#VisualAbstract: Afabicin is non-inferior to vancomycin and linezolid for staphylococcal skin and soft tissue infections

1. Afabicin, a novel, narrow-spectrum antibiotic, was found to be non-inferior to vancomycin and linezolid in treating staphylococcal skin and soft tissue infections.

Evidence Level Rating: 1 (Excellent)

Staphylococcus spp., especially Staphylococcus aureus, are the predominant agents responsible for many serious infections, including acute bacterial skin and skin structure infections (ABSSSIs), infective endocarditis, and prosthetic device infections. Numerous antibiotics are used to treat staphylococcal infections, yet many exhibit reduced efficacy due to antibiotic resistance. In particular, there are many concerns regarding the safety, resistance, and oral bioavailability of agents used to treat ABSSSIs. As such, the need for new agents to treat staphylococcal ABSSSIs are essential. Afabicin is novel antibiotic designed specifically to target fatty acid synthesis in Staphylococcus spp. The objective of this double-blinded, randomized, phase 2 study was to evaluate the efficacy, safety, and tolerability of IV and oral afabicin compared with IV vancomycin and oral linezolid in the treatment of staphylococcal ABSSSIs. Patients were randomized 1:1:1, with 92 patients (mean [SD] age = 43.8 [11.9] years, 66.3% male) receiving low-dose afabicin (80 mg IV BID followed by 120 mg PO BID); 91 patients (mean [SD] age = 42.3 [11.7] years, 65.9% male) receiving high-dose afabicin (160 mg IV BID followed by 240 mg PO BID); and 101 patients (mean [SD] age = 44.9 [10.6] years, 72.6% male) receiving vancomycin/linezolid (vancomycin 1 g IV or 15 mg/kg BID followed by linezolid 600 mg PO BID). All patients received at least two doses of IV antibiotics, after which the decision to transition to oral antibiotics was made at the discretion of the clinician. The primary outcome was clinical response, defined as size change in primary ABSSSI lesion, at 48 to 72 hours. Both low- and high-dose afabicin were found to be non-inferior to vancomycin/linezolid (low-dose: difference -3.5%, 95% CI -10.8 to 3.9%; high-dose: difference 1.0%, 95% CI -7.3 to 9.2%). Furthermore, all patients in the high- and low-dose afabicin groups who had polymicrobial infections were responders for the primary outcome. The most common adverse effect attributed to the intervention was headache, 17.8% in the high-dose afabicin group, compared with 9.1% in the low-dose and 10.3% in the vancomycin/linezolid groups. Overall, this phase 2 trial demonstrated that two different doses and routes of administration of afabicin were non-inferior to, well-tolerated, and showed minimal side effects in the treatment of ABSSSIs when compared with treatment with vancomycin or linezolid. This represents an exciting new development in the realm of narrow-spectrum antibiotics that aligns not only with positive patient outcomes but also with antibiotic stewardship.

Click to read the study in ASM Journals

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