Systemic Quinolones and Risk of Acute Liver Failure II: Systematic Review of Clinical Trials

Background: Quinolones are a class with four generations of synthetic antibiotics characterized by a unique mechanism of action, broad spectrum, potent pharmacologic properties and reasonable safety profile. Their global and growing popularity has been accompanied by an increase in the emergence of antimicrobial resistance and occurrence of unexpected adverse reactions. Nevertheless, physicians continue to prescribe these drugs on an increasing scale, irrespective of the availability of other treatment alternatives. Objective: To systematically review all clinical trials where a quinolone antibiotic was tested or used as a comparator to other drugs or drug combinations, for evidence on quinolones’ association with ALF risk. Methods: We examined 4 major bibliographic databases, 8 clinical trial registries, and major grey literature sources including international conference proceedings, drug review networks and databases of pharmaceutical companies for ongoing or unpublished studies. We also examined the bibliographies of publications selected for inclusion in our review for other relevant studies. PROSPERO registration number: CRD42020148742. Results: We identified 1,264 original clinical trials conducted between 1974 and 2020, in many countries around the world, enlisting men and women from almost all ethnicities, backgrounds, age groups and with different comorbidity burdens. One trial reported a single ALF case with gemifloxacin and the other reported another case with moxifloxacin. Conclusion: There is inadequate evidence from clinical trials to implicate quinolone antibiotics as a cause of acute liver failure.