ArticleAntimicrobial agents and chemotherapy2010
High cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients with mild impairment of renal function.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 71 papers, 6 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Association of Cefepime Trough Levels With Clinical Efficacy and Neurotoxicity in Patients With Febrile Neutropenia
Pharmacokinetics and Modelling of Beta-Lactam in Patients Undergoing Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO)
Who cites it
71 citing papers in PubMed, 6 syntheses or guidelines pooled it, 178 citations in OpenAlex.
- Cefepime and Mortality: A Systematic Review and Bayesian Meta-Analysis.JAMA network open · 2026Pooled it
- Too Much of a Good Thing: Defining Antimicrobial Therapeutic Targets to Minimize Toxicity.Clinical pharmacology and therapeutics · 2021Pooled it
- What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review.Clinical pharmacokinetics · 2019Pooled it
- Optimization of the treatment with beta-lactam antibiotics in critically ill patients-guidelines from the French Society of Pharmacology and Therapeutics (Société Française de Pharmacologie et Thérapeutique-SFPT) and the French Society of Anaesthesia and Intensive Care Medicine (Société Française d'Anesthésie et Réanimation-SFAR).Critical care (London, England) · 2019Guideline
- Neurological Adverse Effects Attributable to β-Lactam Antibiotics: A Literature Review.Drug safety · 2017Pooled it
- Cefepime-induced neurotoxicity: a systematic review.Critical care (London, England) · 2017Pooled it
- Adequacy of high-dose cefepime regimen in febrile neutropenic patients with hematological malignancies.Antimicrobial agents and chemotherapy · 2015Trial
- Pharmacokinetic Analysis of Intravenous Push Cefepime in Critically Ill Patients With Sepsis.Pharmacotherapy · 2026Article
- Article
- Real-world validation of a reduced-dose continuous infusion cefepime regimen: pharmacodynamic target attainment, efficacy and neurotoxicity.The Journal of antimicrobial chemotherapy · 2026Observational
- Evaluation of high dose post-dialytic versus daily beta-lactam dosing in hemodialysis patients using Monte Carlo simulation.International journal of clinical pharmacy · 2026Article
- A Pilot Study of Cefepime and Meropenem Therapeutic Drug Monitoring in Pediatric Patients on Extracorporeal Therapy.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026Article
- Safety concerns associated with high-dose continuous infusion of cefepime among critically ill patients with mild renal impairment to augmented renal clearance at a level 1 trauma center: CEFTOX study.Antimicrobial agents and chemotherapy · 2026Article
- Identification and assessment of paediatric cefepime-induced neurotoxicity in a retrospective cohort of paediatric intensive care patients.The Journal of antimicrobial chemotherapy · 2026Article
- Beta-lactam Antibiotic Cefepime Attenuates Lipopolysaccharide-induced Pain and Depression By Modulating Inflammatory Response and Astroglial Glutamate Transporter in Mice.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Strategies for Safer Cefepime Use to Prevent Neurotoxicity Using the Electronic Health Record.Critical care explorations · 2026Article
- Impact of High-Dose Cefepime During the Initial 48 h on Intensive Care Unit Survival in Sepsis: A Retrospective Observational Study.Antibiotics (Basel, Switzerland) · 2026Article
- Article
- Comparing the mortality of patients with sepsis using empirical piperacillin/tazobactam and cefepime: analysis of the MIMIC-IV database.The Journal of antimicrobial chemotherapy · 2025Article
- Acute kidney injury is associated with abnormal cefepime exposure among critically ill children and young adults.Pediatric nephrology (Berlin, Germany) · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
High-dose cefepime therapy is recommended for febrile neutropenia. Safety issues have been raised in a recent meta-analysis reporting an increased risk of mortality during cefepime therapy. Cefepime-related neurological toxicity has been associated with overdosing due to severe renal dysfunction. This study aimed to investigate the association between cefepime plasma concentrations and neurological toxicity in febrile neutropenic patients. Cefepime trough concentrations (by high-performance liquid chromatography) were retrospectively analyzed for 30 adult febrile neutropenic patients receiving the recommended high-dose regimen (6 g/day for a glomerular filtration rate [GFR] of >50 ml/min). The dose adjustment to renal function was evaluated by the ratio of the cefepime daily dose per 100 ml/min of glomerular filtration. The association between cefepime plasma concentrations and neurological toxicity was assessed on the basis of consistent neurological symptoms and/or signs (by NCI criteria). The median cefepime concentration was 8.7 mg/liter (range, 2.1 to 38 mg/liter) at a median of 4 days (range, 2 to 15 days) after the start of therapy. Neurological toxicity (altered mental status, hallucinations, or myoclonia) was attributed to cefepime in 6/30 (20%) patients (median GFR, 45 ml/min; range, 41 to 65 ml/min) receiving a median dose of 13.2 g/day per 100 ml/min GFR (range, 9.2 to 14.3 g/day per 100 ml/min GFR). Cefepime discontinuation resulted in complete neurological recovery for five patients and improvement for one patient. A multivariate logistic regression model confirmed high cefepime concentrations as an independent predictor of neurological toxicity, with a 50% probability threshold at ≥22 mg/liter (P = 0.05). High cefepime plasma concentrations are associated with neurological toxicity in febrile neutropenic patients with mild renal dysfunction. Careful adherence to normalized dosing per 100 ml/min GFR is crucial. Monitoring of plasma concentrations may contribute to preventing neurological toxicity of high-dose therapy for this life-threatening condition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.