferiority to linezolid (LZD) (600 mg twice daily for 10 days) in patients with acute bacterial skin and skin structure infections (ABSSSI). Use of non-steroidal anti-inflammatory drugs (NSAID) and/or corticosteroids (CS) is common in patients with ABSSSI. Due to their anti-inflammatory properties, it is possible that concomitant use of these agents may reduce lesion size and confound the primary outcome of ≥20% reduction in lesion size at the 48–72 hour visit. This subgroup analysis of pooled data from ESTABLISH-1 and -2 examined the effect of concomitant NSAID/CS use on early clinical response in patients with ABSSSI receiving TZD or LZD.
Methods. Patients with ABSSSI (lesion surface area ≥75 cm2 and ≥1 regional or systemic sign of infection) received TZD 200 mg qd for 6 days or LZD 600 mg bid for 10 days. The use of NSAIDS/CS was documented for each patient and the primary outcome for both therapies at the 48-72 h visit was measured with/without NSAID/CS use.
Results. A total of 1333 patients were randomly assigned to TZD or LZD. Patients were mostly male (63.1%); average age of 44 years. The most common ABSSSI was cellulitis (45.3% and 45.9% in TZD and LZD treatment groups, respectively), followed by major cutaneous abscess (25.3% and 24.8%), and wound infections (29.4% and 29.3%). Overall, 44 of 664 patients (6.6%) in the TZD treatment group and 63 of 669 patients (9.4%) in the LZD group received NSAID or oral CS during the first 72 hours of treatment. Among patients receiving NSAID/CS, early clinical response rates at the 48-72 h visit were similar between TZD and LZD groups (70.5% vs 69.8%), but lower overall than compared with patients not receiving NSAID/CS (82.4% with TZD vs 80.4% with LZD).
Conclusion. Early clinical response rates were similar in patients treated with either TZD or LZD for ABSSSI in the ESTABLISH-1 and -2 trials, regardless of NSAID/CS use. This finding suggests there is an absence of bias with anti-inflammatory use in assessing early clinical response rates in ABSSSI clinical trials.
Disclosures. T. Sandison, Cubist: Employee, Salary C. De Anda, Cubist: Employee and Shareholder, Salary A. Das, Cubist: Consultant, Consulting fee; Cempra: Consultant, Consulting fee; Cerexa: Consultant, Consulting fee; Nabriva: Consultant, Consulting fee; Paratek: Consultant, Consulting fee; Trius: Consultant, Consulting fee; Achaogen: Consultant, Consulting fee; Durata: Consultant, Consulting fee P. Prokocimer, Cubist: Employee and Shareholder, Salary