One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates

Abstract

One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates.

Neonatal gram-negative infections, antibiotic susceptibility and clinical outcome: an observational study

“…However, peak concentrations are rarely measured in routine neonatal practice, which is focused around gentamicin trough levels and the prevention of ototoxicity and nephrotoxicity, and we do not know the peak concentrations of participants in this study. However, the recommended gentamicin dosing regimen of 4–5 mg/kg/dose,8 which was followed by all NNUs in this study, has been shown to achieve these target peak concentrations 23…”

Dose optimisation of antibiotics in children: application of pharmacokinetics/pharmacodynamics in paediatrics

“…This PK/PD target has been reproduced in several other studies in adults [17,18] and is often utilised when deriving individualised PK dosing regimens in children. Although traditional dosing of aminoglycosides involved multiple daily administrations, optimal dosing strategies include high doses administered once daily [19,20]. Such extended-interval dosing takes advantage of the concentration-dependent bactericidal activity of the drugs and is clinically aided by the substantial PAE and leukocyte enhancement, minimising bacterial re-growth after the serum concentration has fallen below the bacterial MIC [14].…”

“…Nephrotoxicity is linked to drug accumulation, which occurs due to binding of the medication to the brush borders of renal cells [21]. Low sustained concentrations result in more effective uptake in these tissues than when exposed to high intermittent levels [20]. Ototoxicity is due to production of free radicals that damage cochlear and vestibular hair cells [22].…”

“…In the case of gentamicin administration for neonatal sepsis, goal peak serum concentrations should be >8–10 μg/mL when treating organisms with an MIC of ≤1 μg/mL, and goal trough concentrations should be <0.5–1 μg/mL prior to re-dosing [19,20]. This represents a prime example for the utility of individualised dose optimisation, as personalised adaptation improves outcomes by reducing toxicity and decreases healthcare costs [27].…”

Therapeutic drug monitoring in neonates

“…This approach is supported by observations of reduced nephrotoxicity in children, but there is only indirect (ie, more TDM observations on target) evidence in neonates 22. Extended interval dosing for aminoglycosides results in the administration of higher doses in order to achieve higher peak concentrations (C max , improved bactericidal effect) and a C max /pathogen specific minimal inhibitory concentration (MIC) ratio >8, with longer time intervals between administration resulting in lower trough concentrations (less adaptive resistance, reduced toxicity) 2 23.…”