Efficacy and Safety of Empirically Used Levonadifloxacin (Intravenous and Oral) in the Treatment of Patients with Bone and Joint Infection: A Multicentric, Investigator-Initiated Study.

Introduction: Bone and joint infections (BJIs) present significant therapeutic challenges due to factors such as limited drug penetration at the infection site, biofilm formation, and concerns regarding the safety of prolonged antibiotic use. If left untreated, these infections may cause lasting disability or death. To address this, an investigator-initiated study evaluated the clinical efficacy and safety of levonadifloxacin in patients with BJIs. Materials and Methods: This was a prospective, multicentric, investigator-initiated study designed to assess the real-world effectiveness and safety of levonadifloxacin, administered either orally or intravenously, in adult patients (≥21 years) with BJIs. A total of 97 participants were enrolled. The treatment duration ranged up to 28 days. That exact duration of treatment was individualized based on the patient's response and the physician's discretion. Clinical response was evaluated on days 4, 8, 14, and 25, whereas the microbiological response was assessed on day 28. Safety monitoring included clinical and laboratory assessments, and the final evaluation was conducted at the end-of-treatment (EoT) (day 28) and test-of-cure (ToC) visit (day 35). Results: Patients received levonadifloxacin for a minimum duration of 14 days (mean duration of treatment was 26.8 days). On day 4, clinical improvement (CI) was observed in 82.6% of patients, and improvement was further seen in 90.2% of patients on day 14, and CI was seen in all the patients on day 28. Significant reduction in wound size (length, width, and total wound area - from 52.2 cm2 to 11.2 cm2) was observed over a period of 28 days with levonadifloxacin (P < 0.0001) with improved mobility. Clinical cure was achieved in 97.8% at EoT and 96.4% at ToC, with no patients with clinical failure. Microbiological success reached 93.5%, with no clinical failures or notable changes in hematology, electrocardiogram, vital signs, or laboratory parameters. Its promising biofilm activity, availability of intravenous and oral formulations, high bioavailability, and adequate bone penetration make levonadifloxacin a compelling empirical choice over traditional agents such as vancomycin, linezolid, and teicoplanin. Conclusion: Levonadifloxacin (IV/oral) provided good clinical efficacy in patients with BJIs. Moreover, it was found to be safe and well-tolerated even after administration for 35 days.