Methods: To evaluate the safety and effectiveness of FA as chronic suppressive therapy in patients with staphylococcal BJI, we enrolled 30 patients in a prospective, single-arm, multi-center study in the US. Eligible patients had refractory infections that could not be managed surgically and/or had not responded to previous antibiotic treatment. In Part A of the study, all patients received 6 months of oral FA treatment. In the first 1-2 weeks, patients could receive a companion antibiotic. Clinical success was based on lack of need for surgery or additional antibiotics. After all patients completed Part A of the study, an interim analysis was performed. In Part B of the study (ongoing), patients who completed Part A and require continued suppressive therapy may continue to receive FA for a total of 24 months.
Results: Most patients (83%) had orthopedic hardware infections. Therapy was considered successful at the 6-month visit in 18 patients (60%). Microbiological persistence was observed in 8 patients, with 3 cases of decreasing FA susceptibility (including 1 case of resistance). Among 29 patients who experienced a treatment-emergent adverse event (TEAE), the most frequently reported events were: urinary tract infection (n=9), peripheral edema/swelling (n=8), nausea/dyspepsia (n=7). Seven patients experienced TEAEs related to study drug; mild gastrointestinal disorders were most common. Two treatment-related events (unrelated to therapeutic failure) led to discontinuation of study drug
Conclusion: Patients with refractory BJI have few treatment options. In our study, 60% of infections were effectively suppressed for 6 months with FA treatment. The frequency of TEAEs was high, though not unexpected in this population with many chronic diseases. FA was well-tolerated with few patients experiencing treatment-related AEs leading to study drug discontinuation. FA administered chronically as monotherapy may lead to decreasing susceptibility and treatment failure in some patients; thus, combination therapy is warranted for this indication.
R. Darouiche, Cempra: Grant Investigator , Grant recipient .
A. Strayer, Melinta Therapeutics, Inc.: Employee and Shareholder , Salary .