Tetracycline is an oral, broad-spectrum antibiotic used to treat mild-to-moderate infections due to susceptible microbial organisms. High doses of several forms of tetracycline given intravenously have been associated with acute fatty liver that can be severe and result in liver failure and death. Oral tetracycline use has been rarely and not very convincingly linked to acute hepatic injury.
Tetracycline is an oral, broad-spectrum antibiotic and semisynthetic derivative of Streptomyces actinobacteria. Tetracycline acts by inhibition of protein synthesis by binding to the 30S subunit of microbial ribosomes. Human cells are less susceptible to this inhibition. Tetracycline was first approved for use in the United States in 1957 and was one of several oral tetracyclines used at that time (oxytetracycline, chlortetracycline), many of which are no longer available or are used in veterinary medicine only. More modern forms of tetracycline include doxycycline and minocycline which are much more commonly used and have similar indications. Currently, tetracycline is most frequently used for upper respiratory and skin and soft tissue infection and more than 2 million prescriptions are filled yearly. Chronic therapy with tetracycline is effective in ameliorating acne, but because of their better absorption and tissue penetration, minocycline and doxycycline have largely replaced tetracycline for this indication. Tetracycline is also active against infections with several rickettsial, spirochetal, chlamydial and mycoplasmas infections and are often used for therapy of nonspecific urethritis and several Rickettsia diseases, such as Rocky Mountain spotted fever and Lyme disease. Tetracycline is available in multiple generic forms as capsules or tablets of 250 and 500 mg and generally recommended in doses of 250 to 500 mg three to four times daily for 7 to 30 days. Chronic therapy is typical for therapy of acne. Pediatric formulations as oral suspension are also available. Parenteral tetracycline is no longer used. Common side effects include gastrointestinal upset, nausea, poor appetitle, diarrhea, glossitis, rash and hypersensitivity reactions. Tetracycline can cause staining of developing teeth (in children or when taken by a pregnant mother).
High doses of intravenous tetracycline can induce fatty liver disease and may result in severe hepatic dysfunction, acute liver failure and death. This syndrome is more common among pregnant women, largely during the last trimester or early postpartum period. However, instances of acute fatty liver attributed to intravenous tetracycline have been reported in nonpregnant women and in men and even in children. The injury is characterized by onset of weakness, fever, fatigue, nausea and abdominal pain after 3 to 10 days of therapy. Laboratory tests show minimal-to-moderate elevations in serum aminotransferase and alkaline phosphatase levels with mild jaundice, but presence of hyperammonemia and coagulopathy. Pancreatitis, renal dysfunction and lactic acidosis are also common, although not always specifically sought. The syndrome may be reversible if tetracycline is stopped promptly, but it is usually recognized late and can progress to multiorgan failure and death despite stopping the agent. This syndrome also occurs with high doses of intravenous doxycycline and minocycline, but quite rarely. This syndrome is rarely seen currently as tetracycline is no longer available in parenteral form and the use of intravenous tetracyclines has been superseded by availability of safer, better tolerated and more effective broad-spectrum antibiotics.
|Medication:||Tetracycline (3 g iv daily for 10 days)|
|Severity:||5+ (death from hepatic failure and lactic acidosis)|
|Other medications:||Colistin and chloramphenicol (after onset of liver injury)|
|Time After Starting||Time After Stopping||ALT (U/L)||Alk P* (U/L)||Bilirubin (mg/dL)||Other|
|0||Pre||32||8||0.3||Started iv tetracycline|
|4 days||190||10||2.4||BUN 39 mg/dL|
|8 days||530||11.5||2.2||Colistin added im q 12 hr|
|10 days||0||Tetracycline stopped; chloramphenicol started.|
|11 days||1 day||1550||15||6.8||BUN 105; CO2 11 mEq/L|
|Increasing stupor and respiratory failure, hemodialysis and resuscitative measures failed.|
|DRUG||CAS REGISTRY NO||MOLECULAR FORMULA||STRUCTURE|