Department of Microbiology and Infectious Diseases, Alfred Hospital, Melbourne, Australia.
Curr Opin Infect Dis. 2012 Dec;25(6):619-25. doi: 10.1097/QCO.0b013e32835915c2.
Febrile neutropenia presents a clinical challenge in which timely and appropriate antibiotic exposure is crucial. In the context of altered pharmacokinetics and rising bacterial resistance, standard antibiotic doses are unlikely to be sufficient. This review explores the potential utility of altered dosing approaches of β-lactam antibiotics to optimize treatment in febrile neutropenia.
There is a dynamic relationship between the antibiotic, the infecting pathogen, and the host. Great advancements have been made in the understanding of the pharmacokinetic changes in critical illness and the pharmacodynamic relationships of antibiotics in these settings.
Antibiotic treatment in febrile neutropenia is becoming increasingly difficult. Patients are of higher acuity, receive more intensive chemotherapy regimens leading to prolonged neutropenia, and are often exposed to multiple antibiotic courses. These patients display significant variability in antibiotic clearances and increases in volume of distribution compared with standard ward-based patients. Rising antibiotic resistance and a lack of new antibiotics in production have prompted alternative dosing strategies based on pharmacokinetic/pharmacodynamic data, such as extended or continuous infusions of β-lactam antibiotics, to maximize the likelihood of treatment success. A definitive study that describes a mortality benefit of such dosing regimens remains elusive and the theoretical advantages require testing in well designed clinical trials.
发热性中性粒细胞减少症是一种临床挑战，及时和适当的抗生素暴露至关重要。在药代动力学改变和细菌耐药性上升的情况下，标准抗生素剂量可能不足以满足需要。本文探讨了改变β-内酰胺类抗生素剂量的方法在发热性中性粒细胞减少症治疗中的潜在应用。
抗生素、感染病原体和宿主之间存在着动态关系。在理解危重病患者的药代动力学变化以及这些环境下抗生素的药效动力学关系方面取得了巨大进展。
发热性中性粒细胞减少症的抗生素治疗变得越来越困难。患者的病情更为严重，接受更密集的化疗方案导致中性粒细胞减少时间延长，并且经常接受多种抗生素疗程。与标准病房患者相比，这些患者的抗生素清除率和分布容积有显著差异。抗生素耐药性的上升和新抗生素的缺乏促使人们根据药代动力学/药效动力学数据制定替代剂量策略，例如延长或连续输注β-内酰胺类抗生素，以最大限度地提高治疗成功率。仍缺乏描述此类剂量方案对死亡率有益的明确研究，理论优势需要在精心设计的临床试验中进行检验。
