TY - JOUR
T1 - Once-daily gentamicin in infants and children
T2 - A prospective cohort study evaluating safety and the role of therapeutic drug monitoring in minimizing toxicity
AU - Best, Emma J.
AU - Gazarian, Madlen
AU - Cohn, Richard
AU - Wilkinson, Monica
AU - Palasanthiran, Pamela
PY - 2011/10
Y1 - 2011/10
N2 - 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.
AB - 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.
KW - adverse drug reaction reporting systems
KW - aminoglycosides
KW - drug monitoring
KW - drug toxicity
KW - gentamicins
KW - hearing loss
KW - MeSH
KW - sensorineural (etiology)
UR - http://www.scopus.com/inward/record.url?scp=80052955039&partnerID=8YFLogxK
U2 - 10.1097/INF.0b013e31821e405d
DO - 10.1097/INF.0b013e31821e405d
M3 - Article
VL - 30
SP - 827
EP - 832
JO - Pediatric Infectious Disease Journal
JF - Pediatric Infectious Disease Journal
SN - 0891-3668
IS - 10
ER -