cefepime and Kidney-Failure--Chronic

BACKGROUND Cefepime, a fourth-generation cephalosporin, has a known adverse effect of neurotoxicity. It occurs notably in patients with end-stage renal disease, but symptom resolution typically occurs within a median of 2 days following drug discontinuation. CASE REPORT We present a patient with end-stage renal disease on hemodialysis (TWThSat) who developed prolonged neurotoxicity lasting longer than 1 week complicated by nonconvulsive status epilepticus 2 days after cefepime discontinuation. She presented initially with a right upper-extremity arteriovenous graft infection from extended-spectrum beta-lactamase Escherichia coli, and was treated with cefepime. She eventually developed acute encephalopathy, and cefepime was discontinued. However, 2 days later, she developed seizures with worsened mental status. She was stabilized on levetiracetam and lorazepam, but developed hypotension in the Neurological Intensive Care Unit (Neuro-ICU), delaying hemodialysis. Hemodialysis was performed 6 days after cefepime discontinuation once she was stabilized, and her mental status improved 1 to 2 days after, with full improvement 20 days after admission. She was discharged on levetiracetam and meropenem. In addition, we review risk factors and symptomology of cefepime-induced neurotoxicity and discuss important management issues. CONCLUSIONS Careful attention should be paid when administering cefepime to patients with end-stage renal disease. Patients showing signs of encephalopathy should not be on cefepime any longer, and more aggressive measures may be taken, such as prompt hemodialysis, assessment of cefepime blood levels, and electroencephalogram (EEG) to monitor for signs of seizures. Prolonging hemodialysis in patients with signs of cefepime neurotoxicity can pose a danger for more serious sequelae, such as status epilepticus. Close monitoring of patients at high risk of developing adverse events from cefepime administration can ensure patient safety and well-being.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Humans; Kidney Failure, Chronic; Neurotoxicity Syndromes; Status Epilepticus

A case of cefepime-induced nonconvulsive status epilepticus in a 15-year-old child with end stage renal disease on hemodialysis is reported. Clinical symptoms and EEG dramatically improved 48 h after discontinuation of cefepime.. Twenty-five cases of nonconvulsive status epilepticus associated with cefepime that have been reported in the literature are reviewed.. The average age was 60 years [15-86], our patient is the second pediatric patient reported, and 56% of cases occurred in women. The cefepime dosage was adjusted to the renal function in 5 cases. All except 1 patient have impaired renal function (CRF: 17 cases, ARF: 7 cases). The symptoms start 1-15 days after starting cefepime, mean 6 days. The outcome was good after discontinuation of cefepime therapy and anticonvulsant treatment, but lethal outcome was also reported in 2 cases. One fatality was related to status epilepticus.. The clinicians' awareness must be increased about cefepime-induced nonconvulsive status epilepticus.

Topics: Adolescent; Anti-Bacterial Agents; Cefepime; Cephalosporins; Female; Humans; Kidney Failure, Chronic; Status Epilepticus

The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (mean age, 52.0 +/- 13.0 years [standard deviation]; mean weight, 96.7 +/- 18.4 kg) received 1 or 2 g of cefepime every 12 or 24 h (total daily doses of 1 to 4 g/day) by intravenous infusion over 15 to 30 min. Pre- and postmembrane blood (serum) samples and corresponding ultrafiltrate or dialysate samples were collected 1, 2, 4, 8, and 12 or 24 h (depending on dosing interval) after completion of the drug infusion. Drug concentrations were measured using validated high-performance liquid chromatography methods. Mean systemic clearance (CL(S)) and elimination half-life (t(1/2)) of cefepime were 35.9 +/- 6.0 ml/min and 12.9 +/- 2.6 h during CVVH versus 46.8 +/- 12.4 ml/min and 8.6 +/- 1.4 h during CVVHDF, respectively. Cefepime clearance was substantially increased during both CVVH and CVVHDF, with membrane clearance representing 40 and 59% of CL(S), respectively. The results of this study confirm that continuous renal replacement therapy contributes substantially to total CL(S) of cefepime and that CVVHDF appears to remove cefepime more efficiently than CVVH. Cefepime doses of 2 g/day (either 2 g once daily or 1 g twice daily) appear to achieve concentrations adequate to treat most common gram-negative pathogens (MIC

Topics: Adult; Aged; Area Under Curve; Cefepime; Cephalosporins; Chromatography, High Pressure Liquid; Critical Illness; Female; Hemofiltration; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Spectrophotometry, Ultraviolet

Topics: Adenocarcinoma; Aged; Cefazolin; Cefepime; Diabetes Mellitus, Type 2; Drug Resistance, Microbial; Drug Resistance, Multiple, Bacterial; Flavobacteriaceae; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Kidney Failure, Chronic; Male; Pancreatic Neoplasms; Pancreatitis; Peritoneal Dialysis; Piperacillin, Tazobactam Drug Combination; Sleep Apnea Syndromes

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

Cupriavidus pauculus is an emerging organism causing infections in immunocompromised and immunocompetent patients. We report a C.pauculus pneumonia case susceptible to cefepime in an infant with end-stage renal failure. To our knowledge, this is the first case report of C. pauculus causing respiratory infections in the Gulf Cooperation Council.

Topics: Anti-Bacterial Agents; Cefepime; Cephalosporins; Cupriavidus; Gram-Negative Bacterial Infections; Humans; Infant; Kidney Failure, Chronic; Male; Microbial Sensitivity Tests; Pneumonia, Bacterial; Saudi Arabia

Dosing of cefepime during high blood flow (Qb; 300 ml/min), high dialysate flow (Qd; 3 liter/h) continuous venovenous hemodialysis (CVVHD) is undefined. Six patients on CVVHD had serum and effluent cefepime concentrations measured at 0.5, 1, 2, 6, and 12 h after dosing. Three patients had cefepime concentrations less than the MIC for Pseudomonas aeruginosa. A dose of 2,000 mg every 12 h or 1,000 mg every 8 h may increase time at a therapeutic concentration.

Topics: Adult; Anti-Bacterial Agents; Cefepime; Cephalosporins; Chromatography, High Pressure Liquid; Female; Half-Life; Hemofiltration; Humans; Kidney Failure, Chronic; Kidney Tubular Necrosis, Acute; Male; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa; Shock, Cardiogenic; Spectrophotometry, Ultraviolet; Young Adult

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; Aphasia; Cefepime; Cephalosporins; Comorbidity; Female; Humans; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Myoclonus; Pulmonary Edema; Renal Dialysis; Respiratory Tract Infections

Topics: Aged; beta-Lactamases; Diabetic Nephropathies; Humans; Kidney Failure, Chronic; Klebsiella Infections; Klebsiella pneumoniae; Male; Renal Dialysis; Republic of Korea

Topics: Aged; Anti-Bacterial Agents; Benzodiazepines; Cefepime; Cephalosporins; Female; Humans; Kidney Failure, Chronic; Pseudomonas aeruginosa; Pseudomonas Infections; Status Epilepticus

This paper discusses a 26-year-old woman with end-stage renal disease on hemodialysis and Acinetobacter calcoaceticus-baumannii complex endocarditis. The patient had an indwelling right internal jugular catheter that was probably the nidus of infection. Transthoracic echocardiogram revealed an atypical presentation of the endocarditis as a large intracardiac mass, measuring in centimeters and occupying more than 50% of the right atrial cavity. The mass was attached to the lateral wall of the right atrium without valvular involvement. The patient was treated with prompt removal of the indwelling catheter, intravenous antibiotics, and surgical resection of the mass with an uneventful recovery. A literature search for cases of "Acinetobacter endocarditis" reveals this as the first case reported of Acinetobacter endocarditis presenting in this manner.

Topics: Acinetobacter Infections; Adult; Anti-Bacterial Agents; Catheters, Indwelling; Cefepime; Cephalosporins; Diagnosis, Differential; Endocarditis, Bacterial; Female; Heart Atria; Humans; Kidney Failure, Chronic; Ofloxacin; Ultrasonography; Vancomycin

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

Topics: Aged; Anti-Bacterial Agents; Asian People; Cefepime; Cephalosporins; Electroencephalography; Female; Humans; Kidney Failure, Chronic; Liver Cirrhosis; Male; Middle Aged; Neurotoxicity Syndromes; Singapore

Non-convulsive status epilepticus related to cefepime has not been reported in childhood dialysis patients, although several adult cases have been reported. We report a state of acute confusion in a 15-year-old boy on continuous ambulatory peritoneal dialysis (CAPD) receiving cefepime that was diagnosed as status epilepticus by electroencephalography (EEG). The EEG improved after anticonvulsive therapy. All clinical symptoms disappeared dramatically within 24 h of discontinuation of cefepime. The differential diagnosis of confusional states and the mechanisms of the convulsive effects of antimicrobials in chronic renal failure are discussed. The importance that the clinician is aware of the rare side effects of antimicrobials is emphasized.

Topics: Adolescent; Cefepime; Cephalosporins; Diagnosis, Differential; Electroencephalography; Humans; Kidney Failure, Chronic; Male; Peritoneal Dialysis, Continuous Ambulatory; Status Epilepticus

Neurotoxicity is an unusual complication of cephalosporin therapy. Only few cases of neurotoxicity induced by Cefepime have been described and probably the frequency of Cefepime-induced status epilepticus is underestimated. We report a case of an 82 year-old male, ESRD patient on chronic hemodialysis program affected by pneumonia, who received a treatment with intravenous Cefepime (1 g/day) and developed a seizure 4 days after the starting antibiotic therapy. Cefepime-induced neurotoxicity was suspected and its administration was immediately discontinued. In order to increase Cefepime clearance a hemodialysis session was urgently started and an improvement of his conscious level was observed. On the following day, after a second hemodialysis session his clinical condition and the status of neurotoxicity were completely recovered. The patient was discharged from the hospital in stable clinical condition one week later. At variance with the cases previously reported, the daily dose of Cefepime administrated to our patient was 50% lower and respected drug prescription dosage. Thus, we speculate on the hypothesis that advanced age of our patient and metabolic encephalopathy induced by chronic uremia made him more sensitive to the neurotoxicity induced by the drug. In conclusion, our case suggests that, in very old patients on long-term hemodialysis, it should be considered, to avoid neurotoxicity, to monitor the clinical neurological status, to use Cefepime at lower dosage than that allowed in patients with severe renal impairment (1 g/day) and, when possible, to evaluate Cefepime plasma levels. However, in these patients, other agents of the same class should be considered such as Cefotaxime and Ceftriaxone which are characterized by both an hepatic and renal excretion. In alternative to cephalosporins, antibiotics with the same action spectrum in the absence of neurological toxicity (i.e. Meropenem) should be recommended.

Topics: Aged; Cefepime; Cephalosporins; Confusion; Epilepsy, Tonic-Clonic; Humans; Kidney Failure, Chronic; Male; Pneumonia; Renal Dialysis

Among uremic patients on hemodialysis, infectious complications leading to a high incidence of morbidity and mortality are a well-documented problem. In this multi-dose study, the safety, tolerance, and pharmacokinetics of cefepime during high-flux hemodialysis were investigated and an improved dosing schedule is presented.. Six long-term hemodialysis patients received 2 g cefepime i.v. at the end of hemodialysis three times per week.. Trough levels of cefepime were 23.3 +/- 7.3 mg/l and peak serum concentrations 165.6 +/- 48.7 mg/l. After 3.5 h of high-flux hemodialysis, 72.2 +/- 6.4% of cefepime was eliminated. The intradialytic half-life was 1.6 +/- 0.29 h and the interdialytic half-life 22.0 +/- 2.14 h.. A dosage of 2 g cefepime after each hemodialysis session achieved drug levels well above the minimal inhibitory concentration (MIC)90 for most of the target pathogens. Thus, the described dosing schedule is an efficient and cost saving antmicrobial therapy for severe infections in long-term hemodialysis patients with no residual renal function.

Topics: Adult; Cefepime; Cephalosporins; Communicable Diseases; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of intravenously administered cefepime (1000 mg over 30 minutes) were studied in 5 healthy volunteers and 20 patients with various degrees of renal impairment. Cefepime concentrations in plasma, urine, and hemodialysate were assayed using reverse-phase HPLC with ultraviolet detection. Mean peak plasma concentrations of cefepime at the end of 30-minute infusion ranges from 63.5 to 73.9 micrograms/ml and were not affected by the degree of renal impairment. The half-life of cefepime was approximately 2.3 hours in subjects with normal kidney function; it increased proportionately as renal function decreased. Significant linear relationships between total body clearance and creatinine clearance, as well as renal clearance and creatinine clearance, were observed. The mean volume of distribution at steady state in healthy volunteers was 20.5 liters and was not significantly altered in subjects with renal insufficiency. The mean cumulative urinary recovery of cefepime in healthy volunteers was 82.9% of the administered dose and significantly decreased in subjects with creatinine clearance less than 30 ml/min. Hemodialysis significantly shortened the elimination half-life from 13.5 hours during the predialysis period to 2.3 hours during the dialysis period. Cefepime dosage should be reduced in proportion to the decline in creatinine clearance.

Topics: Adult; Cefepime; Cephalosporins; Creatinine; Drug Administration Schedule; Half-Life; Humans; Infusions, Intravenous; Kidney Failure, Chronic; Male; Mathematics; Metabolic Clearance Rate; Middle Aged; Renal Dialysis