Linezolid (LZD) in Patients (pts) with Wound Infection or Major Abscess: Pooled Analysis of Two Phase 3 Double-Blind Studies

Author(s):
Phillip Barie, Edward Fang, Sonia Minassian, Philippe Prokocimer, Weill Cornell Medical College

Background: TZD is a novel oxazolidinone antibacterial under investigation for the treatment of gram-positive infections, including methicillin-resistant S aureus.

Hypothesis: TZD results in similar treatment outcomes as LZD in pts with wound infection or cutaneous abscess.

Methods: ESTABLISH-1 and ESTABLISH-2 were randomized, double-blind, phase 3 non-inferiority trials evaluating TZD (200 mg once daily for 6 d) versus LZD (600 mg twice daily for 10 d) for treatment of acute bacterial skin and skin structure infections. This post-hoc analysis included all pts with wound infection or major cutaneous abscess and excluded those with cellulitis/erysipelas (46% of intent-to-treat [ITT] pts). The primary outcome was early clinical response rate (defined as a >20% reduction in lesion area compared to baseline) at 48-72h in the ITT population. Secondary outcomes (also in ITT pts) included programmatic clinical response at end of therapy (EOT) and investigator-assessed response at a post-therapy evaluation (PTE) 7-14 days after the EOT visit.

Results: Overall, 725 pts had a wound infection (N=391; n=377 post-traumatic, n=14 superficial incision surgical site infection) or major cutaneous abscess (N=334). Mean age was 41 years, and 66% were male. The primary infection site was mostly on the lower (32% of patients) or upper extremities (39%); 63% of pts overall underwent an incision and drainage (I&D) procedure in addition to study treatment. Early clinical response was seen in 86.5% and 83.7% of pts treated with TZD and LZD, respectively (difference 2.8%, 95% CI: -2.4, 8.0); outcomes by I&D status were similar. Response rates at EOT were 87.1% and 89.8%, respectively, and at PTE were 85.7% and 87.8%, respectively. Most adverse events (AEs) were mild to moderate in both treatment arms. Gastrointestinal disorders were the most frequent type of AEs (15.2% of TZD and 24.9% of LZD pts; odds ratio 0.54, 95% CI: 0.37, 0.78), including nausea (7.2% and 11.8%, respectively), diarrhea (3.6%, 5.9%), and vomiting (3.0%, 5.0%).

Conclusions: For the treatment of major cutaneous abscesses or wound infections (almost all of which were post-traumatic wounds), a short 6-d course of once-daily TZD demonstrated similar response rates to 10 d of twice-daily LZD at 48-72 h and all later time points evaluated. Both agents were well tolerated, but gastrointestinal disorders were more frequent with LZD.