2007年粒细胞减少患者抗感染指南(中英对照版)

肿瘤合并粒细胞减少病人抗生素使用临床实践指南 2007 UPDATE 进行中 Alison Freifeld, MD IDSA 粒减伴发热治疗专家组主席 2008-01-24 LOGO 一、此处添加标题 CLINICAL PRACTICE GUIDELINE FOR THE USE OF ANTIMICROBIAL AGENTS IN NEUTROPENIC PATIENTS WITH CANCER: 2007 UPDATE In Progress Alison Freifeld, MD Chair, IDSA Expert Panel on Management of Fever and Neutropenia LOGO Disclosures Research support: Enzon, Astellas, Vical Consuling: Schering-Plough Scientific Advisory Board: Enzon Speakers bureaus: none currently (9/06-9/07) LOGO Panel Members Alison Freifeld, MD, Chair Michael Boeckh, MD Eric J. Bow, MD, MSc James I. Ito, MD Craig Mullen, MD, PhD Issam I. Raad, MD Kenneth V.Rolston, MD Kent A. Sepkowitz, MD Jo-Anne van Burik, MD John R. Wingard, MD Stuart Cohen, MD, SPGC Liaison LOGO 专家组成员 Alison Freifeld, MD, Chair Michael Boeckh, MD Eric J.Bow, MD, MSc James I,Ito, MD Craig Mullen, MD,PHD Issam I.Raad, MD Kenneth V.Rolston, MD Kent A.Sepkowitz, MD Jo-Anne van Burik, MD John R.Wingard, MD Stuart Cohen, MD, SPGC Liaison LOGO Guideline Comparison 2002 Guidelines Clinical features of the neutropenic patient Evaluation of the patient Initial antibiotic therapy 2007 Update Clinical features Risk assessment: definitions of high and low risk Evaluation of the patient Initial antibiotic therapy High risk Low risk LOGO 指南对比 2002 指南 粒减病人 的临床特征 病人的评估 初始抗生素治疗 2007 更新 临床特征 风险评估；高危和低危的定义 病人的评估 初始抗生素治疗 高危 低危 LOGO Guideline Comparison cont. (2) 2002 Guidelines Management during the first week Afebrile day 3-5 Persistent fever day 3-5 Duration of antibiotics Afebrile by day 3 Persistent fever on day 3 2007 Update Management during the first week Documented infections Fever of unknown etiology Duration of antibiotics Documented infections Fever of unknown etiology: high risk or low risk patients LOGO 指南对比（ 2） 2002 指南 第一周的治疗 无发热天数 3 5 持续发热天数 3 5 抗生素持续时间 无发热天数 3 持续发热天数 3 2007 更新 第一周的治疗 证实的感染 不明病因的发热 抗生素持续时间 证实的感染 不明病因的发热： 高危和低危 LOGO Guideline Comparison cont. (3) 2002 Guidelines Use of antiviral drugs Granulocyte transfusions Antibiotic prophylaxis Economic issues 2007 Update Antibacterial prophylaxis Antifungal prophylaxis, empiric and pre-emptive therapy Antiviral prophylaxis and treatment Colony-stimulating factors Catheter infections InfeEcntniovuisr Doinsemaseesn Stoacli e ptyr oefc Aamuetriiocans LOGO 指南对比（ 3） 2002 指南 抗病毒药物的使用 粒细胞输入 抗生素预防 经济问题 2007 更新 抗生素预防 抗真菌预防，经验性及先发性治疗 抗病毒预防及治疗 细胞集落刺激因子 导管感染 环境警戒 LOGO IDSA Ranking of Recommendations Strength of Recommendation A Good evidence to support use BModerate evidence to support use C Poor evidence to support use D Moderate evidence against use EGood evidence against use Quality of Evidence I 1 properly randomized, controlled trial II1 trial, non-randomized, cohort or case-control, from multiple time-series or dramatic results III Opinions of respected authorities, based on clinical experience, descriptive studies or expert committee reports LOGO IDSA 推荐序列 推荐强度 A 良好的证据支持使用 B 中等证据支持使用 C 差的证据支持使用 D 中等证据反对使用 E 良好证据反对使用 证据质量 I 1严格的随机、控制良好的试验 II 1试验，非随机，同期组群或病例对照，来源于多重时间序列或引人注目的结果 III 权威专家的意见，基于临床经验，描述性试验或专家委员会报告 LOGO Who requires empiric antibiotic therapy? Patients who meet the standard definitions for fever (T 38.3 or 38.0 over 1 hour) and neutropenia (ANC 5x normal) Renal insufficiency (creatinine clearance 5倍正常值） 肾功能不足（肌酐清除率 500/mm3 x least one day with a rising trend, and the patient is afebrile for at least two days. (C-III) Documented infections: treat for an appropriate length of time for the particular organism and site and continue through the period of neutropenia or beyond, as necessary (C-III) Surrogate markers of myeloid reconstitution may be useful in judging duration of empiric antibiotics. (C-II) absolute monocyte count 100/ mm3, absolute phagocyte count 100/ mm3, reticulocyte fCroapctyiroignh LOGO 经验性抗生素治疗的疗程 不明原因发热： ANC500/mm3至少 1天且有上升趋势，同时病人无发热至少 2天。（ C-III） 证实的感染： 按照需要对特别的病原体及部位保证适当的治疗持续时间，通过粒细胞减少或异常的周期决定继续治疗。（ C-III） 骨髓重组的替代标志对判定抗生素经验治疗的持续时间可能有用。（ C-II） 单核细胞绝对值计数 100/mm3,吞噬细胞绝对值计数 100/mm3,网状红细胞碎片 LOGO Antibacterial prophylaxis High Risk Levofloxacin or Ciprofloxacin prophylaxis is recommended for high risk neutropenic patients (expected neutropenia 7 d). (A-I) Studies have shown reductions in: Febrile episodes Gram-negative & Gram-positive bacteremias Use of empiric antibiotics - without significant increases in bacterial resistance There is no advantage to the addition of a Grampositive active agent to ciprofloxacin for prophylaxis Gafter-Gvili et al. Ann Int Med 2005;142:979; Bucaneve et al NEJM 2005;353:977; Crucianin et al JCO 2003;21:4127;GIMMEMA Ann Int Med 1991; 115:7; von Baum et al JAC 2006; 58:891; Leibovici et al Cancer 2006;107:1743 LOGO 抗菌药物预防 高危 对高危粒减病人推荐左氧氟沙星或环丙沙星预防（预期粒减时间 7天）。（ A-I）研究显示抗生素预防可以减少： 发热的发作 革兰氏阴性菌 &革兰氏阳性菌菌血症 经验性抗生素治疗的使用 致病菌耐药性没有显著的升高 环丙沙星加一个抗革兰氏阳性菌药物作为预防没有显著的优势 Gaftor Gvili et al Ann Int Med 2005;142:979,Bucaneve et al NEJM 2005;353:977. Crucianin et al JCO 2003;21 :4124; GIMMEMA Ann Int Med 1991;115:7;Von Baum et al JAC 2006 58:891. Leibovici et al Cancer 2006;107:1743 LOGO Antibacterial Prophylaxis Low Risk Antibacterial prophylaxis is not routinely recommended for patients with expected durations of neutropenia 7 days. (C-I) Cullen et al NEJM2005;353:988 Randomized trial of levofloxacin vs placebo in patients with solid tumors or lymphoma Minimal reduction in fever episodes but no decrease in documented infections or mortality were observed LOGO 抗菌药物预防 低危 对于预期粒减持续 14 days) (B-III) Autologous HSCT: fluconazole if patient is anticipated to develop severe mucositis (B-I) Cornely NEJM 2007;365:348; Rotstein CID 1999;28:331;Winston Ann Int Med 1993;118:495; Glasmacher JAC 2006; 57:317; Goodman NEJM 1992; 326:845; Slavin JID 1995;171:1545; Winston Ann Int Med 2003;138:705 ; Marr Blood 2004; 103:1557;van Burik CID 2004; 39:1407 LOGO 抗真菌预防 高危 AML诱导：泊沙康唑（对霉菌感染风险最高的病人， 7%）（ A-I），伊曲康唑，氟康唑（ C-I） 异基因 HSCT：氟康唑（ A-I），伊曲康唑，米卡芬净（ B-I）。没有泊沙康唑和伏立康唑 用于异基因 HSCT人群的数据 一些专家推荐对粒减时间延长病人（ 14天）使用一个抗霉菌药物进行预防（ B-III） 自体 HSCT：如果预期病人将发生严重粘膜炎，则应使用氟康唑。（ B-I） Comely NEJM 2007;365:348; Rotstein CID 1999;28:331; Winston Ann Int Med 1993;118:495; Glasmacher JAC 2006;57:317;Goodman NEJM 1992;326-845; Slavin JID 1995;171:1545; Winston Ann Med 2003;138:705;Marr Blood 2004 ;103:1557,van Burik CID 2004;39:1407 LOGO Antifungal Prophylaxis Low risk Antifungal prophylaxis is not routinely recommended for patients anticipated to have a duration of neutropenia 7 days. (C-III) LOGO 抗真菌预防 低危 对于预计粒减时间 90% of patients do not have invasive fungal disease is not justifiable. De Pauw B. NEJM 2005;41:1251 LOGO 经验性抗真菌治疗的选择： 当前的争论 Pizzo Am J Med 1982两性霉素 B（ n=18） VS none（ n=16） EORTC Ann Intern Med 1989 （ n=132） 25 年之后： 抗念珠菌属预防常规用于 HSCT和长期粒减。（ A-I） 侵袭性真菌感染（ IFIs）病菌谱改变。 提高的诊断手段： CT，血清标志物 单独的发热是否是侵袭性真菌感染的指征？ “维持指南中认为 90%的病人没有侵袭性真菌疾病的治疗指示是不合理的 De Pauw B. NEJM 2005;41:1251 LOGO Antifungal Prophylaxis High Risk contd Posaconazole has been shown to prevent Candida and Aspergillus, without impact on mortality, in patients undergoing treatment for GvHD and is recommended in this s