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Does Systemic Methotrexate Therapy Induce Azole Resistance among Endogenous Candida Strains?
Dawid Żyrek1, Joanna Nowicka1, Magdalena Pajączkowska1
1Department of Microbiology, Faculty of Medicine, Wrocław Medical University, 50-367 Wrocław, Poland.
Background:
Research confirms that Candida spp. incubated with methotrexate develop multi-drug resistance to azoles, but it is not clear whether this phenomenon occurs in vivo in patients treated with cytostatics. The aim of the study was to assess whether systemic methotrexate therapy induces resistance to azoles among endogenous Candida strains in patients with rheumatological diseases.
Methods:
The test group consisted of 52 rheumatological patients on methotrexate therapy, who have never been exposed to fluconazole. The control group was composed of 49 individuals who have never been exposed to either methotrexate or fluconazole. Oral swab and clinical information were obtained from each participant. The acquired material was cultured, then each strain was isolated and identified (MALDI TOF). Subsequently, minimal inhibitory concentration (MIC) for fluconazole was determined.
Results:
MIC values ranged from <0.125 to 64 µg/mL with the most common result <0.125 µg/mL. Samples obtained from 4 patients of the test group and 2 patients of the control group contained strains resistant to fluconazole.
Conclusions:
Despite slightly higher incidence of fluconazole-resistant strains among patients on systemic methotrexate therapy, we found no solid evidence to support the hypothesis that methotrexate induces resistance to azoles among endogenous Candida strains in patients with rheumatological diseases.
Insights
Systemic methotrexate therapy in rheumatological patients did not show strong evidence of inducing azole resistance in endogenous Candida strains. Further research is needed to confirm these findings in clinical settings.
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.
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