Life-Threatening Skin Reactions Linked to Commonly Prescribed Antibiotics

According to a large, two-decade-long study of older adults, commonly prescribed oral antibiotics are linked to skin reactions known as cutaneous adverse drug reactions (cADRs), which can be life-threatening. These cADRs can vary significantly in severity and symptoms, ranging from mild, itchy rashes to life-threatening reactions that cause extensive skin peeling and blistering. In severe cases, cADRs can lead to serious complications including infections, scarring, and organ damage. Previously, medications linked to cADRs included Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) such as Ibuprofen; anticonvulsants; antiretrovirals, such as those to treat HIV, and some chemotherapy medications.^{1 2}

Senior author David Juralink, MD, PhD and his coauthors said the study, published in the Journal of the American Medical Association (JAMA) on Aug. 8, 2024, “underscores the importance of judicious prescribing, with preferential use of antibiotics associated with a lower risk when clinically appropriate.”^{1 2}

The study included 21,758 older adults who went to an emergency department (ED) or were hospitalized due to serious cADRs occurring within 60 days of receiving antibiotic therapy. These patients were compared to 87,025 antibiotic-treated controls without reactions. The median duration of antibiotic use was seven days, with a median latency of 14 days between antibiotic prescription and the onset of cADRs. Most cases (86.9 percent) involved only an ED visit, with the remainder requiring hospitalization. The most commonly prescribed antibiotics were penicillins, followed by cephalosporins and fluoroquinolones.^{1 2}

20-40 Percent Mortality Rate for Severe Antibiotic-Induced Reactions

Serious cADRs are described by the authors as “a group of rare but potentially life-threatening drug hypersensitivity reactions involving the skin and, frequently, internal organs.” The researchers explained that “typically delayed in onset, these reactions include drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN)—the most severe cADR—which has a reported mortality rate of 20%-40%.”²

According to Mayo Cinic, TEN is a “rare life-threatening skin reaction, usually caused by medication” that affects more than 30 percent of the skin surface, causing swelling and a painful rash, sores, blistering and peeling skin that damages moist linings of the body (mucous membranes of the mouth, eyes. genitals) and can take weeks or months to heal. Complications include sepsis (blood infection); respiratory failure; blindness; scars and discoloration of the skin and more, including death.³

“We hope our study raises awareness about the importance of drug allergy and gains support for future studies to improve drug allergy care,” lead author Erika Lee, MD, clinical immunology and allergy lecturer at the University of Toronto’s Drug Allergy Clinic, Sunnybrook Health Sciences Centre, said in a statement. “It is important to recognize symptoms and signs of a severe drug rash and promptly stop culprit drugs to prevent worsening reaction.”²

Study Finds Financial Incentives a Driver in Antibiotic Overprescriptions

Antibiotics rank among the most commonly prescribed drugs in the United States, followed closely behind statins and diabetes medications. Their widespread use has been driven by the increasing prevalence of bacterial infections, the growth in pathogen resistance to antibiotics, and the high demand for antibiotics in hospital settings, an environment in which there are severe infections and post-surgical complications. According to a 2023 study, financial incentives for physicians dispensing antibiotic drugs in hospitals and other on-site medical facilities could be driving higher prescription rates, raising concerns about overprescribing and its contribution to antimicrobial resistance.

The study authors noted that “Physicians with the potential to profit from dispensing medication through an on-site pharmacy exhibit higher dispensing rates.” The study also emphasized the need to balance access to medication with the risk of overprescription.⁴

The overprescription of antibiotics isn’t driven solely by provider incentives. Pharmaceutical companies also stand to gain significantly. The global antibiotics market generated approximately $50.41 billion in revenue in 2022 and is projected to grow, reaching a staggering $63.19 billion by 2030. In the United States alone, the antibiotics market was valued at about $45.6 billion in 2023.⁵

Life-Saving or Life-Threatening? The Troubled History of Antibiotics

While antibiotics are widely heralded in the medical community for their life-saving treatment of bacterial infections, surgical safety, and support of advances in organ transplantation and cancer treatments, the risks and side effects of using the drugs cannot be overstated. Numerous antibiotics have been pulled from the market after being licensed by the U.S. Food and Drug Administration (FDA) due to serious side effects or lawsuits.

Trovafloxacin (Trovan), developed by Pfizer and introduced in 1997, was linked to severe liver toxicity and liver failure, leading the FDA to restrict its use in 1999 to only life-threatening infections where other treatments were ineffective. Its reputation suffered further due to legal actions and public outcry, especially after a controversial clinical trial in Nigeria during a meningitis outbreak in 1996. This trial faced significant ethical criticism for lacking informed consent and proper oversight, resulting in the deaths of almost a dozen children and long-term damage to health, including paralysis, brain damage, and organ failure among the other unwitting participants. The fallout from the Trovan trial led to a $75 million settlement with the Nigerian government and affected families, with many parents claiming they were unaware their children were part of an experimental study to begin with.

In 2011, Pfizer settled all outstanding lawsuits involving accusations that it tested the experimental antibiotic on children in Nigeria without receiving adequate prior informed consent from parents. The drug maker characteristically maintained that it was meningitis—not their experimental drug that was later pulled from shelves for its life-threatening side effects—that caused the deaths of 11 children in the 200-patient trial in one of the world’s most impoverished countries.

Other antibiotics removed from the market include Gatifloxacin (Tequin), Raxar (grepafloxacin), and Levaquin (levofloxacin).^{6 7}

Fluoroquinolone antibiotics, such as Cipro, Levaquin, and Avelox, have also been linked to serious and potentially deadly side effects, including aortic aneurysm and aortic dissection. The FDA has issued several safety alerts warning that these medications can double the risk of these potentially fatal conditions. Additionally, in July 2018, the FDA strengthened warnings about the risk of mental health side effects and s9ignificant blood sugar disturbances associated with fluoroquinolones, including symptoms like memory impairment and hypoglycemic coma. The FDA also highlighted the risks of disabling and potentially permanent damage to tendons, muscles, joints, nerves, and the central nervous system, advising that these antibiotics should be reserved for patients without alternative treatment options.^{8 9 10 11}

To date, manufacturers like Bayer and Johnson & Johnson have faced thousands of lawsuits related to injuries and deaths caused by their antibiotic drugs.¹²

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