The efficacy and toxicity of two dosing-regimens of amikacin in neonates with sepsis.

Summary What is known and objective:  Neonatal sepsis is one of the most common reasons for admission to neonatal units in developing countries. Aminoglycosides widely used in its treatment are usually administered two or three times a day. Less frequent doing may be more convenient and as effective. We aim to compare the efficacy and safety (nephrotoxicity) of once daily vs. twice daily dosing of amikacin in neonates with suspected or proven sepsis and report on the drug’s pharmacokinetics in these subjects. Methods:  Thirty neonates of gestational age ≥36 weeks and body weight ≥2500 g with suspected or proven sepsis were randomized to receive amikacin either at a dose of 15 mg/kg once per day; group I (n = 15), or a dose of 7·5 mg/kg twice per day, group II (n = 15). All neonates received classical treatment of sepsis including antibiotics, hemodynamic support, inotropic support based on blood pressure levels and size of the heart in chest X-ray, if needed. Amikacin was infused over 1 h. Peak and trough serum samples for amikacin were measured for all infants at steady state. Nephrotoxicity was assessed by serum creatinine and urinary N-acetyl β-d-glucosaminidase before and 7 days after therapy. Clinical efficacy was compared using both observation of clinical status and normalization of laboratory tests. Results:  All the patients in group I had achieved a trough level 10 μg/mL in group II. No significant difference between group I and group II in either baseline or day 7 serum creatinine was demonstrated (P > 0·05). No significant difference was found between the two groups in clinical efficacy or renal toxicity. The calculated pharmacokinetic parameters were in group I and II, respectively: clearance =63·8 ± 15·9 mL/kg/h and 73·5 ± 18·1 mL/kg/h; volume of distribution =0·54 ± 0·09 L/kg and 0·61 ± 0·13 L/kg, half-life =6·1 ± 1·0 h and 5·95 ± 1·1 h. What is new and conclusion:  As expected, amikacin given once every 24 h to septic neonates of ≥36 weeks of gestation achieved higher peak levels and lower trough concentrations than the twice daily regimen. Treatment with once daily regimen did not lead to more nephrotoxicity than with a twice-daily regimen, and showed comparable efficacy.