Single daily dose amikacin in paediatric patients with severe Gram-negative infections

Abstract

Twenty-five children with serious Gram-negative infections were treated in a prospective study with amikacin 20 mg/kg administered in a single daily dose as a 30 min iv infusion for 4 to 12 days. In nine cases the amikacin was combined with beta-lactam antibiotics. Escherichia coli were the most frequent bacteria isolated followed by K. pneumoniae, Providencia and Enterobacter spp. and Pseudomonas aeruginosa with MICs ranging from 1 to 16 mg/l. Mean (+/- S.D.) peak and trough concentrations of days 1 and 4 of therapy ranged from 49 +/- 13.5 to 53.6 +/- 13.4 mg/l and 6 + 1.4 to 7.7 +/- 4.1 mg/l respectively. All patients were clinically and bacteriologically cured. No significant adverse reactions were observed. The results suggest that administration of a single daily dose of 20 mg/kg amikacin should be considered practical and safe in children. Further studies are needed.

Clinical Issues Surrounding Once‐Daily Aminoglycoside Dosing in Children

“…50 Similarly, a clinical cure rate of 100% (25/25) was achieved in patients treated with once-daily amikacin. 51 In the final trial, 98% of patients receiving once-daily amikacin had a satisfactory clinical response after the end of treatment; however, some patients required additional oral (27%) or parenteral (14%) antimicrobial therapy. 52 …”

“…6,11,[44][45][46][47][48][49][50][51][52][53][54][55][56] This regimen also was investigated in neonates up to 1 month of age but is not discussed here due to the decreased renal function in that patient population. Infectious processes included neutropenic fever, suspected or confirmed gramnegative infections, cystic fibrosis, and suspected or confirmed surgical infections.…”

“…Nine studies evaluated clinical and/or microbiologic efficacy of ODD in approximately 450 children ( Table 2). [44][45][46][47][48][49][50][51] It is important to note that the studies were not adequately powered to show a true statistical difference due to a limited number of subjects.…”

“…48 Four additional studies evaluating clinical efficacy did not compare dosing regimens, but administered aminoglycosides only once/day. [49][50][51][52] In one trial, 76% of febrile episodes (86/113) responded to first-line treatment (gentamicin plus ceftriaxone) with resolution of fever after 48 hours. 49 The remaining 24% of patients required vancomycin and ceftazidime due to unresolved fever with or without the presence of organisms resistant to first-line agents.…”

“…44,45,[47][48][49][50][51][52][53][54][55] Most of them defined nephrotoxicity as a percentage increase in serum creatinine concentration over baseline or a percentage decrease in creatinine clearance from baseline. In addition to creatinine clearance monitoring, 24-hour proteinuria, lysozymuria, and B2 microglobulinuria were measured to determine nephrotoxicity.…”