Pharmacodynamic Evaluation of Oral Amoxicillin,
Amoxicillin/Clavulanate, Cefditoren, and Azithromycin
Against Streptococcus pneumoniae-Caused Respiratory
Tract Infections: A Monte Carlo Simulation
Sermwoot Jannual PharmD1, Preecha Montakantikul BCP2, Jantana Houngsaitong MSc2, Visanu Thamlikitkul MD3,
Paveena Sonthisombat BCP1
Affiliation :
1 Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Thailand
2 Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand
3 Division of Infectious Diseases and Tropical Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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 pro(cid:976)iles 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 MICs90 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 MIC90 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
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