Bolus Versus Prolonged Infusion of Meropenem in Newborn With Late Onset Sepsis

Overview

Newborns in the neonatal intensive care unit (NICU), especially premature ones with immature organ systems, frequently suffer nosocomial infections caused by microorganisms resistant to narrow-spectrum antibiotics like ampicillin and gentamicin and require introduction of new agents with a wider spectrum of activity. Meropenem has activity against wide variety of Gram-negative and Gram-positive bacteria. It is well tolerated by children and neonates, including preterm babies, and allowing monotherapy instead of combined therapy. Severe neonatal infections with increasing antibiotic resistance are major problems affecting morbidity and mortality in the NICU. Few number of new antibacterial agents entering the clinic and new agents for multi-drug resistant Gram-negative bacteria will unlikely be available in the near future.

More research into existing antibiotics with novel mechanisms of action are required to combat the increased resistance and decreased development of antibiotics. Efforts were exerted to maximize antibiotic efficacy by optimal dosing based on pharmacodynamic and pharmacokinetic properties of antibiotics. Meropenem is administered mostly via a 30-min infusion, as some data indicate rapid degradation after reconstitution. Dose recommendations from two pediatric studies using Monte Carlo simulation have emphasized that a 4-h infusion may be needed if microorganisms showed increased minimal inhibitory concentrations (MICs), more specifically, for Pseudomonas aeruginosa. A prolonged-infusion strategy has not been tested in neonates, although some data suggest that extremely small infusion volumes may significantly affect the drug amount actually delivered. Aim of work: The objective of our study is to compare the clinical and bacteriological efficacy of conventional intermittent dosing of meropenem to the prolonged infusions in critically-ill neonates, with a proactive focus on reducing ventilator days in ventilated patients, length of stay in NICU, and neonatal mortality.