ABSTRACT
Extended-interval dosing of gentamicin has several advantages over conventional multiple-daily dosing for the treatment of sepsis. The study was conducted to evaluate the pharmacokinetics of gentamicin for the treatment of neonatal sepsis in predetermined doses at 24- or 48-hour intervals, according to weight category, and to develop a simplified protocol for use in peripheral healthcare settings in developing countries. This prospective observational study was conducted among 59 neonates admitted to the Special Care Nursery at Dhaka Shishu Hospital, Bangladesh, with suspected sepsis and treated with antibiotics, including gentamicin. Intravenous dosing of gentamicin according to weight category was: 10 mg every 48 hours if the infant weighed < 2,000 g (n = 23), 10 mg every 24 hours if the infant weighed 2,000-2,249 g (n = 12), or 13.5 mg every 24 hours if the infant weighed 2,500-3,000 g (n = 24). Peak and trough concentrations of gentamicin and the presence of signs of nephrotoxicity and ototoxicity were determined. The mean +/- standard deviation peak concentration of gentamicin was 12.3 +/- 3.7 microg/mL in infants weighing < 2,000 g, 9.6 +/- 3.1 microg/mL in infants 2,000-2,249 g, and 10.0 +/- 3.4 microg/mL in infants 2,500-3,000 g. Initial peak concentration of gentamicin was > 12 microg/mL in 28.8% and initial trough concentration was > 2 microg/mL in 6.8% of the subjects. No signs of nephrotoxicity or ototoxicity were detected. Favourable pharmacokinetic parameters found with the simplified dosing regimen suggest that it is safe for the treatment of neonatal sepsis.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Gentamicins/administration & dosage , Infant, Newborn, Diseases/drug therapy , Sepsis/drug therapy , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/therapeutic use , Bangladesh , Body Weight , Clinical Protocols , Developing Countries , Drug Administration Schedule , Female , Gentamicins/pharmacokinetics , Gentamicins/therapeutic use , Humans , Infant, Newborn , Infant, Newborn, Diseases/blood , Infusions, Intravenous , Male , Observation , Sepsis/bloodABSTRACT
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.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Drug Administration Schedule , Gentamicins/therapeutic use , Sepsis/drug therapy , Body Weight/physiology , Developed Countries , Developing Countries , Dose-Response Relationship, Drug , Female , Humans , Infant, Newborn , Male , Treatment OutcomeABSTRACT
BACKGROUND: Infectious diseases account for an estimated 36% of neonatal deaths globally. The purpose of this study was to determine safe, effective, simplified dosing regimens of gentamicin for treatment of neonatal sepsis in developing countries. METHODS: Neonates with suspected sepsis in the neonatal intensive care unit (NICU) at Christian Medical College and Hospital (CMC), Vellore, India (n = 49), and Dhaka Shishu Hospital (DSH), Bangladesh (n = 59), were administered gentamicin intravenously according to the following regimens: (1) 10 mg every 48 hours for neonates <2000 g; (2) 10 mg every 24 hours for neonates 2000-2249 g; and (3) 13.5 mg every 24 hours for neonates > or =2500 g. Serum gentamicin concentration (SGC) at steady state and pharmacokinetic indices were determined. Renal function was followed while under treatment and hearing was examined 6 weeks to 3 months after discharge. RESULTS: All neonates, except 1 weighing 2000-2249 g at DSH, had a peak SGC >4 microg/mL. Overall, 5 (10%) and 17 (29%) infants had a peak SGC level > or =12 microg/mL from CMC and DSH, respectively, and 10 (20%) and 4 (7%) cases from CMC and DSH, respectively, had a trough SGC level > or =2 microg/mL. However, no infant <2000 g had a trough SGC level > or =2 microg/mL. We found no evidence of gentamicin nephrotoxicity or ototoxicity. CONCLUSION: Safe, therapeutic gentamicin dosing regimens were identified for treatment of neonatal sepsis in developing country settings. Administration of these doses could be simplified through use of Uniject, a prefilled, single injection device designed to make injections safe and easy to deliver in developing country settings.
