Extended-interval Dosing of Gentamicin for Treatment of Neonatal Sepsis in Developed and Developing Countries

Serious bacterial infections are the single most important cause of neonatal mortality in developing countries. Case-fatality rates for neonatal sepsis in developing countries are high, partly because of inadequate administration of necessary antibiotics. For the treatment of neonatal sepsis in resource-poor, high-mortality settings in developing countries where most neonatal deaths occur, simplified treatment regimens are needed. Recommended therapy for neonatal sepsis includes gentamicin, a parenteral aminoglycoside antibiotic, which has excellent activity against gram-negative bacteria, in combination with an antimicrobial with potent gram-positive activity. Traditionally, gentamicin has been administered 2-3 times daily. However, recent evidence suggests that extended-interval (i.e. ≥ 24 hours) dosing may be applicable to neonates. This review examines the available data from randomized and non-randomized studies of extended-interval dosing of gentamicin in neonates from both developed and developing countries. Available data on the use of gentamicin among neonates suggest that extended dosing intervals and higher doses (>4 mg/kg) confer a favourable pharmacokinetic profile, the potential for enhanced clinical efficacy and decreased toxicity at reduced cost. In conclusion, the following simplified weight-based dosing regimen for the treatment of serious neonatal infections in developing countries is recommended: 13.5 mg (absolute dose) every 24 hours for neonates of ≥ 2,500 g, 10 mg every 24 hours for neonates of 2,000-2,499 g, and 10 mg every 48 hours for neonates of <2,000 g.

Keywords
Developing countries; Drug therapy; Gentamicin; Infant, Newborn; Pharmacokinetics; Review literature; Sepsis