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,MDIDSA 粒减伴发热治疗专家组主席2021-01-242021-01-24LOGO一、此处添加标题一、此处添加标题CLINICAL PRACTICE GUIDELINEFOR THE USE OF ANTIMICROBIALAGENTS IN NEUTROPENICPATIENTS WITH CANCER:2007 UPDATEIn ProgressAlison Freifeld,MDChair,IDSA Expert Panel onManagement of Fever andNeutropeniaLOGODisclosuresResearch support:Enzon,Astellas,VicalConsuling:Schering-PloughScientific Advisory Board:EnzonSpeakers bureaus:none currently (9/06-9/07)LOGOPanel MembersAlison Freifeld,MD,ChairMichael Boeckh,MDEric J.Bow,MD,MScJames I.Ito,MDCraig Mullen,MD,PhDIssam I.Raad,MDKenneth V.Rolston,MDKent A.Sepkowitz,MDJo-Anne van Burik,MDJohn R.Wingard,MDStuart Cohen,MD,SPGC LiaisonLOGO专家组成员专家组成员nAlison Freifeld,MD,Chair nMichael Boeckh,MDnEric J.Bow,MD,MScnJames I,Ito,MDnCraig Mullen,MD,PHDnIssam I.Raad,MDnKenneth V.Rolston,MDnKent A.Sepkowitz,MDnJo-Anne van Burik,MDnJohn R.Wingard,MDnStuart Cohen,MD,SPGC LiaisonLOGOGuideline Comparison2002 Guidelines 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 riskLOGO指南比照指南比照2002 指南n粒减病人 的临床特征n病人的评估n初始抗生素治疗2007 更新n临床特征n风险评估；高危和低危的定义n病人的评估n初始抗生素治疗n高危n低危LOGOGuideline 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 Duration of antibiotics Documented infections Fever of unknownetiology:high risk or lowrisk patientsLOGO指南比照指南比照22002 指南n第一周的治疗n无发热天数 35n持续发热天数35n抗生素持续时间n无发热天数3n持续发热天数32007 更新n第一周的治疗n证实的感染n不明病因的发热n抗生素持续时间n证实的感染n不明病因的发热：n 高危和低危LOGOGuideline Comparison cont.(3)2002 Guidelines Use of antiviral drugs Granulocyte transfusions Antibiotic 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 AamuetriiocansLOGO指南比照指南比照32002 指南n抗病毒药物的使用n粒细胞输入n抗生素预防n经济问题2007 更新n抗生素预防n抗真菌预防，经验性及先发性治疗n抗病毒预防及治疗n细胞集落刺激因子n导管感染n环境警戒LOGOIDSA 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 clinicalexperience,descriptive studies or expert committee reportsLOGOIDSA 推荐序列推荐序列n推荐强度u A 良好的证据支持使用u B 中等证据支持使用u C 差的证据支持使用u D 中等证据反对使用u E 良好证据反对使用n证据质量u I 1严格的随机、控制良好的试验u 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u 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LOGOWho 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 500/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 forempiric antibiotics.LOGO谁需要经验性抗生素治疗？谁需要经验性抗生素治疗？n符合标准发热T38.3或38.0超过1小时及粒减ANC500/mm3或预计48小时后ANC降低至500/mm3以下定义的病人需要经验性抗生素治疗n未发热病人有粒减且有新的腹部疼痛发作，精神状态改变，呼吸病症或其他与感染可能相关的体征或病症，那么应被评估且作为高危候选人进行经验治疗LOGORisk Assessment2002:MASCC scoring systemCharacteristic ScoreBurden of illnessno/mild sx 5moderate sx 3No hypotension 5No COPD 4Solid 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 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.LOGO风险评估风险评估2002 MASCC评分系统 特征 分数 疾病负荷 无/轻度体征 5 中度体征 3无低血压 5无COPD 4实体肿瘤或无真菌感染 4无脱水 3门诊病人发热发作 3年龄 5x normal)Renal insufficiency(creatinine clearance 5倍正常值 肾功能缺乏肌酐去除率30 ml/min)低危粒减预期7天内恢复没有任何高危标准中所列的医学共病足够的肝及肾功能LOGOResponse to Empiric Antibioticsaccording to Duration of NeutropeniaKern WV CID 2006;42:533LOGO粒减持续时间与经验性抗生素治疗有效粒减持续时间与经验性抗生素治疗有效率率经验性抗生素经验性抗生素治疗有效率治疗有效率45%500/mm3 x least one day with a rising trend,andthe patient is afebrile for at least two days.(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)absolute monocyte count 100/mm3,absolute phagocyte count 100/mm3,reticulocyte fCroapctyiroignhLOGO经验性抗生素治疗的疗程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LOGOAntibacterial 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 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;Leibovici et al Cancer 2006;107:1743LOGO抗菌药物预防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 Gaftor Gvili et al Ann Int Med 2005;142:979,Bucaneve et al NEJM 2005;353:977.2005;353:977.Crucianin et al JCO 2003;21:4124;GIMMEMA Ann Int Med 1991;115:7;Von Crucianin et al JCO 2003;21:4124;GIMMEMA Ann Int Med 1991;115:7;Von Baum et al JAC 2006Baum et al JAC 200658:891.Leibovici et al Cancer 2006;107:174358:891.Leibovici et al Cancer 2006;107:1743LOGOAntibacterial 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 placebo in patients withsolid tumors or lymphoma Minimal reduction in fever episodes but no decrease indocumented infections or mortality were observedLOGO抗菌药物预防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 todevelop 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;39:1407LOGO抗真菌预防抗真菌预防高危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，那么应使用氟康唑。B-IComely NEJM 2007;365:348;Rotstein CID 1999;28:331;Winston Ann Int Comely NEJM 2007;365:348;Rotstein CID 1999;28:331;Winston Ann Int Med 1993;118:495;Med 1993;118:495;Glasmacher JAC 2006;57:317;Goodman NEJM 1992;326-845;Slavin JID Glasmacher JAC 2006;57:317;Goodman NEJM 1992;326-845;Slavin JID 1995;171:1545;1995;171:1545;Winston Ann Med 2003;138:705;Marr Blood 2004;103:1557,van Burik CID Winston Ann Med 2003;138:705;Marr Blood 2004;103:1557,van Burik CID 2004;39:14072004;39:1407LOGOAntifungal ProphylaxisAntifungal Prophylaxis Low risk Antifungal prophylaxis is not routinelyrecommended for patients anticipated to have aduration of neutropenia 7 days.(C-III)LOGO抗真菌预防抗真菌预防低危 对于预计粒减时间90%of patients do not have invasive fungal diseaseis not justifiable.De Pauw B.NEJM 2005;41:1251LOGO经验性抗真菌治疗的选择：经验性抗真菌治疗的选择：当前的争论当前的争论Pizzo Am J Med 1982两性霉素Bn=18VS nonen=16EORTC Ann Intern Med 1989 n=13225 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;41:1251LOGOAntifungal ProphylaxisHigh Risk contdPosaconazole has been shown to prevent Candida andAspergillus,without impact on mortality,in patientsundergoing treatment for GvHD and is recommendedin this setting.(A-I)Ullmann AJ,et al.NEJM 2007;356:335-47LOGO抗真菌预防：高危抗真菌预防：高危泊沙康唑已被用于对正在治疗GvHD的病人预防念珠菌属和曲霉菌属的感染，对死亡率没有影响，并被推荐在此环境下使用。AIUllmann AJ,et al.NEJM 2007;356:335-47Ullmann AJ,et al.NEJM 2007;356:335-47LOGOEnvironmental PrecautionsNo specific protective gear(gowns,gloves,masks)forroutine care of neutropenic patients(C-III)Neutropenic patients do not require a single room orspecial ventilation,except allogeneic HSCT recipients(C-III)“Neutropenic diet generally recommended(B-III)No plants,dried or fresh flowers;no pets(B-III)All HCWs must have updated immunizations,especially yearly influenza vaccine(A-I)LOGO环境警戒环境警戒对粒减病人的常规护理不用特别的防护设备隔离衣，手套，面具。C-III粒减病人不需要单独房间或特别通风设备，除了异基因HSCT受体C-III粒减饮食被普遍推荐。B-III无植物，干花或鲜花，无宠物B-III所有的HCWs需要更新免疫，尤其是每年的流感疫苗A-I