1887

Abstract

species are pathogens commonly associated with cases of meningoencephalitis in individuals who are immunosuppressed due to AIDS.

The aim was to evaluate the effects of the antiretroviral darunavir alone or associated with fluconazole, 5-flucytosine and amphotericin B against planktonic cells and biofilms of species.

Susceptibility testing of darunavir and the common antifungals against 12 members of the / species complex was evaluated by broth microdilution. The interaction between darunavir and antifungals against planktonic cells was tested by a checkerboard assay. The effects of darunavir against biofilm metabolic activity and biomass were evaluated by the XTT reduction assay and crystal violet staining, respectively.

Darunavir combined with amphotericin B showed a synergistic interaction against planktonic cells. No antagonistic interaction was observed between darunavir and the antifungals used. All species strains were strong biofilm producers. Darunavir alone reduced biofilm metabolic activity and biomass when added during and after biofilm formation (<0.05). The combination of darunavir with antifungals caused a significant reduction in biofilm metabolic activity and biomass when compared to darunavir alone (<0.05).

Darunavir presents antifungal activity against planktonic cells of species and synergism with amphotericin B. In addition, darunavir led to reduced biofilm formation and showed activity against mature biofilms of species. Activity of the antifungals against mature biofilms was enhanced in the presence of darunavir.

Funding
This study was supported by the:
  • cnpq (Award 305036/2017-3)
    • Principle Award Recipient: Marcos Fábio Gadelha Rocha
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2020-05-27
2024-04-19
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References

  1. May RC, Stone NRH, Wiesner DL, Bicanic T, Nielsen K. Cryptococcus: from environmental saprophyte to global pathogen. Nat Rev Microbiol 2016; 14:106–117 [View Article][PubMed]
    [Google Scholar]
  2. World Health Organization Guidelines on the Diagnosis, Prevention and Management of Cryptococcal Disease in HIV-infected Adults, Adolescents and Children: Supplement to the 2016 Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection Geneva: World Health Organization; 2018
    [Google Scholar]
  3. Chen Y-C, Chang T-Y, Liu J-W, Chen F-J, Chien C-C et al. Increasing trend of fluconazole-non-susceptible Cryptococcus neoformans in patients with invasive cryptococcosis: a 12-year longitudinal study. BMC Infect Dis 2015; 15:1–7 [View Article]
    [Google Scholar]
  4. Dhana A. Diagnosis of cryptococcosis and prevention of cryptococcal meningitis using a novel point-of-care lateral flow assay. Case Rep Med 2013; 2013:1–4 [View Article][PubMed]
    [Google Scholar]
  5. Dos Santos ALS, Gullo FP, Rossi SA, Sardi J, Teodoro VLI, Mendes-Giannini MJS. HIV aspartyl protease inhibitors as promising compounds against Candida albicans André Luis Souza DOS Santos. World J Biol Chem 2010; 1:21 [View Article][PubMed]
    [Google Scholar]
  6. Casolari C, Rossi T, Baggio G, Coppi A, Zandomeneghi G et al. Interaction between saquinavir and antimycotic drugs on C. albicans and C. neoformans strains. Pharmacol Res 2004; 50:605–610 [View Article][PubMed]
    [Google Scholar]
  7. Cordeiro RdeA, Serpa R, Mendes PBL, Evangelista AJdeJ, Andrade ARC et al. The HIV aspartyl protease inhibitor ritonavir impairs planktonic growth, biofilm formation and proteolytic activity in Trichosporon spp. Biofouling 2017; 33:640–650 [View Article][PubMed]
    [Google Scholar]
  8. Monari C, Pericolini E, Bistoni G, Cenci E, Bistoni F et al. Influence of Indinavir on Virulence and Growth of Cryptococcus neoformans . J Infect Dis 2005; 191:307–311 [View Article]
    [Google Scholar]
  9. Brasil Information Note no 007/2017 - antiretroviral regimens for people living with HIV / AIDS (PLHA) and indications of increased use of dolutegravir (DTG) and darunavir (DRV). [in Portuguese]; 2017
  10. Sidrim JJC, Perdigão-Neto LV, Cordeiro RA, Brilhante RSN, Leite JJG et al. Viral protease inhibitors affect the production of virulence factors in Cryptococcus neoformans . Can J Microbiol 2012; 58:932–936 [View Article][PubMed]
    [Google Scholar]
  11. Cordeiro RdeA, Serpa R, Marques FJdeF, de Melo CVS, Evangelista AJdeJ et al. Inhibitory activity of isoniazid and ethionamide against Cryptococcus biofilms. Can J Microbiol 2015; 61:827–836 [View Article][PubMed]
    [Google Scholar]
  12. Clinical and Laboratory Standards Institute Reference method for broth dilution antifungal susceptibility testing of yeasts, 3nd ed; approved standard. Wayne, PA: CLSI document M27-A3. Clinical and Laboratory Standards Institute; 2008
    [Google Scholar]
  13. Chatzimoschou A, Katragkou A, Simitsopoulou M, Antachopoulos C, Georgiadou E et al. Activities of triazole-echinocandin combinations against Candida species in biofilms and as planktonic cells. Antimicrob Agents Chemother 2011; 55:1968–1974 [View Article][PubMed]
    [Google Scholar]
  14. Reichert-Lima F, Busso-Lopes AF, Lyra L, Peron IH, Taguchi H et al. Evaluation of antifungal combination against Cryptococcus spp. Mycoses 2016; 59:585–593 [View Article][PubMed]
    [Google Scholar]
  15. Odds FC. Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 2003; 52:1 [View Article][PubMed]
    [Google Scholar]
  16. Brilhante RSN, Caetano EPde, Oliveira JS, Castelo-Branco DdeSCM, Souza ERY et al. Simvastatin inhibits planktonic cells and biofilms of Candida and Cryptococcus species. Braz J Infect Dis 2015; 19:459–465 [View Article][PubMed]
    [Google Scholar]
  17. Stepanović S, Vuković D, Dakić I, Savić B. A modified microtiter-plate test for quantification of staphylococcal biofilm formation. J Microbiol Methods 2000; 40:175–179 [View Article]
    [Google Scholar]
  18. Cordeiro RdeA, Evangelista AJdeJ, Serpa R, Marques FJdeF, Melo CVSde et al. Inhibition of heat-shock protein 90 enhances the susceptibility to antifungals and reduces the virulence of Cryptococcus neoformans/Cryptococcus gattii species complex. Microbiology 2016; 162:309–317 [View Article][PubMed]
    [Google Scholar]
  19. Srichatrapimuk S, Sungkanuparph S. Integrated therapy for HIV and cryptococcosis. AIDS Res Ther 2016; 13:42 [View Article][PubMed]
    [Google Scholar]
  20. Spitzer M, Griffiths E, Blakely KM, Wildenhain J, Ejim L et al. Cross-Species discovery of syncretic drug combinations that potentiate the antifungal fluconazole. Mol Syst Biol 2011; 7:499 [View Article][PubMed]
    [Google Scholar]
  21. Back D, Sekar V, Hoetelmans RMW. Darunavir: pharmacokinetics and drug interactions. Antivir Ther 2008; 13:1–13[PubMed]
    [Google Scholar]
  22. Brüggemann RJM, Alffenaar J-WC, Blijlevens NMA, Billaud EM, Kosterink JGW et al. Clinical relevance of the pharmacokinetic interactions of azole antifungal drugs with other coadministered agents. Clin Infect Dis 2009; 48:1441–1458 [View Article][PubMed]
    [Google Scholar]
  23. Criptococose GdeCde. Consensus on criptococcosis - 2008. Rev Soc Bras Med Trop 2008; 41:524–544
    [Google Scholar]
  24. Martinez LR, Casadevall A. Susceptibility of Cryptococcus neoformans biofilms to antifungal agents in vitro . Antimicrob Agents Chemother 2006; 50:1021–1033 [View Article][PubMed]
    [Google Scholar]
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