Positive correlation between voriconazole trough concentrations and C-reactive protein levels in patients with chronic pulmonary aspergillosis: A retrospective cohort study

Chronic pulmonary aspergillosis (CPA) is a pulmonary disease caused by Aspergillus. CPA progresses slowly in patients with underlying lung diseases, and exacerbations and remissions often occur [1]. Antifungal drugs, which are the primary treatment, are prescribed long-term for at least 6 months. The therapeutic effects of antifungal drugs are limited, and mortality due to CPA is high [[1], [2], [3]].

In the current Clinical Infectious Diseases guidelines, voriconazole (VRCZ) is the first-line treatment for CPA [1]. The mean VRCZ plasma concentration/minimum inhibitory concentration (MIC) is an indicator of treatment success, and several clinical trials have reported the association of clinical effects with VRCZ trough concentrations [[4], [5], [6]]. The MIC of a clinically isolated strain of Aspergillus and the area under the curve of VRCZ concentration are difficult to measure. Therefore, in the clinical setting, VRCZ trough concentrations are regarded as the best marker during treatment. Most experts agree that dosing should achieve a VRCZ trough of >1–1.5 μg/mL for efficacy but <4 μg/mL to minimize toxicity, which primarily includes central nervous system toxicity [1,7]. Thus, the Infectious Diseases Society of America recommends therapeutic drug monitoring of VRCZ to prevent interruption due to side effects and obtain the optimum therapeutic effects [1].

Although maintaining adequate VRCZ concentrations is important, VRCZ concentrations vary widely between patients and within patients. Variations in VRCZ concentrations are influenced by genetic polymorphisms of cytochrome P450 2C19 (CYP2C19), liver function, drug interactions, and nutritional status [6,[8], [9], [10], [11], [12]]. However, we experienced variabilities in VRCZ trough concentrations, which cannot be explained by these factors. Thus, the variability of VRCZ trough concentrations in patients with CPA was examined, and the factors associated with these variabilities in the same patient at different time points in real-world settings were identified.

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