Wilke Michael H
Dr. Wilke GmbH, inspiring.health, Munich, Germany.
Clin Med Insights Pediatr. 2013 Feb 7;7:7-11. doi: 10.4137/CMPed.S8028. Print 2013.
Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined.
Articles were retrieved form PubMed covering the years 2000-2012. Various search terms were used. Then the articles were clustered in different types like 'review,' 'pharmacokinetics,' 'case reports' and others.
From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed.
The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics.
The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.
儿科重症监护病房(PICU)中的侵袭性真菌感染是一个日益严峻的挑战。念珠菌属是这些感染中最常见的微生物。由于对氟康唑的耐药性不断增加,棘白菌素正被用于适当的治疗。然而,最近的美国感染病学会(IDSA)指南仅在氟康唑或两性霉素B导致治疗失败或禁忌的情况下推荐使用它们。在一项文献综述中,将研究PICU环境中侵袭性真菌感染的重要性以及阿尼芬净的作用。
从PubMed检索2000年至2012年的文章。使用了各种检索词。然后将文章分为不同类型,如“综述”“药代动力学”“病例报告”等。
从67个检索结果中,选择了14篇文章。其中,7篇与阿尼芬净相关,7篇与PICU中的棘白菌素或真菌感染相关。在4项药代动力学/药效学(PK/PD)研究中对阿尼芬净进行了研究,发现其安全性良好。未发生严重不良事件。报告风险因素的文章表明,中心静脉导管、接受抗生素治疗、接受肠外营养和中性粒细胞减少是PICU中侵袭性真菌感染最重要的独立风险因素。三项抗真菌药物综述表明,棘白菌素因其安全性可能有用;米卡芬净是研究最多的一种,还需要进一步试验。
多年来,关于PICU环境中侵袭性真菌感染的已发表文献有所增加。然而,直接与在这种情况下使用阿尼芬净相关的文章很少。最近的一篇出版物显示阿尼芬净具有良好的PK/PD动态和良好的安全性。到目前为止,尚未发表关于婴儿和新生儿侵袭性念珠菌病领域的随机对照试验(RCT)。对ClinicalTrials.gov上当前注册试验的综述显示,还有一项与PK/PD相关的试验以及两项研究阿尼芬净或阿尼芬净与伏立康唑联合在儿科应用的试验。
现有的关于婴儿阿尼芬净的少量文献表明治疗成功、无药物相关不良事件且药效学良好。0.75毫克/千克/天或1.5毫克/千克/天的剂量与成人50毫克/天或100毫克/天的剂量一样有效。应该进行更多关于在PICU或新生儿重症监护病房(NICU)临床实际应用的试验。