Tigecycline is a parenteral glycycline antibiotic used for treatment of serious infections due to susceptible organisms. Tigecycline therapy is sometimes accompanied by minor aminotransferase elevations, but has not been definitely associated with clinically apparent liver injury with jaundice.
Tigecycline (tye" ge sye' kleen) is new generation of tetracycline, known as a glycycline. Like other tetracyclines, tigecycline is a broad spectrum bacteriostatic agent that acts by binding to bacterial ribosomes inhibiting protein synthesis. Tigecycline has activity against both gram-positive and gram-negative bacteria and, importantly, it also has activity against many multidrug resistant organisms. Tigecycline was approved for use in the United States in 2005. Current indications inlcude treatment of community acquired pneumonia and complicated skin, tissue and intra-abdominal infections due to sensitive organisms. Tigecycline is available in vials of 50 mg for parenteral use under the brand name Tygacil. The recommended dose is 100 mg intravenously initially, followed by 50 mg every 12 hours for 5 to 14 days depending on the severity and site of the infection. A reduced dosage is recommended for patients with severe underlying liver disease. Because of its broad spectrum of activity, tigecycline is often reserved for patients with serious multidrug resistant infections and is recommended only for strongly suspected or proven susceptible bacteria. In 2010 an FDA analysis of randomized controlled trials suggested that tigecycline was associated with a higher mortality than comparator antibiotics. Several subsequent systematic reviews have reached conflicting conclusions. The higher mortality rate associated with tigecycline therapy does not seem to be due to adverse events, but rather lower success or cure rates. The most frequent side effects of tigecycline are diarrhea, nausea and vomiting.
Tigecycline is reported to cause mild, transient elevations in serum aminotransferase levels in 2% to 5% of recipients, rates similar to those in patients treated with comparator antibiotics. Cases of clinically apparent liver injury with jaundice must be very rare. Product labels for tigecycline mention isolated cases of significant hepatic dyfunction cholestasis and jaundice identified from postmarketing experience. No information is available on the latency, pattern, and duration of liver injury in cases of tigecycline induced hepatotoxicity. The reports of jaundice and deaths from hepatic dysfunction in large clinical trials of tigecycline more likely reflected complications of sepsis and multiorgan failure rather than drug hepatotoxicity.
Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).
Mechanism of Injury
The cause of the serum enzyme elevations during intravenous therapy with tigecycline is unknown. High doses of intravenous tetracycline was associated with a severe direct hepatic injury marked by microvesicular steatosis, lactic acidosis and hepatic failure. This syndrome resembled Reyes syndrome and was likely due to direct mitochondrial injury. For this reason, intravenous tetracycline was withdrawn from use. This syndrome has not been reported with tigecycline or the other modified tetracyclines such as omadacycline and eravacycline. Tetracyclines are also associated with rare instances of idiosyncratic liver injury with autoimmune features that generally arise with long-term use and are most commonly associated with minocycline. Intravenous tigecycline also has not been this form of liver injury. Tigecycline is minimally metabolized in the liver and most is excreted unchanged in the bile, feces and urine, which may explain its relative lack of hepatotoxicity.
Outcome and Management
Patients with cirrhosis should be monitored during tigecycline therapy for evidence of worsening hepatic function. Patients on intravenous tigecycline who develop serum aminotransferase elevations that rise above 5 times the upper limit of normal or are accompanied by jaundice or symptoms should have tigecycline stopped. Whether there is cross-sensitivity to hepatic injury among the various teracyclines is not known but swithcing to another class of antibiotics would be more appropriate than changing to another tetracycline-like agent in patients who develop evidence of liver injury while receiving tigecycline.
REPRESENTATIVE TRADE NAMES
Tigecycline – Tygacil®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 23 January 2019
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