Relationship between albumin-bilirubin score and ceftriaxone-associated central nervous system toxicity: A matched case-control study.

Background

Ceftriaxone is a widely used third-generation cephalosporin that can cause rare central nervous system (CNS) toxicity. High levels of unbound ceftriaxone because of hypoalbuminemia or hyperbilirubinemia might contribute to this adverse event. This study evaluated the association between the baseline albumin-bilirubin (ALBI) score and ceftriaxone-associated CNS toxicity in hospitalized adult patients.

Methods

We conducted a single-center, retrospective matched case-control study of adult inpatients treated with ceftriaxone between January 2019 and December 2024. Patients aged <18 years, with baseline Japan Coma Scale score ≥10, or missing laboratory data were excluded. Ceftriaxone-associated CNS toxicity was identified by record review, alternative-cause exclusion, and Naranjo Adverse Drug Reaction assessment. Probable or definite cases were analyzed. Controls were selected using 1:5 Mahalanobis distance matching for age, sex, Charlson Comorbidity Index, estimated glomerular filtration rate, hemodialysis status, mean daily and cumulative ceftriaxone dose. Robustness analyses included alternative matching ratios, exploratory specificity analyses, and bootstrap resampling.

Results

Of the 3,014 patients treated with ceftriaxone, 1,730 met the eligibility criteria and 6 had probable or definite ceftriaxone-related CNS toxicity. The median ALBI scores were significantly higher in cases than in controls (-1.47 versus -2.17; P < 0.001). The findings with 1:3 and 1:10 matching were similar. Negative-control analyses using the Fibrosis-4 index and rash showed no significant association. Bootstrap validation yielded significant results in 973 of 1,000 resamples.

Conclusions

Ceftriaxone-associated CNS toxicity was associated with a higher baseline ALBI score. The ALBI score may aid in identifying patients at risk of CNS toxicity.