A 2015 systematic review analyzed 143 articles (N=25,712) studying various antibiotics from different classes to examine the current evidence for seizures associated with antibiotics. Studies were mainly classified as low to very low levels of evidence observing beta-lactam agents. Certain penicillins, fourth-generation cephalosporins, and imipenem have been studied the most and seem to be prevalent with use of high doses or in those with renal dysfunction. However, this does not preclude the potential seizure effects of other antibiotic regimens and there is no direct comparison data. The authors have summarized the known data with defined frequency, which is presented in Table 1. [1]
A 2020 review article discussed the available literature regarding antibiotics and epilepsy. Overall, the agents that have been shown to induce seizures include beta-lactams, macrolides, fluoroquinolones, metronidazole, and polymyxins. Among penicillins, penicillin G is described to have the highest epileptic potential without regards to concentration in the cerebrospinal fluid. Between penicillins and cephalosporins, cephalosporins with heterocyclic rings at position 7 and 3 and 3 of 7-aminocephalosporanic acid seem to have similar or greater potential for epilepsy (e.g. cefazolin). Fluoroquinolones with GABA-like structures at 7 positions seem to also have greater epilepsy potential, such as norfloxacin and ciprofloxacin. There are other factors that have seldom been explored such as co-administration with other agents, fever, electrolyte imbalances, metabolic disturbances, and type of infection treatment. More research is needed before comparative conclusions can be made. [2]
A 2014 review article provided similar insights regarding the clinical features and management of antibiotic neurotoxicity. The antibiotic classes most commonly associated with seizures included penicillins, cephalosporins, carbapenems, and fluoroquinolones. Other antibiotics that have been linked to seizures are metronidazole when taken for prolonged periods and isoniazid in overdose. Seizures from antibiotic use are rare, with reported incidence rates of 0.04% for cephalosporins and 0.1-0.5% for fluoroquinolones. However, seizure risk can differ based on patient factors like brain lesions. It also varies within antibiotic classes, as seizures have more often occurred with levofloxacin compared to other fluoroquinolones and with imipenem versus other carbapenems. [3]