Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Pickl, M.
Hepatotoxicity and hyperbilirubinemia of fusidic acid and rifampin: review of literature
[ Diplomarbeit ] Medical University of Graz; 2013. pp. 98
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Krause Robert
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- Abstract:
- Background. Current recommendations suggest a combination of penicillinase-resistant Penicillin with Rifampin (RMP), Fosfomycin or Fusidic acid (FA) for severe infections with Methicillin-sensible Staphylococcus aureus. Whereas side effects during RMP based on tuberculostatic therapy are well known, data regarding hepatobiliary side effects during RMP or FA treatment of staphylococcal infections are limited. In this literature review hepatobiliary side effects and the underlying mechanisms of FA and RA focussing on treatments of Staphylococcal infections are described. Methods. For data extraction a literature search was done using different subject headings in MedLine database resulting in 44 articles for RMP and 34 articles for FA respectively, including experimental and clinical studies from 1965 until November 2011. Results. The main hepatobiliary adverse reaction in studies in which liver alterations in FA treatment are described is an isolated hyperbilirubinemia (4.3-38%), however, generally mild and reversible on cessation of FA. Possible underlying mechanisms may be due to an interference with bile salts and a direct competitive inhibition of bile salt transporters, such as the multidrug-resistant protein 2 (MRP2) and the bile salt export pump (BSEP). In contrary, RMP predominantely causes elevated transaminase levels and hepatotoxicity, indicating hepatocellular injury. Potential pathomechanisms include direct cytotoxic reactions, interference with tight junctions and bile acid transporters, such as BSEP, MRP2 and organic anion transporting polypeptides (OATPs). The incidence of hepatotoxicity due to RMP (commonly defined as an elevation of aminotransferase levels more than 2-3 times the upper limit of normal, however depending on definition criteria) is generally low or absent (0.08-2 % in latent tuberculosis infection therapy and 2.8-4.3 % in non-mycobacterial infections). Elevations in transaminase levels occur more commonly, but incidences differ (0.1 to 21%). For both agents a lack of significant clinical information regarding other potential confounders, definition criteria and laboratory data is commonly found in surveyed data, making a critical assessment difficult. Conclusion. Priorities for future studies include basic studies to elucidate potential pathogenetic mechanisms of hyperbilirubinemia and hepatotoxicity and further controlled clincial studies to assess the clinical use of RMP and FA in patients with staphylococcal infections.