Infectious Diseases, Infection Control and Employee Health, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA,
Support Care Cancer. 2014 Jan;22(1):7-14. doi: 10.1007/s00520-013-1947-8. Epub 2013 Aug 24.
The goal of this study was to describe the outcomes associated with daptomycin treatment of documented gram-positive infections in patients with neutropenia.
All patients with neutropenia (≤500 cells/m(3)) and at least one documented gram-positive culture from 2006-2009 were identified from a retrospective, multicenter, and observational registry (Cubicin(®) Outcome Registry and Experience (CORE(®))). Investigators assessed patient outcome (cured, improved, failed, nonevaluable) at the end of daptomycin therapy. All patients were included in the safety analysis.
The efficacy population had 186 patients; 159 (85 %) patients had either cure (n = 108, 58 %) or improved (n = 51, 27 %) as an outcome. Success rates (cure plus improved) by the lowest WBC during daptomycin were 98/116 (84 %) for ≤100 cells/m(3) and 61/70 (87 %) for 101-499 cells/m(3), P = 0.6. Most patients had cancer; 135/186 (73 %) had hematological malignancy; 26/186 (14 %) had solid tumors, and 9 (5 %) had both. One hundred fifty-six (84 %) patients received other antibiotics before daptomycin treatment; 82 % vancomycin, of which 31 % failed vancomycin. The most common infections were bacteremia (78 %), skin and skin structure infections (8 %), and urinary tract infections/pyelonephritis (6 %). The most common pathogens were vancomycin-resistant Enterococcus faecium (47 %), methicillin-resistant Staphylococcus aureus (20 %), and coagulase-negative staphylococci (19 %). The median (min, max) initial daptomycin dose was 6 mg/kg (3.6, 8.3). The median (min, max) daptomycin duration of therapy was 14 days (1, 86). Possibly related adverse events occurred in 12/209 patients (6 %), and 13 patients (6 %) discontinued daptomycin due to adverse event.
The results suggest that daptomycin appeared useful and well tolerated in neutropenic patients, and the degree of neutropenia did not affect daptomycin success rates. Comparative clinical trials are needed to confirm these findings.
本研究旨在描述 2006-2009 年接受达托霉素治疗的中性粒细胞减少症患者确诊的革兰阳性感染相关的治疗结局。
从一项回顾性、多中心、观察性登记研究（Cubicin 结局登记和经验研究[CORE]）中确定所有中性粒细胞减少症（≤500 个细胞/μL）且至少有一个革兰阳性培养阳性的患者。研究者在达托霉素治疗结束时评估患者的结局（治愈、改善、失败、无法评估）。所有患者均纳入安全性分析。
疗效人群包括 186 例患者；159 例（85%）患者的结局为治愈（n=108，58%）或改善（n=51，27%）。达托霉素治疗期间白细胞最低时的成功率（治愈加改善）为白细胞计数≤100 个细胞/μL 时为 98/116（84%），白细胞计数为 101-499 个细胞/μL 时为 61/70（87%），P=0.6。大多数患者患有癌症；135/186（73%）患有血液恶性肿瘤；26/186（14%）患有实体肿瘤，9 例（5%）同时患有这两种疾病。156 例（84%）患者在接受达托霉素治疗前接受了其他抗生素治疗；82%接受了万古霉素治疗，其中 31%的患者万古霉素治疗失败。最常见的感染是菌血症（78%）、皮肤和皮肤结构感染（8%）和尿路感染/肾盂肾炎（6%）。最常见的病原体是万古霉素耐药粪肠球菌（47%）、耐甲氧西林金黄色葡萄球菌（20%）和凝固酶阴性葡萄球菌（19%）。初始达托霉素剂量的中位数（最小，最大）为 6mg/kg（3.6，8.3）。达托霉素治疗的中位数（最小，最大）持续时间为 14 天（1，86）。209 例患者中有 12 例（6%）发生可能与药物相关的不良事件，13 例（6%）患者因不良事件停止使用达托霉素。
结果表明，达托霉素在中性粒细胞减少症患者中似乎有效且耐受良好，中性粒细胞减少症的程度并不影响达托霉素的成功率。需要开展临床对照试验来证实这些发现。
