Dosage regimens for meropenem in children with pseudomonas infections

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There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high-risk children and adults” Hassan et al (2019).

Abstract:

There have been literature reports that some recommended meropenem dosage regimens may fail to meet therapeutic targets in some high-risk children and adults. We evaluated this observation in children using literature studies conducted in infants and children. Observed and, as necessary, simulated data from the literature were combined, yielding a dataset of 288 subjects (1 day to ~17 yr). A population pharmacokinetic model was fit to the data and then used to simulate the recommended dosing regimens and estimate the proportion of subjects achieving recommended target exposures. A two-compartment model best fit the data with weight, postnatal age, gestational age, and serum creatinine as covariates. FDA-approved dosing regimens achieved targets in approximately 90% or more of subjects less than three months of age for organisms with MIC’s of 2 and 4 mg/L; however, only 68.4% and 41.7 % of subjects older than three months and weighing less than 50 kg achieved target exposures for organisms with MIC’s of 2 and 4 mg/L, respectively. Moreover, for subjects weighing more than 50 kg, only 41.3 and 17 % achieved these respective targets. Simulation studies were used to explore the impact of changing dose, dosing interval, and infusion duration on the likelihood of achieving therapeutic targets in these groups. Our findings illustrate that current dosing recommendations for children over three months fail to meet therapeutic targets in an unacceptable fraction of patients. Further investigation is needed to develop new dosing strategies in these patients.

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Reference:

Hassan, H.E., Ivaturi, V., Gobburu, J. and Green, T.P. (2019) Dosage regimens for meropenem in children with pseudomonas infections do not meet serum concentration targets. Clinical and Translational Science. November 6th. doi: 10.1111/cts.12710. .

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