Minocycline and Fluconazole Have a Synergistic Effect Against Both and

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2020 May 21

PMID 32431685

Citations 10

Authors

Qinxiang Kong

Zubai Cao

Na Lv

Hui Zhang

Yanyan Liu

Lifen Hu

Jiabin Li

Affiliations

Soon will be listed here.

Abstract

In recent decades, the incidence of infection, which causes cryptococcosis, has consistently increased. Fluconazole (FLU) is frequently used in the treatment of this disease, mainly in the immunocompromised population, and long-term therapy usually produces drug resistance. Research on antifungal sensitizers has gained attention as a possible means of overcoming this drug resistance. Minocycline (MINO) has an inhibitory effect on FLU-resistant , and the combination of MINO and FLU has a synergistic effect on FLU-resistant . A synergistic effect of MINO/FLU has been reported against , but this effect has not been evaluated on FLU-resistant isolates. This study aimed to investigate the interaction of MINO and FLU against FLU-resistant both and . We found that the combination of MINO and FLU had a synergistic effect on FLU-resistant . For all FLU-resistant strains, the minimum inhibitory concentration (MIC) of FLU decreased significantly when used in combination with MINO, dropping from >128 μg/ml down to 4-8 μg/ml. Additionally, MINO and FLU had a synergistic effect on both susceptible and resistant biofilms, in which the MIC of FLU decreased from >256 μg/ml down to 4-16 μg/ml. Compared with FLU alone, the combination of MINO with FLU prolonged the survival rate of larvae infected with FLU-resistant , and also significantly decreased the fungal burden of infected larvae and reduced the tissue damage and destruction caused by FLU-resistant . These findings will contribute to the discovery of antifungal agents and may yield a new approach for the treatment of cryptococcosis caused by FLU-resistant .

Citing Articles

as an Invertebrate Model for Studying Fungal Infections.

Marena G, Thomaz L, Nosanchuk J, Taborda C J Fungi (Basel). 2025; 11(2).

PMID: 39997451 PMC: 11856299. DOI: 10.3390/jof11020157.

Novel combinatorial approach: Harnessing HIV protease inhibitors to enhance amphotericin B's antifungal efficacy in cryptococcosis.

Alkashef N, Seleem M PLoS One. 2024; 19(8):e0308216.

PMID: 39088434 PMC: 11293717. DOI: 10.1371/journal.pone.0308216.

Sensitive bioluminescence imaging of cryptococcosis in improves antifungal screening under conditions.

Vanhoffelen E, Vermoesen L, Michiels L, Lagrou K, Resendiz-Sharpe A, Velde G Virulence. 2024; 15(1):2327883.

PMID: 38465639 PMC: 10939141. DOI: 10.1080/21505594.2024.2327883.

Antifungal activity of the repurposed drug disulfiram against .

Peng M, Zhang C, Duan Y, Liu H, Peng X, Wei Q Front Pharmacol. 2024; 14:1268649.

PMID: 38273827 PMC: 10808519. DOI: 10.3389/fphar.2023.1268649.

Searching for new antifungals for the treatment of cryptococcosis.

de Sousa N, de Almeida J, Frickmann H, Lacerda M, de Souza J Rev Soc Bras Med Trop. 2023; 56:e01212023.

PMID: 37493736 PMC: 10367226. DOI: 10.1590/0037-8682-0121-2023.

References

Sangalli-Leite F, Scorzoni L, de Paula E Silva A, da Silva J, de Oliveira H, Singulani J . Synergistic effect of pedalitin and amphotericin B against Cryptococcus neoformans by in vitro and in vivo evaluation. Int J Antimicrob Agents. 2016; 48(5):504-511. DOI: 10.1016/j.ijantimicag.2016.07.025. View

Shi W, Chen Z, Chen X, Cao L, Liu P, Sun S . 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. 2010; 10(7):885-93. DOI: 10.1111/j.1567-1364.2010.00664.x. View

Kumari P, Mishra R, Arora N, Chatrath A, Gangwar R, Roy P . Antifungal and Anti-Biofilm Activity of Essential Oil Active Components against and . Front Microbiol. 2017; 8:2161. PMC: 5681911. DOI: 10.3389/fmicb.2017.02161. View

Brown G, Denning D, Gow N, Levitz S, Netea M, White T . Hidden killers: human fungal infections. Sci Transl Med. 2012; 4(165):165rv13. DOI: 10.1126/scitranslmed.3004404. View

Lu M, Yang X, Yu C, Gong Y, Yuan L, Hao L . Linezolid in Combination With Azoles Induced Synergistic Effects Against and Protected Against Experimental Candidiasis. Front Microbiol. 2019; 9:3142. PMC: 6365414. DOI: 10.3389/fmicb.2018.03142. View

Garrido-Mesa N, Zarzuelo A, Galvez J . Minocycline: far beyond an antibiotic. Br J Pharmacol. 2013; 169(2):337-52. PMC: 3651660. DOI: 10.1111/bph.12139. View

Silva A, Miranda I, Guida A, Synnott J, Rocha R, Silva R . Transcriptional profiling of azole-resistant Candida parapsilosis strains. Antimicrob Agents Chemother. 2011; 55(7):3546-56. PMC: 3122401. DOI: 10.1128/AAC.01127-10. View

May R, Stone N, Wiesner D, Bicanic T, Nielsen K . Cryptococcus: from environmental saprophyte to global pathogen. Nat Rev Microbiol. 2015; 14(2):106-17. PMC: 5019959. DOI: 10.1038/nrmicro.2015.6. View

Fragkou P, Poulakou G, Blizou A, Blizou M, Rapti V, Karageorgopoulos D . The Role of Minocycline in the Treatment of Nosocomial Infections Caused by Multidrug, Extensively Drug and Pandrug Resistant A Systematic Review of Clinical Evidence. Microorganisms. 2019; 7(6). PMC: 6617316. DOI: 10.3390/microorganisms7060159. View

10.

Rossi S, Trevijano-Contador N, Scorzoni L, Mesa-Arango A, de Oliveira H, Werther K . Impact of Resistance to Fluconazole on Virulence and Morphological Aspects of Cryptococcus neoformans and Cryptococcus gattii Isolates. Front Microbiol. 2016; 7:153. PMC: 4754443. DOI: 10.3389/fmicb.2016.00153. View

11.

Gu W, Yu Q, Yu C, Sun S . In vivo activity of fluconazole/tetracycline combinations in Galleria mellonella with resistant Candida albicans infection. J Glob Antimicrob Resist. 2017; 13:74-80. DOI: 10.1016/j.jgar.2017.11.011. View

12.

Movahed E, Tan G, Munusamy K, Yeow T, Tay S, Wong W . Triclosan Demonstrates Synergic Effect with Amphotericin B and Fluconazole and Induces Apoptosis-Like Cell Death in Cryptococcus neoformans. Front Microbiol. 2016; 7:360. PMC: 4800180. DOI: 10.3389/fmicb.2016.00360. View

13.

da Silva A, de Andrade Neto J, da Silva C, de Sousa Campos R, Costa Silva R, Freitas D . Berberine Antifungal Activity in Fluconazole-Resistant Pathogenic Yeasts: Action Mechanism Evaluated by Flow Cytometry and Biofilm Growth Inhibition in Candida spp. Antimicrob Agents Chemother. 2016; 60(6):3551-7. PMC: 4879420. DOI: 10.1128/AAC.01846-15. View

14.

Song J, Cheong H, Noh J, Kim W . In vitro Comparison of Anti-Biofilm Effects against Carbapenem-Resistant Acinetobacter baumannii: Imipenem, Colistin, Tigecycline, Rifampicin and Combinations. Infect Chemother. 2015; 47(1):27-32. PMC: 4384457. DOI: 10.3947/ic.2015.47.1.27. View

15.

Recio R, Perez-Ayala A . Cryptococcus neoformans Meningoencephalitis. N Engl J Med. 2018; 379(3):281. DOI: 10.1056/NEJMicm1801051. View

16.

Mayer F, Kronstad J . Disarming Fungal Pathogens: Inhibits Virulence Factor Production and Biofilm Formation by and . mBio. 2017; 8(5). PMC: 5626971. DOI: 10.1128/mBio.01537-17. View

17.

Schwartz S, Kontoyiannis D, Harrison T, Ruhnke M . Advances in the diagnosis and treatment of fungal infections of the CNS. Lancet Neurol. 2018; 17(4):362-372. DOI: 10.1016/S1474-4422(18)30030-9. View

18.

Williamson P, Jarvis J, Panackal A, Fisher M, Molloy S, Loyse A . Cryptococcal meningitis: epidemiology, immunology, diagnosis and therapy. Nat Rev Neurol. 2016; 13(1):13-24. DOI: 10.1038/nrneurol.2016.167. View

19.

Jorjao A, Oliveira L, Scorzoni L, Figueiredo-Godoi L, Prata M, Jorge A . From moths to caterpillars: Ideal conditions for Galleria mellonella rearing for in vivo microbiological studies. Virulence. 2017; 9(1):383-389. PMC: 5955185. DOI: 10.1080/21505594.2017.1397871. View

20.

Bongomin F, Oladele R, Gago S, Moore C, Richardson M . A systematic review of fluconazole resistance in clinical isolates of Cryptococcus species. Mycoses. 2018; 61(5):290-297. DOI: 10.1111/myc.12747. View