Dose
There is insufficient evidence whether a 'once a day' regimen of gentamicin is optimal in treating proven neonatal sepsis, however, pharmacokinetic data suggests 'once a day' gentamicin regimens are superior to a 'multiple doses a day' regimens.(17) (LOE I, GOR B)
The recommended dose regimen in this formulary is a pragmatic adaptation of the dosing used in 4 prospective observational studies.(2-5) (LOE III-3, GOR B)
Dose adjustment
An increased dosing interval is recommended in therapeutic hypothermia.(9-13) (LOE IV, GOR B)
An increased dosing interval is recommended in infants on cyclo-oxygenase inhibitors.(6) (LOE IV, GOR B)
Monitoring
The evidence suggests a serum gentamicin concentration performed 22 hours after the 1st dose is useful to guide dosing intervals. (2-4)(LOE III-3, GOR B). However, in daily practice, gentamicin is most often discontinued within 36-48 hours of commencement (once the neonate is deemed no longer at risk of sepsis and septic screen remain negative). Therefore, measurement of drug concentrations is recommended only after the 2nd dose to limit the burden of blood sampling. (ANMF consensus recommendation).
Subsequent concentrations are not routinely required. (2-4) (LOE III-3, GOR B)
Routine peak concentrations are not necessary as high dose extended interval dosing regimens are able to achieve target peak concentrations in the majority of infants (2-4, 17, 18) (LOE III-3, GOR B)
Consider performing peak concentrations if there is poor clinical response in gram negative infections, oedema or macrosomia.(5) (LOE IV, GOR C).
A peak concentration, if required, can be performed after the 2nd or 3rd dose. (29)
Target peak concentrations of 5─12 mg/L. (17-19, 29) (LOE IV, GOR C)
Target trough concentrations of < 2 mg/L to reduce risk of ototoxicity and nephrotoxicity. (33, 34) (LOE IV, GOR C - adult)
Duration of therapy ≥ 7 days – Perform trough concentration prior to dose on day 7 and then weekly thereafter. (4, 35) (LOE IV, GOR B)
Perinatal hypoxia – Perform trough concentrations prior to every dose. (4, 35) (LOE IV, GOR B)
Renal impairment – Perform trough concentrations prior to every dose. (4, 35) (LOE IV, GOR B)
Concomitant use of other nephrotoxic agents – Perform trough concentrations prior to every dose. (4, 35) (LOE IV, GOR B)
ECMO – Perform trough concentration before 2nd dose.(14) (LOE IV, GOR B)
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