Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2025 Aug;91(8):2192-2204.
doi: 10.1002/bcp.70120. Epub 2025 Jun 16.

Unveiling predisposing factors for cefepime-induced neurotoxicity: A systematic review and meta-analysis

Harri Hardi  1 , Melva Louisa  2 , Indah Suci Widyahening  3 , Julia Remi Chandra  4 , Liganda Endo Mahata  1   5 , Vivian Soetikno  2 , Anggi Gayatri  2 , Instiaty Instiaty  2
Affiliations
Meta-Analysis

Unveiling predisposing factors for cefepime-induced neurotoxicity: A systematic review and meta-analysis

Harri Hardi et al. Br J Clin Pharmacol. 2025 Aug.

Abstract

Aims: The aim of this study was to elucidate the risk factors associated with the development of cefepime-induced neurotoxicity (CIN).

Methods: This systematic review utilized keywords "cefepime" and "neurotoxicity", sourced from PubMed, Scopus, Web of Science and Google Scholar. Meta-analysis was conducted using a random effects model utilizing Mantel-Haenszel and inverse variance analysis for dichotomous and continuous outcomes, respectively.

Results: Analysis of 23 articles revealed that estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 is the primary factor in CIN, with an odds ratio of 10.06 (95% confidence interval [CI] = 5.05-20.03, P < 0.0001). Other significant factors include central nervous system (CNS) abnormalities, age, body weight, albumin levels, diabetes mellitus, hypertension, chronic lung disease and inappropriate dosing. Subgroup analysis of continuous cefepime infusion utilization, based on several risk factors, indicated a lower odds ratio in comparison to intermittent infusion. For cefepime therapeutic drug monitoring (TDM) to determine potential CIN cases, the proposed trough concentration (Ctrough) threshold for intermittent infusion is 20 mg/L, while the steady-state concentration (Css) threshold for continuous infusion is 63 mg/L.

Conclusions: Numerous risk factors are significantly associated with CIN, with renal impairment being the most significant. Continuous cefepime infusion is a potential strategy to mitigate CIN, in addition to dose adjustment and TDM.

Keywords: cefepime; continuous infusion; neurotoxicity; risk factor; therapeutic drug monitoring.

PubMed Disclaimer

References

REFERENCES

    1. Magill SS, O'Leary E, Ray SM, et al. Antimicrobial use in US hospitals: comparison of results from emerging infections program prevalence surveys, 2015 and 2011. Clin Infect Dis. 2021;72(10):1784‐1792.
    1. Lacroix C, Kheloufi F, Montastruc F, Bennis Y, Pizzoglio V, Micallef J. Serious central nervous system side effects of cephalosporins: a national analysis of serious reports registered in the French pharmacovigilance database. J Neurol Sci. 2019;398:196‐201.
    1. Haddad NA, Schreier DJ, Fugate JE, et al. Incidence and predictive factors associated with beta‐lactam neurotoxicity in the critically ill: a retrospective cohort study. Neurocrit Care. 2022 Aug;37(1):73‐80. doi:10.1007/s12028‐022‐01442‐1
    1. Appa AA, Jain R, Rakita RM, Hakimian S, Pottinger PS. Characterizing cefepime neurotoxicity: a systematic review. Open Forum Infect Dis. 2017;4(4):ofx170.
    1. Payne LE, Gagnon DJ, Riker RR, et al. Cefepime‐induced neurotoxicity: a systematic review. Crit Care. 2017;21(1):276. doi:10.1186/s13054‐017‐1856‐1

MeSH terms