Antibiotic-associated hepatitis: update from 1990

To review the literature on the recent available evidence of antibiotic-associated acute liver injury.

All published articles from January 1990 to July 1995 were extracted from the monthly updated HEPATOX database. Additional articles were found using MEDLINE, EMBASE, and PASCAL searches. Hepatic injuries associated with antituberculous, antimycotic, antiviral, antiprotozoal, and antiseptic compounds were excluded form this review.

As the amount of literature was large, only case reports, series and epidemiologic data were used. Results from clinical trials were reviewed only when other information was available.

Original articles were reviewed to select relevant material. Information regarding the clinical description, histologic features, severity, outcome, and possible risk factors was extracted. Data on incidence were provided by epidemiologic studies or spontaneous reporting to regulatory agencies.

Antibiotic-associated acute injury is rare, with an incidence not exceeding 1 case 10,000 users for most drugs. Among beta-lactams, amoxicillin/clavulanic acid and penicillinase-resistant penicillins are associated with predominant and sometimes protracted cholestasis. The hepatotoxic potential of all available erythromycin salts is confirmed, and recent evidence suggests that roxithromycin could be added to the list of antibiotic-induced liver injury. Among fluoroquinolones, only ciprofloxacin has been associated with serious hepatitis. Trimethoprim/sulfamethoxazole-induced hepatitis often reported, but trimethoprim alone also appears as a possible cause of acute liver injury. Finally, acute bile duct injuries and ductopenia have been described with several antibiotics.

The most important recent information is the possibility of protracted liver cholestasis with bile duct injuries induced by several antibiotics, particularly penicillinase-resistant penicillins, and the identification of new potentially hepatotoxic antibiotics, namely, roxithromycin, ciprofloxacin, and trimethoprim.