Alt solunum yolu örneklerinden üretilen aspergillus türlerinin in-vitro antifungal duyarlılığının mikrodilüsyon ve e test yöntemleriyle araştırılması
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Date
2007
Authors
Efe, Şirin
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Publisher
Uludağ Üniversitesi
Abstract
Son yıllarda, antifungal duyarlılık testleri, invaziv mikozların artan insidansı nedeniyle gittikçe daha fazla önem kazanmaya başlamıştır. Bu çalışmada da, 222 Aspergillus suşunun (136 A fumigatus, 56 A flavus, 20 A niger ve 10 A terreus), Clinical and Laboratory Standards Institute (CLSI) referans mikrodilüsyon ve E test yöntemleriyle amfoterisin B, ketokonazol, itrakonazol ve vorikonazol aktivitesi değerlendirildi. Kaspofungin etkinliğine ise sadece E test ile bakıldı. 35°C’de, 24 ve 48 saatlik inkübasyonlar sonunda her iki yöntemle de; MİK aralıkları, MİK50, MİK90 ve geometrik ortalamalar belirlendi. Yöntemler arasındaki % uyum, ±1 ve ±2 dilüsyonlarda hesaplandı. Mikrodilüsyon yönteminde, en etkili ilaç vorikonazol olarak bulundu ve izolatların %90’dan fazlası ≤1 µg/ml MİK değerleriyle inhibe oldu. Bunu itrakonazol, amfoterisin B ve ketakonazol takip etti. E test yönteminde ise kaspofungin MİK değerleri, vorikonazolden daha iyi idi ve tüm suşlar ≤0,5 µg/ml MİK değerleriyle inhibe oldu. Vorikonazol ve kaspofunginin, tüm Aspergillus türlerine etkinliği çok iyi bulundu, fakat amfoterisin B’nin, aktivitesinin, A flavus ve A terreus’da düşük olduğu görüldü. İki yöntem arasındaki % uyumun, ±1 ve ±2 dilüsyonlarda her iki inkübasyon süresinde de, en yüksek vorikonazolde olduğu saptandı (sırasıyla % 83-97 ve %82-96). Bu çalışmaya göre, yeni antifungal ajanlar, Aspergillus türlerine karşı amfoterisin B’den daha etkin görülmüştür ve E test yönteminin, filamentöz mantarların duyarlılığını test etmede uygun bir alternatif olduğu görülmektedir.
Antifungal susceptibility tests have gained greater importance in recent years due to increasing incidence of invasive mycoses. This study evaluated the activities of amphotericin B, ketoconazole, itraconazole, and voriconazole by Clinical and Laboratory Standards Institute (CLSI) reference microdilution and E test methods against 222 Aspergillus species (136 A fumigatus, 56 A flavus, 20 A niger and 10 A terreus). Caspofungin activity was evaluated only by E test method. MIC ranges, MIC50, MIC90 and geometric means were determined for both of the methods after 24 and 48 hours of incubations at 35°C. The percent agreements between methods were calculated within ±1 and ±2 dilutions. Among the drugs, voriconazole was most active, inhibiting more than 90% of isolates at ≤1 µg/ml, followed by itraconazole, amphotericin B and ketoconazole by CLSI M38-A method. By E test method the MIC values of caspofungin were found better than voriconazole and all of the isolates were inhibited ≤0,5 µg/ml MIC values. The activity of voriconazol and caspofungin to all Aspergillus species were found excellent but amphotericin B showed decreased activity against A flavus and A terreus. The agreements within ±1and ±2 dilutions between methods for voriconazole were found highest at both incubation times (83-97% and 82-96% respectively). According to this study, the new antifungal agents have seen better than amphotericin B against Aspergillus species and the E test appears to be a suitable alternative procedure for testing the susceptibility of filamentous fungi.
Antifungal susceptibility tests have gained greater importance in recent years due to increasing incidence of invasive mycoses. This study evaluated the activities of amphotericin B, ketoconazole, itraconazole, and voriconazole by Clinical and Laboratory Standards Institute (CLSI) reference microdilution and E test methods against 222 Aspergillus species (136 A fumigatus, 56 A flavus, 20 A niger and 10 A terreus). Caspofungin activity was evaluated only by E test method. MIC ranges, MIC50, MIC90 and geometric means were determined for both of the methods after 24 and 48 hours of incubations at 35°C. The percent agreements between methods were calculated within ±1 and ±2 dilutions. Among the drugs, voriconazole was most active, inhibiting more than 90% of isolates at ≤1 µg/ml, followed by itraconazole, amphotericin B and ketoconazole by CLSI M38-A method. By E test method the MIC values of caspofungin were found better than voriconazole and all of the isolates were inhibited ≤0,5 µg/ml MIC values. The activity of voriconazol and caspofungin to all Aspergillus species were found excellent but amphotericin B showed decreased activity against A flavus and A terreus. The agreements within ±1and ±2 dilutions between methods for voriconazole were found highest at both incubation times (83-97% and 82-96% respectively). According to this study, the new antifungal agents have seen better than amphotericin B against Aspergillus species and the E test appears to be a suitable alternative procedure for testing the susceptibility of filamentous fungi.
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Keywords
Aspergillus, Antifungal duyarlılık, Mikrodilüsyon, E test, Antifungal susceptibility, Microdilution
Citation
Efe, Ş. (2007). Alt solunum yolu örneklerinden üretilen aspergillus türlerinin in-vitro antifungal duyarlılığının mikrodilüsyon ve e test yöntemleriyle araştırılması. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.