title: Extended-interval dosing of gentamicin for treatment of neonatal sepsis in developed and developing countries.
abstract: 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.
authors.affiliation: Department of International Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. gdarmsta@jhsph.edu
authors.forename: Gary L
authors.initials: GL
authors.lastname: Darmstadt
authors.forename: Mary
authors.initials: M
authors.lastname: Miller-Bell
authors.forename: Maneesh
authors.initials: M
authors.lastname: Batra
authors.forename: Paul
authors.initials: P
authors.lastname: Law
authors.forename: Kiely
authors.initials: K
authors.lastname: Law
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000502:physiology; D019049:Developed Countries; D003906:Developing Countries; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D018805:Sepsis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins