Cefepime-induced neurotoxicity: systematic review

Gozun, Maan; Keitoku, Koichi; Kimura, Nobuhiko; Sawada, Haruki; Pham, Andrew; Yeo, Jun Sang; Hagiya, Hideharu; Nishimura, Yoshito

doi:10.1093/jac/dkac271

Cited by 18 publications

(14 citation statements)

References 65 publications

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“…The overall incidence of CRN in patients with end-stage renal disease receiving hemodialysis was low despite the concern for drug accumulation, likely due to conservative empiric dosing in this patient population. 27 Regarding the onset of neurotoxicity in our study, the mean latency period from initiation of cefepime to CRN was 5.6 ± 3.7 days, which is well within the range reported elsewhere (range 1-14 days). 2,3,27 Recognizing CRN, particularly in ICU patients, remains a challenge because of mechanical ventilation and other precipitating factors such as age, presence of complicating comorbidities, infection, or dehydration that can cause delirium, which is difficult to distinguish from CRN.…”

Section: Discussionsupporting

confidence: 90%

“…27 Regarding the onset of neurotoxicity in our study, the mean latency period from initiation of cefepime to CRN was 5.6 ± 3.7 days, which is well within the range reported elsewhere (range 1-14 days). 2,3,27 Recognizing CRN, particularly in ICU patients, remains a challenge because of mechanical ventilation and other precipitating factors such as age, presence of complicating comorbidities, infection, or dehydration that can cause delirium, which is difficult to distinguish from CRN. 28 In these scenarios, cefepime TDM can be an important clinical tool to improve patient safety by helping rule out CRN.…”

Section: Discussionsupporting

confidence: 90%

“…A recent systematic review of cefepime‐induced neurotoxicity revealed that 30 of the 119 patients (25%) reported in case reports had end‐stage renal diseases on hemodialysis or peritoneal dialysis. The overall incidence of CRN in patients with end‐stage renal disease receiving hemodialysis was low despite the concern for drug accumulation, likely due to conservative empiric dosing in this patient population 27 …”

Section: Discussionmentioning

confidence: 95%

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Use of therapeutic drug monitoring to characterize cefepime‐related neurotoxicity

et al. 2022

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Study Objectives Data evaluating cefepime thresholds associated with neurotoxicity remain limited. The objectives of this study were to evaluate the incidence of cefepime‐related neurotoxicity (CRN) in patients with plasma cefepime concentrations, assess the relationship between cefepime exposure and CRN, investigate clinical factors associated with CRN, and describe electroencephalogram (EEG) abnormalities in CRN. Design This was a retrospective study of adult inpatients admitted between 2016 and 2018 who received cefepime therapeutic drug monitoring (TDM). Potential CRN cases were identified utilizing a standard definition. The primary outcomes of the study were to determine the incidence of CRN and evaluate the relationship between cefepime trough concentrations, the average daily AUC, and neurotoxicity. Bayesian posteriors were generated for each patient using a cefepime pharmacokinetic (PK) model, and the mean daily area under the concentration–time curve (AUC) was calculated. Multiple regression was performed to assess the association between CRN, cefepime PK, and clinical predictors of neurotoxicity. Main Results Four hundred eighty‐one patients with 503 hospital encounters received cefepime TDM and were included in the analysis. The incidence of CRN was 4.4% (22/503). Patients with CRN had a higher incidence of renal dysfunction, hypertension, and diabetes mellitus compared to patients without CRN (non‐NT). The mean cefepime trough concentration was significantly greater in the CRN patients than in the non‐NT group (61.8 ± 33.7 vs. 30 ± 27.7 mg/L, respectively, p = 0.0002). Cefepime trough concentration and renal dysfunction were independently associated with increased risk of CRN in the adjusted multiple regression model. Moderate generalized slowing of the background rhythm was the most common EEG pattern associated with CRN. Delaying cefepime TDM greater than 72 h after the initiation of cefepime was associated with a 3‐fold increased risk of CRN. Conclusion Cefepime should be used cautiously in hospitalized patients with renal dysfunction due to the risk of neurotoxicity. Dose optimization utilizing TDM early in cefepime treatment may minimize adverse effects and improve patient safety.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 95%

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Use of therapeutic drug monitoring to characterize cefepime‐related neurotoxicity

et al. 2022

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“…A Neurotoxicidade Induzida pelo Cefepima (NIC) é relatada como uma encefalopatia tóxica ou estado de mal epiléptico não convulsivo. Entre as manifestações estão: convulsão, crise não convulsiva, mioclonias, tremores, sonolência, estado mental alterado com confusão mental ou desorientação, agitação, alucinações, rebaixamento de nível de consciência e coma 1,3 .…”

Section: Rbfhssunclassified

Neurotoxicidade induzida por cefepima em paciente com disfunção renal: um relato de caso

SILVA¹,

VERONEZE²,

GUIMARÃES³

2023

Rev Bras Farm Hosp Serv Saude

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O cefepima é um antimicrobiano extensamente utilizado no ambiente hospitalar. Durante as fases de desenvolvimento o medicamento se demonstrou seguro e por isso foi aprovado e comercializado. Após a comercialização do cefepima, relatos de casos envolvendo uma reação adversa grave foram surgindo. A Neurotoxicidade Induzida por Cefepima (NIC) é uma reação que ocorre, na maioria das vezes, em pacientes que apresentam disfunção renal, danos na barreira hematoencefálica ou com idade avançada. O ajuste de dose deve ser feito conforme a depuração de creatinina, a fim de prevenir a reação adversa. Dentre os sintomas estão sonolência, tremores, mioclonias, agitação, rebaixamento do nível de consciência, convulsões e coma. O eletroencefalograma pode ser utilizado para auxiliar no diagnóstico, mas não é específico para essa condição. Neste artigo apresentaremos um relato de caso de uma mulher de 52 anos, com insuficiência renal aguda, que apresentou a NIC após o uso de cefepima, apesar dos ajustes de dose conforme função renal. A paciente apresentou os sintomas mesmo após a suspensão do medicamento e a hemodiálise não reverteu o quadro. Características fisiológicas da paciente podem ter contribuído para o desfecho do caso. A descrição dos casos de NIC na literatura é importante para melhor compreensão da fisiopatologia que envolve a reação adversa e prevenção de novos casos.

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“…Cefepime has been associated with neurotoxicity including altered mental status, myoclonus, and nonconvulsive seizure epilepticus . The risk for cefepime neurotoxicity appears to be increased with kidney dysfunction and higher cefepime exposures, usually described as elevated trough serum concentrations.…”

mentioning

confidence: 99%

Acute Kidney Injury With Empirical Antibiotics for Sepsis

Tong,

Venkatesh,

McCreary

2023

JAMA

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Sepsis describes life-threatening organ dysfunction due to a dysregulated host response to infection. It is a global health priority affecting 55 million people worldwide causing 11 million deaths annually. 1 Failure to initiate timely antibiotic therapy for sepsis can result in progression to septic shock, which is associated with a mortality rate of 30% to 40%. 2 Accordingly, sepsis is recognized as a time-critical medical emergency.Current management focuses on "bundles" 3 of care incorporating early recognition, timely antibiotic administration, and fluid resuscitation. Two commonly prescribed antibiotics for empirical treatment of sepsis are the β-lactams piperacillin-tazobactam and cefepime. Both provide broad in vitro activity against gram-positive and gram-negative organisms, including Pseudomonas aeruginosa. They are often used in combination with vancomycin to include activity against methicillin-resistant Staphylococcus aureus.Both β-lactam antibiotics are associated with risk. The purported increased risk of acute kidney injury (AKI) from the combination of piperacillin-tazobactam plus vancomycin compared with other β-lactam agents has led to a cultural shift away from the empirical use of piperacillin-tazobactam among many prescribers. Meta-analyses of observational studies found vancomycin plus piperacillin-tazobactam is associated with greater incidence of AKI with odds ratios (ORs) of up to 3.6 4 and an absolute AKI incidence of 22.2% compared with 12.9% in comparators. 5 Based on these data, the US Food and Drug Administration warns that coadministration of piperacillin-tazobactam with vancomycin may increase the incidence of AKI.

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Cefepime-induced neurotoxicity: systematic review

Cited by 18 publications

References 65 publications

Use of therapeutic drug monitoring to characterize cefepime‐related neurotoxicity

Use of therapeutic drug monitoring to characterize cefepime‐related neurotoxicity

Neurotoxicidade induzida por cefepima em paciente com disfunção renal: um relato de caso

Acute Kidney Injury With Empirical Antibiotics for Sepsis

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