Emine YURDAKUL ERTÜRK, Taner KASAR

Çocuk Kardiyoloji Polikliniğine Akut Göğüs Ağrısı Nedeniyle Başvuran Çocukların Etiyolojik Açıdan Değerlendirilmesi

Amaç: Azollerin profilaksi veya tedavi amacıyla yaygın ve tekrarlayan kullanımı Candida albicans (C.albicans) türlerinde direnç gelişimine yol açmıştır. Gereç ve Yöntemler: Bu çalışmada, steril vücut sıvısı kültürlerinden izole edilen C.albicans izolatlarının flukonazol, itrakonazol ve vorikonazole in vitro direnç oranlarının belirlenmesi amaçlanmıştır. Tür düzeyinde tanımlama, geleneksel tanı yöntemleri ve BD Phoenix 100 (BD, ABD) otomatik tanımlama sistemi kullanılarak yapıldı. Antifungal duyarlılık testi, %2 glukoz içeren RPMI kullanılarak mikrodilüsyon yöntemiyle değerlendirildi. Triazoller olan flukonazol, itrakonazol ve vorikonazol için bulanıklığın belirgin (≥%50) olarak azaldığı kuyucuktaki konsantrasyon, MİK50 değeri olarak belirlendi. Çalışmada kontrol suş olarak C.albicans ATCC 90028 kullanıldı. Bulgular: C.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 48 (%94.1)’i kan,1 (%1.96)’i beyin omurilik sıvısı, 1 (%1.96)’i steril vücut sıvısı, 1(%1.96)’i peritoneal sıvı kültüründen tanımlandı. Antifungal duyarlılık test sonuçlarına göre türlerin 7 (%12.2)’si flukonazol, 14 (%27.4)’ü itrakonazol ve 5 (%9.8)’i vorikonazole dirençli bulundu. Toplam 6 (%11.7) örnekte ise çapraz dirence rastlandı. Sonuç: C.albicans izolatlarında triazollere direncin yanısıra diğer azollere karşı da çapraz direnç saptanmıştır. Bu nedenle uygun tedavi için antifungal duyarlılık test sonuçları dikkate alınmalıdır.

Anahtar Kelimeler:

Antifungal ilaç direnci, Candida albicans, Triazol, Vücut sıvısı

Etiological Evaluation of Children Admitted to the Pediatric Cardiology Outpatient Clinic, with Acute Chest Pain

Objective: Widespread and repeated use of azoles for prophylaxis or therapy has led to the development of resistance in Candida albicans (C.albicans) species. In this study, it was aimed to determine the in vitro resistance rates of C.albicans isolates isolated from sterile body fluid cultures to fluconazole, itroconazole and voriconazole. Material and Methods: Fifty one C.albicans species isolated from sterile body fluid cultures of patients hospitalized in 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. 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: Eighty-eight point two percent (n=45) of C.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. Of the isolates, 48 (94.1%) was identified from blood, 1 (1.96%) cerebrospinal fluid, 1(1.96%) sterile body fluid, 1(1.96%) peritoneal fluid culture. 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: In addition to resistance to triazoles, cross-resistance was also detected against other azoles in C.albicans isolates. Therefore, antifungal susceptibility test results should be taken into account for appropriate treatment.

Keywords:

Antifungal drug resistance, Body fluid, Candida albicans, Triazole,

PDF

___

Costa-de-Oliveira S, Rodrigues AG. Candida albicans antifungal resistance and tolerance in bloodstream infections: The triad yeast- host-antifungal. Microorganisms 2020;154(8):1-19.
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.
Erdem I, Ozgultekin A, Inan AS, Engin DO, Akcay SS, Turan G 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):943-946.
Pappas PG, Kauffman CA, Andes D, Clancy CJ, Marr KA, Ostrosky- Zeichner L et al. Clinical practice guidelines for the management of candidiasis:2016 update by the Infectious Diseases Society of America. Clin Infect Dis 2015;62(4):1-50.
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.
Pristov KE, Ghannoum MA. Resistance of Candida to azoles and echinocandins worldwide. Clinical Microbiology and Infection 2019;25:792-798.
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.
Ramage G, Rajendran R, Sherry L, WilliamsC. Fungal biofilm resistance. Int J Microbiol 2012:528521.
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.
Kanafani ZA, Perfect JR. Antimicrobial resistance: Resistance to antifungal agents: mechanisms andclinical impact. Clin Infect Dis 2008;46:120–128.
Pappas, PG, Lionakis, MS, Arendrup MC, Ostrosky-Zeichner L, Kullberg BJ. Invasive candidiasis. Nat Rev Dis Primers 2018; 4:18026.
Hospenthal DR, Murray CK, Rinaldi MG. The role of antifungal susceptibility testing in the therapy of candidiasis. Diagn Microbiol Infect Dis. 2004;48,153–160.
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.
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.
Lindberg E, Hammarström H, Ataollahy, Kondori N. Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia. Scientific Reports 2019;9:3838.
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.
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.
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.
Hope W W, Billaud EM, Lestner J, Denning DW. Therapeutic drug monitoring for triazoles. Curr Opin Infect Dis 2008; 21:580-586.