cefepime and Brain-Diseases

Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research.. Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including 'cefepime', 'neurotoxicity', 'encephalopathy' and 'seizure', from their inception to 20 January 2022.. We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction.Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4 days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of >20 mg/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3 days. No CIN-associated deaths were reported.. This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Humans; Neurotoxicity Syndromes

Since 2017 the world suffers from a piperacillin/tazobactam shortage. Cefepime is then proposed as a broad spectrum antibiotic alternative. Up to 15 % of the patients under treatment develop neurotoxicity, mostly in kidney failure settings. Cefepime serum concentration and electroencephalogram guide diagnosis. Treatment consists in withholding or reducing the dose. Most of the patients recover without neurologic sequelae.. Depuis 2017, une pénurie de pipéracilline/tazobactam sévit dans le monde. Le céfépime est proposé comme alternative antibiotique à large spectre. Lors de l’utilisation de cet antibiotique, jusqu’à 15% des patients traités développent une neurotoxicité, se produisant majoritairement en cas d’insuffisance rénale. Le taux sérique et l’électroencéphalogramme permettent d’orienter le diagnostic. La diminution de la posologie, voire l’arrêt du traitement suffisent à corriger les symptômes et les patients ne gardent en général pas de séquelles neurologiques.

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Humans; Renal Insufficiency

A 64-year-old man with fever, appetite loss, and pain in the back of the neck visited our hospital. We diagnosed him as having bacterial meningitis because of pleocytosis of the cerebrospinal fluid, and started treatment with antibiotics. Multiple cerebral infarcts were found on brain MRI. We suspected that the origin of the bacterial meningitis was infective endocarditis, and administered Cefepime and Gentamicin according to the guidelines for treatment of infective endocarditis. Three days later, he became drowsy and had myoclonus and flapping of the extremities. An electroencephalograph showed generalized periodic discharge and a triphasic wave pattern. We thought that the cause of disturbance in consciousness was Cefepime-induced encephalopathy, and stopped administration of Cefepime. A few days later, he became clear, and the myoclonus and flapping disappeared. It was difficult to distinguish between non-convulsive status epilepticus and Cefepime-induced encephalopathy. However, since stopping Cefepime treatment had made the patient clear, we diagnosed his condition as Cefepime-induced encephalopathy, which often occurs in patients with renal or liver dysfunction, or in brain infarction or meningitis, which results in blood-brain barrier disruption. Thus, care should be taken when administering Cefepime to such patients.

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Diagnosis, Differential; Electroencephalography; Humans; Magnetic Resonance Imaging; Male; Meningitis, Bacterial; Middle Aged; Status Epilepticus

Cefepime is a frequently used fourth-generation cephalosporin antibiotic for a wide variety of infections. Toxic levels of this drug can cause neurological complications. The most common neurological adverse event of cefepime is headache and lightheadedness. Here, we presented a case of cefepime induced encephalopathy in a 57-year-old female patient with acute on chronic kidney disease. With an accurate diagnosis that requires a high index of clinical suspicion, prompt management was instituted. She had full resolution of symptoms following discontinuation of the medication and also emergent dialysis.

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Female; Humans; Middle Aged; Renal Insufficiency, Chronic

Prolonged neurological symptoms such as "brain fog" and cognitive impairment have occurred after coronavirus disease 2019 (COVID-19) infection. In this report, we describe impaired consciousness caused by cefepime hydrochloride (CFPM) in a patient with cognitive sequalae of COVID-19. A 56-year-old male patient was diagnosed with penile abscess after COVID-19 infection, and a blood culture detected two drug-resistant Pseudomonas aeruginosa strains. Therefore, CFPM 2 g × twice/day was administered on day 71 after intensive care unit admission. Approximately 48 h after CFPM administration, the patient showed disturbances in consciousness. Contrast-enhanced computed tomography, magnetic resonance imaging, and spinal fluid examination revealed no obvious abnormalities. Therefore, CFPM-induced neurotoxicity was suspected. CFPM was discontinued and ceftazidime 2 g × three times/day was initiated. The patient's consciousness improved 30 h after the final administration of CFPM. Serum CFPM concentrations were 14.2, 21.7, 21.7, and 11.9 μg/mL on days 1, 2, and 3 after the initiation of CFPM and on the day after CFPM was discontinued, respectively. In conclusion, intensivists should pay attention to new neurological symptoms such as CFPM-induced encephalopathy in patients with prolonged neurological symptoms after COVID-19 infection.

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; COVID-19; COVID-19 Drug Treatment; Humans; Male; Middle Aged

A patient with recurrent plasmacytoma with massive ascites exhibited vancomycin intoxication and cefepime-induced encephalopathy due to renal dysfunction. The ascitic accumulation of these drugs was suspected because of the refractory intoxicated state. To remove these drugs that had accumulated in the blood and ascites, abdominal drainage was performed in addition to online hemodiafiltration. If patients with renal dysfunction and massive ascites develop vancomycin intoxication and cefepime-induced encephalopathy that cannot be improved by drug discontinuation, physicians should suspect ascitic accumulation and evaluate the ascitic concentration. Furthermore, if a high accumulation in massive ascites occurs, physicians should perform abdominal drainage along with blood purification.

Topics: Ascites; Brain Diseases; Cefepime; Drainage; Hemodiafiltration; Humans; Neoplasm Recurrence, Local; Vancomycin

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Humans; Prognosis; Retrospective Studies

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Humans; Prognosis; Retrospective Studies

BACKGROUND Cefepime-induced neurotoxicity has been described in intensive care units (ICUs) and neuro ICU settings, occurring in patients started on cefepime for management of severe infections and sepsis. Most cases occur within 1 to 10 days after starting the drug. We publish a case that occurred on the general medical ward of a patient who had been on cefepime therapy for 4 weeks prior to admission. The aim of this study was to improve the knowledge of this serious condition to general internists as our patient was being managed on the general medical ward. CASE REPORT A 72-year-old female on prolonged intravenous antibiotics for sacral and pelvic osteomyelitis presented with acute encephalopathy and aphasia in the setting of an acute kidney injury. Due to the acute focal neurologic deficit, she was initially admitted as a stroke alert. After a negative magnetic resonance imaging (MRI) of the brain, an electroencephalogram (EEG) was pursued and showed nonconvulsive status epilepticus (NCSE). NCSE was likely a result of cefepime therapy in the setting of an acute kidney injury. CONCLUSIONS Cefepime-induced neurotoxicity should be suspected in any patient on cefepime therapy who develops acute changes in mental status, myoclonus, or evidence of seizures. Risk factors for the disease include older age, renal dysfunction, critical illness, and inappropriate dosing based upon renal function. A high index of suspicion is required and delays in diagnosis are common as there are frequently multiple possible causes for altered mental status in systemically ill patients requiring treatment with broad-spectrum antibiotics.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Anticonvulsants; Aphasia; Brain Diseases; Cefepime; Female; Humans; Levetiracetam; Lorazepam; Osteomyelitis; Status Epilepticus

A 36-year-old woman with a history of hypertension and alcoholism reported 2 days of left upper quadrant pain and jaundice. Within hours of admission, she became somnolent and hypoxic. The patient was then intubated. She had no history of drug abuse, cigarette smoking, liver disease, autoimmune disease, or pancreatitis. She had no home medications.

Topics: Abdominal Pain; Adult; Anti-Bacterial Agents; Antibodies, Anticardiolipin; Anticoagulants; Antiphospholipid Syndrome; Brain Diseases; Cefepime; Diagnosis, Differential; Female; Heparin; Humans; Magnetic Resonance Imaging; Multiple Organ Failure; Respiratory Insufficiency; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Vancomycin

Acute encephalopathy (AE) is a common complication of critical illness and is associated with increased short and long-term mortality. In this study, we evaluated the role of cefepime in causing AE.. Retrospective case-control study involving consecutive patients enrolled in the intensive care units (ICUs) of Mayo Clinic Rochester, MN between July 1, 2004 and December 31, 2015. AE was defined by the presence of delirium or depressed level of consciousness in the absence of deep sedation. Controls were identified as patients not developing AE and were matched by propensity score for age, Charlson Comorbidity Index, 24-h Apache III score and invasive ventilation use.. The total number of eligible ICU admissions during our study period was 152,999. AE was present in 57,726 (37.7%) with a median AE duration of 17 (interquartile range [IQR] 4.0-51.8) hours. We matched 14,645 cases with AE with the same number of controls. Cefepime was used in 1241 (4.2%) patients and its use was associated with greater incidence of AE [713 (4.9%) vs 528 (3.6%), p < 0.001] and duration [unit estimate 0.73; (95% CI 0.542-0.918)]. On multivariate analysis, cefepime was associated with an increased likelihood of AE after controlling for shock, midazolam infusion and acute kidney injury [OR 1.24 (95% CI 1.10-1.27)]. These associations were also present after controlling for prior chronic kidney disease.. The use of cefepime is associated with increased likelihood and duration of AE. These associations are stronger among patients with impaired renal function, but can also occur in patients without renal impairment.

Topics: Acute Kidney Injury; Aged; Anti-Bacterial Agents; Brain Diseases; Case-Control Studies; Cefepime; Critical Illness; Female; Humans; Intensive Care Units; Male; Middle Aged; Retrospective Studies

Topics: Brain Diseases; Case-Control Studies; Cefepime; Critical Illness; Delirium; Humans; Retrospective Studies

Topics: Brain Diseases; Case-Control Studies; Cefepime; Critical Illness; Delirium; Humans; Retrospective Studies

Topics: Brain Diseases; Case-Control Studies; Cefepime; Critical Illness; Humans; Retrospective Studies

Cefepime, a fourth-generation cephalosporin, acts as a GABA. CIE cases documented by a single-center consultation-liaison team between April 2015 and March 2017 were retrospectively reviewed. For further investigation, neural mass modeling was performed in silico.. Three patients with CIE refused medication/examination and showed overt pain, palilalia, and much greater deterioration of eye and verbal response than the motor response, which was possibly related to GABAergic dysfunction. Triphasic wave-like generalized periodic discharges with a high negative component (Tri-HNC) were identified on the EEG of all three cases. The simulation reproduced the characteristic feature of 2-3 Hz Tri-HNC and recovery course on EEG, and a possible involvement of individual differences in pharmacological intervention. It also suggested that auto-inhibition (synaptic inputs from interneuron to interneuron) dysregulation contributed to generating Tri-HNC in CIE.. As CIE is iatrogenic and continues unless cefepime is stopped, early recognition is crucial. Physicians should be vigilant about altered mental status, pain, and verbal changes in patients taking cefepime. Tri-HNC on EEG can expedite the diagnosis of CIE, and the association between Tri-HNC and CIE suggests that an excitatory and inhibitory imbalance due to the dysfunction of GABAergic interneurons is the underlying mechanism. This modeling may offer a new method of investigating disorders related to GABAergic dysfunction.

Topics: Adult; Aged, 80 and over; Brain; Brain Diseases; Cefepime; Computer Simulation; Electroencephalography; Female; Humans; Male; Middle Aged; Models, Neurological; Retrospective Studies

Fatal Outcome of Agranulocytosis after Re-Exposure to Metamizole and Cefepime-Induced Encephalopathy

Topics: Aged, 80 and over; Agranulocytosis; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Brain Diseases; Cefepime; Dipyrone; Fatal Outcome; Female; Humans

Impaired renal function is a risk factor for cefepime (CFPM)-induced encephalopathy (CFPMIE) in patients treated with CFPM; dose-titration to renal function is recommended to prevent CFPMIE. However, available evidence on the incidence of CFPMIE or preventive efficacy of dose adjustment against CFPMIE in end-stage renal disease (ESRD) patients is limited.. Single-centre, retrospective observational study. We reviewed consecutive in-hospital adult patients treated with adjusted-dose of CFPM in the period between September 2012 and September 2016, and assessed the CFPMIE in ESRD patients treated with adjusted-dose of CFPM.. Out of 422 eligible patients, 6 patients (1.4%) were diagnosed with CFPMIE. The incidence of CFPMIE in ESRD patients was 7.5% (5/67). Among ESRD patients, pre-existing central nervous system (CNS) morbidity was significantly associated with the risk of CFPMIE. CFPMIE occurred in ESRD patients regardless of daily dose, and even with 0.5g/day of CFPM.. Pre-existing CNS morbidity may be associated with an increased risk of CFPMIE in ESRD patients. No significant association was observed between CFPM dose and incidence of CFPMIE in ESRD patients, and future investigation on the safer dose-adjustment strategy in ESRD patients is required for achieving balance between successful infectious treatment and reducing CFPMIE.

Topics: Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Comorbidity; Dose-Response Relationship, Drug; Female; Humans; Incidence; Kidney Failure, Chronic; Male; Middle Aged; Retrospective Studies; Risk Factors

Cefepime is an antibiotic that is widely used in patients with haematological malignancies (HM). Although its use has been reported to be associated with encephalopathy, only case reports or small case series have been reported so far.. We conducted a retrospective cohort study of 243 patients with HM treated with cefepime at our hospital between August 2011 and May 2013. We also investigated the clinical features of patients with cefepime-induced encephalopathy (CIE).. Among 243 HM patients treated with cefepime, 10 were diagnosed with CIE, indicating a cumulative incidence of approximately 4.1%. The median creatinine level on commencement of treatment was 2.13 mg/dl (range 0.60-19.85) and the median initial dose of cefepime was 4.0 g/day (range 1.0-6.0). The median time between commencement of treatment and symptoms was 4.0 days (range 2-5). The most common clinical manifestations were decreased level of consciousness and myoclonus. Symptoms resolved fully in all patients. Univariate analyses showed that impaired renal function (creatinine clearance (CLCr) < 30 ml/min, acute renal failure, and chronic dialysis) was significantly associated with the development of CIE (univariate p < 0.0001, p = 0.020, and p = 0.0025, respectively). Receiver operating characteristic (ROC) analysis demonstrated that the threshold levels of creatinine, CLCr, and estimated glomerular filtration rate for CIE were 1.22 mg/dl, 22.96 ml/min, and 43.9 ml/min/1.73 m(2), respectively.. This study indicated that the development of CIE is associated with severely impaired renal function in patients with HM.

Topics: Aged; Aged, 80 and over; Brain Diseases; Cefepime; Cephalosporins; Electroencephalography; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Renal Insufficiency; Retrospective Studies; ROC Curve

The US Food and Drug Administration reported seizures associated with the use of cefepime (primarily in patients with renal impairment who did not receive appropriate dose adjustments of cefepime).. The maximum dose of cefepime in the USA (6 g per day) is higher than that in Japan (4 g per day). We investigated the prevalence of convulsions associated with the use of cefepime by comparing it with that of meropenem.. A retrospective study was undertaken in 183 patients treated with cefepime and 745 patients treated with meropenem over 2 years at Ehime University Hospital. Cefepime or meropenem-associated convulsions were defined according to the following criteria: (1) administration or dose escalation of diazepam, phenytoin, phenobarbital and thiamylal given via the intravenous route (2) convulsions recorded in medical records during administration of cefepime or meropenem.. The prevalence of convulsions was significantly greater in the cefepime treated group than in the meropenem-treated group. Among the patients who had cefepime-associated convulsions, none had renal failure. Cefepime-associated convulsions occurred only in patients with brain disorders.. Cefepime-associated convulsions should be recognized as potential complications even in patients with normal renal function. Brain disorders may increase the risk of cefepime-associated convulsions.

Topics: Adult; Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Female; Hospitals, University; Humans; Infusions, Intravenous; Japan; Male; Meropenem; Neurotoxicity Syndromes; Prevalence; Pseudomonas aeruginosa; Pseudomonas Infections; Renal Insufficiency; Retrospective Studies; Risk; Seizures; Staphylococcal Infections; Staphylococcus aureus; Thienamycins

We report two patients who presented with altered mental status and involuntary movement under administration of cefepime (CFPM). Both cases had impaired renal function. Electroencephalogram (EEG) revealed generalized periodic discharges (GPD) or generalized rhythmic delta activity (GRDA): 3Hz in the case 1 and 1 to 2Hz in the case 2. In spite of the severe abnormality in the EEG, both patients could respond to simple commands, which suggested possible dissociation between clinical findings and EEG. The patients recovered several days after discontinuation of CFPM, and had no clear residuals. We sometimes have difficulty in determining the cause of non-specific altered mental status; drug-induced, toxic, or metabolic encephalopathies are possible differential diagnoses. Arguably, the EEG findings shown here can be a clue to correct diagnosis of CFPM induced encephalopathy.

Topics: Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Consciousness Disorders; Dyskinesia, Drug-Induced; Electroencephalography; Female; Humans; Kidney Failure, Chronic; Male; Severity of Illness Index

Encephalopathy or neurotoxicity can occur with cefepime use in patients with impaired or relatively normal renal function. However, few articles have examined the relationship between cefepime's adverse effects and peritoneal dialysis. Here, we report the case of an 80-year-old woman with chronic renal failure on peritoneal dialysis that developed agitation, confusion, and dystonia after cefepime administration for 2 days. The clinical and electroencephalographic abnormalities improved after discontinuation the drug. We review the role of peritoneal dialysis in the development of cefepime-induced encephalopathy. Peritoneal dialysis is a less efficient way to eliminate cefepime than hemodialysis. Short-term hemodialysis might be considered to facilitate elimination of the drug in patients who have developed neurotoxicity.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Female; Humans; Kidney Failure, Chronic; Peritoneal Dialysis

Topics: Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Consciousness Disorders; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Myoclonus; Renal Dialysis; Status Epilepticus

The metabolism of drugs is altered in dialysed patients. We report three clinical cases of neurological toxicity from cefepime in dialysed patient. This molecule can induce in renal insufficiency patients various reversible neurological manifestations like metabolic encephalopathy, myoclonies, or a state of status epilepticus that mimics sometimes a coma in spite of adequate dosing.

Topics: Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Female; Humans; Male; Middle Aged; Renal Dialysis

Electroencephalography is a useful tool for the diagnosis and follow-up of toxic and metabolic encephalopathies. A pseudo-periodic pattern can indicate various brain pathologies and causes of mental confusion. Among these, cefepime encephalopathy should always be considered, particularly in cases of renal failure, because of the reversibility of the symptoms at drug withdrawal.

Topics: Aged; Anti-Bacterial Agents; Brain Diseases; Cefepime; Cephalosporins; Electroencephalography; Female; Hallucinations; Humans; Mental Disorders

Topics: Aged; Brain Diseases; Cefepime; Cephalosporins; Dialysis; Electroencephalography; Female; Humans; Renal Insufficiency