Effect of carbapenem and VPA coadministration on seizure outcomes: a retrospective single-center study

Background The concomitant use of carbapenem antibiotics and valproate is generally avoided because carbapenems markedly reduce serum valproate concentrations, raising concern about increased seizure risk. However, robust clinical evidence linking this pharmacokinetic interaction to worsened seizure control remains scarce. Methods This single‑center, retrospective, self‑controlled study included 189 patients with epilepsy or status epilepticus who received valproate together with meropenem and/or imipenem. Serum valproate concentrations, seizure incidence, and seizure frequency were compared across the pre‑concomitant, concomitant, and post‑concomitant periods. Results During concomitant therapy, median serum valproate concentration declined by 74.7% (from 48.04 to 12.15 µg/mL). Despite this reduction, no significant increase in seizure rate or frequency was observed. Seizure rates were 28.0% pre‑concomitantly, 20.6% during therapy ( P  = 0.5602), and 8.5% post‑therapy ( P  = 0.0086). Seizure frequency remained 0 (0–0.5), 0 (0–0), and 0 (0–0) per person‑week, respectively. No significant differences in valproate concentrations were found between patients with and without seizures. Conclusions These findings challenge current precautionary recommendations and support a more nuanced, evidence‑based approach to managing this drug combination in clinical practice.