Letter to FDA Commissioner Gottlieb Regarding Banning of OTC Polymyxins
Dear Dr. Gottlieb,

We write to encourage the U.S. Food and Drug Administration (FDA) to take action to eliminate the over-the-counter (OTC) use of polymyxin antibiotics in both human and veterinary medicine.

As you know, doctors rely on polymyxins (colistin and polymyxin B) to treat patients when no other drug works. The World Health Organization (WHO) in 2017 included polymyxins among a handful of “reserve group antibiotics” — those that should only be used in specific settings where other antibiotics would not work. The WHO has also recommended that polymyxins not be used in food animals.

The global spread of bacterial resistance to polymyxins, along with carbapenems, indicates we are already entering a “post-antibiotic” era. The U.S. Centers for Disease Control and Prevention (CDC) has described resistance to polymyxins as one of the two resistance mechanisms of greatest concern.

Despite their incredible importance to medicine, polymyxin antibiotics are available in a topical form and with no prescription in most drug stores and groceries. Today, hundreds of topical products containing polymyxin B are sold over-the-counter, without medical supervision or even demonstration of medical need. The only restriction on their sale is that they must comply with FDA’s over-the-counter regulation regarding indications, labeling, administration, and formulation. This regulation published in 1987, over three decades ago, allows polymyxin B to be legally marketed as part of topical therapies in combination with bacitracin, neomycin sulfate, oxytetracycline, or some combination of these drugs. These topical products can be sold despite limited evidence of efficacy and safety.

When FDA first authorized these over-the-counter human uses, the agency did not require studies showing the potential impact of those uses on the development of resistance. Nor did the FDA require any evidence from head-to-head controlled trials comparing the effectiveness of topical first aid combination therapies with and without the addition of polymyxin B. Subsequently, a 1995 clinical trial found that combinations with polymyxins were no more effective than topical combinations without the last resort drug. FDA did not anticipate how important the polymyxins would become for treating resistant infections, either when it approved OTC uses in humans or when it approved uses in food-producing animals decades ago.

Polymyxin class drugs are currently available in the U.S. for use in cattle and sheep, as an over-the-counter eye ointment, and are approved but not marketed as an injectable in poultry. Injectable antibiotics not containing polymyxins are the recommended treatment for eye infections in cattle and sheep because the ointments are neither effective nor easy to administer. Outside the U.S., livestock producers frequently administer polymyxins to food-producing animals in feed or water. Only in 2011, when researchers in China discovered transferable polymyxin resistance in Escherichia coli from a pig, did public health officials recognize the public health risk created by polymyxin use in food animals. That use was subsequently linked to the global spread of this transferable polymyxin resistance.

Last year, a large review article was published showing that widespread use of topical antibiotics for skin and soft tissue infections has contributed to antimicrobial resistance. Significant resistance has also been reported to the topical ophthalmological antibiotics used in both human and veterinary medicine. Further, topical antibiotic ointments containing polymyxins have also been shown to disrupt the bacterial flora of the skin, and may increase the risk of colonization by disease-causing bacteria such as Staphylococcus aureus. Given the limited clinical data to support the use of over-the-counter topical antibiotics, the aforementioned review article concludes these products should only be available via a prescription in order to limit the spread of resistance.

In conclusion, polymyxins have become some of the most important drugs available for treating very sick patients, even despite their toxicity. At the same time, overuse of polymyxins is rapidly contributing to the global spread of bacterial resistance to them. Given these two facts, combined with the serious lack of evidence that polymyxins work when used topically as first aid therapy, we urge the FDA to act to ensure better stewardship of the precious polymyxin class of drugs by ending their use over-the-counter in both human and veterinary settings. Indeed, the paramount importance of polymyxins as antibiotics of last resort demands the prohibition of their use in food-producing animals altogether.

Jason Newland, MD, MEd, Washington University in St. Louis*
Lance Price, PhD, Milken Institute School of Public Health, the George
Washington University*
Linda Tollefson, DVM, MPH, Rear Admiral, U.S. Public Health Service (Retired)
Debra Goff, PharmD, Associate Professor The Ohio State University Wexner Medical Center*
Robert Lawrence, MD, MACP, Johns Hopkins Bloomberg School of Public Health, Emeritus
Holly Carpenter, RN, American Nurses Association*
James Johnson, MD, Associate Professor of Medicine, University of Minnesota; Chief, Infectious Diseases, Minneapolis VA Health Care System*
Richard Jackson, MD, UCLA Fielding School of Public Health, Professor Emeritus
Thomas Newman, MD, Professor Emeritus of Epidemiology & Biostatistics and Pediatrics, UCSF

Along with 114 other signees

* Affiliations are included for identification purposes only, and do not connote institutional endorsement.

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