Fluoroquinolone Antibiotic Prophylaxis to Prevent Post-Traumatic Bacterial Infectious Endophthalmitis: Using Monte Carlo Simulation to Evaluate the Probability of Success.
Patients with open globe injuries routinely receive fluoroquinolone (FQ) prophylaxis to prevent bacterial infectious endophthalmitis. Owing to the rarity of this infection, there is an absence of clinical trials evaluating optimal prophylactic FQ dosing. To address this knowledge gap, we conducted a Monte Carlo simulation (MCS)-based study to identify the FQ dosing option(s) that optimize pharmacokinetic-pharmacodynamic FQ target attainment against common bacterial pathogens implicated in post-traumatic bacterial infectious endophthalmitis (PTBIE).  Weighted mean pharmacokinetic parameters and standard deviations for ciprofloxacin, levofloxacin, and moxifloxacin were calculated from published studies in healthy volunteers. The incidence and FQ susceptibility profiles for the most common bacteria causing PTBIE were extracted from the literature. MCS was used to determine the cumulative fraction of response (CFR) for 5 FQ dosing options to determine the probability of attaining pathogen-specific target 24-hour area under the curve to minimum inhibitory concentration ratios in the vitreous humor of the eye against the 4 most common causative bacteria seen in PTBIE.  Moxifloxacin 400 mg po daily (M400) achieved the highest CFR (72%). Levofloxacin dosing options achieved CFRs between 54% and 63%. Ciprofloxacin dosing options achieved CFRs between 28% and 35%.  M400 optimized the likelihood of prophylactic success in the prevention of PTBIE, and based on the study findings, M400 is predicted to optimize the probability of success compared with ciprofloxacin and levofloxacin dosing options currently endorsed by expert opinion.
['Peragine|Christine|C|', 'Walker|Sandra A N|SAN|', 'Walker|Scott|S|', 'Palmay|Lesley|L|']
D000900:Anti-Bacterial Agents D019072:Antibiotic Prophylaxis D002939:Ciprofloxacin D016208:Databases, Factual D004305:Dose-Response Relationship, Drug D009877:Endophthalmitis D015818:Eye Infections, Bacterial D015807:Eye Injuries, Penetrating D006801:Humans D064704:Levofloxacin D008826:Microbial Sensitivity Tests D008954:Models, Biological D009010:Monte Carlo Method D000077266:Moxifloxacin D011336:Probability
fluoroquinolone prophylaxis Monte Carlo simulation post-traumatic bacterial endophthalmitis