Does Systemic Methotrexate Therapy Induce Azole Resistance among Endogenous Candida Strains?

Area of Science:

• Medical Mycology
• Pharmacology
• Rheumatology

Background:

• In vitro studies show methotrexate induces azole resistance in Candida species.
• The in vivo relevance of this phenomenon in patients on cytostatic therapy remains unclear.

Purpose of the Study:

• To investigate if systemic methotrexate therapy induces azole resistance in endogenous Candida strains.
• To assess Candida azole resistance in patients with rheumatological diseases undergoing methotrexate treatment.

Main Methods:

• Compared 52 rheumatological patients on methotrexate with 49 controls, all naive to fluconazole.
• Isolated and identified Candida strains from oral swabs using MALDI TOF.
• Determined fluconazole's minimal inhibitory concentration (MIC) for each isolated strain.

Main Results:

• Fluconazole MIC values varied widely, with most strains susceptible (<0.125 µg/mL).
• Resistant Candida strains were found in 4 patients (methotrexate group) and 2 individuals (control group).
• A slightly higher incidence of fluconazole resistance was observed in the methotrexate group.

Conclusions:

• No definitive evidence supports methotrexate inducing azole resistance in endogenous Candida strains in this patient cohort.
• The study did not confirm the hypothesis that systemic methotrexate therapy leads to azole resistance in Candida species in vivo.
• Further investigation is warranted to fully understand the clinical implications of methotrexate use on Candida antifungal susceptibility.