Huang DB, O’Riordan W, Overcash JS, et al. Clin Infect Dis. 2018; 66: 1222-29.
Study Question: Is iclaprim safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSIs) compared to vancomycin?
Study Description: This multicenter, double-blind, randomized phase 3 study treated adult patients with either iclaprim 80 mg IV every 12 hours or vancomycin 15 mg/kg IV every 12 hours for 5-14 days for ABSSSIs due to gram-positive organisms. Patients must have had a fever, lymphadenopathy, leukocytosis, >10% bands, or elevated C-reactive protein. Patients with impaired arterial blood supply, diabetic foot or decubitus ulcers, human or animal bites, necrotizing fasciitis or gangrene, device-related infections or immunosuppression were excluded. The primary endpoint was early clinical response (ECR), defined by a ≥20% decrease in lesion size, 48-72 hours after starting the study drug.
Results: A total of 298 patients received iclaprim and 300 patients received vancomycin. Overall, approximately 34% of patients had methicillin-sensitive S. aureus and 22% methicillin-resistant S. aureus. No difference in the primary outcome was seen between both groups, with each achieving approximately 81% ECR. There was no difference in the rates clinical cure between the two groups at the end of treatment and within 7-14 days after completion of antibiotics. Patients in the iclaprim group had more headaches, nausea, secondary ABSSSI, and fatigue; however, rates of discontinuation as a result of adverse events were similar between the two groups (iclaprim 2.7% vs. vancomycin 4.4%).
Conclusion(s): Iclaprim was noninferior to vancomycin for the treatment of ABSSSIs caused by gram-positive organisms and had a similar incidence of study drug-related adverse events.
Perspective: This study demonstrated the efficacy and safety of a new bactericidal agent, iclaprim, as compared to vancomycin for patients with primarily S. aureus ABSSSIs. Iclaprim has not yet gained FDA approval due to previous phase 3 studies (ASSIST-1 and ASSIST-2) in which iclaprim did not meet the noninferiority margin compared to linezolid. Demonstration of noninferiority to vancomycin may result in iclaprim’s approval and use as an alternate agent for gram-positive skin and soft tissue infections. However, further studies are needed to assess the efficacy of iclaprim against isolates resistant to vancomycin.