[Clinical, pharmacokinetic and therapeutic study of amikacin with single daily dose and in combination in neutropenic children with fever]

Arch Pediatr. 1996 Sep;3(9):854-60. doi: 10.1016/0929-693x(96)87572-5.
[Article in French]

Abstract

Background: The efficacy of single daily dose of amikacin has been recently demonstrated in neutropenic children with fever.

Population and 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.

Conclusion: 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.

Publication types

  • English Abstract

MeSH terms

  • Adolescent
  • Amikacin / administration & dosage
  • Amikacin / blood
  • Amikacin / pharmacokinetics*
  • Amikacin / therapeutic use*
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / blood
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Drug Therapy, Combination
  • Fever / complications*
  • Humans
  • Infant
  • Neutropenia / complications
  • Neutropenia / drug therapy*
  • Penicillins / administration & dosage
  • Penicillins / therapeutic use
  • Piperacillin / administration & dosage
  • Piperacillin / therapeutic use
  • Vancomycin / administration & dosage
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Penicillins
  • Vancomycin
  • Amikacin
  • Piperacillin