Trough Concentration of Meropenem in Term, Preterm and Growth-Restricted Neonates

Abstract

Objective: The success of drug therapy is directly dependent on administration of the optimal dose at the ideal dosing interval. The limited pharmacokinetic data of meropenem currently available in neonates suggest that drug disposition differs substantially from that in adults. Therefore, present study aims to analyse the effects of factors like prematurity and gestational age, especially low birth weight on concentrations of meropenem in term, preterm and growth-restricted term neonates and accordingly determine the optimal dose and dose interval in these neonates. Methods: It was a cross sectional analytical study of neonates who were receiving meropenem in the nursery of pediatrics department at Safdarjung Hospital. Seventy-five patients were successfully recruited in the study and divided into 3 groups with 25 subjects in each group-Group A: term neonates (37-42 w gestational age), Group B: preterm neonates (<37 w gestational age), Group C: small-for-date neonates (<10th percentile for gestational age). All the patients received meropenem, 20-40 mg/kg i. v. 8 hourly (60-120 mg/kg/day) by slow i. v. infusion over 30-60 min and meropenem concentration in the plasma was determined by High-Performance Liquid Chromatography (HPLC). Results: The mean concentration of meropenem in term, preterm and SGA neonates was found to be 10.14±1.53 µg/ml, 11.52±2.53 µg/ml, and 10.75±2.26 µg/ml, respectively. Although the mean concentration of meropenem in preterm group was slightly higher than the other groups, however on applying ANOVA test the results were not found to be satistically significant, with a p-value of 0.082 (p>0.05), implying that there is no significant effect of prematurity and growth restriction on serum concentration of meropenem. The concentration of meropenem was found to be above the 4 times the MIC of common pathogens involved in neonatal sepsis for the total duration of therapy. Conclusion: The current protocol of antimicrobial treatment of meropenem being followed in the department of Pediatrics at Safdarjung Hospital was found to well serve its objective. The blood levels of meropenem were found to be above four times the MIC value of organisms commonly implicatd in neonatal sepsis. It is thus recommended that the present protocol of meropenem therapy continue at Safdarjung Hospital for neonatal sepsis.