Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study.

IF 3.3 3区医学 Q2 MICROBIOLOGY

Pathogens Pub Date : 2025-06-07 DOI:10.3390/pathogens14060574

Dawid Żyrek, Joanna Nowicka, Magdalena Pajączkowska, Mariola Paściak, Katarzyna Machnik, Tomasz Werner, Zygmunt Konieczny, Piotr Jędrzejczak, Dominika Raźniewska, Gabriela Fijałkowska, Michał Piątek, Barbara Radecka, Kinga Żyrek, Elżbieta Woźniak-Grygiel, Iwona Dzieńdziora-Urbińska

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Abstract

Previous studies have demonstrated that Candida spp. isolates exposed in vitro to the folic acid antagonist methotrexate may develop multidrug cross-resistance to azole antifungals. The aim of this study was to determine whether systemic therapy with antineoplastic antifolates-pemetrexed or methotrexate-constitutes a risk factor for colonization or infection with fluconazole-resistant yeasts. The study group comprised 44 cancer patients who received high-dose systemic antifolate therapy, while the control group consisted of 48 patients without prior exposure to either methotrexate or pemetrexed. Oral swabs and relevant clinical data were collected from all participants. In total, 109 fungal strains representing 13 species were isolated, identified, and subsequently tested for fluconazole susceptibility. Fluconazole-resistant isolates were identified in 4 out of 44 (9.1%) antifolate-treated patients and in 3 out of 48 (6.3%) control patients. Our findings suggest that, although this phenomenon occurs in vitro, systemic antineoplastic antifolate therapy does not induce azole resistance among endogenous yeast species in vivo.

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系统性抗叶酸化疗不适合氟康唑耐药念珠菌：一项多中心临床研究

先前的研究表明，体外暴露于叶酸拮抗剂甲氨蝶呤的念珠菌菌株可能对唑类抗真菌药产生多药交叉耐药。本研究的目的是确定抗肿瘤抗叶酸剂（培美曲塞或甲氨蝶呤）的全身治疗是否构成氟康唑耐药酵母定植或感染的危险因素。研究组包括44名接受大剂量全身性抗叶酸治疗的癌症患者，而对照组包括48名先前未接触过甲氨蝶呤或培美曲塞的患者。收集所有参与者的口腔拭子和相关临床资料。共分离、鉴定了13种109株真菌，随后进行了氟康唑敏感性试验。44例抗叶酸治疗患者中有4例（9.1%）和48例对照患者中有3例（6.3%）发现氟康唑耐药菌株。我们的研究结果表明，尽管这种现象在体外发生，但体内内源性酵母菌体内的系统性抗肿瘤抗叶酸治疗不会诱导唑耐药性。

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来源期刊

Pathogens Medicine-Immunology and Allergy

CiteScore

6.40

自引率

8.10%

发文量

1285

审稿时长

17.75 days

期刊介绍： Pathogens (ISSN 2076-0817) publishes reviews, regular research papers and short notes on all aspects of pathogens and pathogen-host interactions. There is no restriction on the length of the papers. Our aim is to encourage scientists to publish their experimental and theoretical research in as much detail as possible. Full experimental and/or methodical details must be provided for research articles.