Gene identified that increases risk of antibiotic reaction
Researchers at Vanderbilt University Medical Center and colleagues have identified a gene that increases the risk for a severe and potentially life-threatening reaction to the commonly prescribed antibiotic vancomycin.
Routine testing for this gene could improve patient safety and reduce unnecessary avoidance of other antibiotics, they reported in the Journal of Allergy and Clinical Immunology.
“We think this test will be important in the clinical care of patients starting vancomycin and will prevent mortality and short- and long-term complications,” said the paper’s senior author, Elizabeth Phillips, MD, an internationally known expert on severe adverse drug reactions.
“This observation also represents significant progress as we zero in on the mechanisms of these life-threatening immune-mediated drug reactions,” she said.
Vancomycin is commonly given in the hospital or as home intravenous therapy for several weeks in combination with other powerful antibiotics to treat serious and potentially life-threatening bacterial infections.
Within two to eight weeks of initiating antibiotic therapy, however, some patients develop a severe reaction known as DRESS — Drug Rash with Eosinophilia and Systemic Symptoms — characterized by fever, widespread skin rash and internal organ damage caused by an aberrant T-cell mediated immune response to the drug.
When DRESS develops, all treatment is stopped. The mortality rate that results, often from a combination of organ damage, the need for strong immunosuppressants such as steroids and compromised treatment options for the underlying infection, approaches 10 percent.
While the true incidence of DRESS is not known, every year in the United States “hundreds of thousands of patients are at risk,” said Phillips, the John A. Oates Professor of Clinical Research and professor of Medicine, Pharmacology and Pathology, Microbiology and Immunology at VUMC and Vanderbilt University School of Medicine.
For several years, vancomycin has been known to be a common antibiotic trigger for DRESS, however the genetic risk factors predisposing specific patients were not known.This new finding shows that vancomycin-associated DRESS occurs in patients who carry specific variations in human leukocyte antigen (HLA) genes. HLA genes encode proteins that present foreign peptides (antigens) to T cells (a kind of white blood cell) to stimulate an immune response.
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