Cefazolin-Induced Encephalopathy in a Uraemic Patient

Prof. Dr. J.P. Fillastre, Nephrology Service, Hôpital de Bois-Guillaume, Rouen University School of Medicine, 147, avenue du Maréchal-Juin, B.P. 100, F-76233 Bois-Guillaume Cédex (France) Dear Sir, In a recent paper, J.D. Schwankhaus et al. [2] reported the occurrence of an encephalopathy in a uraemic patient who had received a high dose of cefazolin: A 62-year-old man received 2 g cefazolin intravenously every 6 h to treat gram-negative septicamia. Blood creatinine was 10.4 mg/dl. Twenty-four hours later he had a generalized tonic-clonic seizure followed by lethargy, disorientation, asterixis and multifocal myoclonus. Cefazolin dosage was reduced, and within 48 h his mental status improved and neurological signs disappeared. We would like to report a similar observation in a haemodialysed 41-year-old female whose renal failure resulted from focal and segmental hyalinosis. Haemodi-alysis treatment was initiated in 1973, and the patient received a renal transplant in 1975. In 1982, osteonecrosis of the femoral head required a hip prosthesis. In 1983, because of recurrence of hyalinosis in the transplant, the patient returned to haemodialysis, during 4 h three times a week. A few days before reinitiation of haemodialysis two clonic seizures occurred and were attributed to metabolic disorders. However, 5 eg phenobaribital per day was prescribed. In January 1984, an abscess around the hip prosthesis was found to be due to Staphylococcus aureus. The patient received 50 mg tobramycin in a 1-hour perfusion after each dialysis (3 times per week) and 3 g cefazolin intravenously per day. Eleven days after the outset of the treatment – the patient had received 33 g cefazolin -‚ a clonic seizure was observed during the dialysis. The barbituric blood level was considered to be insufficient (16 μmol/l) and the daily dose of phenobarbi-tal was increased to 15 eg/day. Antibiotic treatment was continued at the same doses. One week later a status convulsivus occurred, which resisted 3 injections of di-azepam. Respiratory distress required intubation and assisted breathing. Cerebral tomodensitometric results were normal. Drug toxicity was suspected: 48 h after stopping cefazolin, drug plasmatic concentration was still 280 μg/ml, i.e., ten times the effective treatment level. Dialysis was performed daily, and dialysate concentrations of cefazolin were 100–116 μg/ml. The frequency of convulsive episodes decreased, but they ended only 4 days after stopping cefazolin treatment. 75 mg Dibekacin after each dialysis and 1 g erythromycin per day were then prescribed for 9 days. On the 10th day, cefazolin was reintroduced at a dose of 500 mg after each dialysis. Blood levels of cefazolin were determined before each dialysis and did not exceed 128 μg/ml.