Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure

Martínez-Rodríguez, José Enrique; Barriga, Francisco; Santamaría, Joan; Iranzo, Alejandro; Pareja, Juan A.; Revilla, Marián; Rosa, Carmen R dela

doi:10.1016/s0002-9343(01)00767-7

Cited by 146 publications

(136 citation statements)

References 14 publications

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“…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).…”

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confidence: 99%

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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

154

125

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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...

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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

154

125

View full text Add to dashboard Cite

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“…Other conditions causing triphasic waves include brainstemdiencephalic tumors or infarcts, or alternatively diffuse or multifocal encephalopathy from vascular white matter disease or lymphoma [72]. Nonconvulsive status, however, may masquerade as a triphasic encephalopathy (e.g., in association with cephalosporin overdose in the setting of renal dysfunction) [73]. Husain et al [74] sought to discriminate which GPED patterns were most likely to be associated with status epilepticus; GPEDs with high amplitude and longer duration, and those which preserved inter-GPED amplitude were more commonly associated with status epilepticus; however, no cut-point had sufficient receiver-operator characteristics to permit discrimination.…”

Section: Triphasic Waves and Discharges With Triphasic Morphologymentioning

confidence: 99%

The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care

Rosenthal

2012

Neurotherapeutics

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Neuromonitoring is an emerging field that aims to characterize real-time neurophysiology to tailor therapy for acute injuries of the central nervous system. While cardiac telemetry has been used for decades among patients requiring critical care of all kinds, neurophysiology and neurotelemetry has only recently emerged as a routine screening tool in comatose patients. The increasing utilization of electroencephalography in comatose patients is primarily due to the recognition of the common occurrence of nonconvulsive seizures among comatose patients, the development of quantitative measures to detect regional ischemia, and the appreciation of electroencephalography phenotypes that indicate prognosis after cardiac arrest. Other neuromonitoring tools, such as somatosensory evoked potentials have a complementary role, surveying the integrity of the neuroaxis as an indicator of prognosis or illness progression in both acute brain and spinal injuries.

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“…But concepts are changing, and several studies demonstrate the advantage of TDM for these antibiotics (4,32). Clinicians and pharmacologists agree that certain adverse events like encephalopathy, seizure, and pseudolithiasis occur when doses are excessive (2,8,12,15,16,19,23,27). Various infectious diseases, e.g., endocarditis, meningitis, and osteomyelitis, require administration of high-dose antibiotics via intermittent or continuous infusion (6,36,38).…”

mentioning

confidence: 99%

Simultaneous Determination of 12 β-Lactam Antibiotics in Human Plasma by High-Performance Liquid Chromatography with UV Detection: Application to Therapeutic Drug Monitoring

Verdier

Tribut

Tattevin

et al. 2011

Antimicrob Agents Chemother

128

100

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A rapid and specific high-performance liquid chromatography method with UV detection (HPLC-UV) for the simultaneous determination of 12 beta-lactam antibiotics (amoxicillin, cefepime, cefotaxime, ceftazidime, ceftriaxone, cloxacillin, imipenem, meropenem, oxacillin, penicillin G, piperacillin, and ticarcillin) in small samples of human plasma is described. Extraction consisted of protein precipitation by acetonitrile. An Atlantis T3 analytical column with a linear gradient of acetonitrile and a pH 2 phosphoric acid solution was used for separation. Wavelength photodiode array detection was set either at 210 nm, 230 nm, or 298 nm according to the compound. This method is accurate and reproducible (coefficient of variation [CV] < 8%), allowing quantification of beta-lactam plasma levels from 5 to 250 g/ml without interference with other common drugs. This technique is easy to use in routine therapeutic drug monitoring of beta-lactam antibiotics.

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Nonconvulsive status epilepticus associated with cephalosporins in patients with renal failure

Cited by 146 publications

References 14 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

The Utility of EEG, SSEP, and Other Neurophysiologic Tools to Guide Neurocritical Care

Simultaneous Determination of 12 β-Lactam Antibiotics in Human Plasma by High-Performance Liquid Chromatography with UV Detection: Application to Therapeutic Drug Monitoring

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