Serious central nervous system side effects of cephalosporins: A national analysis of serious reports registered in the French Pharmacovigilance Database

Introduction.- Among antibiotics, Central Nervous System (CNS) adverse drug reactions (ADRs) are often under suspected and overlooked. Cephalosporins are an important cause of drug-induced CNS ADRs but the characteristics of such ADR have not been fully explored. We aimed to characterize the profile of cephalosporins serious CNS ADRs. Method: We performed an analysis of serious reports recorded in the French Pharmacovigilance database from 1987 to 2017. Results: A total of 511 serious ADRs reports was analyzed. Patients had a mean age of 67.1 years and were mainly men (52.5%), with a mean creatinine clearance of 32.9 ml/min. The most involved molecules were cefepime (33.1%), ceftriaxone (29.7%), ceftazidime (19.6%), cefotaxime (9%) and cefazoline (2.9%), mostly administered intravenously (87.3%). A CNS history was observed in 25% of the reports (n = 128). Patients exhibited encephalopathy (30.3%), confusional state (19.4%), convulsion (15.1%), myoclonia (9.4%), status epilepticus (9.2%), coma (6.3%) and hallucination (4.3%). The mean time of onset was 7.7 days and the mean duration was 6 days. Cephalosporin plasma levels were recorded for 153 patients (29.9%) and 107 were above the standards including 62 (57.9%) related to renal impairment. Electroencephalograms were performed in 38.2% (n = 195) of the patients and 81% (ri = 158) were abnormal. Conclusion: This study characterizes an off-target CNS ADRs of several cephalosporins. Ceftriaxone represented a large part of our reports after cefepime and it would be relevant to warn healthcare professionals. Investigations (EEG, though plasma levels and renal function) can be precious tools for clinicians to make a prompt diagnosis and improve patients' outcomes.