Once-daily gentamicin in infants and children

A prospective cohort study evaluating safety and the role of therapeutic drug monitoring in minimizing toxicity

Emma J. Best*, Madlen Gazarian, Richard Cohn, Monica Wilkinson, Pamela Palasanthiran

*Corresponding author for this work

    Research output: Contribution to journalArticle

    20 Citations (Scopus)

    Abstract

    BACKGROUND: The clinical evidence base for ototoxicity and nephrotoxicity outcomes with once-daily dosing (ODD) of gentamicin in children is suboptimal. Therapeutic drug monitoring (TDM) in once-daily gentamicin regimens is variable and its role in predicting or preventing clinical toxicity is unclear. We aimed to assess the safety of ODD of gentamicin and the usefulness of TDM in a pediatric cohort. METHODS: Children with suspected sepsis were prospectively enrolled to receive ODD of gentamicin at 7 mg/kg/day. Hearing and renal function were objectively assessed at baseline, during therapy, and after therapy. TDM was performed using an interval-adjusted graphical method (Hartford nomogram). RESULTS: A total of 79 children (median age: 5.6 years; range: 1 month-16 years) received 106 episodes of therapy. In all, 61% of these episodes were for febrile neutropenia. Evaluation was complete in 88% for ototoxicity and 92% for nephrotoxicity. Two patients (1.88%, 95% confidence interval: 0.10%-7.13%) experienced permanent hearing loss. One patient (0.94%, 95% confidence interval: <0.10%-5.73%) experienced transient nephrotoxicity. No abnormal serum gentamicin values were detected, even in those experiencing toxicity. Children experiencing toxicity were undergoing treatment for malignancies and had received nephrotoxic or ototoxic medicines before gentamicin. CONCLUSIONS: In this pediatric cohort receiving ODD of gentamicin, nephrotoxicity was uncommon and reversible, but irreversible ototoxicity occurred more frequently. TDM using a nomogram neither predicted nor prevented toxicity, which was only observed in those with risk factors.

    Original languageEnglish
    Pages (from-to)827-832
    Number of pages6
    JournalPediatric Infectious Disease Journal
    Volume30
    Issue number10
    DOIs
    Publication statusPublished - Oct 2011

    Keywords

    • adverse drug reaction reporting systems
    • aminoglycosides
    • drug monitoring
    • drug toxicity
    • gentamicins
    • hearing loss
    • MeSH
    • sensorineural (etiology)

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