Hepatotoxic reactions induced by beta-lactamase inhibitors

Since amoxicillin/clavulanate was first introduced in the UK in 1981, beta-lactamase inhibitors are used increasingly worldwide. Two more drugs of this class are currently available, sulbactam and tazobactam. Meanwhile, adverse drug reactions associated with amoxicillin/clavulanate occurring late after the end of therapy have been repeatedly published. In many cases, a cholestatic hepatitis was diagnosed that was most likely caused by the clavulanic acid component of the combination. Symptoms were mostly mild and reversible, whereas a number of cases showing a protracted, even fatal course of the disease have been documented. This article summarizes and analyzes all relevant studies and case reports dealing with hepatotoxicity caused by beta-lactamase inhibitors. The description of a typical case from our own patient population illustrates the clinical challenge associated with this adverse drug reaction.