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Steril Vücut Sıvılarından İzole Edilen Candida albicans Türlerinin Mikrodilüsyon Yöntemiyle Triazollere Direnç Oranlarının Belirlenmesi

Yıl 2022, Cilt: 17 Sayı: 2, 41 - 45, 15.07.2022
https://doi.org/10.17517/ksutfd.971050

Öz

Amaç: Azollerin profilaksi veya tedavi amacıyla yaygın ve tekrarlayan kullanımı Candida albicans türlerinde direnç gelişimine yol açmıştır.
Bu çalışmada, steril vücut sıvısı kültürlerinden izole edilen Candida albicans izolatlarının flukonazol, itrokonazol ve vorikonazole in vitro direnç oranlarının belirlenmesi amaçlanmıştır.
Gereç ve Yöntemler: Ocak 2020 ile Nisan 2021 arasında çeşitli kliniklerden gönderilen steril vücut sıvı kültürlerinden izole edilen Candida albicans türleri çalışmaya dahil edildi.
Tür düzeyinde tanımlama, geleneksel tanı yöntemleri ve BD Phoenix 100 (BD, ABD) otomatik tanımlama sistemi kullanılarak yapıldı. Antifungal duyarlılık testi EUCAST önerilerine göre; % 2 glukoz içeren RPMI kullanılarak mikrodilüsyon yöntemiyle değerlendirildi.
Triazoller olan flukonazol, itrokonazol ve vorikonazol için bulanıklığın belirgin (≥ % 50) olarak azaldığı kuyucuktaki konsantrasyon, MİK50 değeri olarak belirlendi. Çalışmada kontrol suş olarak C.albicans ATCC 90028 kullanıldı.
Bulgular:Kandidemi etkenlerinin 51/99 (% 51.5)’unun Candida albicans olduğu görüldü. Candida albicans izolatlarının % 88.2'si (n=45) yoğun bakım ünitelerinden alınan örneklerden izole edildi. Örneklerin 26 (% 50.9)’sı yaş ortalaması 68.6 ± 18.29 yıl olan kadın hastalardan, 25 (% 49)’i yaş ortalaması 62.22 ± 21.08 yıl olan erkek hastalardan alındı. İzolatların 1 (% 1.9)’i beyin omurilik sıvısı, 1 (% 1.9)’i steril vücut sıvısı, 1(% 1.9)’i bronkoalveolar lavaj, 48 (% 94.1)’i kan kültürlerinden tanımlandı.
Antifungal duyarlılık test sonuçlarına göre türlerin7(% 12.2)’si flukonazol, 14 (% 27.4)’ü itrokonazol ve 5 (% 9.8)’i vorikonazole dirençli bulundu. Toplam 6 (% 11.7) örnekte ise çapraz dirence rastlandı.
Sonuç: C. albicans, kandidemiye neden olan ajanlar arasında hala en sık izole edilen türdür. Azol direnci ile birlikte diğer triazollere karşı da çapraz direnç gözlenmiştir. Bu nedenle uygun tedavi için antifungal duyarlılık test sonuçları dikkate alınmalıdır.

Kaynakça

  • 1.Costa-de-Oliveira S and Rodrigues AG. Candida albicans antifungal resistance and tolerance in bloodstream infections:The triad yeast-host-antifungal. Microorganisms 2020; 154 (8):1-19.
  • 2. Cheng MF, Yang YL, Yao TJ, Lin CY, Liu JS, Tang RB, et al. Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species. BMC Infectious Diseases 2005; 5: 22.
  • 3. Erdem I, Ozgultekin A, Inan AS, et al. Bloodstream infections in a medical-surgical intensive care unit:incidence, aetiology, antimicrobial resistance patterns of gram-positive and gram-negative bacteria. Clin Microbiol Infect 2009; 15(10): 943-6.
  • 4.Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48(5): 503-35.
  • 5.Hitkova HY, Georgieva DS, Hristova PM and Sredkova MP. Antifungal susceptibility of Candida albicans isolates at a tertiary care hospital in Bulgaria. Jundishapur J Microbiol 2019. In Press (In Press):e92079.
  • 6. Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide. Clinical Microbiology and Infection 2019; 25: 792-798.
  • 7. Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA. Mechanism of fluconazole resistance in Candida albicans biofilms: Phase-specific role of efflux pumps and membrane sterols. Infect Immun 2003; 71: 4333–4340.
  • 8. Ramage G, Rajendran R, Sherry L, WilliamsC. Fungal biofilm resistance. Int J Microbiol 2012: 528521.
  • 9. Ramage G, Bachmann S, Patterson TF, Wickes BL, Lopez-RibotJL. Investigation of multidrug effluxpumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother. 2002; 49: 973–980.
  • 10. Kanafani ZA, Perfect JR. Antimicrobial resistance: Resistance to antifungal agents: mechanisms andclinical impact. Clin Infect Dis 2008; 46: 120–128.
  • 11. Pappas, PG, Lionakis, MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis.Nat Rev Dis Primers 2018; 4: 18026.
  • 12. HospenthalDR, Murray CK, Rinaldi MG. The role of antifungal susceptibility testing in the therapy ofcandidiasis. Diagn Microbiol Infect Dis. 2004; 48, 153–160.
  • 13. Alastruey-Izquıerdo A, Melhem MSC, Bonfıettı LX & Rodrıguez-Tudela JL Susceptibility test for fungi: Clinical and laboratorial correlations in medical mycology. Rev Inst Med Trop Sao Paulo 2015; 57 (19):57-64.
  • 14. Orasch C, Marchetti O, Garbino J, Schrenzel J, Zimmerli S, Mühlethaler K, et al,Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: A 6-year prospective candidaemia survey from the fungal infection network of Switzerland. Clin Microbiol Infect 2014; 20: 698–705.
  • 15. Lindberg E, Hammarström H, Ataollahy N & Kondori N. Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia. Scientific Reports 2019; 9: 3838.
  • 16. Dalyan Cilo B, Topaç T, Ağca H, Sağlam S, Efe K, Ener B. Comparison of Clinical Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution methods for determining the susceptibilities of Candida isolates. Bulletin of Microbiology 2018; 52 (1): 35-48.
  • 17. Gülat S, Doluca Dereli M. Investigation of the expression levels of efflux pumps in fluconazole-resistant Candida albicans isolates. Bulletin of Microbiology 2014; 48 (2): 325-334.
  • 18. Coşkun Ö, Beşirbellioğlu B,Yıldıran ŞT, Gönlüm A, Pahsa A. In-vitro susceptibilities of Candida species isolated from candidemic patients against amphotericin B and fluconazole. Bulletin of Microbiology 2001; 35: 565-571.
  • 19. Hope W W, Billaud EM, Lestner J, Denning DW. Therapeutic drug monitoring for triazoles. Curr Opin Infect Dis 2008; 21: 580-6.

Determination of Resistance Rates of Candida albicans Species Isolated from Sterile Body Fluids to Triazoles by Microdilution Method

Yıl 2022, Cilt: 17 Sayı: 2, 41 - 45, 15.07.2022
https://doi.org/10.17517/ksutfd.971050

Öz

Aim: Widespread and repeated use of azoles for prophylaxis or therapy has led to the development of resistance in Candida albicans species.
In this study, it was aimed to determine the in vitro resistance rates of Candida albicans isolates isolated from sterile body fluid cultures to fluconazole, itroconazole and voriconazole.
Material and Methods: Candida albicans species isolated from sterile body fluid cultures sent from various clinics between January 2020 and April 2021 were included in the study.
Species-level identification was assessed using conventional methods and the BD Phoenix 100 (BD, USA) automated identification system. Antifungal susceptibility testing was performed by microdilution method using RPMI medium containing 2 % glucose according to EUCAST recommendations.
For the triazoles fluconazole, itroconazole and voriconazole, the concentration in the well at which turbidity was reduced significantly (≥50%) was determined as the MIC50 value. C.albicans ATCC 90028 was used as control strain.
Results: It was found that 51/99 (51.5%) of the candidemia agents were Candida albicans.
88.2% (n=45) of Candida albicans isolates were isolated from samples taken from intensive care units.Twenty-six (50.9%) of the samples were taken from female patients with a mean age of 68.6 ± 18.29 years, and 25 (49%) from male patients with a mean age of 62.22 ± 21.08 years. One (1.9 %) of the isolates were identified from cerebrospinal fluid, 1 (1.9 %) sterile body fluid, 1 (1.9 %) bronchoalveolar lavage, and 48 (94.1%) blood cultures. According to the antifungal susceptibility test results; 7 (12.2 %) of the species were resistant to fluconazole, 14 (27.4 %) to itroconazole, and 2 (3.9%) to 5 (9.8 %) voriconazole. Cross-resistance was detected in a total of 6 (11.7 %) samples.
Conclusion: C. albicans is still the most frequently isolated species among the candidemia agents detected in our hospital. Cross-resistance to other triazoles was observed along with azole resistance. Therefore, antifungal susceptibility test results should be taken into account for appropriate treatment.

Kaynakça

  • 1.Costa-de-Oliveira S and Rodrigues AG. Candida albicans antifungal resistance and tolerance in bloodstream infections:The triad yeast-host-antifungal. Microorganisms 2020; 154 (8):1-19.
  • 2. Cheng MF, Yang YL, Yao TJ, Lin CY, Liu JS, Tang RB, et al. Risk factors for fatal candidemia caused by Candida albicans and non-albicans Candida species. BMC Infectious Diseases 2005; 5: 22.
  • 3. Erdem I, Ozgultekin A, Inan AS, et al. Bloodstream infections in a medical-surgical intensive care unit:incidence, aetiology, antimicrobial resistance patterns of gram-positive and gram-negative bacteria. Clin Microbiol Infect 2009; 15(10): 943-6.
  • 4.Pappas PG, Kauffman CA, Andes D, et al. Clinical practice guidelines for the management of candidiasis:2009 update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 48(5): 503-35.
  • 5.Hitkova HY, Georgieva DS, Hristova PM and Sredkova MP. Antifungal susceptibility of Candida albicans isolates at a tertiary care hospital in Bulgaria. Jundishapur J Microbiol 2019. In Press (In Press):e92079.
  • 6. Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide. Clinical Microbiology and Infection 2019; 25: 792-798.
  • 7. Mukherjee PK, Chandra J, Kuhn DM, Ghannoum MA. Mechanism of fluconazole resistance in Candida albicans biofilms: Phase-specific role of efflux pumps and membrane sterols. Infect Immun 2003; 71: 4333–4340.
  • 8. Ramage G, Rajendran R, Sherry L, WilliamsC. Fungal biofilm resistance. Int J Microbiol 2012: 528521.
  • 9. Ramage G, Bachmann S, Patterson TF, Wickes BL, Lopez-RibotJL. Investigation of multidrug effluxpumps in relation to fluconazole resistance in Candida albicans biofilms. J Antimicrob Chemother. 2002; 49: 973–980.
  • 10. Kanafani ZA, Perfect JR. Antimicrobial resistance: Resistance to antifungal agents: mechanisms andclinical impact. Clin Infect Dis 2008; 46: 120–128.
  • 11. Pappas, PG, Lionakis, MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis.Nat Rev Dis Primers 2018; 4: 18026.
  • 12. HospenthalDR, Murray CK, Rinaldi MG. The role of antifungal susceptibility testing in the therapy ofcandidiasis. Diagn Microbiol Infect Dis. 2004; 48, 153–160.
  • 13. Alastruey-Izquıerdo A, Melhem MSC, Bonfıettı LX & Rodrıguez-Tudela JL Susceptibility test for fungi: Clinical and laboratorial correlations in medical mycology. Rev Inst Med Trop Sao Paulo 2015; 57 (19):57-64.
  • 14. Orasch C, Marchetti O, Garbino J, Schrenzel J, Zimmerli S, Mühlethaler K, et al,Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: A 6-year prospective candidaemia survey from the fungal infection network of Switzerland. Clin Microbiol Infect 2014; 20: 698–705.
  • 15. Lindberg E, Hammarström H, Ataollahy N & Kondori N. Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia. Scientific Reports 2019; 9: 3838.
  • 16. Dalyan Cilo B, Topaç T, Ağca H, Sağlam S, Efe K, Ener B. Comparison of Clinical Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) broth microdilution methods for determining the susceptibilities of Candida isolates. Bulletin of Microbiology 2018; 52 (1): 35-48.
  • 17. Gülat S, Doluca Dereli M. Investigation of the expression levels of efflux pumps in fluconazole-resistant Candida albicans isolates. Bulletin of Microbiology 2014; 48 (2): 325-334.
  • 18. Coşkun Ö, Beşirbellioğlu B,Yıldıran ŞT, Gönlüm A, Pahsa A. In-vitro susceptibilities of Candida species isolated from candidemic patients against amphotericin B and fluconazole. Bulletin of Microbiology 2001; 35: 565-571.
  • 19. Hope W W, Billaud EM, Lestner J, Denning DW. Therapeutic drug monitoring for triazoles. Curr Opin Infect Dis 2008; 21: 580-6.
Toplam 19 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Filiz Orak 0000-0001-5153-7391

Erken Görünüm Tarihi 11 Temmuz 2022
Yayımlanma Tarihi 15 Temmuz 2022
Gönderilme Tarihi 13 Temmuz 2021
Kabul Tarihi 31 Ağustos 2021
Yayımlandığı Sayı Yıl 2022 Cilt: 17 Sayı: 2

Kaynak Göster

AMA Orak F. Determination of Resistance Rates of Candida albicans Species Isolated from Sterile Body Fluids to Triazoles by Microdilution Method. KSÜ Tıp Fak Der. Temmuz 2022;17(2):41-45. doi:10.17517/ksutfd.971050