Comparison of 5 milligrams of netilmicin per kilogram of body weight once daily versus 2 milligrams per kilogram thrice daily for treatment of gram-negative pyelonephritis in children

Abstract

The efficacy and safety of netilmicin, 5 mg/kg of body weight once daily or 2 mg/kg thrice daily for 10 days, for the treatment of gram-negative pyelonephritis in children were compared in a prospective, randomized trial. Explicit criteria were used to define the site of infection, treatment outcome, and adverse effects.Netilmicin was given to 74 children once daily and to 70 children three times daily. At 1 week posttreatment, 73 (99%) of 74 children treated with netilmicin once daily and 70 (100%) of 70 children treated with netilmicin three times daily were cured. At 4 weeks posttreatment, no relapse was detected and the rate of reinfection was essentially identical in the two treatment groups. Peak serum netilmicin concentrations were higher in patients given the once-daily regimen, whereas a higher trough level was detected in patients given the three-times-daily regimen. Nephrotoxicity, which was defined as an increase in the serum creatinine level of >0.3 mg/dl over the baseline, was rare (3%) and reversible and occurred regardless of the treatment regimen. Ototoxicity, which was assessed by pure-tone audiometry (250 to 8,000 Hz) and brain stem-evoked response (6,000 Hz), occurred in 2 of 32 children who were evaluated. In these two children, who were given the once-daily regimen, wave V was not evokable monolateraily below 25 and 40 dB normal hearing level, respectively. Thus, it may be possible to treat childhood pyelonephritis with netilmicin once daily. However

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

“…However it is opportune to have a netilmicin serum concentration of 5-12 μg/ml. The trough concentration obtained with 6 μg/ml every 36 h [33] is lower than that obtained after 2.5 mg/kg twice daily [34] and with 2 mg/kg thrice daily [55]. This suggests that the extended-interval dosing regimen is safer than fractioning the dose of netilmicin during the day.…”

Treatment of Urinary Tract Infections Among Febrile Young Children With Daily Intravenous Antibiotic Therapy at a Day Treatment Center

“…Administration of IV gentamicin every 24 hours for the treatment of APN is considered appropriate for children with adequate renal function. 1 Three trials provide data to support the safety and efficacy of ODD with aminoglycosides (gentamicin 7,8 and netilmicin 9 ), compared with 8-hourly or standard daily dosing, for children with APN. The effectiveness of ODD with 5 mg/kg IV gentamicin for the treatment of pediatric UTI has been demonstrated, 8 and daily doses of 7.5 mg/kg gentamicin have been used in some studies.…”

Extended-Interval Aminoglycoside Administration for Children: A Meta-analysis

“…The pooled ototoxicity rates for studies that provided auditory testing results 21,23,25,[35][36][37][38][39][40]42,44,46,47 were 2.3% (10 of 436 cases) in the ODD arms and 2.0% (8 of 406 cases) in the MDD arms. The fixedeffects risk ratio was 1.06 (95% CI: 0.51-2.19; P ϭ .92) ( Table 3).…”

“…Twenty-four eligible studies [21][22][23][24][25][26][27][28][29][30][31][35][36][37][38][39][40][41][42][43][44][45][46][47] published between 1991 and 2003 were identified (Table 1). Aminoglycosides were used in different clinical settings (neonatal intensive care unit: 6 studies; cystic fibrosis: 3 studies; cancer: 5 studies; urinary tract infections: 4 studies; diverse infectious indications: 5 studies; pediatric intensive care unit: 1 study).…”