Wrenn Rebekah H, Cluck David, Kennedy LeAnne, Ohl Christopher, Williamson John C
1 Department of Pharmacy, Duke University Hospital, Durham, NC, USA.
2 Department of Pharmacy Practice, ETSU Gatton College of Pharmacy, Johnson City, TN, USA.
J Oncol Pharm Pract. 2018 Apr;24(3):170-175. doi: 10.1177/1078155216687151. Epub 2017 Jan 11.
Background Extended infusion (EI) dosing provides a longer time above the minimum inhibitory concentration, which is important for the clinical success of β-lactam antibiotics, especially for patients with impaired immunity. The aim of this study was to determine the feasibility and clinical impact of administering cefepime by EI as treatment of febrile neutropenia. Methods This was a prospective, randomized, comparative pilot study. All patients received cefepime 2 g IV every 8 h, with the first dose administered using a 30-min infusion. After the first dose, patients were randomized to receive cefepime over 30 min as a standard infusion (SI) or 3 h (EI). Patients were >18 years old with febrile neutropenia (neutrophil count <500 cells/mm and temperature >38.0ºC) and received chemotherapy or stem cell transplant as treatment for malignancy. Patients were excluded for the following: allergy to a cephalosporin, creatinine clearance (CrCl) < 50 mL/min, receipt of concurrent Gram-negative antimicrobial, sepsis, or solid tumor malignancy. The primary outcome was defervescence by 72 h. Secondary outcomes included time to defervescence, clinical success, in-hospital mortality, hospital length of stay, and need for additional antimicrobials. Main results Sixty-three patients were enrolled: 33 in the SI arm and 30 in the EI arm. The groups were similar with regard to age, gender, weight, estimated creatinine clearance, and duration of neutropenia. None of the patients in the EI arm withdrew due to practical complications of receiving EI cefepime. Twenty-three patients in the SI arm and 20 patients in the EI arm defervesced by 72 h ( p = 0.99). There were no differences in secondary outcome measures; however, patients in the EI arm appeared to have defervesced more rapidly (median 19 vs. 41 h, p = 0.305). Conclusion Administration of cefepime by EI for the treatment of febrile neutropenia is feasible. Larger clinical trials are necessary to determine if EI cefepime imparts a clinical benefit in the treatment of febrile neutropenia.
背景 延长输注（EI）给药可使药物在最低抑菌浓度之上维持更长时间，这对于β-内酰胺类抗生素的临床疗效很重要，尤其是对免疫功能受损的患者。本研究的目的是确定采用EI方式给予头孢吡肟治疗发热性中性粒细胞减少症的可行性及临床影响。方法 这是一项前瞻性、随机、对照试验性研究。所有患者均每8小时静脉注射2克头孢吡肟，首剂采用30分钟输注。首剂之后，患者被随机分为接受30分钟标准输注（SI）或3小时（EI）的头孢吡肟治疗组。患者年龄大于18岁，患有发热性中性粒细胞减少症（中性粒细胞计数<500个细胞/mm且体温>38.0ºC），并接受化疗或干细胞移植作为恶性肿瘤的治疗手段。排除标准如下：对头孢菌素过敏、肌酐清除率（CrCl）<50 mL/min、同时接受革兰氏阴性抗菌药物治疗、患有败血症或实体瘤恶性肿瘤。主要结局指标为72小时内退热。次要结局指标包括退热时间、临床疗效、院内死亡率、住院时间以及是否需要加用其他抗菌药物。主要结果 共纳入63例患者：SI组33例，EI组30例。两组在年龄、性别、体重、估计肌酐清除率及中性粒细胞减少持续时间方面相似。EI组中没有患者因接受EI方式的头孢吡肟治疗出现实际并发症而退出研究。SI组23例患者和EI组20例患者在72小时内退热（p = 0.99）。次要结局指标方面没有差异；然而，EI组患者退热似乎更快（中位数分别为19小时和41小时，p = 0.305）。结论 采用EI方式给予头孢吡肟治疗发热性中性粒细胞减少症是可行的。需要开展更大规模的临床试验以确定EI方式的头孢吡肟在治疗发热性中性粒细胞减少症时是否具有临床益处。
