Meropenem pharmacokinetics in children and adolescents receiving hemodialysis

The emergence of multi-drug-resistant bacteria is of great concern to the care of pediatric end-stage renal disease (ESRD) patients who receive either hemodialysis or peritoneal dialysis via a catheter. Infections with gram-negative organisms, especially Pseudomonas aeruginosa, are difficult to eradicate and often necessitate catheter removal. Meropenem, a broad-spectrum antibiotic of the carbapenem class of beta-lactams, is effective against most gram-positive and gram-negative bacteria and has enhanced activity against P. aeruginosa. We studied the pharmacokinetics of meropenem during and between hemodialysis treatments in seven pediatric patients. Meropenem was given as a single dose of 20 mg/kg (maximum 500 mg) before and after two separate hemodialysis treatments. Meropenem administration was tolerated without any adverse effects. Hemodialysis effectively cleared meropenem in a manner that correlated with percent urea reduction. Median drug half-life was 7.3 h off dialysis (range 4.9-11.7 h). The dose of 20 mg/kg was not sufficient to produce an acceptable interdialytic pharmacodynamic profile of 70% duration with a meropenem concentration >4 microg/ml, the MIC90 of meropenem for P. aeruginosa. Dosing simulations revealed that a daily dose of 25 mg/kg or an alternate day dose of 40 mg/kg would result in an acceptable pharmacodynamic profile. Both simulated doses achieved acceptable peak concentrations.