All Oral Antibiotics Tied to Increased Risk of Serious Skin Reactions: Study

New research suggests that older adults face an increased risk of severe skin reactions from antibiotics, regardless of the specific version of the oral medication they receive, potentially resulting in the need for hospitalization due to symptoms associated with Stevens-Johnson syndrome (SJS) or other conditions.

Stevens-Johnson syndrome is a serious and potentially life-threatening skin reaction that has been linked to side effects of several different classes of medications, producing painful blisters and rashes that can lead to the skin separating from the body.

When the skin lesions affect more than 30% of the body, SJS is then referred to as toxic epidermal necrolysis (TEN), which typically requires treatment in a hospital intensive care unit (ICU) or burn unit, often leading to disfiguring injuries, blindness or death.

In a study published this month in the Journal of the American Medical Association (JAMA), Erika Lee and other researchers from the University of Toronto report that the use of all oral antibiotics by individuals 66 or older can result in severe cutaneous adverse drug reactions (cADRs), such as Stevens-Johnson syndrome.

SJS Hospitalizations Vary Depending on Antibiotics Prescribed

Researchers designed the study to assess whether different types of commonly prescribed oral antibiotics carry the same risks of serious skin irritations. Prior JAMA studies have already shown that side effects of antibiotics increase risks of Stevens-Johnson syndrome, with some estimates suggesting that the drugs result in a quarter of all reported SJS cases.

Lee’s team focused on 21,578 adults aged 66 or older in Ontario, Canada who received at least one oral antibiotic between 2002 and 2022, and either visited an emergency room or were hospitalized.

From the sample group, the study identified 2,852 adults that required hospitalization for skin reaction symptoms, which may be consistent with SJS. The researchers used this information to examine which common antibiotics may be the most likely to result in hospitalizations due to skin reactions.

The study determined that the greatest number of hospitalizations were caused by two classes of antibiotics that treat bacterial infections in different ways, sulfonamide antibiotics and cephalosporins. Sulfonamide antibiotics keep bacteria from synthesizing compounds necessary for life, while cephalosporins destroy bacterial cell walls to kill the bacteria.

Although these two classes of antibiotics were responsible for the greatest number of observed hospitalizations, the researchers found that Stevens-Johnson syndrome and toxic epidermal necrolysis can be caused by all commonly prescribed antibiotics, including other popular classes of medications, like nitrofurantoin, penicillins and fluoroquinolone.

Nitrofurantoin is most commonly used to treat urinary tract infections. Penicillins are commonly considered to be the first modern antibiotic, while fluoroquinolone antibiotics treat a range of bacterial infections, including pneumonia, urinary tract infections and gastroenteritis.

Another group of prescribed antibiotics, known as macrolides, were used to create a reference group of patients for Lee’s research, since that class is already known from previous studies to have a low risk of causing Stevens-Johnson syndrome. However, side effects of macrolides can increase the risk of heart attack when prescribed.

Out of the 2,852 cases of antibiotic users who required hospitalization for SJS in the study, the median length of a patient’s stay was six days. Almost 10% of hospitalized patients required transfer to the ICU or burn unit, and more than 5% of patients died in the hospital.

“Commonly prescribed oral antibiotics are associated with an increased risk of serious cADRs compared with macrolides, with sulfonamides and cephalosporins carrying the highest risk. Prescribers should preferentially use lower-risk antibiotics when clinically appropriate,” Lee said.

Other Drugs Can Cause Stevens-Johnson Syndrome

The risks of SJS and TEN from drug reactions are not limited to antibiotics. In August 2013, the FDA issued a drug safety communication about the potential link between Tylenol and SJS skin reactions, indicating that acetaminophen in the popular pain killer may cause Stevens-Johnson syndrome, although these cases are rare.

In recent years, other JAMA studies have warned that in addition to antibiotics several types of anticonvulsants and non-steroidal anti-inflammatory drugs (NSAIDS) may cause SJS. Particular links have been drawn to an increased risk of life-threatening SJS side effects from gout drugs, such as Allopurinol, which is in the medications Zyloprim and Aloprim.

Although Stevens-Johnson syndrome and toxic epidermal necrolysis can lead to death, corticosteroids and intravenous immunoglobulins have been identified as the most effective treatment options for these conditions.