Background:The bactericidal efficacy of Aminoglycosides (Ags) is directly related to peak (P) serum concentrations (C), particularly the first one. Transitory high C of Ags do not result in such a high-drug uptake by renal and cochlear tissues because of the saturation of cell binding sites. In most clinical practice using conventional schedule of Ags administration in sick neonates (N), pharmacokinetic profiles remain inadequate (low P and too elevated trough (T) C), which diminishs efficacy, increases risks of toxicity and emergence of bacterial resistance. Objective: Prospective evaluation of a new dosing-chart of Amikacin (Ak),based on a previous pharmacokinetic population study, in high risk N suspected of infection within the 2 first days of life. Study Design: 177 N (69 females and 108 males); mean gestational age (GA) ±1SD: 33.6 ± 4.1 Weeks (W) received Ak regimen dosage according to the following dosing-chart: Group (Gr) 1a GA <28 W: 20 mg/kg/42 hours (H); Gr 1b GA 28-<31 W: 20 mg/kg/36 H; Gr 2 GA 31-<34 W: 18.5 mg/kg/30 H; Gr 3 GA 34-<37 W: 17 mg/kg/24 H; Gr 4 GA≥37 W: 15.5 mg/kg/24 H. In case of asphyxia, hypoxic episodes and intercourse treatment with indometacin, interval was systematically increased by 6 H wathever the GA. Brain Evoked Auditive Potentials (BEAP's) and time-course Creatininemia (Cr), were used to assess possible toxicity.Results: At day 1 of treatment, there was no correlation between the first Ak P serum C and GA (mean: 27.8 μg/ml ± 5.21 (±1SD); median: 28; r =-0.003; range: 10-40). In the same way, there was no correlation between the first Ak T serum C and GA (mean: 3.7 μg/ml ± 2.0 (±1 SD); median: 3.0; r = -0.33; range: 0-10).Cr showed a significant and normal decrease (p<0.01) in each group during the first postnatal W. Threshold values of BEAP's at 30 dB showed no significant difference (p>0.05) between the treated Gr and the corresponding non-treated control Gr. While the primary aim was not to test the bactericidal efficacy of this new regimen, the recovery was excellent in 37 N with proven or highly suspected infection. Conclusion:The proposed scheme of Ak Administration, even in high-risk N, allows to achieve adequate Ak P and T serum C (whatever the GA at birth), while drug-induced renal and cochlear toxicity is kept minimal. These serum C would allow for a P-Minimal Inhibitory Concentration (MIC) ratio ≥ 8 to be easily reached, which is now considered as optimal for Ags treatment.