Pharmacokinetic/Pharmacodynamic Study Of Meropenem In Patients With Abdominal Sepsis

ObjectiveTo investigate the distribution of trough concentrations of meropenem in adult patients with abdominal sepsis in the intensive care unit（ICU）and its influencing factors.Based on the pharmacokinetics（Pharmacokinetics,PK）parameters of meropenem in patients with abdominal sepsis,simulate the probability of reaching the target with different dosing regimens,to provide a basis for the rational use of antibiotics in clinical practice.MethodsFirst,select 29 patients with abdominal sepsis who received meropenem antibacterial therapy in the intensive care unit（ICU）ward of the First Hospital of Jilin University from September 2020 to December 2020.The dose of meropenem is calculated according to the severity of infection and creatinine clearance rate,and the infusion method can be selected from traditional 30-minute or 2-step method.Collect the etiological culture before the administration,and collect the drug trough concentration information of 30 minutes before the fifth dose of meropenem.In order to investigate the current situation of meropenem treatment concentration and its influencing factors in the comprehensive ICU ward of our hospital.Based on the trough concentration（Cmin）≤8 mg/L,8 mg/LMIC（40%,60%,80%,100%）and %f T>4MIC（40%,60%,80%,100%）of the suspected strains and different MICs（0.25,2,4,8,16,32,64）mg/L under different dosing regimens.The general clinical data of the above patients were collected,such as: APACHE II score and SOFA score at admission,gender,age,body mass index,creatinine clearance rate,and related infection indicators such as PCT,blood routine,drug sensitivity results report,the patient’s hospitalization time and the prognosis.Results1.The trough concentration（Cmin）of 29 patients with abdominal sepsis treated with meropenem in the comprehensive ICU of our hospital were as follows: group A（Cmin≤8 mg/L）,a total of 9 patients（31%）,group B（8 mg/LMIC reaching the target of the simulated dosing regimen under different MIC conditions: when MIC≤0.25mg/L,the dosing regimens under the three infusion time conditions of 0.5h,3h,and 6h can achieve 100%f T>MIC;when MIC=16mg/L,only the dosing regimen of 2.0g/q12 h 6h intravenously can make the therapeutic concentration of meropenem reach the effective therapeutic target of40% f T>MIC,but cannot achieve the ideal therapeutic target of 100% f T>MIC.When MIC≥32mg/L,all the dosage regimens failed to meet the target.5.The probability of %f T>4MIC reaching the target of the simulated dosing regimen under different MIC conditions: When MIC ≤ 0.25mg/L,except for2.0g/q12 h,the other dosing regimens can achieve the therapeutic target of 100%f T>4MIC under the three infusion time conditions of 0.5h,3h and 6h;When MIC=4mg/L,only the dosing regimen of 2.0g/q12 h 6h intravenously can make the therapeutic concentration of meropenem reach the effective treatment target of 40%f T>4MIC,but cannot achieve the ideal treatment target of 100% f T>4MIC.When MIC≥8mg/L,all dosing regimens could not reach the target.6.The probability of reaching the standard of the simulated dosing regimen with Escherichia coli as the suspected pathogen: The dosing regimen of meropenem1.0g/q6 h can make its therapeutic concentration reach the target of 100% f T>4MIC under two infusion time conditions（0.5h intravenous or 3h intravenous）.The probability of reaching the standard of the simulated dosing regimen with Klebsiella pneumoniae as the suspected pathogen: The dosing regimen of meropenem 1.0g/q6 h can make its therapeutic concentration reach the target of 100% f T>4MIC under two infusion time conditions（0.5h intravenous or 3h intravenous）,and the dosing regimens of 0.5g/q6 h and 1.0g/q8 h can also achieve this goal with extended infusion time to 3h.7.The optimal dosing regimen recommended for meropenem in the treatment of abdominal sepsis under different MIC conditions: When the MIC of the strain is less than or equal to 0.25 mg/L,it is recommended to give a dosing regimen of 0.5g/q6h0.5h intravenous infusion;When the strain MIC=2 mg/L,it is recommended to give a dosing regimen of 0.5g/q6 h 3h intravenous infusion;When the strain MIC=4 mg/L,it is recommended to give a dosing regimen of 1.0g/q8 h 6h intravenous infusion.8.For the most common strains in patients with abdominal sepsis,in order to achieve the therapeutic target of 100% f T>4MIC and have the highest comprehensive cost-effectiveness,the recommended optimal dosing regimen is: For Escherichia coli,we recommend a 1.0g/q6 h 0.5h intravenous infusion dosing regimen;For Klebsiella pneumoniae,we recommend a 0.5g/q6 h 3h intravenous infusion dosing regimen.ConclusionsThe PK parameters of meropenem in patients with abdominal sepsis in the ICU changed,manifested as increased apparent volume of distribution,decreased clearance,and prolonged half-life.With the same dose of meropenem,the probability of reaching the 100% f T>4MIC target increases with the prolongation of the infusion time.The trough concentration of meropenem in patients with abdominal sepsis is highly variable,so it is necessary to monitor the blood concentration of meropenem in clinical practice and use PK/PD theory to select the best dosing regimen.