AIMS: To assess (i) the safety of once daily dosing (ODD) of gentamicin by systematic evaluation of ototoxicity and nephrotoxicity; and (ii) the usefulness of therapeutic drug monitoring (TDM) in a paediatric cohort. METHOD: Infants and children with suspected or proven gram negative sepsis were enrolled prospectively to receive ODD gentamicin at 7 mg/kg/day. Neonates were excluded. Hearing and renal function were assessed at baseline, during and after therapy by otoacoustic emissions (OAE) and by either serum creatinine or glomerular filtration rate. Abnormal OAE were followed with audiometry. TDM was performed using an interval adjusted graphical method (Hartford nomogram) with levels taken between 6-14 hours after dose. Assessment of efficacy (clinical and microbiological) was a secondary outcome measure. RESULTS: There were 106 episodes of therapy in 79 children (median age 5.6 years; range 1 month - 16 years), 60% of which were for febrile neutropaenia. Evaluation was complete in 88% (93/106) for ototoxicity and 92% (98/106) for nephrotoxicity. Two children (1.88%, 95% CI 0.10 - 7.13) experienced permanent hearing loss. Three children did not complete full assessment after preliminary abnormalities on OAE. Incorporating these cases gives a ???worst case scenario??? incidence of 4.71% (95% CI 1.71 - 10.91) possible ototoxicity. One child (0.94%, 95% CI < 0.10 - 5.73) experienced transient nephrotoxicity. No ???toxic??? serum gentamicin levels were detected, including in those children who experienced clinical toxicity. All children with detectable toxicity were undergoing treatment for malignancies and had received nephro or ototoxic medications prior to the gentamicin course. Complete or partial efficacy was seen in 93% (non oncology) and 78% (oncology) treatment episodes, equivalent to prior literature reports. CONCLUSION: In this systematically evaluated paediatric cohort receiving ODD gentamicin, toxicity occurred infrequently and only in those with identifiable risk factors. TDM did not identify children who developed clinical toxicity. The development of toxicity appears to be associated with factors such as underlying medical condition, prior courses of gentamicin, exposure to other oto or nephrotoxic medications, all of which may be more predictive of toxicity than elevated serum gentamicin levels. TDM in healthy children on short course gentamicin appears unnecessary, but may be warranted in conjunction with renal and hearing assessments in those with risk factors.
| Identifer | oai:union.ndltd.org:ADTP/242583 |
| Date | January 2007 |
| Creators | Best, Emma, Women's & Children's Health, Faculty of Medicine, UNSW |
| Publisher | Awarded by:University of New South Wales. |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Emma Best, http://unsworks.unsw.edu.au/copyright |
Page generated in 0.0021 seconds