Pharmacodynamic Evaluation of Oral Amoxicillin, Amoxicillin/Clavulanate, Cefditoren, and Azithromycin Against Streptococcus pneumoniae -Caused Respiratory Tract Infections: A Monte Carlo Simulation

Objective: To estimate the probability of oral amoxicillin, amoxicillin/clavulanate, cefditoren, and azithromycin achieving pharmacokinetic/pharmacodynamics [PK/PD] targets against Streptococcus pneumoniae in Thais. Materials and Methods: A Monte Carlo simulation of 10,000 S. pneumoniae infected patients was conducted. Steady-state serum drug concentration-time profiles were created to determine the probability of target attainments at each minimum inhibitory concentration [MIC]. The MICs of 100 S. pneumoniae isolates were used. The cumulative fraction of responses [CFRs] were calculated to provide a single estimate of the probability of achieving PK/PD targets for dosage regimens against S. pneumoniae populations. A CFR of more than 90% was required. Results: One third of S. pneumoniae isolates were susceptible to penicillin. The MICs 90 of amoxicillin-based regimens, cefditoren, and azithromycin against S. pneumoniae were 2, 0.5, and 128 μg/ml, respectively. The probability of achieving PK/PD targets of all amoxicillin-based regimens and cefditoren 200 mg every eight hours were more than 90% for MIC 90 values, while that of azithromycin 500 mg daily was 0%. All amoxicillin-based regimens, cefditoren 200 mg every eight hours, and cefditoren 400 mg every 12 hours achieved the CFR target, while azithromycin did not. Conclusion: Based on the simulations, amoxicillin-based regimens or high-dose cefditoren provided a greater likelihood of achieving optimal PK/PD targets in adults with S. pneumoniae -related respiratory tract infections [RTIs]. Keywords:  Streptococcus pneumoniae , Amoxicillin-based regimens, Cefditoren, Azithromycin, Pharmacokinetics/pharmacodynamics, Monte Carlo simulation