Extended Interval Dosing of Gentamicin in Neonates

Extended Interval Dosing of Gentamicin in Neonates to Achieve Target Drug Concentrations

A previous pharmacy residency project was done 20 years ago looking at the best dosing for the antibiotic gentamicin for babies up to 7 days old. This study showed that giving the dose less often leads to better drug concentrations than giving the dose more often. Our gentamicin dosing at the Children's Hospital at London Health Sciences Centre is based on the better dosing from the study. This dosing is gentamicin 3 mg/kg every 24 hours for babies less than 35 weeks gestational age and 3.5 mg/kg every 24 hours for babies at least 35 weeks gestational age. These results were never published. Different dosing is used at different hospitals. It is important that we check that our gentamicin dosing is still reaching safe and effective drug concentrations in the current study. The study will look at the gentamicin drug concentrations of babies up to 7 days old, including premature and term babies. We will also confirm if the babies have kidney or hearing damage from gentamicin. We will compare the gentamicin drug concentrations from this study to the past data to see if the dosing is still the best. The results can help form a guideline for the Children's Hospital and surrounding hospitals.

Study Overview

• Status: Recruiting
• Conditions: Early Onset Sepsis
• Intervention / Treatment: Other: Standard of care administration of gentamicin dosed at 3 mg/kg every 24 hours; Other: Standard of care administration of gentamicin dosed at 3.5 mg/kg every 24 hours

Detailed Description

Current gentamicin dosing at the Children's Hospital is based on the previous projects completed at LHSC. Different gentamicin dosing recommendations exist depending on the reference used. This study would help validate if the current extended interval dosing in neonates is still achieving target gentamicin concentration levels. We will compare the results of the current study to our historic data. The results will help determine if infants are receiving effective and safe treatment with gentamicin. Depending on the results of the study, further evaluation on changes to gentamicin dosing may be needed or an official guideline may be published if gentamicin levels are being adequately achieved with the current dosing. This official guideline will help prescribers at the Children's Hospital and hospitals in the surrounding region that will adopt our dosing when treating infants. There will be an overall benefit to prescribers and patients ensuring safe and effective of gentamicin dosing is followed. If the infant meets the study inclusion criteria, a letter of information will be provided to the parent(s)/guardian(s) if agreeable using REDCap. Consent must be obtained prior to enrollment.

• Study Type: Observational
• Enrollment (Estimated): 42

Contacts and Locations

• Study Contact: Name: Sarah H.P. Vo, PharmD; Phone Number: 52162 519-685-8500; Email: sarah.vo@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • Children's Hospital: London Health Sciences Centre
      • Contact: Venita Harris, BScPharm, PharmD; Phone Number: 52642 519-685-8500; Email: venita.harris@lhsc.on.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Neonates admitted to the Neonatal Intensive Care Unit, Paediatric Critical Care Unit (PCCU), or Paediatrics Unit (B6) at the Children's Hospital, London Health Sciences Centre

Description

Inclusion Criteria:

• Neonates up to 7 days of age,
• Neonate must be on gentamicin, and
• Gentamicin trough and peak levels must be available for the third dose of gentamicin.

Exclusion Criteria:

• Incorrect dose for weight (+/- 10% allowed to account for dose rounding)
• Multiple levels from the same patient; only the first set of levels will be collected
• Baseline renal dysfunction (e.g. congenital kidney disease)
• On other nephrotoxic or ototoxic drugs concurrently with the first 3 days of gentamicin

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Neonates less than 35 weeks gestational age	Other: Standard of care administration of gentamicin dosed at 3 mg/kg every 24 hours; No interventions will be made to the neonates. Standard of care will be followed with empiric gentamicin and levels ordered for the neonates at the discretion of the medical team.
Neonates at least 35 weeks gestational age	Other: Standard of care administration of gentamicin dosed at 3.5 mg/kg every 24 hours; No interventions will be made to the neonates. Standard of care will be followed with empiric gentamicin and levels ordered for the neonates at the discretion of the medical team.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trough gentamicin levels	The primary objective is to measure and monitor the number of trough gentamicin levels within target range < 2 mg/L with the current extended interval dosing regimen compared to traditional dosing in neonates ≤ 7 days of age.	Day 3 of treatment: prior to the third gentamicin dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak gentamicin levels	Maintain peak gentamicin levels within target range (6-10 mg/L)	Day 3 of treatment: following the third gentamicin dose
Incidence of suspected nephrotoxicity	Monitor the incidence of suspected nephrotoxicity (serum creatinine > 53 umol/L, Blood Urea Nitrogen (BUN) > 10 mmol/L, and urine output < 1 mL/kg/h)	Seven days after discontinuation of gentamicin
Incidence of suspected ototoxicity	Monitor the incidence of suspected ototoxicity (failed on newborn hearing screening) in different dosing regimens. Newborn hearing screening tests follow electrophysiological methods with automated distortion product otoacoustic emissions and automated auditory brainstem response	Up to 7 days following gentamicin discontinuation while infant is still admitted in hospital

Collaborators and Investigators

• Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
• Investigators: Principal Investigator: Venita Harris, PharmD, London Health Sciences Centre

Publications and helpful links

General Publications

• Kearns GL, Abdel-Rahman SM, Alander SW, Blowey DL, Leeder JS, Kauffman RE. Developmental pharmacology--drug disposition, action, and therapy in infants and children. N Engl J Med. 2003 Sep 18;349(12):1157-67. doi: 10.1056/NEJMra035092. No abstract available.
• Core Lab [Phone correspondence]. London; 2025 October 10. Analytical range of gentamicin concentrations.
• van Maarseveen EM, Sprij A, Touw DJ. Extended-Interval Dosing of Gentamicin Aiming for a Drug-Free Period in Neonates: A Prospective Cohort Study. Ther Drug Monit. 2016 Jun;38(3):402-6. doi: 10.1097/FTD.0000000000000283.
• Konig K, Lim A, Miller A, Saker S, Guy KJ, Barfield CP. Gentamicin trough levels using a simplified extended-interval dosing regimen in preterm and term newborns. Eur J Pediatr. 2015 May;174(5):669-73. doi: 10.1007/s00431-014-2450-z. Epub 2014 Nov 12.
• The Hospital for Sick Children Electronic Formulary [Internet]. c2025 [cited 2025 November 24]. Gentamicin.
• El-Chaar GM, Supaswud-Franks T, Venugopalan L, Kohn N, Castro-Alcaraz S. Extended-interval gentamicin administration in neonates: a simplified approach. J Perinatol. 2016 Aug;36(8):660-5. doi: 10.1038/jp.2016.37. Epub 2016 Mar 17.
• Fullas F, Padomek MT, Thieman CJ, Van Gorp AE. Comparative evaluation of six extended-interval gentamicin dosing regimens in premature and full-term neonates. Am J Health Syst Pharm. 2011 Jan 1;68(1):52-6. doi: 10.2146/ajhp100114.
• Rao SC, Srinivasjois R, Moon K. One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev. 2016 Dec 6;12(12):CD005091. doi: 10.1002/14651858.CD005091.pub4.
• LexiDrug (Pediatric & Neonatal Lexi-Drugs) [Internet]. c2025 [cited 2025 November 24]. Gentamicin (Systemic).
• LexiDrug [Internet]. c2025 [cited 2025 November 24]. Gentamicin (Systemic).
• Hodiamont CJ, van den Broek AK, de Vroom SL, Prins JM, Mathot RAA, van Hest RM. Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review. Clin Pharmacokinet. 2022 Aug;61(8):1075-1094. doi: 10.1007/s40262-022-01143-0. Epub 2022 Jun 27.
• Yun A. Extended Interval Dosing of Gentamicin in Neonates. Pharmacy Residency Manuscript 2005-2006.

Helpful Links

• Stanford Health Care Aminoglycoside Dosing Guideline
• CHEO Outreach - Gentamicin
• Children's Hospital London Health Sciences Centre - Neonatal Intensive Care Unit - Gentamicin
• London Health Sciences Centre Pathology and Laboratory Medicine - Gentamicin
• PROTOCOL FOR UNIVERSAL NEWBORN HEARING SCREENING IN ONTARIO

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: February 26, 2026
• First Submitted That Met QC Criteria: March 3, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 9, 2026
• Last Update Submitted That Met QC Criteria: June 5, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: neonates; gentamicin; extended interval dosing
• Other Study ID Numbers: 128253

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: This is a small scale cohort study that is less likely to be useful for a wider population. Our ethics submission did not include a plan to share the study database.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No