The Evaluation of Meropenem Dosing Regimens Against ESBL-Producing Escherichia coli in ICU Patients Using Monte Carlo Simulation
Issued Date
2022-01-01
Resource Type
eISSN
11786973
Scopus ID
2-s2.0-85124503397
Journal Title
Infection and Drug Resistance
Volume
15
Start Page
439
End Page
453
Rights Holder(s)
SCOPUS
Bibliographic Citation
Infection and Drug Resistance Vol.15 (2022) , 439-453
Suggested Citation
Win E.E., Htun K.W., Tragulpiankit P., Tangtrakultham S., Montakantikul P. The Evaluation of Meropenem Dosing Regimens Against ESBL-Producing Escherichia coli in ICU Patients Using Monte Carlo Simulation. Infection and Drug Resistance Vol.15 (2022) , 439-453. 453. doi:10.2147/IDR.S345385 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86674
Title
The Evaluation of Meropenem Dosing Regimens Against ESBL-Producing Escherichia coli in ICU Patients Using Monte Carlo Simulation
Author's Affiliation
Other Contributor(s)
Abstract
Purpose: To evaluate the optimal dosing regimens of meropenem against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL E. coli) in critically ill patients with varying degrees of renal function using Monte Carlo simulation (MCS). Methods: The MCS was performed using the minimum inhibitory concentration (MIC) data from Right Laboratory and Health Screen in Naypyitaw, Myanmar, as well as reported meropenem pharmacokinetic parameters in the target population and the pharmacokinetic-pharmacodynamic index. For each dosing regimen, 10,000 virtual patients were generated to assess the probability of target attainment (PTA) and the cumulative fraction of response (CFR). The most effective dosage regimens were determined using PTA and a CFR of 90%. Results: ESBL E. coli made up 93 of the 396 clinical E. coli isolates, and they are all multidrug-resistant, with resistance to at least five antibiotic classes. The MIC50 and MIC90 were determined to be 0.25 μg/mL. The PTA was affected by five factors: creatinine clearance (CLcr), vasopressor usage, MIC, infusion time, and dosage fractionation. In patients who did not receive vasopressors, the current regimens (US-FDA and EMA) were ineffective in all renal function for MIC >0.25μg/mL. In the subset group of CLcr >80 mL/min for MIC 2μg/mL, the maximum total daily dose of 6g/day (2g q 8hr; 3hr infusion) was still ineffective, but 4g/day (1g q 6hr; 3hr infusion) achieved 98.96% PTA. Almost majority of the simulated regimens produced >90% PTA in vasopressor-dependent patients with all levels of renal function, resulting in a decreased total daily dose requirement. Conclusion: For high MIC (>1μg/mL) patients who do not use vasopressors and have a CLcr >80 mL/min, a combination of dosage fractionation and the extended infusion was considered as an effective technique to maximize target attainment. Neither prolonged infusion nor dosage fractionation should be explored in patients using vasopressors.