Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) is a growing problem in the United States and Europe and is a major cause of acute bacterial skin and skin structure infections (ABSSSIs) among otherwise healthy people in the community. Daniel Jorgensen, MD, Cellceutix, Beverly, Massachusetts, USA, presented safety and efficacy data from a phase 2b trial that compared brilacidin (BRI) with daptomycin (DAP) in treating community-acquired ABSSSI caused by S aureus.

BRI is a novel synthetic mimic of host defense proteins that has shown in vitro activity against multidrug-resistant S aureus in phase 1 and 2a trials. Antibiotics in this category, also known as defensin mimetics, kill bacteria in the same manner as the human immune system and thus are less likely to induce antimicrobial resistance. According to Dr Jorgensen, previously presented phase 2a data suggested that BRI was as effective as DAP over 7 days in treating ABSSSI [Jorgensen D et al. ICAAC 2012 (poster L1-1662)]. However, a transient dose-dependent elevation in blood pressure, likely the result of overdosing, was also noted. Therefore, the highest total dose of BRI used in the phase 2b trial (1.2 mg/kg) was less than the lowest total dose (1.6 mg/kg) used in the phase 2a trial.

The phase 2B trial included 215 patients in the United States with an ABSSSI as defined by the FDA [FDA. Guidance for Industry. 2013]. Patients were randomized to 1 of 3 BRI injections: low (0.6 mg/kg, single dose), medium (0.8 mg/kg, single dose), or high (0.6 mg/kg on day 1 and 0.3 mg/kg on days 2 and 3). The comparator was DAP (4 mg/kg) for 7 days. The primary end point was early clinical response (48 to 72 hours). Clinical response was defined as a percentage reduction in lesion size ≥ 20% compared to baseline.

The US clinical response rates are shown in Table 1.

According to Dr Jorgensen, there was an early and sustained percentage change in lesion area from baseline to day 7 and again through short-term follow-up (days 10 to 14) in both the all-treated/safety population and the microbiological intent-to-treat population. The most commonly isolated pathogen was S aureus, including MRSA. Safety data suggested that patients who received BRI were more likely to experience mild and transient numbness or tingling as compared with the DAP group; however, no increase in hypertension was noted in those randomized to BRI, and no deaths in any group were reported.

In conclusion, Dr Jorgenson emphasized that BRI appears to offer high activity against MRSA. A single dose was safe and effective when compared to a 7-day dose of DAP for the treatment of ABSSSI, which might offer treatment, pharmacoeconomic, and compliance advantages to health care providers and patients.