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Dose & administration
There are different schools of thought regarding gentamicin dosing in neonates and tertiary dosing references vary in their dosing recommendations.  Commonly accepted dosing regimens include both a gestational age based dosing approach as well as birth-weight based dosing approach. 

Doses range from 4-5mg/kg per dose administered every 24 to 48 hours with lower gestational ages requiring the higher weight based dosing and longer dosing interval than older gestational age infants. The NICE guidelines (UK) recommend 5 mg/kg every 36 hours as the starting dose.

The dose and interval should be guided by measurements of blood gentamicin concentrations, typically immediately before the second dose and before later doses if the serum concentration is high. The recommended concentration is < 2 mg/L.

Widely used in the NICU in combination with a beta lactam or other antibiotic as empiric therapy in both early onset and late onset sepsis.

Contraindications and special considerations (including incompatibilities)
Caution should be used in infants with decreased renal function or history that might suggest poor renal perfusion such as asphyxiation, indomethacin exposure, PDA, etc.

May interact with neuromuscular blockers.

Additional monitoring of gentamicin levels may be required during ECMO and/or therapeutic hypothermia as either may affect gentamicin pharmacokinetics. 

Target peaks of 8-12 mcg/mL; target troughs < 1 to minimize toxicity.

Due to incompatibility, gentamicin should not be administered in the same line with ampicillin, indomethacin, amphotericin B, and furosemide.

Adverse effects
May enhance neuromuscular blockade when administered concomitantly with neuromuscular blockers

Pharmacological  aspects
Gentamicin, like other aminoglycosides, exhibits its action by inhibiting protein synthesis by irreversibly binding to ribosomal RNA of the microorganism.  Gentamicin is active against Gram-negative bacteria including Pseudomonas aeruginosa.  It may be used with other agents for synergy against Gram-positive organisms, but should not be used alone to treat these infections.

Aminoglycosides are concentration dependent antibiotics.  They work best when the serum concentration of the drug reaches very high concentrations.  Conversely, they also possess a unique property known as post-antibiotic effect where bacterial killing continues to occur when the drug is no longer present in appreciable amounts in the bloodstream.

Neonatal infection: antibiotics for prevention and treatment. NICE guidelines [CG149]. 2012. https://www.nice.org.uk/guidance/CG149/
Effect of hypothermia and extracorporeal life support on drug disposition in neonates.  Seminars in Fetal & Neonatal Medicine.  2013; 18(1): 23-27. PMID 23158109.
Dose optimisation of antibiotics in children: application of pharmacokinetics/ pharmacodynamics in paediatrics.  Int J Antimicrob Agents. 2014 Mar;43(3):223-30.  PMID: 24389079.
Developmental pharmacokinetics of gentamicin in preterm and term neonates: population modelling of a prospective study.  Clin Pharmacokinet.  2009 Jan;48(4):253-63.  PMID: 19492870.

Document version history
Created 2016/06/22 / Amy Holmes

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