Vancomycin is a broad spectrum antibiotic that has activity against methicillin-resistant strains of Staphylococcus aureus and is generally reserved for serious drug resistant gram-positive infections. Vancomycin therapy has been linked many to instances of hypersensitivity with fever, rash and eosinophilia that can be associated with mild hepatic injury, but despite over 50 years of use, it has not been linked to cases of serious hepatotoxicity.
Vancomycin (van" koe mye' sin) is a glycopeptide antibiotic produced by Streptococcus orientalis with primary activity against gram positive bacteria. Vancomycin has a large, complex and unusual structure and is believed to act by inhibition of bacterial cell wall synthesis via binding to the cell wall precursor molecules. Vancomycin is active against, and its major use is in therapy of, infections due to methicillin-resistant Staphylococcus aureus (MRSA), including antibiotic-induced pseudomembranous colitis, staphylococcal enterocolitis, bacterial endocarditis, and sepsis. For systemic infections, vancomycin is given intravenously. For localized or nonsystemic infections, other routes of administration are used, including oral, rectal, topical, inhalational, intrathecal, intraperitoneal, and intraventricular. The recommended parenteral dosage in adults is 500 mg iv every 6 hours or 1000 mg every 12 hours, with modification to achieve a therapeutic range as needed. The recommended oral dosage in the treatment of antibiotic induced pseudomembranous enterocolitis is 125 to 500 mg every 6 hours for 7 to 10 days. Vancomycin is available generically and under several commercial names including Vancoled, Vancor, Lyphocin, and Vancocin in 125 and 250 mg pulvules and as power for injection or oral administration. Vancomycin was first approved for use in the United States in 1958 and it continues to be widely used, particularly with the recent rise in incidence of serious MRSA infections. Vancomycin is largely well tolerated; common side effects include diarrhea, nausea, nephrotoxicity and neutropenia.
Intravenous vancomycin is associated with minor, transient and asymptomatic elevations in serum aminotransferase levels in 1% to 5% of patients, but similar or minimally lower rates of abnormalities are usually reported with comparative agents. In rare instances, the serum enzyme elevations are more marked and may be associated with mild symptoms, although usually without jaundice. In recent years, vancomycin has been linked to hypersensitivity reactions, including Stevens Johnson syndrome, toxic epidermal necrolysis and the distinctive syndrome of drug rash, eosinophilia and systemic symptoms (DRESS). These forms of hypersensitivity generally arise within a few days to 3 to 4 weeks after initiation of intravenous (iv) vancomycin therapy. Fever and severe skin rash generally dominate the clinical presentation, but systemic symptoms can include renal, respiratory or heart failure, neutropenia, thrombocytopenia, and mild liver injury. Cases of DRESS syndrome associated with vancomycin are often accompanied by serum enzyme elevations, but marked elevations, symptoms and jaundice are rare. Nevertheless, instances of death with hepatic failure have been described, although the features of hypersensitivity are usually more prominent than the liver injury. In addition, patients who received intravenous vancomycin usually have multiple comorbidities including sepsis, and receive multiple antibiotics making the association of the hypersensitivity reaction and liver injury with vancomycin sometimes difficult. Other more well known causes of DRESS syndrome include allopurinol, sulfonamides, and the aromatic anticonvulsants. These other causes of DRESS syndrome are more likely to be associated with clinically apparent and even fatal liver injury.
Mechanism of Injury
Vancomycin is rapidly excreted in the urine without significant hepatic metabolism, which perhaps explains the absence of significant hepatotoxicity. Hypersensitivity probably accounts for the instances of mild anicteric hepatitis associated with DRESS syndrome and Stevens Johnson syndrome due to iv vancomycin. The association of ALT elevations with oral vancomycin is surprising in view of its lack of oral absorption, but the presence of active colitis may allow for some systemic exposure.
Outcome and Management
In published cases, the hepatic injury has usually been self-limited, but rare instances of acute liver failure in the context of hypersensitivity reactions have been linked to vancomycin therapy. Vancomycin should be discontinued promptly in patients who develop immunoallergic features. Corticosteroids are often used to treat the systemic hypersensitivity and relapse is common when they are discontinued early. In general, recovery is usually slow despite early discontinuation of vancomycin. There is no evidence for cross sensitivity to hypersensitivity reactions to vancomycin with other antibiotics, except for teicoplanin, a vancomycin-like antibiotic available in some countries, but not the United States.
REPRESENTATIVE TRADE NAMES
Vancomycin – Generic, Vancocin®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 01 December 2013
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