Adjunctive N-Acetyl-L-Cysteine in Treatment of Murine Pneumococcal

Despite antibiotic therapy, acute and long-term complications are still frequent in pneumococcal meningitis. One important trigger of these complications is oxidative stress, and adjunctive antioxidant treatment withN-acetyl-L-cysteine was suggested to be protective in experimental pneumococcal meningitis. However, studies of effects on neurological long-term sequelae are lim-ited. Here, we investigated the impact of adjunctiveN-acetyl-L-cysteine on long-term neurological deficits in a mouse model of meningitis. C57BL/6 mice were intracisternally infected with Streptococcus pneumoniae. Eighteen hours after infection, mice were treated with a combination of ceftriaxone and placebo or ceftriaxone andN-acetyl-L-cysteine, respectively. Two weeks after infection, neurologic deficits were assessed using a clinical score, an open field test (explorative activity), a t-maze test (memory function), and auditory brain stem responses (hearing loss). Furthermore, cochlear histomorphological correlates of hearing loss were assessed. AdjunctiveN-acetyl-L-cysteine reduced hearing loss after pneumococcal meningitis, but the effect was minor. There was no significant benefit of adjunctiveN-acetyl-L-cysteine treatment in regard to other long-term complications of pneu-mococcal meningitis. Cochlear morphological correlates of meningitis-associated hearing loss were not reduced by adjunctive N-acetyl-L-cysteine. In conclusion, adjunctive therapy withN-acetyl-L-cysteine at a dosage of 300 mg/kg of body weight intra-peritoneally for 4 days reduced hearing loss but not other neurologic deficits after pneumococcal meningitis in mice. These re-sults make a clinical therapeutic benefit ofN-acetyl-L-cysteine in the treatment of patients with pneumococcal meningitis questionable