PMID- 35177911
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220501
IS  - 1178-6973 (Print)
IS  - 1178-6973 (Electronic)
IS  - 1178-6973 (Linking)
VI  - 15
DP  - 2022
TI  - The Evaluation of Meropenem Dosing Regimens Against ESBL-Producing Escherichia 
      coli in ICU Patients Using Monte Carlo Simulation.
PG  - 439-453
LID - 10.2147/IDR.S345385 [doi]
AB  - 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 
      MIC(50) and MIC(90) were determined to be 0.25 mug/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 
      >0.25mug/mL. In the subset group of CLcr >80 mL/min for MIC 2mug/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 (>1mug/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.
CI  - (c) 2022 Win et al.
FAU - Win, Ei Ei
AU  - Win EE
AUID- ORCID: 0000-0002-6181-5073
AD  - Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmacy, 
      Mahidol University, Bangkok, 10400, Thailand.
FAU - Htun, Khaing Win
AU  - Htun KW
AD  - Right Laboratory and Health Screen, Naypyitaw, Myanmar.
FAU - Tragulpiankit, Pramote
AU  - Tragulpiankit P
AD  - Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmacy, 
      Mahidol University, Bangkok, 10400, Thailand.
FAU - Tangtrakultham, Suwida
AU  - Tangtrakultham S
AD  - Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmacy, 
      Mahidol University, Bangkok, 10400, Thailand.
FAU - Montakantikul, Preecha
AU  - Montakantikul P
AD  - Division of Clinical Pharmacy, Department of Pharmacy, Faculty of Pharmacy, 
      Mahidol University, Bangkok, 10400, Thailand.
LA  - eng
PT  - Journal Article
DEP - 20220211
PL  - New Zealand
TA  - Infect Drug Resist
JT  - Infection and drug resistance
JID - 101550216
PMC - PMC8846559
OTO - NOTNLM
OT  - PKPD
OT  - carbapenem
OT  - critically ill patients
OT  - dosing simulation
OT  - gram-negative bacteria
COIS- The authors report no conflicts of interest in this work.
EDAT- 2022/02/19 06:00
MHDA- 2022/02/19 06:01
PMCR- 2022/02/11
CRDT- 2022/02/18 05:46
PHST- 2021/11/05 00:00 [received]
PHST- 2022/01/13 00:00 [accepted]
PHST- 2022/02/18 05:46 [entrez]
PHST- 2022/02/19 06:00 [pubmed]
PHST- 2022/02/19 06:01 [medline]
PHST- 2022/02/11 00:00 [pmc-release]
AID - 345385 [pii]
AID - 10.2147/IDR.S345385 [doi]
PST - epublish
SO  - Infect Drug Resist. 2022 Feb 11;15:439-453. doi: 10.2147/IDR.S345385. eCollection 
      2022.