Early Onset Sepsis
Conditions
Keywords
gentamicin, extended interval dosing, neonates
Brief summary
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.
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.
Interventions
OTHERStandard 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.
OTHERStandard 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.
Sponsors
London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
0 Days to 7 Days
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Trough gentamicin levels | Day 3 of treatment: prior to the third gentamicin dose | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak gentamicin levels | Day 3 of treatment: following the third gentamicin dose | Maintain peak gentamicin levels within target range (6-10 mg/L) |
| Incidence of suspected nephrotoxicity | Seven days after discontinuation of gentamicin | 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) |
| Incidence of suspected ototoxicity | Up to 7 days following gentamicin discontinuation while infant is still admitted in hospital | 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 |
Countries
Canada
Contacts
CONTACTSarah H.P. Vo, PharmD
PRINCIPAL_INVESTIGATORVenita Harris, PharmD
London Health Sciences Centre
Outcome results
None listed