Abstract
To investigate the relationship between ganciclovir trough concentration and its clinical efficacy and safety in patients with pulmonary cytomegalovirus (CMV) infection and to evaluate the target value of therapeutic drug monitoring (TDM) for predicting clinical efficacy or toxicity, an observational study was conducted on patients with CMV lung infection between Jan. 2021 and Dec. 2023. Target trough ganciclovir concentrations were collected during TDM, and clinical outcomes and adverse events (AEs) were assessed. Multiple regression analyses or binary logistic regression were used to analyze the factors affecting ganciclovir trough concentrations and clinical efficacy. The receiver operating characteristic (ROC) curve analysis identified ganciclovir trough concentration cutoffs as predictors of toxicity. Of 149 included patients, only 19.22% of trough concentrations reached the target range of 2-4 μg/mL. Diabetes, organ transplantation, and elevated hemoglobin levels decrease trough concentrations, whereas elevated blood creatinine and continuous renal replacement therapy (CRRT) increase trough concentrations. No relationship was found between the trough concentrations and the clinical outcomes. Organ transplantation, duration of ganciclovir administration, and albumin levels affect clinical efficacy. The ROC analysis identified ganciclovir trough concentrations of 0.985 (AUC = 0.600) and 0.995 µg/mL (AUC = 0.701) to be associated with decreased hemoglobin and elevated blood creatinine levels, respectively. No association was observed between ganciclovir trough concentration and clinical efficacy. However, thresholds for ganciclovir trough concentrations causing decreased hemoglobin and increased blood creatinine levels were identified. Renal replacement therapy is more likely to lead to elevated trough concentrations of ganciclovir. These findings suggest the importance of TDM for ganciclovir, and a new target range should be considered.IMPORTANCEAn observational study investigated the relationship between ganciclovir trough concentrations and clinical efficacy and safety. Only 19.22% of ganciclovir trough concentrations reached the target range of 2.0-4.0 μg/mL. Diabetes, organ transplantation, and elevated hemoglobin decreased trough concentrations, while elevated creatinine and CRRT increased concentrations. No relationship was found between ganciclovir trough concentrations and clinical outcomes in CMV lung infection. Organ transplantation, duration of ganciclovir administration, and albumin levels affected the clinical efficacy of ganciclovir. Critical ganciclovir trough concentrations of 0.985 and 0.995 μg/mL were associated with toxicity. The findings suggest the importance of therapeutic drug monitoring (TDM) with ganciclovir treatment.