Table 1.

Summary of Published Studies On Concurrent VPA-Carbapenem Therapy

References	Study design	Population	VPA dose	Carbapenem used	Level reduction (VPA)	Outcome
Miranda Herrero et al9	Retrospective study	28 children	29.1-55.3 mg/kg/d	Meropenem	88% of levels were subtherapeutic	Seizure in 54.5% of patients
Huang et al7	Observational study	54 adults	1600 mg/d (average)	Meropenem Ertapenem Imipenem	Average level reduced to 16.9 µg/mL	Seizure in 48.1% of patients
Wu et al10	Retrospective study	52 adults	24.1 ± 10.2 mg/kg/d	Meropenem Ertapenem Imipenem	Subtherapeutic in 90% of patients, level reduced within 24 hours of administration by approximately 60%	Seizure (at least 2 patients)
Haroutiunian et al8	Retrospective study	36 patients	2040 ± 70 mg/d	Meropenem	VPA mean ± SEM plasma concentration decreased from 50.8 ± 4.5 µg/mL to 9.9 ± 2.1 µg/mL	NA
Vélez Díaz-Pallarés et al20	Retrospective followed by prospective period with intervention	26 patients	NA	Meropenem	Retrospective period: 2.14-22.76 µg/mL Prospective period: 1.63-43.87 µg/mL	Seizure in 1 patient
Spriet et al11	Retrospective study	39 patients	1600 ± 680 mg/daily (mean)	Meropenem	Average drop in VPA level of 66%	Electroclinical deterioration in 55% of patients. Increase in number of epileptic seizures in 3 patients

Note. VPA = valproic acid; N/A = not available.