Jornal de doenças infecciosas e terapia

Abstrato

A Pilot Study of Nemonoxacin in Patients with Diabetic Foot Infections

Benjamin A Lipsky, Mashra Ganib, Lee C Rogers, Jawl-Shan Hwang, Cheng-Yuan Tsaie, Li-Wen Chang, Yu-Ting Chang and Ming-Chu Hsue

Background: Diabetic foot infections (DFIs) are usually caused by a mixture of bacterial pathogens, especially staphylococci (including methicillin-resistant strains). Nemonoxacin, a broad-spectrum non-fluorinated quinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA), could potentially be an effective agent to treat DFIs. The efficacy, safety, pharmacokinetics, and pharmacodynamics of nemonoxacin were evaluated in patients with DFI. Methods: Patients with mild or moderate DFI were treated with nemonoxacin 750 mg orally once daily for 7-14 days in this open-label, single-arm, multi-center study. Clinical and microbiological responses were evaluated. Blood and tissue samples were collected for assessment of the ability of nemonoxacin to penetrate into infected soft tissue wounds. Results: Thirty-eight patients were enrolled, 25 successfully completed the study. The predominant wound isolate was Staphylococcus aureus (in 69.7%), four of which were MRSA. Clinical success rate in evaluable patients at the test-of-cure (TOC) visit was achieved in 95.7% of patients in the intent-to-treat (ITT) and 94.7% in the per-protocol (PP) populations. Microbiological success rate at TOC in ITT and PP populations were 82.6% and 89.5%, respectively. Wound healing response (a validated wound score) demonstrated that the severity of infection was substantially reduced after treatment. Treatment with nemonoxacin was well tolerated. Nemonoxacin was rapidly absorbed and distributed to soft tissue following oral administration, with Cmax,ss attained at ~2 hours after dosing. Drug concentrations in soft tissue were >2.5 times of that in plasma at most sampling points. The ratio of AUC0-24 (tissue/plasma) was 3.08, with fAUC/MICs in plasma ranging from 13.1 to 1747.9, while AUC/MICs in soft tissue were 48.0 to 3200.0. Conclusion: In this small sample of DFI patients, nemonoxacin demonstrated good clinical and microbiological success rates, was well tolerated, and penetrated extensively into infected tissues. These results suggest that oncedaily oral nemonoxacin may be suitable for treating patients with DFI. ClinicalTrials.gov identifier: NCT00685698.