Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MTX | Methotrexate |
PMX | Pemetrexed |
FLU | Fluconazole |
MIC | Minimum inhibitory concentrations |
CLSI | Clinical and Laboratory Standards Institute |
OD | Optical density |
K- | Negative control |
K+ | Positive control |
SDD | Susceptible-dose dependent |
SD | Standard deviation |
AC | Adenocarcinoma |
SCC | Squamous cell carcinoma |
SCLC | Small cell lung cancer |
NSCLC | Non-small cell lung cancer; unspecified |
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Study Group | Control Group | |
---|---|---|
Age ± SD, (median) [years] p = 0.71 | 67.8 ± 6.7, (69) | 67.5 ± 9.9, (68.5) |
Gender p = 0.27 | Male: 24/44 (54.6%) Female: 20/44 (45.5%) | Male: 30/48 (62.5%) Female: 18/48 (37.5%) |
Cumulative Pemetrexed dose ± SD, (median) [mg] | 4844.8 ± 4490.3, (2960) | - |
Cumulative Methotrexate dose ± SD, (median) [mg] | 120 ± 0, (0) | - |
Azole intake in the last 3 months (% of participants) p = 0.63 | 1/44 (2.3%) | 2/48 (4.2%) |
Hospitalization status (% of participants) p = 0.25 | Outpatient: 9/44 (20.5%) Inpatient: 35/44 (79.6%) | Outpatient: 6/48 (12.5%) Inpatient: 42/48 (87.5%) |
Prior hospitalization in the last 3 months (% of participants) p = 0.10 | 35/44 (79.6%) | 42/48 (64.6%) |
Type of neoplasm | Lung cancer: 40/44 (90.9%) - AC: 40/44 | Lung cancer: 36/48 (75.0%) - AC: 16/48 - SCC: 12/48 - SCLC: 4/48 - NSCLC, nonspecified: 4/48 |
Pleural mesothelioma: 3/44 (6.8%) | Pleural mesothelioma: 1/48 (2.1%) | |
Urinary bladder cancer: 1/44 (2.3%) | Urinary bladder cancer: 1/48 (2.1%) | |
Gastric cancer: 2/48 (4.2%) Colorectal cancer: 4/48 (8.3%) Cholangiocarcinoma: 1/48 (2.1%) Pancreatic cancer: 1/48 (2.1%) Pharyngeal cancer: 1/48 (2.1%) Prostate cancer: 1/48 (2.1%) |
Study Group | Control Group | |
---|---|---|
Culture-positive samples | 34/44 (77.3%) | 41/48 (85.4%) |
Total number of strains | 52 | 56 |
Average number of strains per positive sample ± SD | 1.5 ± 0.6 | 1.4 ± 0.5 |
Fluconazole-resistant isolates (% of samples) | 4/44 (9.1%) | 3/48 (6.3%) |
Average MIC ± SD [µg/mL] | 2.235 ± 3.921 | 2.674 ± 4.526 |
Number of strains (% of samples containing the species) | - Nakaseomyces glabratus (formerly Candida glabrata)—10 (22.7%) - Candida albicans—25 (47.7%) - Candida dubliniensis—4 (9.1%) - Candida tropicalis—4 (4.5%) - Pichia kudriavzevii (formerly Candida krusei)—2 (4.5%) - Pichia cactophila—1 (2.3%) - Kluyveromyces marxianus (formerly Candida kefyr)—1 (2.3%) - Kluyveromyces lactis—1 (2.3%) - Saccharomyces cerevisiae—2 (4.5%) - Hyphopichia burtonii—1 (2.3%) - Hanseniaspora uvarum—1 (2.3%) | - Nakaseomyces glabratus (formerly Candida glabrata)—16 (31.3%) - Candida albicans—27 (56.3%) - Candida dubliniensis—9 (16.7%) - Pichia kudriavzevii (formerly Candida krusei)—2 (4.2%) - Kluyveromyces marxianus (formerly Candida kefyr)—1 (2.1%) - Clavispora lusitaniae (formerly Candida lusitaniae)—1 (2.1%) - Torulaspora delbrueckii—1 (2.1%) |
Before Antifolate | Cumulative Dose | After Antifolate | |
---|---|---|---|
Patient 15 |
| 905 mg of PMX |
|
Patient 18 |
| 11,000 mg of PMX |
|
Patient 19 | NEGATIVE CULTURE | 3920 mg of PMX |
|
Patient 21 |
| 3240 mg of PMX |
|
Patient 22 |
| 3360 mg of PMX | NEGATIVE CULTURE |
Patient 23 |
| 2340 mg of PMX |
|
Patient 28 | NEGATIVE CULTURE | 120 mg of MTX | NEGATIVE CULTURE |
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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Żyrek, D.; Nowicka, J.; Pajączkowska, M.; Paściak, M.; Machnik, K.; Werner, T.; Konieczny, Z.; Jędrzejczak, P.; Raźniewska, D.; Fijałkowska, G.; et al. Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study. Pathogens 2025, 14, 574. https://doi.org/10.3390/pathogens14060574
Żyrek D, Nowicka J, Pajączkowska M, Paściak M, Machnik K, Werner T, Konieczny Z, Jędrzejczak P, Raźniewska D, Fijałkowska G, et al. Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study. Pathogens. 2025; 14(6):574. https://doi.org/10.3390/pathogens14060574
Chicago/Turabian StyleŻyrek, Dawid, Joanna Nowicka, Magdalena Pajączkowska, Mariola Paściak, Katarzyna Machnik, Tomasz Werner, Zygmunt Konieczny, Piotr Jędrzejczak, Dominika Raźniewska, Gabriela Fijałkowska, and et al. 2025. "Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study" Pathogens 14, no. 6: 574. https://doi.org/10.3390/pathogens14060574
APA StyleŻyrek, D., Nowicka, J., Pajączkowska, M., Paściak, M., Machnik, K., Werner, T., Konieczny, Z., Jędrzejczak, P., Raźniewska, D., Fijałkowska, G., Piątek, M., Radecka, B., Żyrek, K., Woźniak-Grygiel, E., & Dzieńdziora-Urbińska, I. (2025). Systemic Antifolate Chemotherapy Does Not Select for Fluconazole-Resistant Candida: A Multicenter Clinical Study. Pathogens, 14(6), 574. https://doi.org/10.3390/pathogens14060574