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Children’s Mercy Physicians’ Investigation Prompts Revised FDA Labeling for Bactrim, Septra


Children’s Mercy Physicians’ Investigation Prompts Revised FDA Labeling for Bactrim, Septra

Headshot of Jenna O. Miller, MD, FAAP
Jenna O. Miller, MD, FAAP
Medical Director, Extracorporeal Membrane Oxygenation (ECMO) Services; Associate Professor of Pediatrics, University of Missouri-Kansas City School of Medicine
Full Biography
Headshot of Jennifer L. Goldman, MD
Jennifer L. Goldman, MD
Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Research Assistant Professor of Pediatrics, University of Kansas School of Medicine
Full Biography

New Food and Drug Administration labeling warns prescribers and patients of a rare and previously unrecognized—but potentially deadly—pulmonary risk for a decades-old antibiotic, identified by pediatric physicians at Children’s Mercy in Kansas City, Mo.

This summer the FDA’s Office of Pediatric Therapeutics and Center for Drug Evaluation and Research, Division of Pediatric and Maternal Health, Division of Anti-Infectives and Office of Surveillance and Epidemiology approved revised labeling for trimethoprim-sulfamethoxaloe (TMP-SMX) products, known commercially as Bactrim and Septra. The updated labeling advises medical providers to watch for patient reports of cough, shortness of breath or rapid, shallow breathing that could lead to acute respiratory distress syndrome requiring mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or lung transplantation, potentially resulting in death.

The FDA’s action follows June 2019 publication of a case series in which pediatric physicians at Children’s Mercy Kansas City and the University of Missouri-Kansas City School of Medicine described severe acute respiratory failure related to Bactrim treatment in five previously healthy adolescent patients. Additional cases have since been identified now totaling 16 cases, with six—including two international cases—now under active review by pediatric intensivist Jenna Miller, MD, FAAP, and pediatric infectious disease specialist Jennifer Goldman, MD, MS-CR.

There’s a window of opportunity to avert serious complications.

Jennifer Goldman, MD, MS-CR
Pediatric Infectious Disease Specialist

Bactrim and Septra are regularly prescribed to treat skin and soft tissue and urinary tract infections as well as acne. 

Dr. Goldman emphasized the effort to gather data about the drugs’ link to life-threatening respiratory failure in a tiny number of cases is not an effort to deter their use, but rather to alert providers and patients to the symptoms before an adverse reaction becomes severe.

“These are good drugs, and this is a very rare condition, but it’s not commonly known, and needs to be,” Dr. Goldman said. “In medical school we learn about blistering, jaundice and other symptoms of severe reactions to these popular antibiotics, and we want to add ‘difficulty breathing’ to the list and potential for severe reaction considered.

“There’s a window of opportunity to avert serious complications,” she added.

The Children’s Mercy physicians are partnering with Massachusetts General Hospital in identifying pathology markers. In addition, the Children’s Mercy Genomic Medicine Center is performing testing in hopes of identifying genetic predictors of a reaction that, while rare, is fatal to 40% of patients who experience it. They have published two papers with a third currently under peer review describing that all cases evaluated by the Genomic Center have the same HLA genotype.

“The group of people who have a severe reaction is rare, and not all those with this genotype have this reaction, but all we have studied who have this reaction have this genotype,” Dr. Miller said. “So it’s not a sole risk factor, but it is another clue to the puzzle.”

Zei Uwadia at Children's Mercy. She is smiling and has a tube coming from her neck that helps her breathe.
Children's Mercy patient, Zei Uwadia

The link between antibiotic and severe respiratory illness only became suspected in 2018, when Children’s Mercy patient, Zei Uwadia, made national headlines for her extraordinary resolve to walk the halls of the hospital while on ECMO support as she battled a mysterious lung ailment. After the news reports about Zei’s respiratory failure, another patient and parent with a child similarly afflicted reached out to Dr. Miller. It was through review of their medical records that Bactrim emerged as the common thread and the basis for the physicians’ 2019 paper, leading to the larger cohort published in 2021.

Zei ultimately died of the illness shortly after her 17th birthday, but the Children’s Mercy physicians feel her presence acutely as they step up their efforts in the hope that what they learn and share will prevent others from going through similar struggles.

“This link would not have been seen across the U.S., and now internationally, without families and health care professionals learning about Zei and coming forward,” Dr. Miller said. “Our understanding is evolving and we continue this work in their honor.”       

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