Abstract
Objective: Several studies showed that amoxicillin plus clavulanic acid (co-amoxiclav) is one of the most common agents associated to serious Drug Induced Liver Injury (DILI). We estimated the risk of acute serious DILI associated with amoxicillin alone compared with co-amoxiclav, through a multicenter case-control study carried out in nine Italian hospitals from October 2010 to January 2014. Methods: Cases were adults, with a diagnosis of acute liver injury. Controls presented acute clinical disorders, not related to chronic conditions and not involving the liver. Adjusted Odds Ratio (ORs) with 95% CI were calculated initially with a bivariate and then multivariate analysis. Results: We analysed 179 cases matched to 1770 controls. Seven cases were exposed to amoxicillin (adjusted OR 1.69, 95% CI 0.72-3.98) and 22 cases to co-amoxiclav (adjusted OR 3.00, 95% CI 1.76-5.40). Conclusions: Co-amoxiclav almost doubled the risk of serious acute liver injury compared to amoxicillin alone. The incidence of co-amoxiclav induced DILI is very low but the widespread use of this drug by the general population makes the risk clinically relevant. The often inappropriate prescription of antimicrobial agents, and in particular of co-amoxiclav, could expose a given patient to a life-threatening risk compared to a negligible clinical benefit.
Highlights
Beta-lactams are the most commonly prescribed antibacterial agents, with large variability across geographical areas [1]
Several studies showed that co-amoxiclav is one of the most common agents associated to severe drug induced liver injury (DILI) [2,3,4] and multiple case reports of co-amoxiclav hepatotoxicity have been published since its first marketing [5,6]
2232 patients with diagnosis of acute serious liver injury were recorded in Drug-Induced Liver Injury casecontrol study in Italy (DILI-IT) Study; of those, 2028 were not included in the study, according to the primary exclusion criteria
Summary
Beta-lactams are the most commonly prescribed antibacterial agents, with large variability across geographical areas [1]. Amoxicillin is used to treat infections caused by susceptible bacteria, such as Escherichia coli, Haemophilus influenzae, Staphylococcus aureus (non-penicillinase producing) and Streptococcus pneumoniae; its combination with clavulanic acid (co-amoxiclav), a potent inhibitor of many bacterial beta-lactamase enzymes, broadens its antimicrobial spectrum. These drugs have been widely used in the outpatient setting for the treatment of community-acquired respiratory tract and other mild-to-moderate infections and in recent years an increased consumption of co-amoxiclav compared to amoxicillin alone has been observed [1].
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