Factors associated with beyond-therapeutic serum voriconazole trough level among critically ill patients with invasive fungal infections

Various kinds of clinical characteristics predispose patients receiving voriconazole therapy to high variability of serum voriconazole level. However, little is known about the predictors of drug level variability among critically ill patients. This retrospective study was executed to investigate the associated factors. Between January 2020 and June 2021, all adult patients with invasive pulmonary aspergillosis receiving parenteral voriconazole for more than four days during their stay in intensive care were recruited. The enrolled subjects were classified into within- and beyond-therapeutic group based on their serum voriconazole trough levels. A total of 34 patients were studied; serum voriconazole levels ranged from < 0.1 to 11.38 mg/L, and 35.3% were categorized as beyond-therapeutic group. The all-cause in-hospital mortality rate was 17.7%. Multivariate logistic regression showed that lower body mass index (BMI) value [odds ratio (OR), 15.16; 95% CI, 2.10–109.51; p = 0.007] and increase in total bilirubin level (OR, 9.23; 95% CI, 1.16–73.21; p = 0.035) were independently associated with variability of serum voriconazole troughs. Further investigation of appropriate prescribing doses of voriconazole, likely with regards to BMI value, might be needed to attain target drug concentrations to achieve better clinical effectiveness and avoid drug-related toxicity.