Uludağ Üniversitesi Çocuk Kliniğinde yatan hastalarda kullanılan intravenöz antifungal ilaçların etki ve yan etkilerinin değerlendirilmesi
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Date
2013
Authors
Yenigül, Cengiz
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Publisher
Uludağ Üniversitesi
Abstract
Bu çalışmada Uludağ Üniversitesi Tıp Fakültesi Çocuk Sağlığı ve Hastalıkları Kliniğinde Eylül 2009-Mart 2013 tarihleri arasında yatan ve sistemik antifungal tedavi alan yaşları 0 gün-18 yaş arasında değişen 302 olgu antifungal ilaç etki ve yan etkileri açısından prospektif olarak takip edildi. Olgular klasik amfoterisin-B (D-AmB), lipozomal amfoterisin-B (L-AmB, kaspofungin, flukonazol, vorikonazol tedavilerini aldılar. Tedavi başlangıcı, 48. saat, 7. gün, 14. gün ve tedavi kesiminde, lökosit, hemoglobin, trombosit, kreatinin, AST, ALT, CRP, GFR değerleri takip edilerek forma kayıt edildi. Olguların klinik tanılarına göre yaş dağılımları istatistiksel olarak anlamlı farklılık arzettiğinden, antifungal ilaçların yan etkilerinin karşılaştırılması için olgular lösemi grubu, solid tümör grubu ve yenidoğan grubu olmak üzere 3 klinik gruba ayrıldı. Her ilacın tedavi süresince laboratuvar parametreleri izlendi. D-AmB alan hastaların, AST değerlerinde tedavi başlangıcına göre, 48. saat, 7. gün ve tedavi kesiminde değişiklikler saptandı. L-AmB alan hastalarda, tedavi başlangıcına göre, lökosit, trombosit, ANS sayılarında saptadığımız değişiklikler olguların sıklıkla febril nötropenili hastalar olup, izlemde nötropenilerinin düzelmesi nedeniyle ortaya çıkan değişiklikler olarak yorumlandı. Flukonazol verilen olguların GFR sonuçlarında anlamlı değişiklikler saptandı. Flukonazol grubunda çoğunluk olarak yenidoğan bebekler olduğundan GFR'nin düşük bulunması, hasta grubu ile ilgili olarak değerlendirildi. Vorikonazol alan hastalarda, lökosit, trombosit, ANS sayılarında, hemoglobin değerlerinde, anlamlı değişiklikler saptandı. Bu grup olgular daha çok lösemi grubu hastalar olup nötropenisi olan hastalar olduğundan, lökosit, trombosit, ANS sayıları arasında farklılık hastaların zaman içinde nötropeni ve diğer kan hücrelerinin sayılarının tedavi ile düzelmesine bağlı olan değişiklikler olarak yorumlandı. Kullanılan antifungallerde tespit edilen yan etkilere bakıldığına, ilaç grubu olgularda en sık rastlanan yan etki transaminaz artışı olarak saptanmıştır. Olguların kullandıkları ilaçlar yan etkileri bakımından karşılaştırıldıklarında D-AmB alan hasta grubu, hipopotasemi yan etkisi yönünden diğer ilaç gruplarından anlamlı farklılık göstermiştir. Toplam yan etki yönünden değerlendirildiğinde ilaç grupları arasında fark saptandı. D-AmB, toplam yan etkiler bakımından L-AmB, kaspofungin, flukonazol ve vorikonazol ile karşılaştırıldığında istatiksel anlamda fark saptandı. Antifungallerin tedaviye yanıt ve ilaç değişim oranları incelendiğinde, D-AmB'de alerjik reaksiyonlar, kaspofungin, flukonazol ve vorikonazol'den anlamlı oranda yüksek saptandı. Konvasyonel amfoterisin B ve flukonazol alan alan hastalarda diğer antifungal ilaçlarla karşılaştırıldığında tedavi yanıtsızlık anlamlı oranda yüksek bulundu. Hipopotesemi D-AmB grubunda diğer antifungal ilaç gruplarına göre anlamlı oranda yüksek bulundu. Transaminaz yüksekliği nedeni ile ilaç değişimi flukonazol grubunda diğer antifungal ilaç gruplarına göre anlamlı oranda yüksek bulundu. L-AmB kullanan iki olguda anaflaksi gözlendi. Antifungal başlanan olguların tümü aynı zamanda geniş spektrumlu antibiyotik tedavileride almakta idi, ayrıca glikopeptit yapıdaki antibiotik kullanan olgular da mevcuttu. Olgular glikopeptit yapıdaki antibiotikler kullanım yönünden karşılaştırıldılar, gruplar arasında, istatiksel olarak fark saptanmadı. Antifungal tedavi verilen olguların %4,2'sinde kan kültüründe kandida üremesi saptandı.
In this study, 302 cases between the ages of 0 days to 18 years who were internalized and given systematic antifungal therapy in Uludag University School of Medicine Pediatrics Clinics from September 2009 to March 2013 has been studied prospectively according to medicine effects and side effects. Cases have been treated with classical amphotericin-B (D-AmB), liposomal amphotericin-B (L-AmB), caspofungin, fluconazole, voriconazole. Leukocyte, haemoglobin, thrombocyte, creatinine, AST, ALT, CRP, GFR values measured and recorded at the beginning, 48th hours, 7th days, 14th days and at the end of the treatment. Since age distributions are statistically significant according to clinical diagnosis of cases; they are grouped in three as leukaemia, solid tumors and newborns to compare the side effects of antifungal medicine. Laboratory parameters of each medicine have been monitored during the treatment. In AST values of the patients, who has taken D-AmB; changes were detected at 48th hours, 7th days and end of the treatment compared to start of treatment. The patients whose leukocyte, thrombocyte, ANS values changed compared to beginning of the treatment were mostly febrile neutropenic patients, and these changes were interpreted as results of healed neutropenia. Significant changes have been detected in the GFR results of cases who has taken fluconazole. Since fluconazole group is mostly newborns, low GFR levels were considered to be related to patient group. Significant changes at the leukocyte, thrombocyte, ANS and haemoglobin values were detected with the patients who have taken voriconazole. Since these patients were from leukemia group and had neutropenia, the changes in the leukocyte, thrombocyte, ANS values are considered to be result of changes in neutropenia and other blood values with treatment in time. The most revealed side effect in the drug group cases was detected as elevated transaminases in examining the side effects of used antifungal drugs. Medication of cases in comparison of side effects, D-AmB received patients' group revealed significant differences in terms of side effects of hypokalaemia rather than other drug groups. In comparison of total side effects, significant differences were detected between drug groups. In terms of overall side effects, statistically significant difference was found between D-AmB and L-AmB, caspofungin, fluconazole and voriconazole, When we examined the response to treatment and the rate of change antifungal drugs, the rate of allergic reactions with D-AmB was detected significantly higher than caspofungin, fluconazole and voriconazole drugs. The rate of unresponsiveness to treatment in the patients receiving conventional amphotericin B and fluconazole was detected significantly high, compared with the patients receiving other antifungal drugs. Hypokalemia in the D-AmB group was found significantly higher than other antifungal drug groups. Medication change due to elevated transaminases, in the fluconazole group was found significantly higher than other antifungal drugs. Anaphylaxis was observed in two patients medicated with L-AmB. All patients who have started antifungal drug therapy were also receiving broad-spectrum antibiotics treatments at the same time and there were also some patients who were used glycopeptide antibiotics. No statistically significant difference was found between the groups in the comparison of use of glycopeptide antibiotics. Of the 4.2% patients given antifungal treatment, growth of candida in the blood cultures was detected.
In this study, 302 cases between the ages of 0 days to 18 years who were internalized and given systematic antifungal therapy in Uludag University School of Medicine Pediatrics Clinics from September 2009 to March 2013 has been studied prospectively according to medicine effects and side effects. Cases have been treated with classical amphotericin-B (D-AmB), liposomal amphotericin-B (L-AmB), caspofungin, fluconazole, voriconazole. Leukocyte, haemoglobin, thrombocyte, creatinine, AST, ALT, CRP, GFR values measured and recorded at the beginning, 48th hours, 7th days, 14th days and at the end of the treatment. Since age distributions are statistically significant according to clinical diagnosis of cases; they are grouped in three as leukaemia, solid tumors and newborns to compare the side effects of antifungal medicine. Laboratory parameters of each medicine have been monitored during the treatment. In AST values of the patients, who has taken D-AmB; changes were detected at 48th hours, 7th days and end of the treatment compared to start of treatment. The patients whose leukocyte, thrombocyte, ANS values changed compared to beginning of the treatment were mostly febrile neutropenic patients, and these changes were interpreted as results of healed neutropenia. Significant changes have been detected in the GFR results of cases who has taken fluconazole. Since fluconazole group is mostly newborns, low GFR levels were considered to be related to patient group. Significant changes at the leukocyte, thrombocyte, ANS and haemoglobin values were detected with the patients who have taken voriconazole. Since these patients were from leukemia group and had neutropenia, the changes in the leukocyte, thrombocyte, ANS values are considered to be result of changes in neutropenia and other blood values with treatment in time. The most revealed side effect in the drug group cases was detected as elevated transaminases in examining the side effects of used antifungal drugs. Medication of cases in comparison of side effects, D-AmB received patients' group revealed significant differences in terms of side effects of hypokalaemia rather than other drug groups. In comparison of total side effects, significant differences were detected between drug groups. In terms of overall side effects, statistically significant difference was found between D-AmB and L-AmB, caspofungin, fluconazole and voriconazole, When we examined the response to treatment and the rate of change antifungal drugs, the rate of allergic reactions with D-AmB was detected significantly higher than caspofungin, fluconazole and voriconazole drugs. The rate of unresponsiveness to treatment in the patients receiving conventional amphotericin B and fluconazole was detected significantly high, compared with the patients receiving other antifungal drugs. Hypokalemia in the D-AmB group was found significantly higher than other antifungal drug groups. Medication change due to elevated transaminases, in the fluconazole group was found significantly higher than other antifungal drugs. Anaphylaxis was observed in two patients medicated with L-AmB. All patients who have started antifungal drug therapy were also receiving broad-spectrum antibiotics treatments at the same time and there were also some patients who were used glycopeptide antibiotics. No statistically significant difference was found between the groups in the comparison of use of glycopeptide antibiotics. Of the 4.2% patients given antifungal treatment, growth of candida in the blood cultures was detected.
Description
Keywords
Klasik amfoterisin-B (D-AmB), Lipozomal amfoterisin-B (L-AmB), Kaspofungin, Flukonazol, Vorikonazol, Classical amphotericin-B (D-AmB), Liposomal amphotericin-B (L-AmB), Caspofungin, Fluconazole, Voriconazole
Citation
Yenigül, Ç. (2013). Uludağ Üniversitesi Çocuk Kliniğinde yatan hastalarda kullanılan intravenöz antifungal ilaçların etki ve yan etkilerinin değerlendirilmesi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.