The Journal of antimicrobial chemotherapy · 2026
Can pharmacokinetic/pharmacodynamic targets be achieved with voriconazole in the treatment of urinary tract infections caused by Candida spp. with reduced susceptibility to fluconazole?
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Boglione-Kerrien Christelle, Lemaitre Florian, Gautier-Veyret Elodie, Baklouti Sarah, Hulin Anne, Cornet Muriel, Botterel Françoise, Morcet Jeff, Le Bot Audrey, Verdier Marie-Clémence, Gangneux Jean-Pierre, Guegan Hélène
Аннотация
BACKGROUND: Treating Candida spp. urinary tract infections (UTIs) are challenging when isolates have reduced susceptibility to fluconazole. Voriconazole may be a therapeutic alternative despite its low urinary excretion as an unchanged compound.
OBJECTIVES: To quantify voriconazole and its main metabolite, voriconazole N-oxide, in urine and plasma, determine minimum inhibitory concentrations (MICs) of voriconazole and voriconazole N-oxide, and assess the antifungal activity of urine from voriconazole-treated patients.
METHODS: Sixty patients receiving oral voriconazole were prospectively included. Voriconazole and voriconazole N-oxide concentrations in urine (12-h urine volume) and plasma were measured by liquid chromatography-tandem mass spectrometry. MICs were determined by broth microdilution according to EUCAST guidelines. Urinary antifungal activity was assessed using a disk diffusion bioassay, including against N. glabratus. A pharmacokinetic/pharmacodynamic target concentration/MIC >1 in urine was defined.
RESULTS: Median voriconazole urinary concentration was 1.9 mg/L [1.1-3.1], similar to plasma trough concentration (2.2 mg/L) and positively correlated (R2 = 0.82). Voriconazole N-oxide urinary concentrations (median 20.4 mg/L) were substantially higher than plasma trough concentrations (median 2.1 mg/L). Voriconazole MICs ranged from 0.155 to 0.75 mg/L, while voriconazole N-oxide MICs were 32-48 mg/L for reduced susceptibility to fluconazole isolates. Urine with voriconazole concentrations above 3 mg/L was more likely to inhibit N. glabratus. The median urinary voriconazole concentration/MIC ratio of 4.75 supports potential clinical efficacy.
CONCLUSIONS: Voriconazole can achieve therapeutically relevant urinary concentrations for treating UTIs with reduced susceptibility to fluconazole. Therapeutic drug monitoring may facilitate individualized dosing and optimize treatment outcomes.
OBJECTIVES: To quantify voriconazole and its main metabolite, voriconazole N-oxide, in urine and plasma, determine minimum inhibitory concentrations (MICs) of voriconazole and voriconazole N-oxide, and assess the antifungal activity of urine from voriconazole-treated patients.
METHODS: Sixty patients receiving oral voriconazole were prospectively included. Voriconazole and voriconazole N-oxide concentrations in urine (12-h urine volume) and plasma were measured by liquid chromatography-tandem mass spectrometry. MICs were determined by broth microdilution according to EUCAST guidelines. Urinary antifungal activity was assessed using a disk diffusion bioassay, including against N. glabratus. A pharmacokinetic/pharmacodynamic target concentration/MIC >1 in urine was defined.
RESULTS: Median voriconazole urinary concentration was 1.9 mg/L [1.1-3.1], similar to plasma trough concentration (2.2 mg/L) and positively correlated (R2 = 0.82). Voriconazole N-oxide urinary concentrations (median 20.4 mg/L) were substantially higher than plasma trough concentrations (median 2.1 mg/L). Voriconazole MICs ranged from 0.155 to 0.75 mg/L, while voriconazole N-oxide MICs were 32-48 mg/L for reduced susceptibility to fluconazole isolates. Urine with voriconazole concentrations above 3 mg/L was more likely to inhibit N. glabratus. The median urinary voriconazole concentration/MIC ratio of 4.75 supports potential clinical efficacy.
CONCLUSIONS: Voriconazole can achieve therapeutically relevant urinary concentrations for treating UTIs with reduced susceptibility to fluconazole. Therapeutic drug monitoring may facilitate individualized dosing and optimize treatment outcomes.