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Several physicians at our institution have written orders for pediatric
patients to receive 5-7mg/kg/day doses of gentamicin/tobramycin, and
15mg/kg/day of amikacin. Our pharmacy dosing service does not authorize this
dosing method in pediatric patients because of limited safety/efficacy data.
I have done several literature searches, and have not been able to find any
information regarding once daily aminoglycoside dosing in pediatric patients.
Is anyone out there doing "high dose" gentamicin/tobramycin/amikacin dosing
in children/neonates? Does anyone know if true controlled studies have even
been done on this?
R. Timothy Gendron, RPh.
Inpatient Clinical Coordinator
Naval Medical Center
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There is one study that I know of using once-daily aminoglycosides in full
term neonates. The dose used was 4mg/kg with the aim being to keep the
concentrations within the normal therapeutic range (peak 4 to 12, trough
<2). The study was published in The Pediatric Infectious Disease Journal,
Vol 14, No 1, January 1995, pg 71-72. I would be interested if anyone knows
of any other publications & if anyone is using this approach in full term
Baton Rouge, LA
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Here are a few references. There are few data on "standard" dosing in
never mind high dose. Also, some studies of so-called "once daily" dosing
achieve "normal" target concentrations. This is especially true for neonates
where even "conventional" therapy demands long dosage intervals to achieve
reasonable peaks and troughs.
Kafetzis DA, Sianidou L, Vlachos E, Davros J, Bairamis T, Papandreou
Y, Paraskaki E, Scouroliakou M, Hadzis A, Papadatos J. Clinical and
pharmacokinetic study of a single dose of amikacin in paediatric
patients with severe Gram-negative infections. J Antimicrob Chemother
27 (Suppl C) 105-112, 1991.
Viscoli C, Dudley M, Ferrea G, Boni L, Castagola E, Barretta MA,
Lanino E, Loy A, Moroni C, Somenzi M, Stura M, Pozzo L. Serum
concentrations and safety of single daily dosing of amikacin in
children undergoing bone marrow transplantation. J Antimicrob
Chemother 27 (Suppl C) 113-120, 1991.
Trujillo H, Robledo J, Robledo C, Espinal D, Garces GN, Mejia J,
Restrepo C, Restrepo F, De Rodriquez GIM, de Guitierrez MCT. Single
daily dose amikacin in paediatric patients with severe gram-negative
infections. J Antimicrob Chemother. 27: (Suppl C) 141-147, 1991.
Marik PE, Lipman J, Kobilski S, Scribante J. A prospective randomised
study comparing once- versus twice-daily amikacin dosing in critically
ill adult and paediatric patients. J Antimicrob Chemother 28: 753-764,
Bouffet E, Fuhrmann C, Frappaz D, Couillioud D, Artiges V, Charra C,
Bouhour D, Brunat Mentigny M. Once daily antibiotic regimen in
paediatric oncology. Arch Dis Child 70: 484-487, 1994.
Beaucaire G, Leroy O, Beuscart C, Karp P, Chidiac C, Caillaux M, Study
Group. Clinical and bacteriological efficacy, and practical aspects of
amikacin given once daily for severe infections. J. Antimicrob
Chemother 27 (Suppl C) 91-103, 1991.
Elhanan K, Siplovich L, Raz R. Gentamicin once-daily versus
thrice-daily in children. J. Antimicrob Chemother. 35: 327-332, 1995.
Skopnik H, Wallraf R, Nies B, Tr=F6ster K, Heimann G. Pharmacokinetics
and antibacterial activity of daily gentamicin. Arch Dis Child 67:
Skopnik H. Heimann G. Once daily aminoglycoside dosing in full term
neonates. Ped Inf Dis J. 14: 71-72, 1995.
Wagner BP, Pfenninger J. Once daily dosing of netilmicin in neonatal
and pediatric intensive care. Int Care Med. 20: 365-367, 1994.
Vigan=F2 A, Principi N, Brivio L, Tommasi P, Stasi P, Villa AD.
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. Antimicrob Agents
Chemother. 36: 1499-1503, 1992.
Clinical Pharmacokinetics & Biometrics Unit
Dept of Medicine & Therapeutics
West Glasgow Hospitals Trust
Glasgow G11 6NT
Tel #44 141 211 2022
=46ax #44 141 339 2800
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We use once-daily administrations of tobramycin in pediatric patients with
fibrosis, with dosage regimen adjustement with the Abbott PKS software. The
goal is to
obtain an AUC of about 50-75 mg.h/L (i.e. an average plasma concentration
mg/L). This usually results in peaks higher than 20 mg/L.
This approach has been recently validated (with amikacin) in a French MD
has been shown that a high peak facilitates the diffusion of the antibiotic
bronchial secretions, from which the antibiotic is released very slowly, thus
justifying the long time interval between administrations.
I hope this helps.
Laboratoire de Pharmacologie, Faculte de Medecine
2 Rue du Docteur Marcland, F-87025 Limoges, France
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