Gene Elevates Risk of Life-Threatening Reaction to Common Antibiotic

New Test Could Prevent Short- and Long-term Complications

Researchers have discovered a gene that increases the risk for a severe and potentially life-threatening reaction to vancomycin, a commonly prescribed antibiotic.

The studies also led to the development of a rapid, inexpensive test to identify the gene responsible. Routine testing could improve patient safety and reduce the unnecessary avoidance of other antibiotics, researchers reported in the Journal of Allergy and Clinical Immunology and the Journal of Molecular Diagnosis.

Within weeks of starting antibiotic therapy, some patients develop DRESS (Drug Rash with Eosinophilia and Systemic Symptoms), a severe reaction characterized by fever, widespread skin rash, and internal organ damage caused by an aberrant T-cell mediated immune response to the drug.

Once DRESS develops, all treatment is halted. The resulting mortality rate is close to 10%. Although vancomycin was known to be a common antibiotic trigger for DRESS, the genetic risk factors that predispose certain patients were not previously known.

The new data show that vancomycin-associated DRESS occurs in patients with specific variations in human leukocyte antigen (HLA) genes. These genes encode proteins that present antigens to T cells to stimulate an immune response.

Through a detailed search and review of patient records from BioVu, a Vanderbilt University Medical Center biobank of 250,000 DNA samples, the researchers discovered that patients who developed DRESS while taking vancomycin had an over-representation of the genetic variant HLA-A*32:01.

The researchers then confirmed their findings in a prospective cohort of patients from Australia and BioVu who had been diagnosed with DRESS. The combined data showed that 86% of patients who developed probable vancomycin-associated DRESS carried HLA-A*32:01, compared to none of the matched control patients who received vancomycin for several weeks and did not develop a reaction.

After conducting a survival analysis of BioVU patients with HLA-A*32:01 with controls who did not carry the gene, the researchers determined that approximately 20% of patients who started vancomycin and who carried the HLA variant developed DRESS within four weeks.

The researchers have now developed a simple and inexpensive diagnostic test for HLA-A*32:01 for use in routine diagnostic laboratories.

Source: MedicalXpress, June 11, 2019