The purpose of this study was to investigate the pharmacokinetic profile and safety of voriconazole treatment in patients with Child-Pugh class B and C cirrhosis. Liver cirrhosis patients who had received the recommended voriconazole maintenance dose (group A) or halved maintenance dose (group B), orally or intravenously, were included. Voriconazole-related adverse events (AEs) were defined according to the Common Terminology Criteria for Adverse Events. A total of 110 trough plasma concentrations of voriconazole (Cmin) were measured in 78 patients. There was a significant difference in voriconazole Cmin between group A and group B (Cmin, 6.95±3.42mg/l vs. 4.02±2.00mg/l; p<0.001). No significant difference in voriconazole Cmin between Child-Pugh class B and C cirrhosis patients was observed in either of the two groups. The international normalized ratio and co-medication with a CYP2C19 inhibitor had a significant effect on voriconazole Cmin in group B. The incidence of AEs in group A was 26.5% and in group B was 15.9%, and 87.5% of AEs developed within 7days after starting voriconazole treatment. These results suggest that the recommended dose and halved maintenance dose may be inappropriate in patients with Child-Pugh class B and C cirrhosis due to the high Cmin, and that voriconazole Cmin should be monitored earlier to avoid AEs.

Purpose: Voriconazole (VRC) is an antifungal agent which is used for treatment and prophylaxis of invasive fungal infections. The common clinical adverse reactions mainly include central nervous system (CNS) toxicity and abnormal liver function. These adverse reactions limit the clinical use of voriconazole to a certain extent. Therefore, the aim of this study was to analyze the risk factors of voriconazole neurotoxic side effects and to determine the plasma trough concentration (C_min) threshold of voriconazole-induced CNS toxicity, so as to improve the safety of voriconazole treatment. Patients and Methods: This study retrospectively collected the clinical data of 165 patients who received voriconazole and underwent therapeutic drug monitoring (TDM). CNS toxicity was defined using the National Cancer Institute (NCI) criteria, logistic regression was used to analyze the risk factors of CNS toxicity, classification and Regression tree (CART) model was used to determine the C_min threshold for CNS toxicity. Results: Voriconazole-related CNS toxicity occurred during treatment in 34 of 165 patients (20.6%) and the median time from administration to onset of CNS toxicity was 6 days (range, 2– 19 days). The overall incidence of CNS toxicity was 20.6% (34/165), including visual disturbances in 4.8% (8/165) and nervous system disorders in 15.8% (26/165). C_min significantly affects the occurrence of CNS toxicity and the threshold of C_min for voriconazole CNS toxicity was determined to be 4.85 mg/L, when C_min > 4.85 mg/L and ≤ 4.85 mg/L, the incidence of CNS was 32.9% and 11.6%, respectively. Conclusion: Voriconazole trough concentration of C_min is an independent risk factor for CNS toxicity, and the threshold of C_min for CNS toxicity is 4.85mg/L. TDM should be routinely performed in patients with clinical use of voriconazole to reduce the occurrence of CNS toxicity of voriconazole.

Introduction: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is rapidly emerging as a life-threatening nosocomial infection. In this study, we aimed to identify risk factors, especially antibiotic use and co-carriage with other bacteria for CRPA infection or colonization. Methodology: A retrospective study was conducted in the First Affiliated Hospital of Xi’an Jiaotong University, which involved a cohort of patients with Pseudomonas aeruginosa infection or colonization from January 2014 to June 2016. Univariate analysis and multivariate analysis were performed to estimate the risk factors of CRPA occurrence. Results: Eight hundred and eighty-eight patients were included in the study. More than 50% of the risk factors were associated with CRPA infection or colonization according to univariate analysis (P < 0.05), such as invasive procedures, co-carriage with Gram-negative pathogens, and prior treatment with some antibiotics. However, only prior exposure to carbapenems (OR: 8.005; CI:4.507-14.217, P<0.001), the days of carbapenems treatment (OR: 1.190; CI: 1.073-1.272; P < 0.001), and co-carriage with Escherichia coli (OR: 1.824; CI: 1.005-3.310, P = 0.048) were considered independent risk factors by multivariate analysis. A higher mortality was found among patients with CRPA infection or colonization (P < 0.05). Conclusions: Risk factors for CRPA infection or colonization were prior exposure to carbapenems, the days of carbapenems treatment, and co-carriage with Escherichia coli. The prevalence of CRPA could be influenced by Gram-negative pathogens, especially in Escherichia coli, and it need more researches. Moreover, restrictions in the clinical use of carbapenems should be taken into account.