Severe but reversible encephalopathy associated with cefepime

Jallon, Pierre; Fankhauser, Lilian; Pasquier, Renaud Du; Coeytaux, Alessandra; Picard, Fabienne; Hefft, S; Assal, Frédéric

doi:10.1016/s0987-7053(00)00234-3

Cited by 80 publications

(59 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…More recent observations have reported a higher incidence of cefepime-associated encephalopathy (1%) and have suggested that the frequency of insidious neurological toxicity other than seizures, such as confusion, depressed level of consciousness, altered mental status, or myoclonia, is underestimated during therapy with cefepime or other cephalosporins (7,10,13,17). This neurological toxicity was described mainly for patients with severe renal dysfunction, but data on cefepime plasma concentrations are lacking in the majority of these cases.…”

Section: Discussionmentioning

confidence: 99%

“…In vitro and in vivo studies have attributed the proconvulsive effect of cephalosporins to the drug-induced suppression of inhibitory neurotransmission via a concentration-dependent modulation of the ␥-amino-butyric acid [(GABA) A ] receptors (24). Cefepime-related neurological toxicity, including encephalopathy, confusion, myoclonia, seizures, or nonconvulsive status epilepticus, has been reported for patients with severe renal dysfunction (2,6,7,13,17,23). Coma leading to death has been observed in some cases (1,6,23).…”

mentioning

confidence: 99%

See 1 more Smart Citation

High Cefepime Plasma Concentrations and Neurological Toxicity in Febrile Neutropenic Patients with Mild Impairment of Renal Function

Lamoth

Buclin

Pascual

et al. 2010

Antimicrob Agents Chemother

159

125

View full text Add to dashboard Cite

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.Cefepime, an extended-spectrum cephalosporin, is recommended for the empirical therapy of febrile neutropenia (11). The time during which the antibiotic plasma concentration is higher than the MIC for the causative pathogen is crucial for efficacy under this life-threatening condition (16). High-dose cefepime therapy (6 g/day for a glomerular filtration rate [GFR] of Ͼ50 ml/min) is recommended to achieve coverage of the most frequent bacterial pathogens in febrile neutropenia, including Pseudomonas aeruginosa (9, 26). Despite success rates of up to 60 to 80%, similar to those of other broadspectrum beta-lactams, cefepime therapy has recently been found to be associated with higher mortality rates (29). These findings indirectly suggest that the excess mortality might be due to toxicity. In vitro and in vivo studies have attributed the proconvulsive effect of cephalosporins to the drug-induced suppression of inhibitory neurotransmission via a concen...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

High Cefepime Plasma Concentrations and Neurological Toxicity in Febrile Neutropenic Patients with Mild Impairment of Renal Function

Lamoth

Buclin

Pascual

et al. 2010

Antimicrob Agents Chemother

159

125

View full text Add to dashboard Cite

show abstract

“…The diagnosis of NCSE may be difficult, since the EEG pattern is not always typical: for instance, the presence of atypical spike and wave complexes with triphasic aspect may be confused with the EEG pattern of encephalopathy [7,13]. However, triphasic waves with a frequency greater than 1 Hz and a spiky morphology should encourage to consider NCSE as a possible diagnosis [14], which can be confirmed by an expert integration of EEG findings and clinical data [15].…”

Section: Discussionmentioning

confidence: 99%

Nonconvulsive Status epilepticus during Cephalosporin Therapy

Primavera

Cocito²,

Audenino³

2004

Neuropsychobiology

View full text Add to dashboard Cite

Cephalosporins may induce nonconvulsive status epilepticus (NCSE), a potentially reversible condition. Despite the wide use of these antibiotics, there are only few reported cases, because this condition is probably underestimated. We report two new cases of NCSE occurring during treatment with cefepime and ceftazidime, and emphasize the utility of emergent electroencephalogram in patients with an acute altered state of consciousness while receiving treatment with cephalosporins, particularly when there is evidence of impaired renal function.

show abstract

“…A evolução deste padrão do EEG é diretamente afetada pela etiologia, sendo este padrão potencialmente reversível quando associado a condições tóxico-metabólicas 15 . É também este o padrão de descargas periódicas descrito por Jallon e col. na encefalopatia induzida por cefepime: atividade pseudo-rítmica de ondas periódicas trifásicas, inicialmente positivas, a 2 Hz, predominantes nas áreas frontais, e não-reativas; são freqüentemente assíncronas e multifocais 16 . As alterações do EEG que observamos em nossos pacientes correspondem a este padrão: a análise de polaridade das ondas agudas permite perceber que elas são geralmente negativas em uma ou outra região frontal, mais do que bilaterais e sincrônicas, isto é, apresentam assimetrias variáveis.…”

Section: Resultsunclassified

Encefalopatia induzida por cefepime: achados clínicos e eletroencefalográficos em sete pacientes

Rossato

Ziomkowski

Kliemann

2005

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

RESUMO -Cefepime, uma cefalosporina de quarta geração, com amplo espectro de ação, é um antibiótico largamente utilizado no tratamento de infecções graves em ambientes hospitalares. O registro de segurança deste fármaco é considerado favorável. Vários casos de encefalopatia grave, associada ao uso de cefepime, reversível, foram descritos recentemente. No presente artigo, descrevemos sete casos de encefalopatia induzida por cefepime, com achados eletroencefalográficos (EEG) característicos, que apresentaram reversão do quadro com a suspensão da droga. As relações do padrão EEG encontrado nestes pacientes com estado epiléptico não-convulsivo são consideradas, bem como a possibilidade de enquadrar os pacientes estudados na entidade "encefalopatia epileptiforme". PALAVRAS-CHAVE: encefalopatia epileptiforme, padrão EEG periódico, estado epiléptico não-convulsivo, neurotoxicidade, cefepime. Cefepime-induced encephalopathy : clinical and electroencephalographic features in seven patientsABSTRACT -Cefepime, a fourth-generation cephalosporin, with large antibacterial spectrum, is a commonly used antibiotic for the treatment of serious hospitalar infections. Its security report is considered favourable. Recently, many cases of a severe and reversible cefepime-induced encephalopathy were described. In this p a p e r, we report seven patients with reversible cefepime-induced encephalopathy, with a peculiar EEG pattern, characterized by semiperiodic diffuse triphasic waves. We discuss the EEG abnormalities found and their association with nonconvulsive status epilepticus.

show abstract

Severe but reversible encephalopathy associated with cefepime

Cited by 80 publications

References 4 publications

High Cefepime Plasma Concentrations and Neurological Toxicity in Febrile Neutropenic Patients with Mild Impairment of Renal Function

High Cefepime Plasma Concentrations and Neurological Toxicity in Febrile Neutropenic Patients with Mild Impairment of Renal Function

Nonconvulsive Status epilepticus during Cephalosporin Therapy

Encefalopatia induzida por cefepime: achados clínicos e eletroencefalográficos em sete pacientes

Contact Info

Product

Resources

About