Cycloserine-induced neuropsychiatric toxicity in multidrug-resistant tuberculosis: association with peak plasma concentration.

Cycloserine (Cs) is a crucial anti-multidrug-resistant tuberculosis medication with significant clinical efficacy. However, its clinical application is limited by neuropsychiatric-related adverse drug reactions (ADRs). This study retrospectively evaluated the peak plasma concentration () of Cs and Cs-related neuropsychiatric ADRs and analyzed the risk factors of developing neuropsychiatric ADRs. A multivariable ordinal logistic regression model was built to predict the incidence of neuropsychiatric ADRs. This study enrolled a total of 136 participants, with a cumulative incidence of neuropsychiatric ADRs of 12.5%. Patients experiencing ADRs had significantly higher Cscompared to those without ADRs. The risk of ADRs rose with increasing Cs exposure, especially whenexceeded 30 mg/L. Receiver operating characteristic analysis demonstrated the strong predictive value offor neuropsychiatric ADRs. Notably, the predictive efficacy of the logistic regression model significantly improved after incorporating drinking history as a covariate, achieving a final predictive accuracy of 87.6%. Csserves as a critical indicator for predicting Cs-related neuropsychiatric ADRs. Dynamic monitoring of Cscombined with alcohol history assessment can enable accurate identification of high-risk populations for neuropsychiatric ADRs, thereby providing a scientific basis for developing individualized medication regimens and implementation of early interventions.IMPORTANCECycloserine (Cs) is a vital medication for treating multidrug-resistant tuberculosis (MDR-TB), but its use is often limited by severe neuropsychiatric side effects such as depression, anxiety, and seizures. This study highlights the critical role of monitoring Cs peak plasma concentration () to predict and mitigate these adverse reactions. By analyzing data from 136 patients, the researchers found that higher Cslevels significantly increase the risk of neuropsychiatric toxicity, particularly when concentrations exceed 30 mg/L. Additionally, a history of alcohol consumption further elevates this risk. These findings provide a practical approach for clinicians: regular monitoring of Cs levels and assessing alcohol use can help identify high-risk patients early, enabling timely adjustments to treatment plans. This work not only enhances patient safety but also supports the broader goal of improving MDR-TB treatment outcomes by minimizing harmful side effects.