A double-blind study of the efficacy and safety of multiple daily doses of amikacin versus one daily dose for children with perforated appendicitis in Costa Rica.

BACKGROUND: There is evidence that aminoglycosides given in a single daily dose (once daily dose, ODD) are as effective and safe as multiple daily doses (MDD). However, the published pharmacokinetic and pharmacodynamic data are overly representative of pediatric populations in Europe and the USA, and not representative of low or middle-income countries such as Costa Rica, in which the patient population might differ from those in higher income settings.

METHODS: A double-blind, randomized clinical trial of the efficacy and safety of ODD vs. MDD amikacin therapy was conducted for children aged 2-12 years with an intraoperative diagnosis of perforated appendicitis. One hundred patients were randomized following a one-to-one randomization to receive either amikacin 7.5 mg/kg every 8 h (MDD) or 22.5 mg/kg as a single dose (ODD). Patients in both groups were given clindamycin 10 mg/kg every 6 h. Efficacy was evaluated by the occurrence of intra-abdominal abscesses, documented by abdominal ultrasound, and therapeutic failure. Safety was determined by the presence of renal or cochlear toxicity.

RESULTS: Fifty patients were enrolled in each group. There were no statistically significant differences in the incidence of intra-abdominal abscesses or therapeutic failures, or in the occurrence of cochlear or renal toxicity, between the MDD and ODD treatment groups.

CONCLUSIONS: In this patient population of Costa Rican children with perforated appendicitis, we found that amikacin ODD is as safe and effective as the MDD regimen. This could have implications for national health systems such as that in Costa Rica, as ODD is presumably a more economic option and may reduce the cost of antibiotic treatment in patients with perforated appendicitis. This would need to be confirmed through an economic analysis, which is outside the purview of this paper.