Lestner J M, Versporten A, Doerholt K, Warris A, Roilides E, Sharland M, Bielicki J, Goossens H
Pediatric Infectious Diseases Unit, St. George's Hospital, London, United Kingdom
Laboratory of Medical Microbiology, Vaccine & Infectious Disease Institute, Faculty of Medicine and Health Science, University of Antwerp, Antwerp, Belgium.
Antimicrob Agents Chemother. 2015 Feb;59(2):782-9. doi: 10.1128/AAC.04109-14. Epub 2014 Nov 17.
The appropriate use of systemic antifungals is vital in the prevention and treatment of invasive fungal infection (IFI) in immunosuppressed children and neonates. This multicenter observational study describes the inpatient prescribing practice of antifungal drugs for children and neonates and identifies factors associated with prescribing variability. A single-day point prevalence study of antimicrobial use in hospitalized neonates and children was performed between October and December 2012. The data were entered through a study-specific Web-based portal using a standardized data entry protocol. Data were recorded from 17,693 patients from 226 centers. A total of 136 centers recorded data from 1,092 children and 380 neonates receiving at least one antifungal agent. The most frequently prescribed systemic antifungals were fluconazole (n=355) and amphotericin B deoxycholate (n=195). The most common indications for antifungal administration in children were medical prophylaxis (n=325), empirical treatment of febrile neutropenia (n=122), and treatment of confirmed or suspected IFI (n=100 [14%]). The treatment of suspected IFI in low-birthweight neonates accounted for the majority of prescriptions in the neonatal units (n=103). An analysis of variance (ANOVA) demonstrated no significant effect of clinical indication (prophylaxis or treatment of systemic or localized infection) on the total daily dose (TDD). Fewer than one-half of the patients (n=371) received a TDD within the dosing range recommended in the current guidelines. Subtherapeutic doses were prescribed in 416 cases (47%). The predominance of fluconazole and high incidence of subtherapeutic doses in participating hospitals may contribute to suboptimal clinical outcomes and an increased predominance of resistant pathogenic fungi. A global consensus on antifungal dosing and coordinated stewardship programs are needed to promote the consistent and appropriate use of antifungal drugs in neonates and children.
合理使用全身性抗真菌药物对于预防和治疗免疫抑制儿童及新生儿的侵袭性真菌感染（IFI）至关重要。这项多中心观察性研究描述了儿童及新生儿抗真菌药物的住院处方情况，并确定了与处方差异相关的因素。2012年10月至12月期间，对住院新生儿和儿童的抗菌药物使用情况进行了单日点患病率研究。数据通过特定研究的基于网络的门户，使用标准化数据录入协议录入。记录了来自226个中心的17,693名患者的数据。共有136个中心记录了1,092名儿童和380名新生儿至少接受一种抗真菌药物的数据。最常处方的全身性抗真菌药物是氟康唑（n = 355）和两性霉素B脱氧胆酸盐（n = 195）。儿童抗真菌治疗最常见的适应证是医学预防（n = 325）、发热性中性粒细胞减少症的经验性治疗（n = 122）以及确诊或疑似IFI的治疗（n = 100 [14%]）。低出生体重新生儿疑似IFI的治疗占新生儿病房处方的大多数（n = 103）。方差分析（ANOVA）表明临床适应证（全身性或局部感染的预防或治疗）对每日总剂量（TDD）无显著影响。不到一半的患者（n = 371）接受的TDD在当前指南推荐的剂量范围内。416例（47%）患者开具了低于治疗剂量的药物。参与研究的医院中氟康唑的主导地位以及低于治疗剂量的高发生率可能导致临床效果欠佳以及耐药致病真菌的优势增加。需要就抗真菌药物剂量达成全球共识并开展协调的管理计划，以促进新生儿和儿童抗真菌药物的一致和合理使用。
