Extended-Interval Aminoglycosides in Children: More Guidance Is Needed: In Reply

In Reply.—We thank Best et al for their comments. We fully agree that safety aspects in randomized trials of aminoglycoside dosing, as in the vast majority of biomedical fields,1 is suboptimal and that the situation needs to be improved.2 Large-scale studies on the ototoxicity profile of single daily doses would be welcome. However, realistically, these studies are likely to be mostly, if not exclusively, nonrandomized at this point.We disagree that the current evidence does not suggest that we can confidently recommend universal change in aminoglycoside dosing for children. Of course, evidence can never be final, but there are few topics in pediatrics for which so many trials have been done with uniformly reassuring results. We disagree about the fear of an “incomplete evidence base.” The incomplete evidence base pertains mostly to the inappropriate continued use of multiple daily doses in children. In fact, multiple daily dosing of aminoglycosides was universally adopted for both adults and children a long time ago based on absolutely no evidence. Multiple daily dosing has remained a common, if not prevalent, strategy for both children and adults despite the fact that evidence from many dozens of randomized trials and meta-analyses has failed to show its superiority and have even suggested its inferiority.3As far as subgroup populations are concerned, there is no evidence to suggest that multiple daily dosing is indicated in any patient subgroup. Perpetuating emphasis on spurious subgroup differences4 is only likely to inappropriately delay the wider adoption of single daily dosing.Finally, therapeutic dose monitoring is a different question, and robust evidence is needed to decide when (or if ever) it is indeed indicated to optimize single daily dosing.5 Single daily dosing translates to lower trough values and should simplify the need for monitoring anyhow.6