Antifungal Activity of Minocycline and Azoles Against Fluconazole-Resistant Candida Species
Open accessAbstract
Candida species are the most common fungal pathogens to infect humans, and can cause life-threatening illnesses in individuals with compromised immune systems. Fluconazole (FLU) is the most frequently administered antifungal drug, but its therapeutic efficacy has been limited by the emergence of drug-resistant strains. When co-administered with minocycline (MIN), FLU can synergistically treat clinical Candida albicans isolates in vitro and in vivo. However, there have been few reports regarding the synergistic efficacy of MIN and azoles when used to treat FLU-resistant Candida species, including Candida auris. Herein, we conducted a microdilution assay wherein we found that MIN and posaconazole (POS) showed the best in vitro synergy effect, functioning against 94% (29/31) of tested strains, whereas combinations of MIN+itraconazole (ITC), MIN+voriconazole (VOR), and MIN+VOR exhibited synergistic activity against 84 (26/31), 65 (20/31), and 45% (14/31) of tested strains, respectively. No antagonistic activity was observed for any of these combinations. In vivo experiments were conducted in Galleria mellonella, revealing that combination treatment with MIN and azoles improved survival rates of larvae infected with FLU-resistant Candida. Together, these results highlight MIN as a promising synergistic compound that can be used to improve the efficacy of azoles in the treatment of FLU-resistant Candida infections.
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The obtained results are consistent with recent studies, which noticed that due to the wide usage of azole drugs and prolonged antifungal therapy, the number of azole-resistant Candida isolates is still increasing.
“The obtained results are consistent with recent studies, which noticed that due to the wide usage of azole drugs and prolonged antifungal therapy, the number of azole-resistant Candida isolates is still increasing (Bhattacharya et al. 2020; Zhang et al. 2020; Tan et al. 2021).”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Tan et al. 2021
The Introduction (page not provided) says fluconazole is commonly prescribed and that emerging drug-resistant strains increasingly limit its use. It does not say that widespread azole use or prolonged antifungal therapy causes resistance, or establish that the number of resistant Candida isolates is still increasing. (LLM, conf=0.84)
Experimental — accuracy not yet measuredAt present, clinical isolates of Candida spp. are considered to be one of the highly resistant fungi to most traditional antifungal drugs.
“At present, clinical isolates of Candida spp. are considered to be one of the highly resistant fungi to most traditional antifungal drugs(Costa-de-oliveira and Rodrigues 2020; Tan et al. 2021)”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Tan et al. 2021
The Introduction reports emerging fluconazole resistance in Candida and high fluconazole resistance in C. auris. It also gives much lower resistance frequencies for several other Candida species and does not establish that clinical Candida isolates are highly resistant to most traditional antifungal drugs. The Methods describe a selected set of fluconazole-resistant clinical isolates, not clinical isolates generally. (LLM, conf=0.88)
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Cites
The Promise of Minocycline in Neurology
Yong, V. W., Wells, J., Giuliani, F., Casha, S., Power, C., & Metz, L. M. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00937-8 · Cited by 518 · see citing works
Burden of Candidemia in the United States, 2017
Tsay, S. V., Mu, Y., Williams, S., Epson, E., Nadle, J., Bamberg, W. M., Barter, D. M., Johnston, H. L., Farley, M. M., Harb, S., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa193 · Cited by 163 · see citing works
Flagged first, then by citations
Research works printed but not linked: 18
- Asadi A. Abdi M. Kouhsari E. Panahi P. Sholeh M. Sadeghifard N.. (2020). Minocycline, focus on mechanisms of resistance, antibacterial activity, and clinical effectiveness: Back to the future. J. Glob. Antimicrob. Resist. 22, 161– 174. 10.1016/j.jgar.2020.01.022, PMID: 32061815 · DOI
- Berkow E. L. Lockhart S. R. (2017). Fluconazole resistance in Candida species: a current perspective. Infect Drug Resist. 10, 237– 245. 10.2147/IDR.S118892, PMID: 28814889 PMC5546770 · DOI · Paper page
- Fiori A. Van Dijck P. (2012). Potent synergistic effect of doxycycline with fluconazole against Candida albicans is mediated by interference with iron homeostasis. Antimicrob. Agents Chemother. 56, 3785– 3796. 10.1128/AAC.06017-11, PMID: 22564841 PMC3393430 · DOI · Paper page
- Firacative C. (2020). Invasive fungal disease in humans: are we aware of the real impact? Mem. Inst. Oswaldo Cruz 115: e200430. 10.1590/0074-02760200430, PMID: 33053052 PMC7546207 · DOI
- Forsberg K. Woodworth K. Walters M. Berkow E. L. Jackson B. Chiller T.. (2019). Candida auris: The recent emergence of a multidrug-resistant fungal pathogen. Med. Mycol. 57, 1– 12. 10.1093/mmy/myy054, PMID: 30085270 · DOI · Paper page
- Gao L. j. Sun Y. Yuan M. Z. Li M. Zeng T. X. (2020). In Vitro and In Vivo study on the synergistic effect of minocycline and azoles against pathogenic fungi. Antimicrob. Agents Chemother. 64: e00290-20. 10.1128/AAC.00290-20, PMID: 32253207 PMC7269466 · DOI
- Gao Y. Zhang C. Q. Lu C. Y. Liu P. Li Y. Li H.. (2013). Synergistic effect of doxycycline and fluconazole against Candida albicans biofilms and the impact of calcium channel blockers. FEMS Yeast Res. 13, 453– 462. 10.1111/1567-1364.12048, PMID: 23577622 · DOI
- Goemaere B. Becker P. Van W. E. Maertens J. Spriet I. Hendrickx M.. (2018). Increasing candidaemia incidence from 2004 to 2015 with a shift in epidemiology in patients preexposed to antifungals. Mycoses 61, 127– 133. 10.1111/myc.12714, PMID: 29024057 · DOI
- Gu W. R. Yu Q. Yu C. X. Sun S. J. (2018). In vivo activity of fluconazole/tetracycline combinations in Galleria mellonella with resistant Candida albicans infection. J. Glob. Antimicrob. Resist. 13, 74– 80. 10.1016/j.jgar.2017.11.011, PMID: 29191612 · DOI
- Jiang T. Tang J. Wu Z. Q. Sun Y. Tan J. W. Yang L. J. (2020). The combined utilization of Chlorhexidine and Voriconazole or Natamycin to combat Fusarium infections. BMC Microbiol. 20: 275. 10.1186/s12866-020-01960-y, PMID: 32891143 PMC7487579 · DOI
- Kong Q. X. Cao Z. B. Lv N. Zhang H. Liu Y. Y. Hu L. F.. (2020). Minocycline and fluconazole have a synergistic effect against Cryptococcus neoformans both in vitro and in vivo. Front. Microbiol. 11: 836. 10.3389/fmicb.2020.00836, PMID: 32431685 PMC7214679 · DOI
- McCarty T. P. Pappas P. G. (2016). Invasive candidiasis. Infect. Dis. Clin. N. Am. 30, 103– 124. 10.1016/j.idc.2015.10.013, PMID: 26739610 · DOI · Paper page
- Oliver B. G. Silver P. M. Marie C. Hoot S. J. Leyde S. E. White T. C. (2008). Tetracycline alters drug susceptibility in Candida albicans and other pathogenic fungi. Microbiology 154, 960– 970. 10.1099/mic.0.2007/013805-0, PMID: 18310042 PMC2615396 · DOI
- Perfect J. R. Ghannoum M. (2020). Emerging issues in antifungal resistance. Infect. Dis. Clin. N. Am. 34, 921– 943. 10.1016/j.idc.2020.05.003, PMID: 33131575 · DOI
- Sapadin A. N. Fleischmajer R. (2006). Tetracyclines: nonantibiotic properties and their clinical implications. J. Am. Acad. Dermatol. 54, 258– 265. 10.1016/j.jaad.2005.10.004, PMID: 16443056 · DOI
- Shi W. N. Chen Z. Z. Chen X. Cao L. L. Liu P. Sun S. J. (2010). The combination of minocycline and fluconazole causes synergistic growth inhibition against Candida albicans: an in vitro interaction of antifungal and antibacterial agents. FEMS Yeast Res. 10, 885– 893. 10.1111/j.1567-1364.2010.00664.x, PMID: 20707818 · DOI
- Vatanshenassan M. Boekhout T. Mauder N. Robert V. Maier T. Meis J. F.. (2020). Evaluation of microsatellite typing, ITS sequencing, AFLP fingerprinting, MALDI-TOF MS, and Fourier-transform infrared spectroscopy analysis of Candida auris. J. fungi 6: 146. 10.3390/jof6030146, PMID: 32854308 PMC7576496 · DOI
- Waterworth P. M. (1974). The effect of minocycline on Candida albicans. J. Clin. Pathol. 27, 269– 272. 10.1136/jcp.27.4.269, PMID: 4212409 PMC478100 · DOI
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Candida albicans the main opportunistic pathogenic fungus in humans
Macias-Paz, I. U., Pérez-Hernández, S., Tavera-Tapia, A., Luna-Arias, J. P., Guerra-Cárdenas, J. E., & Reyna-Beltrán, E. (2023) · Revista Argentina de Microbiología · doi:10.1016/j.ram.2022.08.003 · Cited by 141 · see citing works
Mahmoud, D. E., Faraag, A. H. I., & Abu El-Wafa, W. M. (2021) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-021-03158-4 · Cited by 26 · see citing works
- Authors
- Tan, J., Jiang, S., Tan, L., Shi, H., Yang, L., Sun, Y., & Wang, X.
- Affiliations
- Tongji University (CN)
- Yangtze University (CN)
- Corresponding author
- Sun, Yi
- Wang, Xiuli
- Venue
- Frontiers in Microbiology
- Publisher
- Frontiers Media SA
- Published
- 2021-05-13
- Volume
- 12
- Pages
- 649026-649026
- ISSN
- 1664-302X (ISSN-L)
- PMC
- PMC8155715
- OpenAlex
- W3162083512
- Cited by
- 28
- References
- 2
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 11 · 2021: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Microbiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Natural Science Foundation of Hubei Province (2019CFB567)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Fungal Plant Pathogen Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- minocycline, azoles, fluconazole resistance, Candida, Candida auris, Candida albicans, posaconazole, itraconazole, voriconazole, drug synergy, combination antifungal therapy, Galleria mellonella infection model, antifungal resistance
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