NHMRC National Centre for Infections in Cancer, University of Melbourne, Melbourne, Victoria, Australia.
Department of Immunology and Infectious Diseases, Sydney Children's Hospital, Randwick, Sydney, NSW, Australia.
PLoS One. 2020 Sep 16;15(9):e0238787. doi: 10.1371/journal.pone.0238787. eCollection 2020.
Aminoglycosides are commonly prescribed to children with febrile neutropenia (FN) but their impact on clinical outcomes is uncertain and extent of guideline compliance is unknown. We aimed to review aminoglycoside prescription and additional antibiotic prescribing, guideline compliance and outcomes for children with FN. We analysed data from the Australian Predicting Infectious ComplicatioNs in Children with Cancer (PICNICC) prospective multicentre cohort study, in children <18 years with FN between November 2016 and January 2018. Impact of aminoglycoside use in the first 12 hours of FN on composite unfavourable outcome of death, ICU admission, relapse of infection or late-onset sepsis was assessed using multivariable Cox regression. The study was conducted in Australia where antimicrobial resistance among gram negative organisms is relatively low. Data from 858 episodes of FN in 462 children from 8 centres were assessed, median age 5.8 years (IQR 3.5-10.8 years). Early empiric aminoglycosides were prescribed in 255 episodes (29.7%). Guideline non-compliance was common: in 46% (184/400) of eligible episodes, patients did not receive aminoglycosides, while aminoglycosides were prescribed in 9% (39/458) of guideline-ineligible episodes. Adjusted hazard of the composite unfavourable outcome was 3.81 times higher among patients prescribed empiric aminoglycosides than among those who weren't (95% confidence interval, 1.89-7.67), with no increased risk of unfavourable outcome in eligible patients who did not receive aminoglycosides. In a large paediatric FN cohort, aminoglycoside prescription was common and was often non-compliant with guidelines. There was no evidence for improved outcome with aminoglycosides, even in those who met guideline criteria, within a low-resistance setting. Empiric aminoglycoside prescription for children with FN requires urgent review in guidelines and in national practice.
氨基糖苷类药物常用于治疗发热性中性粒细胞减少症（FN）患儿，但它们对临床结局的影响尚不确定，且指南遵循情况也不清楚。我们旨在评估 FN 患儿的氨基糖苷类药物处方和其他抗生素处方、指南遵循情况以及结局。我们分析了澳大利亚预测癌症患儿感染并发症（PICNICC）前瞻性多中心队列研究的数据，该研究纳入了 2016 年 11 月至 2018 年 1 月期间年龄＜18 岁、FN 的患儿。采用多变量 Cox 回归评估 FN 后 12 小时内使用氨基糖苷类药物对死亡、入住 ICU、感染复发或迟发性脓毒症的复合不良结局的影响。该研究在澳大利亚进行，该地区革兰氏阴性菌的耐药率相对较低。对来自 8 个中心的 462 名患儿的 858 例 FN 发作的数据进行了评估，中位年龄为 5.8 岁（IQR 3.5-10.8 岁）。在 255 例（29.7%）FN 发作中，早期经验性给予了氨基糖苷类药物。常见指南不遵守情况：在 400 例符合条件的发作中，46%（184/400）的患儿未接受氨基糖苷类药物治疗，而在 9%（39/458）的指南不适用发作中，给予了氨基糖苷类药物。与未接受氨基糖苷类药物治疗的患儿相比，接受经验性氨基糖苷类药物治疗的患儿复合不良结局的调整风险比为 3.81 倍（95%置信区间，1.89-7.67），而符合指南标准但未接受氨基糖苷类药物治疗的患儿不良结局风险无增加。在大型 FN 患儿队列中，氨基糖苷类药物的处方很常见，且常常不符合指南。在低耐药环境下，即使符合指南标准的患儿，使用氨基糖苷类药物也没有改善结局的证据。FN 患儿经验性氨基糖苷类药物的处方需要在指南和国家实践中进行紧急审查。
