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FLUKONAZOLE DİRENÇLİ CANDIDA SPP. İZOLATLARINDA, GENTAMİSİNİN FLUKONAZOLÜN ETKİNLİĞİ ÜZERİNE ETKİSİ

Year 2022, Volume: 1 Issue: 2, 35 - 45, 13.02.2023

Abstract

Amaç: Antifungal ilaçlara karşı gelişen direnç, antifungallerin etkinliğinin azalmasına katkıda bulunmaktadır. Bu nedenle kullanılmakta olan ilaçların başka moleküller ile kombine kullanımları, yeni ilaç keşfine kıyasla daha gerçekçi bir yöntem olduğu düşünülmektedir. Bu çalışmada, flukonazolün gentamisin ile kombine kullanılmasının, flukonazole dirençli kandida izolatlarının flukonazolün MİK değeri üzerine etkisi saptanarak, flukonazol direncini ortadan kaldıran ideal gentamisin konsantrasyonlarının hesaplanması ve böylece flukonazole dirençli kandida enfeksiyonlarının tedavisi için alternatif olabilecek bir flukonazol+antibiyotik kombinasyonu belirlenmesi amaçlanmıştır.
Yöntem: Flukonazol ve gentamisinin birlikte etkisininin belirlenmesi için dama tahtası testi yapılmıştır. Bu yöntemle, ilaçların 96 kuyucuklu plak üzerinde karşılaştırılarak kombinasyon etkinlikleri test edildi.
Bulgular: Çalışmamıza dahil edilen 33 adet C. albicans izolatının 14’nün (%42) flukonazole dirençli olduğu tespit edilmiştir. Flukonazol dirençli C. albicans izolatları üzerinde gentamisinin tek başına etkili olduğu gözlenmemiştir. Ancak gentamisin ve flukonazol birlikte kullanıldığında aditif ve sinerjik etkiler gözlemlenmiştir. Bu çalışmanın sonunda 14 örnekten iki tanesinde sinerjik etki 11 tanesinde aditif etki tespit edilmiştir. İlaçların, çalışmaya alınan izolatlar üzerine herhangi bir antagonistik etkisi saptanmamıştır.
Sonuç: Flukonazole dirençli C. albicans izolatlarında gentamisin'nin flukonazol etkinliği üzerindeki etkileri belirlenerek flukonazol duyarlılığını artıracak uygun gentamisin konsantrasyonları hesaplandı ve alternatif olabilecek gentamisin+flukonazol kombinasyonları belirlenmiştir.

References

  • Referans1 Abbasoğlu U, Çevikbaş A, (ed.). Farmasötik Mikrobiyoloji. Ankara: 2011. s.293-294.
  • Referans2 Chen TC, Chen YH, Chen YC and Lu PL. Fluconazole exposure rather than clonal spreading is correlated with the emergence of Candida glabrata with cross-resistance to triazole antifungal agents. The Kaohsiung.Journal Medical Sciences 2012;28(6):306-315.
  • Referans3 Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). Reference Method for Broth Dilution Antifungal Susceptibility Testing Yeast; Approved Standard. 2th ed. CLSI M27-A3, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne Pennsylvania, USA. 2008.
  • Referans4 Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. Mechanisms of antifungal drug resistance. Cold Spring Harbor Perspectives in Medicine 2015;5(7):a019752.
  • Referans5 Cui J, Ren B, Tong Y, Dai H, Zhang L. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans. Virulence 2015;6(4):362-371. Referans6 Ener B. Fungal Hastane enfeksiyonları: Epidemiyoloji ve kontrol. Hastane Enfeksiyonları Dergisi 1998;2:150-155.
  • Referans7 Dösler S, Gürler B. Antimikrobik etkili katyonik peptitlerin tek başına ve kombinasyon halindeki etkilerinin araştırılması. Ankem Dergisi 2006;20(3):173-179.
  • Referans8 Guo F, Yang Y, Kang Y, Zang B, Cui W, Qin B. Invasive Candidiasis in Intensive Care Units in China: A Multicentre Prospective Observational Study. Journal of Antimicrobial Chemotherapy 2013;68:1660-1668.
  • Referans9 https://www.researchgate.net/figure/5-Germ-tube-formation-by-C-albicans-40X_fig5_326734793 erişim tarihi: 05.07.2022
  • Referans10 Kantarcıoğlu S, Yücel A. In Vıtro activity of terbinafine in combination with fluconazole agaınst Candıda albicans isolates. Turkish Journal of Infection 2003;17(1):71-75.
  • Referans11 Kayaalp O, (ed.). Klinik Farmakolojinin Esasları ve Temel Düzenlemeler. İstanbul: Pelikan Yayınları. 2013.
  • Referans12 Karabıçak N, Alem N. Candida türlerinin triazol antifungal duyarlılık profilleri: antifungal direncin belirlenmesinde yeni CLSI türe özgü klinik direnç sınır değerleri ve epidemiyolojik eşik değerlerinin uygulanması. Mikrobiyoloji Bülteni 2016;50(1):122-132.
  • Referans13 Koçoğlu E, Bayram A, Balcı I. Klinik örneklerden izole edilen Kandida türleri ve antifungal duyarlılıkları. Van Tıp Dergisi 2005;12(3):195-200.
  • Referans14 Liu S, Yue L, Gu W, Li X, Zhang L, Sun S. Synergistic effect of fuconazole and calcium channel blockers against resistant Candida albicans. PLoS One 2016;11(3):1-12.
  • Referans15 Lu M, Yu C, Cui X, Shi J, Yuan L, Sun S. Gentamicin Synergises with azoles against drug-resistant Candida albicans. International Journal of Antimicrobial Agents 2018;51:107-114.
  • Referans16 Özseven AG, Sesli Çetin E, Özseven L. Dama Tahtası Sinerji Testi sonuçlarının farklı yöntemlerle yorumlanması sonuçlarımızı etkiliyormu? Mikrobiyoloji Bülteni 2012;46(3):410-20.
  • Referans17 Perlin DS, Shor E, Zhao Y. Uppdate on antifungal drug resistance. Current Clinical Microbiology Report 2015;2:84-95.
  • Referans18 Pfaller MA, Diekema DJ, Jones RN, Sader HS, Fluit AC, Hollis RJ, Messer SA. International surveillance of bloodstream infections due to Candida species: Frequency of occurrence and In Vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the sentry antimicrobial surveillance program. Journal of Clinical Microbiology 2001;39(9):3254-3259.
  • Referans19 Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, Rotstein C, Azie NE. Epidemiology and outcomes of invasive Candidiasis due to non-albicans species of Candida in 2,496 patients: Data from the Prospective Antifungal Therapy (PATH) Registry 2004–2008. PloS One. 2004;9(7):e101510.
  • Referans20 Pfaller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Antimicrobial Agents and Chemotherapy 2006;19:435-447.
  • Referans21 Pfaller MA, Rhomberg PR, Messer SA, Jones RN, Castanheira M. Isavuconazole, micafungin, and 8 comparator antifungal agents' susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: Temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and proposed epidemiological cut off values. Diagnostic Microbiology and Infections Diseases 2015;82(4):303-313.
  • Referans22 Rex JH, Pfaller MA, Walsh TJ, Chaturvedi V, Espinel-Ingroff A, Ghannoum MA, Warnock DW. Antifungal susceptibility testing: Practical aspects and current challenges. Clinical Microbiology Reviews 2001;14(4):643-658.
  • Referans23 The European Committee on Antimicrobial Susceptibility Testing. Antifungal Agents Breakpoint Tables for Interpretation of MICs. Version 9.0. 2018.

INVESTIGATION OF THE EFFECT OF GENTAMICIN TO FLUCONAZOLE IN FLUCONAZOLE RESISTANT ISOLATES OF CANDİDA SPP.

Year 2022, Volume: 1 Issue: 2, 35 - 45, 13.02.2023

Abstract

Aim: Resistance to antifungal drugs contributes to the decrease in the effectiveness of antifungals. Therefore, the combined use of drugs in use with other molecules is considered to be a more realistic method than the discovery of new drugs. In this study, the effect of the combined use of fluconazole with gentamicin on the MIC value of fluconazole resistant Candida isolates of fluconazole was determined, and an ideal combination of fluconazole for the treatment of fluconazole-resistant candida infections was determined.
Method: It was conducted checkerboard test for identifying the combined effect of gentamicin and fluconazole. In this method, combination efficacy was tested by comparing drugs on a 96-wells plate with this method.
Results: Of the 33 Candida albicans isolates included in our study, 14 (42%) were found to be resistant to fluconazole. Gentamicin alone has not been found to be effective on fluconazole-resistant C. albicans isolates. However, when gentamicin and fluconazole were used together, additive and synergistic effects were observed. At the end of this study, synergistic effect was detected in 2 of 14 samples and additive effect in 11 of them. No antagonistic effect of the drugs on the study isolates was detected.
Conclusion: the proper gentamicin concentrations to increase fluconazole susceptibility were calculated by identifying the effects of gentamicin on fluconazole efficiency in fluconazole-resistant C. albicans isolates, and gentamicin+fluconazole combinations were identified as an alternative.

References

  • Referans1 Abbasoğlu U, Çevikbaş A, (ed.). Farmasötik Mikrobiyoloji. Ankara: 2011. s.293-294.
  • Referans2 Chen TC, Chen YH, Chen YC and Lu PL. Fluconazole exposure rather than clonal spreading is correlated with the emergence of Candida glabrata with cross-resistance to triazole antifungal agents. The Kaohsiung.Journal Medical Sciences 2012;28(6):306-315.
  • Referans3 Clinical and Laboratory Standards Institute (CLSI) (formerly NCCLS). Reference Method for Broth Dilution Antifungal Susceptibility Testing Yeast; Approved Standard. 2th ed. CLSI M27-A3, Clinical and Laboratory Standards Institute, 940 West Valley Road, Wayne Pennsylvania, USA. 2008.
  • Referans4 Cowen LE, Sanglard D, Howard SJ, Rogers PD, Perlin DS. Mechanisms of antifungal drug resistance. Cold Spring Harbor Perspectives in Medicine 2015;5(7):a019752.
  • Referans5 Cui J, Ren B, Tong Y, Dai H, Zhang L. Synergistic combinations of antifungals and anti-virulence agents to fight against Candida albicans. Virulence 2015;6(4):362-371. Referans6 Ener B. Fungal Hastane enfeksiyonları: Epidemiyoloji ve kontrol. Hastane Enfeksiyonları Dergisi 1998;2:150-155.
  • Referans7 Dösler S, Gürler B. Antimikrobik etkili katyonik peptitlerin tek başına ve kombinasyon halindeki etkilerinin araştırılması. Ankem Dergisi 2006;20(3):173-179.
  • Referans8 Guo F, Yang Y, Kang Y, Zang B, Cui W, Qin B. Invasive Candidiasis in Intensive Care Units in China: A Multicentre Prospective Observational Study. Journal of Antimicrobial Chemotherapy 2013;68:1660-1668.
  • Referans9 https://www.researchgate.net/figure/5-Germ-tube-formation-by-C-albicans-40X_fig5_326734793 erişim tarihi: 05.07.2022
  • Referans10 Kantarcıoğlu S, Yücel A. In Vıtro activity of terbinafine in combination with fluconazole agaınst Candıda albicans isolates. Turkish Journal of Infection 2003;17(1):71-75.
  • Referans11 Kayaalp O, (ed.). Klinik Farmakolojinin Esasları ve Temel Düzenlemeler. İstanbul: Pelikan Yayınları. 2013.
  • Referans12 Karabıçak N, Alem N. Candida türlerinin triazol antifungal duyarlılık profilleri: antifungal direncin belirlenmesinde yeni CLSI türe özgü klinik direnç sınır değerleri ve epidemiyolojik eşik değerlerinin uygulanması. Mikrobiyoloji Bülteni 2016;50(1):122-132.
  • Referans13 Koçoğlu E, Bayram A, Balcı I. Klinik örneklerden izole edilen Kandida türleri ve antifungal duyarlılıkları. Van Tıp Dergisi 2005;12(3):195-200.
  • Referans14 Liu S, Yue L, Gu W, Li X, Zhang L, Sun S. Synergistic effect of fuconazole and calcium channel blockers against resistant Candida albicans. PLoS One 2016;11(3):1-12.
  • Referans15 Lu M, Yu C, Cui X, Shi J, Yuan L, Sun S. Gentamicin Synergises with azoles against drug-resistant Candida albicans. International Journal of Antimicrobial Agents 2018;51:107-114.
  • Referans16 Özseven AG, Sesli Çetin E, Özseven L. Dama Tahtası Sinerji Testi sonuçlarının farklı yöntemlerle yorumlanması sonuçlarımızı etkiliyormu? Mikrobiyoloji Bülteni 2012;46(3):410-20.
  • Referans17 Perlin DS, Shor E, Zhao Y. Uppdate on antifungal drug resistance. Current Clinical Microbiology Report 2015;2:84-95.
  • Referans18 Pfaller MA, Diekema DJ, Jones RN, Sader HS, Fluit AC, Hollis RJ, Messer SA. International surveillance of bloodstream infections due to Candida species: Frequency of occurrence and In Vitro susceptibilities to fluconazole, ravuconazole, and voriconazole of isolates collected from 1997 through 1999 in the sentry antimicrobial surveillance program. Journal of Clinical Microbiology 2001;39(9):3254-3259.
  • Referans19 Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, Rotstein C, Azie NE. Epidemiology and outcomes of invasive Candidiasis due to non-albicans species of Candida in 2,496 patients: Data from the Prospective Antifungal Therapy (PATH) Registry 2004–2008. PloS One. 2004;9(7):e101510.
  • Referans20 Pfaller MA, Diekema DJ, Sheehan DJ. Interpretive breakpoints for fluconazole and Candida revisited: a blueprint for the future of antifungal susceptibility testing. Antimicrobial Agents and Chemotherapy 2006;19:435-447.
  • Referans21 Pfaller MA, Rhomberg PR, Messer SA, Jones RN, Castanheira M. Isavuconazole, micafungin, and 8 comparator antifungal agents' susceptibility profiles for common and uncommon opportunistic fungi collected in 2013: Temporal analysis of antifungal drug resistance using CLSI species-specific clinical breakpoints and proposed epidemiological cut off values. Diagnostic Microbiology and Infections Diseases 2015;82(4):303-313.
  • Referans22 Rex JH, Pfaller MA, Walsh TJ, Chaturvedi V, Espinel-Ingroff A, Ghannoum MA, Warnock DW. Antifungal susceptibility testing: Practical aspects and current challenges. Clinical Microbiology Reviews 2001;14(4):643-658.
  • Referans23 The European Committee on Antimicrobial Susceptibility Testing. Antifungal Agents Breakpoint Tables for Interpretation of MICs. Version 9.0. 2018.
There are 22 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research Articles
Authors

Bahar Genç 0000-0002-5950-521X

Suzan Ökten 0000-0003-3372-5617

Melek Tikveşli 0000-0001-5069-9479

Publication Date February 13, 2023
Published in Issue Year 2022 Volume: 1 Issue: 2

Cite

Vancouver Genç B, Ökten S, Tikveşli M. INVESTIGATION OF THE EFFECT OF GENTAMICIN TO FLUCONAZOLE IN FLUCONAZOLE RESISTANT ISOLATES OF CANDİDA SPP. Balkan Health Sci J. 2023;1(2):35-4.

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