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Hepatic side-effects of antibiotics
J F Westphal1, D Vetter, J M Brogard
1Internal Medicine Service, Medical B Clinic, 1 place de l'Hôpital, CHRU, Strasbourg, France.
The Journal of Antimicrobial Chemotherapy
|March 1, 1994
Summary
Antibiotic-induced liver injury, though rare, can be severe and presents diverse forms of hepatic dysfunction. Identifying the cause is challenging, necessitating improved drug safety monitoring and pharmacogenetic insights.
Area of Science:
- Hepatology
- Pharmacology
- Toxicology
Background:
- The liver's high drug exposure contrasts with the relative infrequency of antibiotic-induced hepatic side-effects compared to other adverse reactions.
- Despite lower incidence, antibiotic-related liver injury can be severe and clinically diverse.
Purpose of the Study:
- To review the spectrum of antibiotic-induced liver injuries.
- To discuss the mechanisms, diagnosis, and management of antibiotic hepatotoxicity.
Main Methods:
- Literature review of antibiotic-induced liver injury.
- Analysis of clinical and pathological presentations.
- Discussion of toxicological mechanisms and diagnostic challenges.
Main Results:
- Antibiotic hepatotoxicity manifests as cytotoxic hepatitis, intrahepatic cholestasis, mixed hepatitis, chronic active hepatitis, and microvesicular steatosis.
- Toxicity is often idiosyncratic, with mechanisms including metabolite-dependent, hypersensitivity-mediated, or combined processes.
- Examples include isoniazid (cytotoxic), macrolides/penicillins (cholestasis), cephalosporins (hypoprothrombinaemia), and rifampicin/fusidic acid (bilirubin metabolism).
Conclusions:
- Establishing causality between antibiotics and liver injury is difficult due to host factors and co-medications.
- Diagnosis relies on temporal relationships between drug exposure and liver dysfunction.
- Enhanced drug safety surveillance and pharmacogenetics are crucial for identifying at-risk individuals and improving outcomes.