Optimizing Dosing Regimen Of Amoxicillin Based On PK/PD Model

Due to inappropriate drug dose selection,antimicrobial resistance has become an important public health threat.As a common clinical beta-lactam antibiotic,amoxicillin has developed resistance to amoxicillin in some bacterial species.In order to avoid drug abuse and reduce the drug resistance of bacteria,it is necessary to study the optimal dosing regimen of amoxicillin.This study optimized and evaluated six amoxicillin dosing regimens from two aspects of urinary tract infection patients and blood infection patients,and discussed the choice of dosing regimens under different administration routes and covariates.In this study,the target bacteria species and MIC distribution data of amoxicillin were firstly collected,the pharmacokinetic model of amoxicillin was constructed according to the pharmacokinetic parameters,and the drug concentration data were obtained by Monte Carlo simulation.This paper preliminarily describes the change rule of drug concentration in urine with time.the PK/PD index of amoxicillin(%fT>MIC)was constructed according to the PD index,and the optimal dosing regimen and bacterium species was evaluated from probability of target attainment(PTA)and cumulative fraction of response(CFR).Secondly,study the effect of different administration routes on the choice of dosing schedules for blood infection patients.Then,the pros and cons of oral administration,intravenous administration,and intravenous drip administration were evaluated by PTA and CFR.Finally,two dosing regimens were simulated by Monte Carlo,and the PTA value was used to evaluate the advantages and disadvantages of them.At the same time,the two covariates of weight and age were incorporated into the two-compartment model,and the decision tree model was used to predict the optimal dosing regimen for different weights and ages.The experimental results show that for patients with urinary tract infection,when the MIC is less than or equal to 64μg·mL-1,the six dosage regimens have good antibacterial effects,and it is recommended to choose a low dose of "0.5g Q8h".It has antibacterial effect on most bacterial species.For drug-resistant bacteria such as Proteus mirabilis,a high-dose and multiple-dose regimen should be used.For patients with blood infection,all three administration routes of amoxicillin can fight against colonies with MIC less than 4μg·mL1.Oral administration is recommended because it is more convenient and the dose is lower.Oral administration of "0.5g Q8h" can eliminate Helicobacter pylori and Streptococcus pneumoniae.The recommended regimen for killing Enterococcus faecalis and Haemophilus influenzae is oral administration of "1g Q6h".Weight and age affect the choice of dosing regimen,and "0.75g Q6h" is better than "1g Q8h".The prediction accuracy of the decision tree model established by the CART algorithm is 95.38%,which has a good prediction result for the dosing regimen and can be used as the basis for the initial clinical dosing regimen.