Our response to the comments included in the letter by Fletcher and colleagues have already been previously submitted to the manufacturer of amoxicillin and clavulanate potassium (Augmentin, SmithKline Beecham Pharmaceuticals, Philadelphia, Pa). Two of the authors of this letter have been consultants for this drug company and have reviewed our data at the company's request. In summary, the reply to all concerns raised by Fletcher and colleagues is as follows:
Table 4 presents stratified analyses for age, concurrent hepatotoxic drugs, and duration of treatment. The results clearly show that adjusting for these factors further increases the relative risk of acute liver injury associated with the combination of amoxicillin and clavulanic acid.
As stated in our article, we adapted the criteria of the consensus publication such that when the values for alanine aminotransferase were not available we used those for aspartate aminotransferase instead. Also, as we stated, agreement on