Efficacy and safety of AFN-1252, the first staphylococcus-specific antibacterial agent, in the treatment of ABSSSI, including patients with significant co-morbidities.
Antimicrob Agents Chemother. 2015 Dec 28;
Authors: Hafkin B, Kaplan N, Murphy B
This open-label non-controlled phase II multi-center trial was designed to evaluate safety, tolerability and efficacy of oral AFN-1252, a selective inhibitor of S. aureus enoyl-ACP reductase (FabI), given 200 mg PO twice-daily in the treatment of acute bacterial skin and skin structure infections (ABSSSI) due to staphylococci. Important aspects of the current study included a comparison of early response efficacy endpoints, end-of-treatment and follow-up endpoints. Many patients in the intent-to-treat population (n= 103) had significant co-morbidities. Overall early response rate at Day 3 was 97.3% (wound 100%, abscess 96.6%, cellulitis 94.4%) in the microbiologically evaluable population (ME). Within the ME population, 82.9% of patients had a ≥20% decrease in the area of erythema and 77.9% of patients had a ≥20% decrease in the area of induration on Day 3. S. aureus was detected in 97.7% of patients (37 patients with MRSA and 39 with MSSA). No isolates had increased AFN-1252 MICs post-treatment. Microbiologic eradication rates for S. aureus were 93.2% at short-term follow-up (STFU) and 91.9% at long-term follow-up (LTFU) in the ME population. Eradication rates for MRSA and MSSA were 91.9% and 92.3% at STFU, and 91.9% and 89.7% at LTFU. The most frequently reported drug-related adverse events were headache (26.2%) and nausea (21.4%), mostly mild or moderate. These studies demonstrate that AFN-1252 is generally well tolerated and effective in the treatment of ABSSSI due to S. aureus, including MRSA. (This study has been registered at ClinicalTrials.gov under registration no. NCT01519492.).
PMID: 26711777 [PubMed - as supplied by publisher]