Fatal Liver Disease after Intravenous Administration of Tetracycline in High Dosage

Schultz, Jo El J.; Adamson, James S.; Workman, Wayne W.; Norman, Tom D.

doi:10.1056/nejm196311072691903

Cited by 196 publications

(35 citation statements)

References 17 publications

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“…No reports of maternal hepatic toxicity associated with doxycycline use have been published (215)(216)(217). Rarely, fatty liver of pregnancy has occurred in patients who received high-dose intravenous tetracycline (215,218); however, the dosages administered in these cases exceeded what is recommended for the treatment of tickborne rickettsial disease.…”

Section: Pregnancy and Lactationmentioning

confidence: 99%

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States

Biggs¹,

Behravesh²,

et al. 2016

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Section: Pregnancy and Lactationmentioning

confidence: 99%

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States

Biggs¹,

Behravesh²,

et al. 2016

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“…In particular, most cases of fatty liver were observed in patients receiving large intravenous dosages (>1.5 g/day) of tetracycline derivatives [5,261]. However, tetracycline-induced steatosis is no longer observed since such huge intravenous doses have been abandoned.…”

Section: Drug Dosage and Duration Of The Treatmentmentioning

confidence: 99%

Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver

Begriche¹,

Massart²,

Robin³

et al. 2011

Journal of Hepatology

472

413

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Numerous investigations have shown that mitochondrial dysfunction is a major mechanism of drug-induced liver injury, which involves the parent drug or a reactive metabolite generated through cytochromes P450. Depending of their nature and their severity, the mitochondrial alterations are able to induce mild to fulminant hepatic cytolysis and steatosis (lipid accumulation), which can have different clinical and pathological features. Microvesicular steatosis, a potentially severe liver lesion usually associated with liver failure and profound hypoglycemia, is due to a major inhibition of mitochondrial fatty acid oxidation (FAO). Macrovacuolar steatosis, a relatively benign liver lesion in the short term, can be induced not only by a moderate reduction of mitochondrial FAO but also by an increased hepatic de novo lipid synthesis and a decreased secretion of VLDL-associated triglycerides. Moreover, recent investigations suggest that some drugs could favor lipid deposition in the liver through primary alterations of white adipose tissue (WAT) homeostasis. If the treatment is not interrupted, steatosis can evolve toward steatohepatitis, which is characterized not only by lipid accumulation but also by necroinflammation and fibrosis. Although the mechanisms involved in this aggravation are not fully characterized, it appears that overproduction of reactive oxygen species by the damaged mitochondria could play a salient role. Numerous factors could favor drug-induced mitochondrial and metabolic toxicity, such as the structure of the parent molecule, genetic predispositions (in particular those involving mitochondrial enzymes), alcohol intoxication, hepatitis virus C infection, and obesity. In obese and diabetic patients, some drugs may induce acute liver injury more frequently while others may worsen the pre-existent steatosis (or steatohepatitis).

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“…The association with pregnancy may be explained by the histopathology of tetracycline injury, which is similar to that seen in fatty liver disease of pregnancy and mainly due to the inhibition of mitochondrial beta-oxidation of fatty acids, leading to microvesicular fat accumulation in the hepatocytes [27]. Cases of fatal hepatotoxicity in nonpregnant patients [28,29] and the development of alternatives resulted in the discontinuation of intravenous tetracycline usage in 1991.…”

Section: Clinical Data Tetracyclines Nitrofurantoin Sulfonamides Amentioning

confidence: 99%

Hepatotoxicity of Antibacterials: Pathomechanisms and Clinical Data

2010

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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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Fatal Liver Disease after Intravenous Administration of Tetracycline in High Dosage

Cited by 196 publications

References 17 publications

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States

Diagnosis and Management of Tickborne Rickettsial Diseases: Rocky Mountain Spotted Fever and Other Spotted Fever Group Rickettsioses, Ehrlichioses, and Anaplasmosis — United States

Drug-induced toxicity on mitochondria and lipid metabolism: Mechanistic diversity and deleterious consequences for the liver

Hepatotoxicity of Antibacterials: Pathomechanisms and Clinical Data

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