Evaluation of a non-parametric modelling for meropenem in critically ill patients using Monte Carlo simulation
- 91 Downloads
In critically ill patients treated with meropenem, the proposed pharmacokinetics/pharmacodynamics (PK/PD) efficacy index is to keep the free drug concentration 4–5 times above the minimum inhibitory concentration (MIC) of the germ isolated, for 100% of the interval regimen. The objectives were to design a population pharmacokinetics model for meropenem in critically ill patients and to evaluate different dosage schemes that achieve the optimal PK/PD objectives.
This retrospective, observational, single-centre study included 80 critically ill patients (154 samples) treated with meropenem between May 2011 and December 2017. Patient data, concentrations, treatment and bacteriological variables were collected from electronic medical records. Total and free concentrations of meropenem were modelled in Pmetrics. Monte Carlo simulations were performed to assess the probability of achieving the PK/PD target for different dosage regimens. For patients with available data, the number of patients with a free concentration 4 times higher or lower than the observed MIC for the P. aeruginosa and E. coli was investigated.
A one-compartment model with first-order elimination adequately described serum total and free meropenem concentrations. The only variable that significantly influenced the elimination constant of meropenem was the creatinine clearance (CLcr) calculated using the CKD-EPI formula. The highest probability of achieving the pharmacodynamic objective was with 3-h infusion dosage regimens. Sixty percent and 89% of patients attained a free drug concentration 4 times above the MIC for P. aeruginosa and E. coli respectively.
This study proposed different dosing regimens depending on renal clearance strata and the MIC of the germ targeted.
KeywordsMeropenem Population pharmacokinetics Pmetrics Probability of target attainment
We are grateful to K. Poole for manuscript editing.
The project was supported by FBCN (Fundación Bancaria Caja Navarra) through a “mobility grant for Ph.D. research studies” for Ana Isabel Idoate Grijalba.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- 13.Roberts JA, Kirkpatrick CMJ, Roberts MS, Robertson TA, Dalley AJ, Lipman J (2009) Meropenem dosing in critically ill patients with sepsis and without renal dysfunction: intermittent bolus versus continuous administration? Monte Carlo dosing simulations and subcutaneous tissue distribution. J Antimicrob Chemother 64:142–150CrossRefGoogle Scholar
- 20.Wittau M, Scheele J, Kurlbaum M, Brockschmidt C, Wolf AM, Hemper E, Henne-Bruns D, Bulitta JB (2015) Population pharmacokinetics and target attainment of meropenem in plasma and tissue of morbidly obese patients after laparoscopic intraperitoneal surgery. Antimicrob Agents Chemother 59:6241–6247CrossRefGoogle Scholar
- 21.Olaechea PM, Insausti J, Blanco A, Luque P (2010) Epidemiology and impact of nosocomial infections. Med Int 34:256–267Google Scholar
- 22.Vincent JL, Bihari DJ, Suter PM, Bruining HA, White J, Nicolas-Chanoin MH et al (1995) The prevalence of nosocomial infection in intensive care units in Europe. Results of the European prevalence of infection in intensive care (EPIC) study. EPIC international advisory committee. JAMA 274:639–644CrossRefGoogle Scholar