cefepime and Aphasia

Cefepime is known to exert bactericidal activity against Pseudomonas aeruginosa. Cefepime-induced neurotoxicity, most likely caused by increased exposure, has recently become a major concern in clinical practice; therefore, appropriate dose reduction of cefepime should be applied with respect to patients with low cefepime clearance (mostly eliminated by the kidneys). Here, we report a case in which Bayesian prediction-based therapeutic drug monitoring (Bayes-TDM) was effectively used to reduce the dose of cefepime in a patient with pneumonia to prevent neurotoxic complications. A woman (age: 59 years, body weight: 32.5 kg, serum creatinine concentration: 1.02 mg/dL) developed pneumonia caused by P. aeruginosa while receiving treatment for scleroderma and systemic lupus erythematosus. She started treatment with a dosing regimen of 1.0 g of cefepime every 8 h (day X). On day X+5, aphasia developed, and the serum cefepime concentration was 71.3 mg/L at trough. This concentration was twice or thrice higher than the reported safe concentration of cefepime (22 or 35 mg/L at trough). Therefore, we reduced the dose of cefepime to 0.5 g every 12 h using Bayes-TDM from day X+7. As a result, the severity of aphasia decreased by day X+10, and this dose was successfully continued up to day X+13 without further adjustment. In conclusion, individualizing doses by Bayes-TDM may be useful in preventing adverse effects associated with cefepime treatment.

Topics: Anti-Bacterial Agents; Aphasia; Bayes Theorem; Cefepime; Dose-Response Relationship, Drug; Drug Monitoring; Female; Humans; Middle Aged; Pneumonia; Pseudomonas aeruginosa

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

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: Aphasia; Cefepime; Cephalosporins; Confusion; Humans; Neurotoxicity Syndromes; Renal Dialysis; Tremor