Three cases of fungemia caused by Blastoschizomyces capitatus

Blastoschizomyces capitatus özellikle bağışıklık sistemi baskılanmış kişilerde ciddi ve fatal seyreden sistemik enfeksiyonlara neden olabilmektedir. B.capitatus suşlarının hastane enfeksiyonuna neden olduğu ve salgınlar yaptığı da bildirilmektedir. Bu raporda, hematolojik malignensisi olan üç hastada B.capitatus suşlarının neden olduğu fungemi olguları sunulmaktadır. Sunulan birinci olgu akut lenfoblastik lösemi tanısı alan 20 yaşında kadın hasta, ikinci olgu B hücreli malign lenfoma tanısı alan 26 yaşında kadın hasta ve üçüncü olgu B hücreli akut lenfoblastik lösemi tanısı alan 7 yaşında erkek hastadır. Olguların tümü kemoterapi almakta olup, nötropeni nedeniyle antibakteriyel ve antifungal ilaç tedavisi uygulanan hastalardır. Ampirik kaspofungin tedavisi altında iken ikinci ve üçüncü olguların kan kültüründe B.capitatus üremesi olmuş, etkenin tanımlanmasından sonra bu hastalara vorikonazol ve amfoterisin B tedavisi başlanmış ve takiplerinde iyileşme olduğu belirlenmiştir. Yine ampirik kaspofungin tedavisi alan birinci hasta ise, kan kültüründe B.capitatus üremesi saptanmadan önce kaybedilmiştir. Suşların tanımlanmasında konvansiyonel mikolojik yöntemler [mikroskobik ve makroskobik morfoloji, germ tüp testi, üre hidrolizi, karbonhidrat asimilasyon testleri (API 20C AUX; BioMerieux, Fransa), üreme ısısı ve sikloheksimid duyarlılığı] kullanılmış ve izolatlar annellokonidya oluşturma, üreaz negatifliği, karbonhidrat kullanımı, 45°C’de üreme ve sikloheksimide dirençli olmaları ile B.capitatus olarak tanımlanmıştır. Suşların antifungal duyarlılığı, mikrodilüsyon yöntemi (amfoterisin B, vorikonazol, itrakonazol, flukonazol, ketakonazol) ve E-test (kaspofungin) ile araştırılmıştır. Çalışmada, üç B.capitatus izolatının minimum inhibitör konsantrasyon (MİK) değerleri amfoterisin B için sırasıyla 0.25, 0.125, 0.032 ?g/ml; flukonazol için 2, 2, 16 ?g/ml; itrakonazol için 0.064, 0.032, 0.032 ?g/ml; ketokonazol için 0.125, 0.064, 0.064 ?g/ml; vorikonazol için tümünde 0.032 ?g/ml ve kaspofungin için tümünde > 32 ?g/ml olarak bulunmuştur. Olguların kan kültürlerinden B.capitatus izolasyonu yaklaşık 15 gün içinde -ard arda- yapılmış olduğundan, benzerlik oranının araştırılması için suşların genotipi “repetitive sequence-based PCR” (DiversiLab System; BioMerieux, Fransa) yöntemiyle belirlenmiştir. Analiz sonucunda benzerlik oranı suşların ikisinde (1. ve 2. olgu) %97, birinde (3. olgu) %94.9 olarak bulunmuş; ancak çevresel örnekler alınmadığından bulaş şekli açıklık kazanmamıştır. Sonuç olarak, immün yetmezlikli hastalarda sistemik fırsatçı mantar enfeksiyonlarında B.capitatus’un da akılda tutulması gerekmektedir. Klinik B.capitatus suşlarının in vitro antifungal duyarlılıklarının belirlenmesi, tedavi yaklaşımlarına ve epidemiyolojik verilere katkı sağlayacaktır.Blastoschizomyces capitatus is a rare fungal pathogen that may lead to severe and fatal systemic infections especially in immunosuppressive individuals. B.capitatus strains have also been reported as the cause of hospital-acquired infections and outbreaks. In this report, three fungemia cases caused by B.ca- pitatus with hematologic malignancies have been presented. The first case was a 20-year-old female with acute lymphoblastic leukemia, the second was a 26-year-old female with B-cell malignant lymphoma and the third was a 7-year-old male with B-cell acute lymphoblastic leukemia. All of the patients have been receiving chemotherapy, and treated with antibacterial and antifungal agents due to neutropenia. The blood cultures obtained from the second and third patients yielded B.capitatus although they were under empirical caspofungin therapy. Those patients have been treated with voriconazole and ampho- tericin B after the identification of B.capitatus, and clinical improvement were noted during their follow- up. However the first patient who was also under caspofungin therapy had died just before the isolation of B.capitatus from her blood culture. Conventional mycological methods [macroscopic and microscopic morphology, germ tube test, urea hydrolysis, carbohydrate assimilation tests (API 20C AUX; Bi- oMerieux, France), growth temperature, cycloheximide sensitivity] were used for the identification of the isolates. The strains were identified as B.capitatus with the characteristics of annelloconidia formation, urease negativity, carbohydrate utilization, growth at 45ºC and resistance to cycloheximide. Antifungal susceptibilities of isolates were determined by using microdilution method (for amphotericin B, fluconazole, itraconazole, voriconazole, ketoconazole) and E-test (for caspofungin). Minimum inhibitory concentration (MIC) values of the three B.capitatus strains were detected as 0.25, 0.125, 0.032 µg/ml for amphotericin B; 2, 2, 16 µg/ml for fluconazole; 0.064, 0.032, 0.032 µg/ml for itraconazole and 0.125, 0.064, 0.064 µg/ml for ketoconazole, respectively, while MIC values of all strains were 0.032 µg/ml for voriconazole and > 32 µg/ml for caspofungin. Since B.capitatus strains were isolated from the cases within about 15 days -sequentially-, the genotypes of the isolates were determined by repetitive sequence- based PCR (DiversiLab System; BioMerieux, France) to investigate the similarity rates. The results of analysis indicated 97% similarity between two (case 1 and 2) strains and 94.9% similarity in one strain (case 3) of B.capitatus, however the transmission route could not be clarified due to the absence of environmental sampling. In conclusion, B.capitatus should also be considered as a cause of systemic fun- gal infections in immunocompromised patients. Determination of the in vitro antifungal susceptibilities of clinical B.capitatus strains may contribute to the therapeutic approaches and epidemiological data

Three Cases of Fungemia Caused by Blastoschizomyces capitatus

Blastoschizomyces capitatus is a rare fungal pathogen that may lead to severe and fatal systemic infections especially in immunosuppressive individuals. B.capitatus strains have also been reported as the cause of hospital-acquired infections and outbreaks. In this report, three fungemia cases caused by B.capitatus with hematologic malignancies have been presented. The first case was a 20-year-old female with acute lymphoblastic leukemia, the second was a 26-year-old female with B-cell malignant lymphoma and the third was a 7-year-old male with B-cell acute lymphoblastic leukemia. All of the patients have been receiving chemotherapy, and treated with antibacterial and antifungal agents due to neutropenia. The blood cultures obtained from the second and third patients yielded B.capitatus although they were under empirical caspofungin therapy. Those patients have been treated with voriconazole and amphotericin B after the identification of B.capitatus, and clinical improvement were noted during their follow-up. However the first patient who was also under caspofungin therapy had died just before the isolation of B.capitatus from her blood culture. Conventional mycological methods [macroscopic and microscopic morphology, germ tube test, urea hydrolysis, carbohydrate assimilation tests (API 20C AUX; BioMerieux, France), growth temperature, cycloheximide sensitivity] were used for the identification of the isolates. The strains were identified as B.capitatus with the characteristics of annelloconidia formation, urease negativity, carbohydrate utilization, growth at 45 degrees C and resistance to cycloheximide. Antifungal susceptibilities of isolates were determined by using microdilution method (for amphotericin B, fluconazole, itraconazole, voriconazole, ketoconazole) and E-test (for caspofungin). Minimum inhibitory concentration (MIC) values of the three B.capitatus strains were detected as 0.25, 0.125, 0.032 mu g/ml for amphotericin B; 2, 2, 16 mu g/ml for fluconazole; 0.064, 0.032, 0.032 mu g/ml for itraconazole and 0.125, 0.064, 0.064 mu g/ml for ketoconazole, respectively, while MIC values of all strains were 0.032 mu g/ml for voriconazole and > 32 mu g/ml for caspofungin. Since B.capitatus strains were isolated from the cases within about 15 days -sequentially-, the genotypes of the isolates were determined by repetitive sequence-based PCR (DiversiLab System; BioMerieux, France) to investigate the similarity rates. The results of analysis indicated 97% similarity between two (case 1 and 2) strains and 94.9% similarity in one strain (case 3) of B.capitatus, however the transmission route could not be clarified due to the absence of environmental sampling. In conclusion, B.capitatus should also be considered as a cause of systemic fungal infections in immunocompromised patients. Determination of the in vitro antifungal susceptibilities of clinical B.capitatus strains may contribute to the therapeutic approaches and epidemiological data