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[儿童米卡芬净使用情况评估]

[Evaluation of Micafungin Use in Children].

作者信息

Yeşil Edanur, Çelebi Solmaz, Sezgin Evim Melike, Özer Arife, Turan Cansu, Timur Demet, Çakır Salih Çağrı, Bülbül Beyhan, Ener Beyza, Güneş Adalet Meral, Köksal Nilgün, Özkan Hilal, Sevinir Betül, Düzcan Kilimci Duygu, Hacımustafaoğlu Mustafa

机构信息

Uludag University Faculty of Medicine, Department of Pediatric Infectious Diseases, Bursa, Turkey.

Uludag University Faculty of Medicine, Department of Pediatric Hematology, Bursa, Turkey.

出版信息

Mikrobiyol Bul. 2020 Jan;54(1):120-134. doi: 10.5578/mb.68832.

Abstract

Micafungin is recommended especially in patients with liver and kidney failure and in the presence of other side effects due to antifungals apart from its known priority indications such as invasive candidiasis. The aim of this study was to evaluate the children who have received micafungin treatment. In the study, 125 children who were hospitalized in the pediatric wards and intensive care units of our hospital and had used micafungin between November 2016 and January 2019 were analyzed retrospectively. Clinical data, micafungin indication, blood values on the first and fourth days of the treatment, side effects of the drug and efficacy were evaluated. Sixty percent (75/125) of the patients were male and the mean age of all the patients were 58 ± 67 (0-215, 30) months. Approximately half of the cases (48%) had malignancy and 13% of them were premature. Sixty-two percent (n= 37) of the malignencies were hematological (27 acute lymphocytic leukemia, nine acute myeloid leukemia, one myelodysplastic syndrome) and 38% (n= 23) were oncological (six neuroblastoma, four Hodgkin lymphoma, two Non-Hodgkin's lymphoma, five sarcomas, one hepatoblastoma, five others) malignencies. The major cause of hospitalization was sepsis (53%). The patients had several risk factors like immunosuppressive therapy (n= 68, 54%), neutropenia (n= 61, 49%), central venous catheter (n= 102, 82%), nasogastric tube (n= 63, 50%), endotracheal intubation tube (n= 49, 39%), urinary catheter (n= 14, 11%) and total parenteral nutrition (n= 81, 65%). Thirteen percent (n= 16) of the cases were post-operative patients. Candida species were cultivated in 97 clinical specimens (blood, endotracheal aspirate, sputum, urine, etc.) among 23 (18%) of the patients. Thirteen (10%) of the patients had candidemia and 62% of them were non-albicans strains. In all candidemias, strains were echinocandin susceptible, and blood cultures were negative within four days. When all the patients (n= 125) were evaluated, a significant decrease in C-reactive protein, an increase in sodium, and a decrease in alanine aminotransferase were observed on the fourth day of micafungin treatment (p<0.05). A total of 39 (31%) patients underwent various antifungal treatments for median seven (1-60) days prior to micafungin treatment. Fourteen (36%) of these 39 patients, had elevated liver function tests (LFT), 10 (26%) of them had hypokalemia, and five (13%) of them had elevated renal function tests. Ten (26%) patients had antifungal-induced hypokalemia previously; and potassium levels were normalized after micafungin treatment (p= 0.0001). The patients for which micafungin treatment was chosen due to elevated liver function tests (n= 47, 38%), whether the antifungalinduced or not; alanine aminotransferase and aspartate aminotransferase levels were decreased after micafungin treatment (p= 0.0001 and p= 0.0001, respectively). Nineteen (15%) of the patients have died within the first 30 days of micafungin treatment and one of them had candidemia. No micafungin treatment related significant side effects were observed in any of the patients. Our study showed that micafungin could be a safe and effective option in pediatric cases including newborns with high liver and kidney function tests.

摘要

米卡芬净尤其适用于肝肾功能衰竭患者以及因使用抗真菌药物出现其他副作用的患者,其已知的优先适应症如侵袭性念珠菌病除外。本研究的目的是评估接受米卡芬净治疗的儿童。在该研究中,对2016年11月至2019年1月期间在我院儿科病房和重症监护病房住院并使用过米卡芬净的125名儿童进行了回顾性分析。评估了临床数据、米卡芬净适应症、治疗第1天和第4天的血液值、药物副作用及疗效。60%(75/125)的患者为男性,所有患者的平均年龄为58±67(0 - 215, 30)个月。约一半的病例(48%)患有恶性肿瘤,其中13%为早产儿。62%(n = 37)的恶性肿瘤为血液系统疾病(27例急性淋巴细胞白血病、9例急性髓细胞白血病、1例骨髓增生异常综合征),38%(n = 23)为肿瘤性疾病(6例神经母细胞瘤、4例霍奇金淋巴瘤、2例非霍奇金淋巴瘤、5例肉瘤、1例肝母细胞瘤、5例其他)。住院的主要原因是败血症(53%)。患者有多种危险因素,如免疫抑制治疗(n = 68, 54%)、中性粒细胞减少(n = 61, 49%)、中心静脉导管(n = 102, 82%)、鼻胃管(n = 63, 50%)、气管插管(n = 49, 39%)、尿管(n = 14, 11%)和全胃肠外营养(n = 81, 65%)。13%(n = 仅适用于肝肾功能检查结果较高的儿科病例,包括新生儿。16)的病例为术后患者。23例(18%)患者的97份临床标本(血液、气管吸出物、痰液、尿液等)中培养出念珠菌属。13例(10%)患者发生念珠菌血症,其中62%为非白色念珠菌菌株。在所有念珠菌血症中,菌株对棘白菌素敏感,且4天内血培养转阴。当评估所有患者(n = 125)时,米卡芬净治疗第4天观察到C反应蛋白显著降低、钠升高、丙氨酸转氨酶降低(p < 0.05)。共有39例(31%)患者在米卡芬净治疗前接受了中位时间为7(1 - 60)天的各种抗真菌治疗。这39例患者中有14例(36%)肝功能检查(LFT)升高,10例(26%)有低钾血症,5例(13%)肾功能检查升高。10例(26%)患者先前有抗真菌药物引起的低钾血症;米卡芬净治疗后血钾水平恢复正常(p = 0.0001)。因肝功能检查升高而选择米卡芬净治疗的患者(n = 47, 38%),无论是否由抗真菌药物引起;米卡芬净治疗后丙氨酸转氨酶和天冬氨酸转氨酶水平均降低(分别为p = 0.0001和p = 0.0001)。19例(15%)患者在米卡芬净治疗的前30天内死亡,其中1例有念珠菌血症。未在任何患者中观察到与米卡芬净治疗相关的严重副作用。我们的研究表明,米卡芬净对于包括肝肾功能检查结果较高的新生儿在内的儿科病例可能是一种安全有效的选择。

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