腫瘤合并粒細胞減少病人抗生素使用臨床實踐指南(中英對照版)

1、腫瘤合并粒細胞減少病人抗生素使用臨床實踐指南2007 UPDATE進行中Alison Freifeld, MDIDSA 粒減伴發(fā)熱治療專家組主席2008-01-24一、此處添加標題CLINICAL PRACTICE GUIDELINEFOR THE USE OF ANTIMICROBIALAGENTS IN NEUTROPENICPATIENTS WITH CANCER:2007 UPDATEIn ProgressAlison Freifeld, MDChair, IDSA Expert Panel onManagement of Fever andNeutropeniaDisclosures

2、Research support: Enzon, Astellas, VicalConsuling: Schering-PloughScientific Advisory Board: EnzonSpeakers bureaus: none currently (9/06-9/07)Panel MembersAlison Freifeld, MD, ChairMichael Boeckh, MDEric J. Bow, MD, MScJames I. Ito, MDCraig Mullen, MD, PhDIssam I. Raad, MDKenneth , MDKent A. Sepkowi

3、tz, MDJo-Anne van Burik, MDJohn R. Wingard, MDStuart Cohen, MD, SPGC Liaison專家組成員Alison Freifeld, MD, Chair Michael Boeckh, MDEric , MD, MScJames I,Ito, MDCraig Mullen, MD,PHDIssam , MDKenneth , MDKent , MDJo-Anne van Burik, MDJohn , MDStuart Cohen, MD, SPGC LiaisonGuideline Comparison2002 Guideline

4、s Clinical features of theneutropenic patient Evaluation of thepatient Initial antibiotic therapy2007 Update Clinical features Risk assessment:definitions of high andlow risk Evaluation of the patient Initial antibiotic therapy High risk Low risk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 更新臨床特征風險評估；高危和低危

5、的定義病人的評估初始抗生素治療高危低危Guideline Comparison cont. (2)2002 Guidelines Management during thefirst week Afebrile day 3-5 Persistent fever day 3-5 Duration of antibiotics Afebrile by day 3 Persistent feveron day 32007 Update Management during thefirst week Documented infections Fever of unknownetiology Dura

6、tion of antibiotics Documented infections Fever of unknownetiology: high risk or lowrisk patients指南對比（2）2002 指南第一周的治療無發(fā)熱天數(shù) 35持續(xù)發(fā)熱天數(shù)35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)32007 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Guideline Comparison cont. (3)2002 Guidelines Use of antiviral drugs Granulocyte transfusions An

7、tibiotic prophylaxis Economic issues2007 Update Antibacterial prophylaxis Antifungal prophylaxis,empiric and pre-emptivetherapy Antiviral prophylaxis andtreatment Colony-stimulating factors Catheter infections InfeEcntniovuisr Doinsemaseesn Stoacli e ptyr oefc Aamuetriiocans指南對比（3）2002 指南抗病毒藥物的使用粒細胞

8、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)防及治療細胞集落刺激因子導管感染環(huán)境警戒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

9、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 clinicalexperience, descriptive studies or expert committee reportsIDSA 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

10、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Who requiresempiric antibiotic therapy? Patients who meet the standard definitions for fever(T 38.3 or 38.0 over 1 hour) and neutropenia(ANC 500/mm3 or whose ANC is expected to fallbelow 50

11、0/mm3 over the next 48 hours) requireempiric antibiotic therapy. Afebrile patients who are neutropenic and have newonset of abdominal pain, mental status changes,respiratory symptoms or other signs or symptomscompatible with possible infection should beevaluated and considered high risk candidates f

12、orempiric antibiotics.誰需要經(jīng)驗性抗生素治療？符合標準發(fā)熱（或超過1小時）及粒減（ANC500/mm3或預(yù)計48小時后ANC降低至500/mm3以下）定義的病人需要經(jīng)驗性抗生素治療未發(fā)熱病人有粒減且有新的腹部疼痛發(fā)作，精神狀態(tài)改變，呼吸癥狀或其他與感染可能相關(guān)的體征或癥狀，則應(yīng)被評估且作為高危候選人進行經(jīng)驗治療Risk Assessment2002: MASCC scoring systemCharacteristic ScoreBurden of illnessno/mild sx 5moderate sx 3No hypotension 5No COPD 4Solid

13、 tumor or no fungal infxn 4No dehydration 3Outpatient at onset fever 3Age 60 yrs 22007: MASCC scoring system now validated: 95% of pts categorized as lowrisk could be successfully treated orally. (AII) High vs Low risk factors better elucidated byclinical trials & experience (AIII)A risk index score

14、 of 21 indicatesthat the patient is likely to be at lowrisk forcomplications and morbidity.Klastersky JCO 2006; 24:4129; Kern WV CID 2006; 42:533, Innes SuppCare Cancer Sept 25,2007 epub.風險評估2002 MASCC評分系統(tǒng) 特征 分數(shù) 疾病負荷 無/輕度體征 5 中度體征 3無低血壓 5無COPD 4實體腫瘤或無真菌感染 4無脫水 3門診病人發(fā)熱發(fā)作 3年齡 5x normal)Renal insuffici

15、ency(creatinine clearance 5倍正常值） 腎功能不足（肌酐清除率30 ml/min)低危粒減預(yù)期7天內(nèi)恢復(fù)沒有任何高危標準中所列的醫(yī)學共病足夠的肝及腎功能Response to Empiric Antibioticsaccording to Duration of NeutropeniaKern WV CID 2006; 42:533粒減持續(xù)時間與經(jīng)驗性抗生素治療有效率經(jīng)驗性抗生素治療有效率 500/mm3 x least one day with a rising trend, andthe patient is afebrile for at least two d

16、ays. (C-III) Documented infections: treat for an appropriate length of time for theparticular organism and site and continue through theperiod of neutropenia or beyond, as necessary (C-III) Surrogate markers of myeloid reconstitution may be useful injudging duration of empiric antibiotics. (C-II) ab

17、solute monocyte count 100/ mm3, absolute phagocyte count 100/mm3, reticulocyte fCroapctyiroignh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?shù)闹委煶掷m(xù)時間，通過粒細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）單核細胞絕對值計數(shù)100/mm3,吞噬細胞絕對值計數(shù)100/mm3,網(wǎng)狀紅細胞碎片Antibacteria

18、l prophylaxis High Risk Levofloxacin or Ciprofloxacin prophylaxis isrecommended for high risk neutropenic patients(expected neutropenia 7 d). (A-I) Studies have shownreductions in: Febrile episodes Gram-negative & Gram-positive bacteremias Use of empiric antibiotics- without significant increases in

19、 bacterial resistance There is no advantage to the addition of a Grampositiveactive agent to ciprofloxacin for prophylaxisGafter-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; L

20、eibovici et al Cancer 2006;107:1743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 1

21、991;115:7;Von Baum et al JAC 200658:891. Leibovici et al Cancer 2006;107:1743Antibacterial ProphylaxisLow Risk Antibacterial prophylaxis is not routinelyrecommended for patients with expecteddurations of neutropenia 7 days. (C-I)Cullen et al NEJM2005;353:988 Randomized trial of levofloxacin vs place

22、bo in patients withsolid tumors or lymphoma Minimal reduction in fever episodes but no decrease indocumented infections or mortality were observed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 todevelop severe mucositis (B-I)Cornely NEJM 2007;365:348; Rotstei

23、n 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抗真菌預(yù)防高危AML誘導：泊沙康唑（對霉菌感染風險最高的病人，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

24、（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;

25、Marr Blood 2004 ;103:1557,van Burik CID 2004;39:1407Antifungal Prophylaxis Low risk Antifungal prophylaxis is not routinelyrecommended for patients anticipated to have aduration of neutropenia 7 days. (C-III)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 diseaseis not justifiable.”De Pa

26、uw B. NEJM 2005;41:1251經(jīng)驗性抗真菌治療的選擇：當前的爭論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;41:1251Antifungal ProphylaxisHigh Risk contdPosaconazole has b