Case Reports
Saturday, October 12, 2024
11:30 AM–01:00 PM
Abstract
Introduction: Ceftaroline is a fifth-generation, broad-spectrum cephalosporin with activity against methicillin-resistant
Staphylococcus aureus (MRSA). U.S. clinicians often use off-label higher dosing for severe or difficult-to-treat infections. Although reported adverse effects are generally mild, several case reports exist of adult patients with renal dysfunction experiencing neurotoxicity. This is the first case report of a pediatric patient developing ceftaroline-induced neurotoxicity.
Case: An adolescent male presented with acute kidney injury and septicemia due to perinephric abscess and septic emboli. Cefepime and vancomycin were initiated and cultures resulted in vancomycin-sensitive MRSA. Vancomycin was continued with substantial clinical improvement. On Hospital Day 12, the patient developed persistent fevers and new chest pain and was transitioned to high-dose, renally adjusted ceftaroline. On ceftaroline Day (CD) 4, he endorsed headache and general malaise, with progressive sedation and decreased affect over the next 48 hours. On CD 7, new bilateral foot numbness, fine hand tremors and auditory hallucinations were noted. The patient experienced new-onset delirium and more pronounced limb tremors the following day. On CD 9, ceftaroline was discontinued and linezolid and levofloxacin were initiated. The patient’s mental status and tremors improved over the following days.
Discussion: Cephalosporin-induced neurotoxicity (CIN) is hypothesized to result from the binding of the cephalosporin beta lactam ring to neuronal GABAA receptors. Patient CIN risk factors include high-dose therapy, critical illness and renal dysfunction. A Naranjo score of ‘probable’ indicates likelihood of causality. Symptom onset and resolution also correspond with the timing of toxicity reported in literature. Pediatric high-dose and renal adjustment recommendations are extrapolated from adult data using pharmacokinetic (PK) modeling. However, new pediatric PK publications illustrate previous dosing recommendations may be inadequate.
Conclusion: Pediatric patients prescribed high-dose ceftaroline with renal dysfunction should be monitored closely for CIN. More robust clinical trials are needed to confirm appropriate dosing for pediatric patients.
Presenting Author
Courtney Kain Pharm.D., BCPPSNemours Children's Health
Authors