Kan kültürlerinden izole edilen flukonazol dirençli candida parapsilosis suşlarındaklonal ve klinik ilişki
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Date
2021
Authors
Semet, Cihan
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Journal ISSN
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Publisher
Bursa Uludağ Üniversitesi
Abstract
Nozokomiyal kan dolaşımı enfeksiyonlarında kandidemiler 4. sırada yer almakta ve bunların %50’den fazlasında etken olarak C. albicans saptanmıştır. Ancak son yıllarda albicans dışı Candida’lar da artmaktadır. Özellikle yenidoğan ve cerrahi yoğun bakım birimlerinde C. parapsilosis’in ve C.glabrata’nın artan sıklıkla izole edildiği bildirilmektedir. Bu durum ampirik vekanıtlanmış antifungal seçimini etkilemektedir. Son çalışmalar, C. parapsilosis kandidemi insidansının %7-24 oranında arttığını göstermiştir. Özellikle invazif girişimlerin artışı, port ve benzeri kalıcı kataterlerin kullanımının yaygınlaşması, uzun yatış süreleri, antibiyotik kullanımının artması, total parenteral nutrisyon (TPN) desteklerinin çoğalması bu insidans artışı nedenleri arasında sayılmaktadır. C. parapsilosis’e bağlı kandidemilerde mortalite diğer kandidemilere göre düşük olsa da etken hastanede salgın yapabilir, yatış süresinin uzamasına, katater değişimine neden olabilir, en kısa sürede uygun ve etkili antifungal tedavi başlanmasını gerektirir. Kandidemilerde uygun, ampirik tedavinin bir an önce başlanmasının mortalite ve yatış süresini etkilediği bilinmektedir. Bu nedenle hastalarda kandidemi riskini, mortaliteyi etkileyen faktörleri belirlemek, etkenlerin tür tayini, duyarlılık profillerinin bilinmesi yararlıdır. Hastalarda uygun ve etkili tedaviye hızla başlanması için hastane veya bölümde epidemiyolojinin bilinmesi önemlidir. Ayrıca antifungal tedavilerin giderek yaygın kullanılması, dirençli etkenlerin ortaya çıkabilmesi, hasta profillerindeki değişim bu konularda yeni çalışmalara ihtiyaç doğurmaktadır. Bu çalışmanın amacı laboratuvarımızda, kan kültürlerinden izole edilen flukonazol dirençli C. parapsilosis tür kompleksi suşları arasında genotipik ilişki ve belirlenmesi ve bu suşlarla enfekte hastaların özellikleri ve klinik seyrinin incelenmesidir. Çalışmada 1997-2019 yılları arasında, flukonazol dirençli 88 C. parapsilosis kandidemisi tanılı hasta değerlendirildi. 30. gün mortalitesi %21.5 (n=19) olarak bulundu. Risk faktörlerine bakıldığında kemoterapi almanın iii mortaliyeti arttığı görüldü. İstatistiksel olarak santral venöz kateterin (SVK) çekilmesinin ve antifungal tedavi seçiminin mortalite üzerinde etkisi anlamlı bulunmadı. 88 suştan, izole edilebilen 47 suş genotipik olarak mikrosatellit yöntemi ile analiz edildi. Bu suşlar içinde, altı farklı genotip tespit edilmiş olup, en küçük ağaç yolu çizimi ve dendogram değerlendirilmesi neticesinde esas olarak iki farklı grup halinde kümelendikleri gösterilmiştir. Aynı dönemde, aynı klinikte yatan hastalarda aynı genotipe sahip etkenler tespit edilmiş ve etkenin endojen kaynaklı olmasından ziyade, çevre kaynaklı yayıldığı düşünülmüştür. Bu sonuçlar ile C. parapsilosis’e bağlı kandidemi görülen, genel durumu kötü ve altta yatan hastalıkları fazla olan hasta grubunda kataterlerin çekilmesinin bir süre ertelenebileceği, in vitro dirençli olmasına karşın flukonazol veya ekinokandin seçeneklerinin tedavide tercih edilebileceği, C. parapsilosis salgınlarından şüphelenildiği durumlarda salgın analizinde mikrosatellit analiz yönteminin uygun bir seçenek olarak düşünülebileceği gösterilmiştir.
Candidemias take the 4th place in nosocomial bloodstream infections and C. albicans has been detected as the agent in more than 50% of them. However, in recent years, non-albicans Candida are also on the increase. It has been reported that C. parapsilosis and C. glabrata are isolated with increasing frequency, especially in neonatal and surgical intensive care units. This affects empirical and proven antifungal selection. Recent studies have shown that the incidence of C. parapsilosis candidemia increases by 7-24%. Especially the increase in invasive interventions, widespread use of ports and similar permanent catheters, long hospitalization periods, increased use of antibiotics, and the increase in total parenteral nutrition (TPN) support are among the reasons for this increase in incidence. Although mortality in candidemia due to C. parapsilosis is lower than other candidemias, the agent may cause an epidemic in the hospital, prolong the hospitalization period, cause catheter change, and require appropriate and effective antifungal treatment as soon as possible. It is known that initiating appropriate empirical treatment as soon as possible affects mortality and length of stay in candidemias. For this reason, it is useful to determine the risk of candidemia, the factors affecting mortality, the determination of the factors and their susceptibility profiles. It is important to know the epidemiology in the hospital or department for the rapid initiation of appropriate and effective treatment in patients. In addition, the widespread use of antifungal treatments, the emergence of resistant agents, and the change in patient profiles call for new studies on these issues. The aim of this study is to determine and determine the genotypic relationship between fluconazole-resistant C. parapsilosis strains isolated from v blood cultures in our laboratory, and to examine the characteristics and clinical course of patients infected with these strains. Eighty-eight fluconazole-resistant patients diagnosed with C. parapsilosis candidemia between 1997 and 2019 were evaluated in the study. 30th day mortality was found as 21.5% (n = 19). Considering the risk factors, it was seen that the mortality of receiving chemotherapy increased. Statistically, the effect of withdrawal of central venous catheter (CVC) and choice of antifungal therapy on mortality was not significant. 47 strains that can be isolated from 88 strains were genotypically analyzed by microsatellite method. Six different genotypes were identified among these strains, and it was shown that they were clustered in two different groups as a result of the smallest tree path drawing and dendogram evaluation. In the same period, factors with the same genotype were identified in patients hospitalized in the same clinic and it was thought that the agent was spread by environmental rather than endogenous origin. With these results, the withdrawal of catheters may be delayed for a while in the patient group with candidemia due to C. parapsilosis, whose general condition is poor and with high underlying diseases, fluconazole or echinocandin treatment may be preferred for treatment despite in vitro resistance, and in epidemic analysis in cases where C. parapsilosis outbreaks are suspected. It has been shown that microsatellite analysis method can be considered as a suitable option.
Candidemias take the 4th place in nosocomial bloodstream infections and C. albicans has been detected as the agent in more than 50% of them. However, in recent years, non-albicans Candida are also on the increase. It has been reported that C. parapsilosis and C. glabrata are isolated with increasing frequency, especially in neonatal and surgical intensive care units. This affects empirical and proven antifungal selection. Recent studies have shown that the incidence of C. parapsilosis candidemia increases by 7-24%. Especially the increase in invasive interventions, widespread use of ports and similar permanent catheters, long hospitalization periods, increased use of antibiotics, and the increase in total parenteral nutrition (TPN) support are among the reasons for this increase in incidence. Although mortality in candidemia due to C. parapsilosis is lower than other candidemias, the agent may cause an epidemic in the hospital, prolong the hospitalization period, cause catheter change, and require appropriate and effective antifungal treatment as soon as possible. It is known that initiating appropriate empirical treatment as soon as possible affects mortality and length of stay in candidemias. For this reason, it is useful to determine the risk of candidemia, the factors affecting mortality, the determination of the factors and their susceptibility profiles. It is important to know the epidemiology in the hospital or department for the rapid initiation of appropriate and effective treatment in patients. In addition, the widespread use of antifungal treatments, the emergence of resistant agents, and the change in patient profiles call for new studies on these issues. The aim of this study is to determine and determine the genotypic relationship between fluconazole-resistant C. parapsilosis strains isolated from v blood cultures in our laboratory, and to examine the characteristics and clinical course of patients infected with these strains. Eighty-eight fluconazole-resistant patients diagnosed with C. parapsilosis candidemia between 1997 and 2019 were evaluated in the study. 30th day mortality was found as 21.5% (n = 19). Considering the risk factors, it was seen that the mortality of receiving chemotherapy increased. Statistically, the effect of withdrawal of central venous catheter (CVC) and choice of antifungal therapy on mortality was not significant. 47 strains that can be isolated from 88 strains were genotypically analyzed by microsatellite method. Six different genotypes were identified among these strains, and it was shown that they were clustered in two different groups as a result of the smallest tree path drawing and dendogram evaluation. In the same period, factors with the same genotype were identified in patients hospitalized in the same clinic and it was thought that the agent was spread by environmental rather than endogenous origin. With these results, the withdrawal of catheters may be delayed for a while in the patient group with candidemia due to C. parapsilosis, whose general condition is poor and with high underlying diseases, fluconazole or echinocandin treatment may be preferred for treatment despite in vitro resistance, and in epidemic analysis in cases where C. parapsilosis outbreaks are suspected. It has been shown that microsatellite analysis method can be considered as a suitable option.
Description
Keywords
C. parapsilosis, Fungemi, Direnç, Risk faktörleri, Fungemia, Resistance, Risk factors
Citation
Semet, C. (2021). Kan kültürlerinden izole edilen flukonazol dirençli candida parapsilosis suşlarındaklonal ve klinik ilişki. Yayınlanmamış tıpta uzmanlık tezi. Bursa Uludağ Üniversitesi Tıp Fakültesi.