Stanford University School of Medicine and Stanford Distinguished Careers Institute, Stanford University, Stanford, California (P.A.P.).
Ann Intern Med. 2019 Mar 19;170(6):389-397. doi: 10.7326/M18-3192. Epub 2019 Mar 12.
The association between fever and neutropenia and the risk for life-threatening infections in patients receiving cytotoxic chemotherapy has been known for 50 years. Indeed, infectious complications have been a leading cause of morbidity and mortality in patients with cancer. This review chronicles the progress in defining and developing approaches to the management of fever and neutropenia through observational and controlled clinical trials done by single institutions, as well as by national and international collaborative groups. The resultant data have led to recommendations and guidelines from professional societies and frame the current principles of management. Recommendations include those guiding new treatment options (from monotherapy to oral antibiotic therapy) and use of prophylactic antimicrobial regimens in high-risk patients. Of note, risk factors have changed with the advent of hematopoietic cytokines (especially granulocyte colony-stimulating factor) in shortening the duration of neutropenia, as well as with the discovery of more targeted cancer treatments that do not result in cytotoxicity, although these are still the exception. Most guiding principles that were developed decades ago-about when to begin empirical treatment after a neutropenic patient becomes febrile, whether and how to modify the initial treatment regimen (especially in patients with protracted neutropenia), and how long to continue antimicrobial therapy-are still used today. This review describes how the treatment principles related to the management of fever and neutropenia have responded to changes in the patients at risk, the microbes responsible, and the tools for their treatment, while still being sustained over the arc of time.
发热和中性粒细胞减少与接受细胞毒性化疗的患者发生危及生命的感染的风险相关，这一现象已经被人们认识了 50 年。事实上，感染并发症一直是癌症患者发病率和死亡率的主要原因。本文回顾了通过单机构、国家和国际合作组进行的观察性和对照临床试验，在定义和制定发热和中性粒细胞减少管理方法方面所取得的进展。这些数据导致了专业协会的建议和指南，并构成了当前管理原则的框架。建议包括指导新的治疗选择（从单药治疗到口服抗生素治疗）和在高危患者中使用预防性抗菌方案的建议。值得注意的是，随着造血细胞因子（尤其是粒细胞集落刺激因子）的出现，中性粒细胞减少的持续时间缩短，以及发现了不会导致细胞毒性的更有针对性的癌症治疗方法，风险因素发生了变化，尽管这些仍然是例外。几十年前制定的大多数指导原则——中性粒细胞减少症患者发热后何时开始经验性治疗，是否以及如何修改初始治疗方案（尤其是在中性粒细胞减少持续时间较长的患者中），以及抗菌治疗需要持续多长时间——至今仍在使用。本文描述了与发热和中性粒细胞减少管理相关的治疗原则如何应对风险患者、负责的微生物以及治疗这些微生物的工具的变化，同时在时间的长河中仍然得以维持。
