2007年粒細(xì)胞減少患者抗感染指南(中英對照版)

腫瘤合并粒細(xì)胞減少病人抗生素使用臨床實踐指南 2007 UPDATE 進行中 Alison Freifeld, MD IDSA 粒減伴發(fā)熱治療專家組主席 2008-01-24 LOGO 一、此處添加標(biāo)題 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 專家組成員 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 指南對比 2002 指南 粒減病人 的臨床特征 病人的評估 初始抗生素治療 2007 更新 臨床特征 風(fēng)險評估；高危和低危的定義 病人的評估 初始抗生素治療 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 指南對比（ 2） 2002 指南 第一周的治療 無發(fā)熱天數(shù) 3 5 持續(xù)發(fā)熱天數(shù) 3 5 抗生素持續(xù)時間 無發(fā)熱天數(shù) 3 持續(xù)發(fā)熱天數(shù) 3 2007 更新 第一周的治療 證實的感染 不明病因的發(fā)熱 抗生素持續(xù)時間 證實的感染 不明病因的發(fā)熱： 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 指南對比（ 3） 2002 指南 抗病毒藥物的使用 粒細(xì)胞輸入 抗生素預(yù)防 經(jīng)濟問題 2007 更新 抗生素預(yù)防 抗真菌預(yù)防，經(jīng)驗性及先發(fā)性治療 抗病毒預(yù)防及治療 細(xì)胞集落刺激因子 導(dǎo)管感染 環(huán)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 推薦序列 推薦強度 A 良好的證據(jù)支持使用 B 中等證據(jù)支持使用 C 差的證據(jù)支持使用 D 中等證據(jù)反對使用 E 良好證據(jù)反對使用 證據(jù)質(zhì)量 I 1嚴(yán)格的隨機、控制良好的試驗 II 1試驗，非隨機，同期組群或病例對照，來源于多重時間序列或引人注目的結(jié)果 III 權(quán)威專家的意見，基于臨床經(jīng)驗，描述性試驗或?qū)＜椅瘑T會報告 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） 腎功能不足（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 經(jīng)驗性抗生素治療的療程 不明原因發(fā)熱： ANC500/mm3至少 1天且有上升趨勢，同時病人無發(fā)熱至少 2天。（ C-III） 證實的感染： 按照需要對特別的病原體及部位保證適當(dāng)?shù)闹委煶掷m(xù)時間，通過粒細(xì)胞減少或異常的周期決定繼續(xù)治療。（ C-III） 骨髓重組的替代標(biāo)志對判定抗生素經(jīng)驗治療的持續(xù)時間可能有用。（ C-II） 單核細(xì)胞絕對值計數(shù) 100/mm3,吞噬細(xì)胞絕對值計數(shù) 100/mm3,網(wǎng)狀紅細(xì)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 抗菌藥物預(yù)防 高危 對高危粒減病人推薦左氧氟沙星或環(huán)丙沙星預(yù)防（預(yù)期粒減時間 7天）。（ A-I）研究顯示抗生素預(yù)防可以減少： 發(fā)熱的發(fā)作 革蘭氏陰性菌 &革蘭氏陽性菌菌血癥 經(jīng)驗性抗生素治療的使用 致病菌耐藥性沒有顯著的升高 環(huán)丙沙星加一個抗革蘭氏陽性菌藥物作為預(yù)防沒有顯著的優(yōu)勢 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 抗菌藥物預(yù)防 低危 對于預(yù)期粒減持續(xù) 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 抗真菌預(yù)防 高危 AML誘導(dǎo)：泊沙康唑（對霉菌感染風(fēng)險最高的病人， 7%）（ A-I），伊曲康唑，氟康唑（ C-I） 異基因 HSCT：氟康唑（ A-I），伊曲康唑，米卡芬凈（ B-I）。沒有泊沙康唑和伏立康唑 用于異基因 HSCT人群的數(shù)據(jù) 一些專家推薦對粒減時間延長病人（ 14天）使用一個抗霉菌藥物進行預(yù)防（ B-III） 自體 HSCT：如果預(yù)期病人將發(fā)生嚴(yán)重粘膜炎，則應(yīng)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 抗真菌預(yù)防 低危 對于預(yù)計粒減時間 90% of patients do not have invasive fungal disease is not justifiable. De Pauw B. NEJM 2005;41:1251 LOGO 經(jīng)驗性抗真菌治療的選擇： 當(dāng)前的爭論 Pizzo Am J Med 1982兩性霉素 B（ n=18） VS none（ n=16） EORTC Ann Intern Med 1989 （ n=132） 25 年之后： 抗念珠菌屬預(yù)防常規(guī)用于 HSCT和長期粒減。（ A-I） 侵襲性真菌感染（ IFIs）病菌譜改變。 提高的診斷手段： CT，血清標(biāo)志物 單獨的發(fā)熱是否是侵襲性真菌感染的指征？ “維持指南中認(rèn)為 90%的病人沒有侵襲性真菌疾病的治療指示是不合理的 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