Efficacy and Safety of AFN-1252, the First Staphylococcus-Specific Antibacterial Agent, in the Treatment of Acute Bacterial Skin and Skin Structure Infections, Including Those in Patients with Significant Comorbidities.

Abstract

This open-label noncontrolled, phase II multicenter trial was designed to evaluate the safety, tolerability, and efficacy of 200 mg of AFN-1252, a selective inhibitor of Staphylococcus aureus enoyl-acyl carrier protein reductase (FabI), given by mouth 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 with end-of-treatment and follow-up endpoints. Many patients in the intent-to-treat population (n = 103) had significant comorbidities. The overall early response rate at day 3 was 97.3% (wound, 100%; abscess, 96.6%; cellulitis, 94.4%) in the microbiologically evaluable (ME) population. 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 (n = 37 patients with methicillin-resistant S. aureus [MRSA], and n = 39 with methicillin-sensitive S. aureus [MSSA]). No isolates had increased AFN-1252 MICs posttreatment. 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%, respectively, at STFU and 91.9% and 89.7%, respectively, at LTFU. The most frequently reported drug-related adverse events, which were mostly mild or moderate, were headache (26.2%) and nausea (21.4%). 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.).

• Authors: B Hafkin, N Kaplan, B Murphy
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 60 Issue 3 Pg. 1695-701 (Dec 28 2015) ISSN: 1098-6596 [Electronic] United States
• PMID: 26711777 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study)
• Copyright: Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Chemical References

• API 1252
• Anti-Bacterial Agents
• Benzofurans
• Pyrones
• Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)

Topics

• Adult
• Aged
• Anti-Bacterial Agents (adverse effects, therapeutic use)
• Benzofurans (adverse effects, therapeutic use)
• Comorbidity
• Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) (antagonists & inhibitors)
• Female
• Humans
• Male
• Methicillin-Resistant Staphylococcus aureus (drug effects)
• Middle Aged
• Pyrones (adverse effects, therapeutic use)
• Skin (drug effects)
• Skin Diseases, Infectious (drug therapy, microbiology)
• Staphylococcal Infections (drug therapy, microbiology)
• Treatment Outcome
• Young Adult