Hepatotoxicity of Antibacterials: Pathomechanisms and Clinical Data
Dept. of Internal Medicine I, Medical University of Vienna, General Hospital of Vienna, Austria.Infection (Impact Factor: 2.62). 02/2010; 38(1):3-11. DOI: 10.1007/s15010-009-9179-z
Drug-induced hepatotoxicity is a frequent cause of liver disease and acute liver failure, particularly in patients treated with multiple drugs. Several antibacterial drugs have the potential to cause severe liver injury and failure. This article aims to increase the awareness and understanding of drug induced liver injury (DILI) due to antibacterial drugs. It reviews the pattern of antibacterial DILI and provides details on molecular mechanisms and toxicogenomics, as well as clinical data based on epidemiology studies. Certain antibacterial drugs are more frequently linked to hepatotoxicity than others. Therefore, the hepatotoxic potential of tetracyclines,sulfonamides, tuberculostatic agents, macrolides, quinolones,and beta-lactams are discussed in more detail. Efforts to improve the early detection of DILI and the acquisition of high-quality epidemiological data are pivotal for increased patient safety.
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- "Although similar in their antibiotic spectrum, the types and frequencies of adverse effects of the most commonly prescribed tetracyclines appear to differ among patients. For example , drug-induced hepatotoxicity and steatosis, reported rarely in the context of doxycycline treatment   , is more frequently associated with minocycline    and tetracycline  . Tetracyclines are strong metal ion-chelating agents, leading to their accumulation in calcium-rich organs such as bones and teeth . "
ABSTRACT: Tetracyclines have long been used as valuable broad-spectrum antibiotics. The high antibacterial activity of tetracyclines, combined with their good tolerability, has led to their widespread use in treating various infectious diseases. However, similar to other antibiotics, tetracyclines are also known for their adverse effects on different human tissues, including hepatic steatosis. We observed that tetracyclines, including doxycycline and minocycline, caused enhanced expression of the liver chalone inhibin βE in HepG2 cells, mediated by the cell stress-regulated transcription factor ATF4. ATF4 and its target genes ATF3, CHOP, and inhibin βE are involved in cell cycle control, cell survival, cell metabolism, and modulation of cytokine expression. Furthermore, we observed that long term tetracycline incubation also caused inhibition of the mTOR complex, a central regulator of cell metabolism, further contributing to the observed cell-cycle arrest and autophagy in doxycycline- and minocycline-treated cell lines. ATF4 activation and mTOR inhibition link two crucial regulators of the cellular stress response and cell metabolism to the effects of tetracyclines on eukaryotic cell metabolism, and may help to understand the antibiotic-independent influence of these drugs on human tissues. Since the observed effects of tetracyclines on human cells were also found to be dependent on the magnesium ion concentrations supplied, the data further indicate the importance of magnesium supplementation to reduce or prevent side effects of long term treatment with tetracyclines.
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ABSTRACT: Parasitic, bacterial and fungal infections of the liver are much rarer compared to viral infections and are often associated with congenital or acquired dysfunctions of the immune system. Parasitic infections are seen particularly in children after returning from trips to tropical countries. In these children an amoebic liver abscess is to be considered in the case of abdominal pain and signs of inflammation. In children from migrant families hepatopathy occurs due to malaria, kala-azar and schistosomiasis. Pyogenic liver abscess is an acute illness of hematogenic origin. Treatment should be selected with reference to the pathogen responsible and the size of the abscess. Liver disease with reduced function of the bile ducts is found associated with ascending bacterial cholangitis. In a broader sense of bacterial origin hepatopathies are caused by hepatotoxic effects of antibiotic drugs and are often overlooked because of the prominence of the management of the bacterial infection. Fungal infections affecting the liver are often associated with impaired granulocyte function.
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ABSTRACT: Dental treatment of a patient who is medically compromised can be modified by using information obtained from specific laboratory tests. Part one of this two-part series reviews the tests and modifications for patients with HIV/AIDS, disorders of hemostasis, and liver diseases.
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