1887

Journal of Medical Microbiology logo

Volume 64, Issue 9

An and study on the synergistic effect and mechanism of itraconazole or voriconazole alone and in combination with tetrandrine against Free

Abstract

In this study, we investigated the antifungal effects of itraconazole/voriconazole (ITR/VRC) alone and in combination with tetrandrine (TET) against 23 clinical isolates of using a chequerboard microdilution method. The dynamic antifungal effects of TET with ITR/VRC against were assessed using time–kill curves following systemic infection of mice with . After treatment, efflux pump activity was determined by the efflux of rhodamine 6G (R6G). When ITR was combined with TET, ITR MICs were reduced from 0.125–32 to 0.0625–2 μg ml, and TET MICs were reduced from 256–512 to 8–64 μg ml. When VRC was combined with TET, VRC MICs were reduced from 0.125–2 to 0.03125–0.5 μg ml, and TET MICs were reduced from 256–512 to 8–256 μg ml. Time–kill curves revealed that viability was reduced after treatment with ITR/VRC combined with TET versus ITR/VRC alone. ITR/VRC combined with TET significantly prolonged mouse survival and reduced kidney and brain tissue burdens versus ITR/VRC alone ( < 0.05). Moreover, TET inhibited R6G efflux of . Thus, and , TET acted synergistically with ITR/VRC against , and the synergistic mechanism was related to inhibition of the drug efflux pump.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jmm/10.1099/jmm.0.000120
2015-09-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jmm/64/9/1008.html?itemId=/content/journal/jmm/10.1099/jmm.0.000120&mimeType=html&fmt=ahah

References

  1. Alanio A., Beretti J. L., Dauphin B., Mellado E., Quesne G., Lacroix C., Amara A., Berche P., Nassif X., Bougnoux M. E. 2011; Matrix-assisted laser desorption ionization time-of-flight mass spectrometry for fast and accurate identification of clinically relevant Aspergillus species. Clin Microbiol Infect 17:750–755 [View Article][PubMed]
     [Google Scholar]
  2. Balajee S. A., Borman A. M., Brandt M. E., Cano J., Cuenca-Estrella M., Dannaoui E., Guarro J., Haase G., Kibbler C. C., other authors. 2009; Sequence-based identification of Aspergillus, Fusarium, and Mucorales species in the clinical mycology laboratory: where are we and where should we go from here?. J Clin Microbiol 47:877–884 [View Article][PubMed]
     [Google Scholar]
  3. Brun S., Bergès T., Poupard P., Vauzelle-Moreau C., Renier G., Chabasse D., Bouchara J. P. 2004; Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrob Agents Chemother 48:1788–1796 [View Article][PubMed]
     [Google Scholar]
  4. Bueid A., Howard S. J., Moore C. B., Richardson M. D., Harrison E., Bowyer P., Denning D. W. 2010; Azole antifungal resistance in Aspergillus fumigatus: 2008 and 2009. J Antimicrob Chemother 65:2116–2118 [View Article][PubMed]
     [Google Scholar]
  5. Bugli F., Posteraro B., Papi M., Torelli R., Maiorana A., Paroni Sterbini F., Posteraro P., Sanguinetti M., De Spirito M. 2013; In vitro interaction between alginate lyase and amphotericin B against Aspergillus fumigatus biofilm determined by different methods. Antimicrob Agents Chemother 57:1275–1282 [View Article][PubMed]
     [Google Scholar]
  6. Cornely O. A., Vehreschild J. J., Vehreschild M. J., Würthwein G., Arenz D., Schwartz S., Heussel C. P., Silling G., Mahne M., other authors. 2011; Phase II dose escalation study of caspofungin for invasive Aspergillosis. Antimicrob Agents Chemother 55:5798–5803 [View Article][PubMed]
     [Google Scholar]
  7. da Silva Ferreira M. E., Capellaro J. L., dos Reis Marques E., Malavazi I., Perlin D., Park S., Anderson J. B., Colombo A. L., Arthington-Skaggs B. A., other authors. 2004; In vitro evolution of itraconazole resistance in Aspergillus fumigatus involves multiple mechanisms of resistance. Antimicrob Agents Chemother 48:4405–4413 [View Article][PubMed]
     [Google Scholar]
  8. Dannaoui E., Borel E., Monier M. F., Piens M. A., Picot S., Persat F. 2001; Acquired itraconazole resistance in Aspergillus fumigatus. J Antimicrob Chemother 47:333–340 [View Article][PubMed]
     [Google Scholar]
  9. Denning D. W., Hope W. W. 2010; Therapy for fungal diseases: opportunities and priorities. Trends Microbiol 18:195–204 [View Article][PubMed]
     [Google Scholar]
  10. Denning D. W., Radford S. A., Oakley K. L., Hall L., Johnson E. M., Warnock D. W. 1997; Correlation between in-vitro susceptibility testing to itraconazole and in-vivo outcome of Aspergillus fumigatus infection. J Antimicrob Chemother 40:401–414 [View Article][PubMed]
     [Google Scholar]
  11. Espinel-Ingroff A., Diekema D. J., Fothergill A., Johnson E., Pelaez T., Pfaller M. A., Rinaldi M. G., Canton E., Turnidge J. 2010; Wild-type MIC distributions and epidemiological cutoff values for the triazoles and six Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document). J Clin Microbiol 48:3251–3257 [View Article][PubMed]
     [Google Scholar]
  12. Guo H., Xie S. M., Li S. X., Song Y. J., Lv X. L., Zhang H. 2014; Synergistic mechanism for tetrandrine on fluconazole against Candida albicans through the mitochondrial aerobic respiratory metabolism pathway. J Med Microbiol 63:988–996 [View Article][PubMed]
     [Google Scholar]
  13. Howard S. J., Cerar D., Anderson M. J., Albarrag A., Fisher M. C., Pasqualotto A. C., Laverdiere M., Arendrup M. C., Perlin D. S., Denning D. W. 2009; Frequency and evolution of Azole resistance in Aspergillus fumigatus associated with treatment failure. Emerg Infect Dis 15:1068–1076 [View Article][PubMed]
     [Google Scholar]
  14. Krishnan Natesan S., Wu W., Cutright J. L., Chandrasekar P. H. 2012; In vitro-in vivo correlation of voriconazole resistance due to G448S mutation (cyp51A gene) in Aspergillus fumigatus. Diagn Microbiol Infect Dis 74:272–277 [View Article][PubMed]
     [Google Scholar]
  15. Li F., Zhang H., Shan K. 2006; In vitro study of the synergistic effect of tetrandrine and fluconazole against Candida albicans. Chinese J Dermatol 39:454–456
     [Google Scholar]
  16. Luque J. C., Clemons K. V., Stevens D. A. 2003; Efficacy of micafungin alone or in combination against systemic murine aspergillosis. Antimicrob Agents Chemother 47:1452–1455 [View Article][PubMed]
     [Google Scholar]
  17. Meletiadis J., Mouton J. W., Meis J. F. G. M., Bouman B. A., Donnelly J. P., Verweij P. E., EUROFUNG Network. 2001; Colorimetric assay for antifungal susceptibility testing of Aspergillus species. J Clin Microbiol 39:3402–3408 [View Article][PubMed]
     [Google Scholar]
  18. Mellado E., Garcia-Effron G., Alcázar-Fuoli L., Melchers W. J., Verweij P. E., Cuenca-Estrella M., Rodríguez-Tudela J. L. 2007; A new Aspergillus fumigatus resistance mechanism conferring in vitro cross-resistance to azole antifungals involves a combination of cyp51A alterations. Antimicrob Agents Chemother 51:1897–1904 [View Article][PubMed]
     [Google Scholar]
  19. Nascimento A. M., Goldman G. H., Park S., Marras S. A. E., Delmas G., Oza U., Lolans K., Dudley M. N., Mann P. A., Perlin D. S. 2003; Multiple resistance mechanisms among Aspergillus fumigatus mutants with high-level resistance to itraconazole. Antimicrob Agents Chemother 47:1719–1726 [View Article][PubMed]
     [Google Scholar]
  20. Natesan S. K., Lamichchane A. K., Swaminathan S., Wu W. 2013; Differential expression of ATP-binding cassette and/or major facilitator superfamily class efflux pumps contributes to voriconazole resistance in Aspergillus flavus. Diagn Microbiol Infect Dis 76:458–463 [View Article][PubMed]
     [Google Scholar]
  21. Odds F. C. 2003; Synergy, antagonism, and what the chequerboard puts between them. J Antimicrob Chemother 52:1 [View Article][PubMed]
     [Google Scholar]
  22. Olson J. A., George A., Constable D., Smith P., Proffitt R. T., Adler-Moore J. P. 2010; Liposomal amphotericin B and echinocandins as monotherapy or sequential or concomitant therapy in murine disseminated and pulmonary Aspergillus fumigatus infections. Antimicrob Agents Chemother 54:3884–3894 [View Article][PubMed]
     [Google Scholar]
  23. Planche V., Ducroz S., Alanio A., Bougnoux M. E., Lortholary O., Dannaoui E. 2012; In vitro combination of anidulafungin and voriconazole against intrinsically azole-susceptible and -resistant Aspergillus spp. Antimicrob Agents Chemother 56:4500–4503 [View Article][PubMed]
     [Google Scholar]
  24. Salas V., Pastor F. J., Calvo E., Sutton D. A., Fothergill A. W., Guarro J. 2013; Evaluation of the in vitro activity of voriconazole as predictive of in vivo outcome in a murine Aspergillus fumigatus infection model. Antimicrob Agents Chemother 57:1404–1408 [View Article][PubMed]
     [Google Scholar]
  25. Samson R. A., Hong S., Peterson S. W., Frisvad J. C., Varga J. 2007; Polyphasic taxonomy of Aspergillus section Fumigati and its teleomorph Neosartorya. Stud Mycol 59:147–203 [View Article][PubMed]
     [Google Scholar]
  26. Shukla S., Saini P., Smriti, Jha S., Ambudkar S. V., Prasad R. 2003; Functional characterization of Candida albicans ABC transporter Cdr1p. Eukaryot Cell 2:1361–1375 [View Article][PubMed]
     [Google Scholar]
  27. Slaven J. W., Anderson M. J., Sanglard D., Dixon G. K., Bille J., Roberts I. S., Denning D. W. 2002; Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet Biol 36:199–206 [View Article][PubMed]
     [Google Scholar]
  28. Snelders E., van der Lee H. A., Kuijpers J., Rijs A. J., Varga J., Samson R. A., Mellado E., Donders A. R., Melchers W. J., Verweij P. E. 2008; Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism. PLoS Med 5:e219 [View Article][PubMed]
     [Google Scholar]
  29. Snelders E., Karawajczyk A., Schaftenaar G., Verweij P. E., Melchers W. J. 2010; Azole resistance profile of amino acid changes in Aspergillus fumigatus CYP51A based on protein homology modeling. Antimicrob Agents Chemother 54:2425–2430 [View Article][PubMed]
     [Google Scholar]
  30. Steinbach W. J., Stevens D. A., Denning D. W. 2003; Combination and sequential antifungal therapy for invasive aspergillosis: review of published in vitro and in vivo interactions and 6281 clinical cases from 1966 to 2001. Clin Infect Dis 37:(Suppl. 3)S188–S224 [View Article][PubMed]
     [Google Scholar]
  31. Sun S., Li Y., Guo Q., Shi C., Yu J., Ma L. 2008; In vitro interactions between tacrolimus and azoles against Candida albicans determined by different methods. Antimicrob Agents Chemother 52:409–417 [View Article][PubMed]
     [Google Scholar]
  32. Sun L., Sun S., Cheng A., Wu X., Zhang Y., Lou H. 2009; In vitro activities of retigeric acid B alone and in combination with azole antifungal agents against Candida albicans. Antimicrob Agents Chemother 53:1586–1591 [View Article][PubMed]
     [Google Scholar]
  33. Tashiro M., Izumikawa K., Minematsu A., Hirano K., Iwanaga N., Ide S., Mihara T., Hosogaya N., Takazono T., other authors. 2012; Antifungal susceptibilities of Aspergillus fumigatus clinical isolates obtained in Nagasaki, Japan. Antimicrob Agents Chemother 56:584–587 [View Article][PubMed]
     [Google Scholar]
  34. Tobin M. B., Peery R. B., Skatrud P. L. 1997; Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus. Gene 200:11–23 [View Article][PubMed]
     [Google Scholar]
  35. Wang K., Zhang H., Jiang H., Shi J., Gao A., He H., Cao H. 2007; In vitro study on tetrandrine as a synergist to fluconazole in murine model of vaginal candidiasis. Chin J Zoonoses 23:474–478, 483
     [Google Scholar]
  36. Warn P. A., Sharp A., Mosquera J., Spickermann J., Schmitt-Hoffmann A., Heep M., Denning D. W. 2006; Comparative in vivo activity of BAL4815, the active component of the prodrug BAL8557, in a neutropenic murine model of disseminated Aspergillus flavus. J Antimicrob Chemother 58:1198–1207 [View Article][PubMed]
     [Google Scholar]
  37. Worth L. J., Blyth C. C., Booth D. L., Kong D. C., Marriott D., Cassumbhoy M., Ray J., Slavin M. A., Wilkes J. R. 2008; Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders. Intern Med J 38:521–537 [View Article][PubMed]
     [Google Scholar]
  38. Zhang H., Gao A., Li F., Zhang G., Ho H. I., Liao W. 2009; Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps. Yakugaku Zasshi 129:623–630 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jmm/10.1099/jmm.0.000120
Loading
An in vitro and in vivo study on the synergistic effect and mechanism of itraconazole or voriconazole alone and in combination with tetrandrine against Aspergillus fumigatus
J. Med. Microbiol. 64, 1008 (2015); https://doi.org/10.1099/jmm.0.000120
/content/journal/jmm/10.1099/jmm.0.000120
/content/journal/jmm/10.1099/jmm.0.000120
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error