WITHDRAWN: Nemonoxacin treatment of patients with diabetic foot infection: A pilot study

Abstract

Abstract Background/purpose Diabetic foot infections (DFIs) are typically polymicrobial, often involving staphylococci (including methicillin-resistant strains). To investigate if nemonoxacin, a broad-spectrum non-fluorinated quinolone with activity against methicillin-resistant Staphylococcus aureus (MRSA), is effective in DFIs, we evaluated the efficacy, safety, pharmacokinetics, and pharmacodynamics of nemonoxacin in DFI patients. Methods Patients with mild or moderate DFI received 750 mg nemonoxacin orally once daily for 7-14 days in this open-label, single-arm, multi-center study. We evaluated clinical and microbiological responses and collected blood and tissue samples to assess nemonoxacin’s penetration into infected soft tissue. Results Among 38 enrolled patients, 25 completed the study. Staphylococcus aureus was the predominant wound isolate (69.7%), including four MRSA strains. Clinical success rates at the test-of-cure (TOC) visit were 95.7% in the intent-to-treat (ITT) and 94.7% in the per-protocol (PP) populations. Microbiological success rates at TOC in ITT and PP populations were 82.6% and 89.5%, respectively. Validated wound scoring revealed that the treatment significantly reduced infection severity. Nemonoxacin was well tolerated, rapidly absorbed and distributed to soft tissues following oral administration, attaining Cmax,ss ∼2 hours after dosing. Drug concentrations in soft tissue were >2.5 times of that in plasma at most samplings. The AUC0-24 tissue/plasma ratio was 3.08, with ratio ranges of 13.1–1747.9 and 48.0–3200.0 for plasma fAUC/MIC and soft tissue AUC/MIC, respectively. Conclusion In this small DFI patient population, nemonoxacin produced excellent clinical and microbiological responses, was well tolerated, and effectively penetrated infected tissues. Once-daily oral nemonoxacin treatment appears effective in DFI patients. NCT registration number NCT00685698.