Objectives:To determine the in vitroantibacterial activity and spectrum of levomidazole and its metabolites against anaerobic isolates and explore the bactericidal kinetics of levornidazoleanduse Monte Carlo simulation toevaluate the PK/PD parameters.Methods:Agar dilution method was used to determine the minimum inhibitory concentrations (MICs) of levornidazole, 3 comparators and 5 metabolites of levomidazole against 365anaerobic isolates.The minimum bactericidal concentrations (MBCs) of levomidazole and metronidazole were measured againstBacteroidesfragilis.The static time-kill curve was constructed by plotting the mean log10 CFU per milliliter versus time.A pharmacodynamic model was built to analyze the relationship between ALogCFU24h and drug concentration and define the bactericidal kinetics of levornidazole.Based on the results from our pharmacokinetics studies in healthy Chinese subjects to evaluate the safety and PK profile of levornidazole, we estimated the cumulative fraction of response (CFR) of levomidazole against anaerobes and the probability of target attainment (PTA) under various MIC levels using Monte Carlo simulation.Results:Levornidazole showedgood activity against B.fragilis, other Bacteroides, Clostridium difficile, Clostridium perfringens, and Peptostreptococcusmagnus.For anaerobic gram-negative bacilli, anaerobic gram-positive bacilli, and anaerobic gram-positive cocci, levomidazole displayed activity similar to or slightly higher than that of metronidazole, omidazole and dexomidazole.Favorable anti-anaerobic activity was also seen with levornidazole metabolites M 1 and M4.MBC50 of levornidazolewas2 mg/L and MBC904mg/L against22 clinical B.fragilis strains.MBC90/MIC90ratio of levomidazole was 4, similar to that of metronidazole.Static killing curve and sigmoid Emax model analysis suggested that levornidazole was a concentration-dependent antibiotic.For both of the two dose regimes of 750mg,q24h and 500mg,ql2h to B.fragilis, C.difficile, C.perfringens, P.magnus, the CFR for AUC0-24h/MIC =70 were all higher than 99.9%.The results of the PTA calculation showed that when the MIC≤ 2 mg/L, the pharmacodynamic target value probability were all 100% for the 2 dose regimens.Conclusions:The in vitro anti-anaerobic activity of levomidazole is similar to or slightly higher than that of metronidazole, ornidazole and dextrornidazole.Levornidazole hasgood activity against most anaerobic species.Favorable anti-anaerobic activity is also seen with levornidazole metabolites M1 and M4.Levomidazole is a concentration-dependent antibiotic.According to the calculation results of CFR and PTA, both of the 2 dose regimens can obtain good clinical and microbiological effect.