Background: Animal studies and trials in older children and adults suggest that a one dose per day regimen of gentamicin is superior to a multiple doses per day regimen.
Objectives: To compare the efficacy and safety of one dose per day compared to multiple doses per day of gentamicin in suspected or proven sepsis in neonates.
Search methods: Eligible studies were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, April 2011), MEDLINE (1966 to April 2011), EMBASE 1980 to April 2011, and CINAHL (December 1982 to April 2011). Abstracts of the Society for Pediatric Research were searched from 1980 to 2010 inclusive.
Selection criteria: All randomised or quasi randomised controlled trials comparing one dose per day ( 'once a day') compared to multiple doses per day ( 'multiple doses a day') of gentamicin to newborn infants < 28 days of life.
Data collection and analysis: Data collection and analysis was performed according to the standards of the Cochrane Neonatal Review Group.
Main results: Eleven studies were included (N = 574) and nineteen excluded. All infants in both 'once a day' as well as 'multiple doses a day' regimen showed adequate clearance of sepsis [typical RD 0.00 (95% CI - 0.19 to 0.19); 3 trials; N = 36]. For the other primary outcome measures relating to gentamicin pharmacokinetics 'once a day' dosing of gentamicin was superior. 'Once a day' gentamicin regimen was associated with less failures to attain peak level of at least 5 µg/ml [typical RR 0.22 (95% CI 0.11 to 0.47); 9 trials; N = 422] and less failures to achieve trough levels of < 2 µg/ml [typical RR 0.38 (95% CI 0.27 to 0.55); 11 trials N = 503] compared to 'multiple doses a day' regimen.Ototoxicity and nephrotoxicity were not noted with either of the treatment regimens.
Authors' conclusions: There is insufficient evidence from the currently available RCTs to conclude whether 'once a day' or 'multiple doses a day' regimen of gentamicin is superior in treating proven neonatal sepsis. However, data suggests that pharmacokinetic properties of 'once a day' gentamicin regimen are superior to 'multiple doses a day' regimen in that it achieves higher peak levels while avoiding toxic trough levels. There is no change in nephrotoxicity or auditory toxicity. Based on this assessment of pharmacokinetics, 'once a day regimen' may be superior in treating neonatal sepsis in neonates greater than 32 weeks gestation.