Randomized, controlled trial comparing once daily and three times daily gentamicin in children with urinary tract infections.
OBJECTIVE
To undertake population pharmacokinetic modeling and to determine the safety and efficacy of once daily (OD) gentamicin dosing in children with severe urinary tract infections (UTI).


METHODS
An open, randomized, controlled trial comparing OD with three times daily (TD) gentamicin dosing in hospitalized children ages 1 month to 12 years with UTI. Daily doses (milligrams per kg per day) of gentamicin in both groups were 7.5 (<5 years old), 6.0 (5 to 10 years old) and 4.5 (>10 years old).


RESULTS
There were 179 children enrolled (90 OD, 89 TD). Baseline clinical characteristics and pathogens were similar, except that circulatory compromise and renal cortical scintigraphic defects were more common in the OD group. Median gentamicin treatment durations were 3.0 (OD) and 2.7 (TD) days. Mean peak gentamicin concentrations were 17.3 (OD) vs. 6.4 (TD) mg/l; 99% of peak concentrations were >7 mg/l in the OD group whereas 16% of peak concentrations were <5 mg/l in the TD group. Mean trough concentrations were 0.35 (OD) vs. 0.55 (TD) mg/l. In the OD group 4% of trough concentrations were > or = 2 mg/l, whereas in the TD group only 0.7% were > or = 2 mg/l. Age or prior elevated peak concentrations did not predict high trough concentrations. Population pharmacokinetic modeling of the data fitted a one-compartment model with first order elimination. There were no clinical or bacteriologic failures. The two disease-related complications were confined to the OD group. No nephro- or ototoxicity was identified.


CONCLUSIONS
With age-appropriate dosing and measurement of serum trough concentrations before the second dose, OD gentamicin is safe and effective for the treatment of UTI requiring parenteral treatment in children aged 1 month to 12 years.
Carapetis
J R
JR
Department of Microbiology and Infectious Diseases, Royal Children's Hospital, University of Melbourne, Australia.
Jaquiery
A L
AL
Buttery
J P
JP
Starr
M
M
Cranswick
N E
NE
Kohn
S
S
Hogg
G G
GG
Woods
S
S
Grimwood
K
K
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D013997:Time Factors; D014552:Urinary Tract Infections / Q000188:drug therapy*
D000900:Anti-Bacterial Agents; D005839:Gentamicins