Why Antibiotic Exposure Matters in Pediatric Intensive Care
Research By: Sonya Tang Girdwood, MD, PhD
Post Date: June 3, 2026 | Publish Date: March 7, 2026
A study led by Cincinnati Children’s researchers suggests that higher cefepime exposure may increase the risk of neurologic symptoms in critically ill children
In pediatric intensive care units, cefepime is a workhorse antibiotic. It is widely used to treat serious infections, including sepsis, because of its broad antimicrobial coverage and ability to reach the central nervous system. But that same penetration into the brain raises a difficult clinical question: how often might cefepime itself contribute to neurologic symptoms in critically ill children?
While cefepime‑induced neurotoxicity is well described in adults, pediatric evidence has been limited mostly to case reports. This leaves uncertainty about how to tell when neurologic symptoms are related to the medication versus the many other risks of pediatric critical illness.
That gap is the focus of a study published in April 2026 in the Journal of Antimicrobial Chemotherapy, led by investigators at Cincinnati Children’s. In a retrospective cohort of critically ill children, the study found that higher cefepime exposure—particularly higher peak concentrations—was associated with a greater likelihood of neurotoxicity.
“These findings matter because we don’t yet know whether cefepime affects children the same way it affects adults. Without that understanding, it’s hard to know when neurologic symptoms might be related to the antibiotic itself, rather than a child’s illness or from interventions from being in the intensive care unit,” says Sonya Tang Girdwood, MD, PhD, senior author of the study. “This study begins to clarify how drug exposure may relate to neurologic symptoms, helping clinicians better balance effective treatment with patient safety.”
Understanding Neurologic Uncertainty
Neurologic symptoms are common in pediatric intensive care units for many reasons. Severe infection, organ dysfunction, sedating medications and underlying neurologic conditions can all affect mental status. In young or developmentally delayed children, subtle changes may be difficult to recognize or document.
At the same time, cefepime is known to cross the blood–brain barrier. Adult studies suggest this property may underlie its neurotoxic effects at high concentrations, potentially through interference with inhibitory neurotransmission in the brain. While these effects are increasingly well characterized in adults, pediatric data have not kept pace, leaving uncertainty about whether similar exposure–toxicity relationships apply in children.
Tracking Exposure for Clarity
The investigators analyzed data from children and young adults treated with cefepime in a large pediatric intensive care unit between 2018 and 2021. All patients had cefepime concentration data from prior pharmacokinetic studies, allowing researchers to estimate drug exposure over time.
Medical records were reviewed for new or worsening neurologic symptoms that appeared after at least 24 hours of cefepime therapy. These included altered mental status, depressed level of consciousness, irritability, sudden, uncontrolled muscle jerks, seizures and delirium. To better assess whether symptoms were related to the drug, cases were independently reviewed by blinded clinicians using a standardized adverse drug reaction scoring system.
Among 73 patients with complete data, five were classified as having probable cefepime‑induced neurotoxicity. Although this group was small, clear differences emerged. These patients had significantly higher cefepime peak concentrations and higher overall drug exposure, compared with patients who had no or doubtful neurotoxicity.
Notably, traditional clinical risk factors seen in adults—such as age, severity of illness, or measured kidney dysfunction—did not clearly distinguish patients who developed neurotoxicity from those who did not. Furthermore, standard dosing adjustments based solely on creatinine‑based kidney function alone may not reduce high exposure and neurotoxicity risk, as the patients with neurotoxicity did not have particularly low kidney function.
“This is the first time cefepime exposure and neurotoxicity risk have been examined at a cohort level in children,” says Tang Girdwood. “This study suggests that cefepime exposure may be one contributing factor in some cases, but it also highlights how difficult it is to draw clear conclusions without larger studies.”
Looking Ahead
The authors caution that the findings do not support specific dosing changes or using routine blood tests to measure drug levels at this time. However, the study does provide some data on how to adjust dosing if cefepime concentrations were available for clinical care. They emphasize the need for larger, prospective studies to confirm these findings and identify which pharmacokinetic measures best predict risk. Future work may also explore alternative markers of kidney function, such as cystatin C, to better estimate drug clearance in critically ill children, as well as metabolomic approaches to identify metabolites that may drive cefepime-induced neurotoxicity.
“This study supports greater awareness of neurologic symptoms associated with antibiotic exposure and lays important groundwork for improving how cefepime is used and monitored in critically ill children,” says Tang Girdwood.
About the Study
Kathryn Pavia, MD was the first author of the study. Additional Cincinnati Children’s co-authors included Melissa Day, MD, H. Rhodes Hambrick, MD, Anna Sibilia, MD, Matthew Fenchel, MS, Kelli Paice, MD and Jennifer Kaplan, MD, representing a collaborative effort across the Divisions of Critical Care Medicine, Translational and Clinical Pharmacology, Infectious Diseases, Nephrology, Biostatistics and Epidemiology and Hospital Medicine.
Funding to support the study was provided by National Institute of Child Health and Human Development through its Pediatric Clinical and Developmental Pharmacology Training Program and by the National Institute of General Medical Sciences at the National Institutes of Health.
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| Original title: | Identification and assessment of paediatric cefepime-induced neurotoxicity in a retrospective cohort of paediatric intensive care patients |
| Published in: | Journal of Antimicrobial Chemotherapy |
| Publish date: | March 7, 2026 |
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