[Clinical, pharmacokinetic and therapeutic study of amikacin with single daily dose and in combination in neutropenic children with fever].
BACKGROUND
The efficacy of single daily dose of amikacin has been recently demonstrated in neutropenic children with fever.


METHODS
Eighteen children aged 1 to 15 years were included in the study. All patients were febrile and granulocytopenic and had indwelling intravenous catheter. Amikacin was administered as a 30-minute intravenous infusion once daily (20 mg/kg on day 1, then 15 mg/kg) for 3 to 30 days; the patients received amikacin in combination with piperacillin and vancomycin. Serum levels of amikacin were measured on days 1, 3, 6 and 10, and 30 min, 60 min and 180 min after the end of the infusion.


RESULTS
All patients responded favourably to the antibiotic therapy. Sixty-two kinetics were performed: peak amikacin concentrations measured (30 min after 30-min infusion) on day 1 averaged 43.7 micrograms/mL (+/- 13.8). A significant increase in peak serum concentrations was observed during the treatment (day 3 vs day 10) without change in the trough serum concentrations. The volumes of distribution were considerably important in these granulocytopenic children and there was a large inter and intra-patient variability; the elimination half-life of the amikacin was short (1.45 h). There was no significant nephrotoxicity in any patient.


CONCLUSIONS
The use of single daily dose amikacin in combination with a broad spectrum beta-lactam antibiotic and vancomycin was efficient and safe in febrile granulocytopenic children. The simulation of the amikacin behaviour in the deep compartment should be evaluated; in fact, it might reflect better accumulation of the drug than serum concentrations.
Bertrand
Y
Y
Service d'hématologie-immunologie pédiatrique et de transplantation de moelle osseuse, Institut Pasteur, France.
Bréant
V
V
Vray
C
C
Nakache
C
C
Barbé
G
G
Dürr
F
F
Aulagner
G
G
D000293:Adolescent; D000583:Amikacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D005334:Fever / Q000150:complications*; D006801:Humans; D007223:Infant; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy*; D010406:Penicillins / Q000008:administration & dosage / Q000627:therapeutic use; D010878:Piperacillin / Q000008:administration & dosage / Q000627:therapeutic use; D014640:Vancomycin / Q000008:administration & dosage / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D010406:Penicillins; D014640:Vancomycin; D000583:Amikacin; D010878:Piperacillin
Etude clinique, pharmacocinétique et thérapeutique de l'amikacine en dose unique journalière et en association chez l'enfant neutropénique fébrile.