全套MRSA指南

Liu et al. Clin Infect Dis 2011 Jan 4,最新美国IDSA MRSA 感染治疗指南解读,制定指南的背景-MRSA持续增高,自1961年发现第一株对甲氧西林耐药的菌株,MRSA流行率就一直在稳定升高12005: 在美国发生将近 94,360 侵袭性疾病,1. Klevens RM, et al. JAMA 2007;298:1763-71. 2. Herold BC, et al. JAMA 1998;279:593-8.,制定指南的背景-万古霉素敏感性在下降,1. Klevens RM, et al. JAMA 2007;298:1763-71. 2. Herold BC, et al. JAMA 1998;279:593-8.,万古霉素对MRSA的MIC值随着时间在飘移,Steinkraus G et al. J Antimicrobial Chemother 2007;60:788794,0.125 0.19 0.25 0.38 0.5 0.7 1.0 1.5 2.0 3.0 4.0,Vancomycin MIC (g/ml),80 7060 5040 3020 100,Isolates (%),200120032005,Susceptibility breakpoint,MICs measured by Etest,MRSA isolates (n=662) measured in a single US tertiary care institution,万古霉素耐药性,1997 日本首次报道 VISA 2002年美国首次报道 VRSAMMWR July 20021st 例 Michigan 导管及糖尿病溃疡培养2nd 例 Pennsylvania Tenover et al 2004足跟溃疡先前无万古霉素暴露Whitener et al 2004USA：迄今，临床已发现9株VRSA,6,目前hVISA在中国的发生情况Sun W, AAC 2009; 53(9): 3642-9,1012株MRSA于2002-7年（主要为05-07）分离自14个城市检测方法：含药平皿及MET初筛，菌群分析策略-曲线下面积方法确认,2007年分离自14个城市315株MRSA，hVISA 9.5(30/315) (陈宏斌，中华检验医学杂志 2009; 32(11): 1223-7),万古霉素MIC值越高临床成功率越低,Vancomycin MIC,Adapted from Sakoulas, et. al., 2004 JCM 42:2398; Moise-Broder et al. 2004 CID 38: 1700-5; Hidayat et al. 2006 Arch Intern Med 166:2138-2144; Moise wt al. 2007 AAC 51:2582-6,Percent Success,万古霉素治疗失败与MIC增高呈正相关,Vancomycin MIC,Stevens. CID 2006; 42:S517,The numbers on the plot are the % failure rates,增加万古霉素剂量能增加疗效？,万古霉素杀菌活性与AUC0-24/MIC 相关谷浓度10mg/ml可能防止MIC增高和出现hVISA,VISAAUC/MIC400ug.h/ml，谷浓度15-20ug/ml 疗效良好 (ATS/IDSA Guidelines for management of adults with HAP,VAP,HCP)近期研究万古MIC 2 ug/ml 疗效减低剂量增加导致肾毒性增加,高剂量和低剂量万古霉素达到 AUC/MIC 400的可能性,*P8周 (A-II)一些专家建议添加利福平 (B-III)如果同时出现菌血症, 菌血症治愈后添加利福平一些专家建议添加1-3月以上的以利福平为主的口服联合治疗(C-III)脓毒性关节炎 关节间隙的清创或引流 (A-II); 使用3-4周的抗生素 (A-III),31,MRSA=methicillin-resistant Staphylococcus aureus; TMP-SMX=trimethoprim-sulfamethoxazole,1. Liu C, Bayer A, Cosgrove SE et al. Clinical practice guidelines by the Infectious Diseases Society of America for the 药剂 of methicillin-resistant Staphylococcus aureus infections in 成人s and children. Clin Infect Dis. 2011 Jan 4 Epub ahead of print,治疗骨髓炎的理想疗程未能确定指南推荐至少8周 (A-II)一些专家推荐要额外增加1-3个月(尤其对于慢性感染或者未进行清创手术可能需延长疗程) 的口服治疗，以利福平为基础联合应用TMP/SMX, 多西环素-米诺环素, 克林霉素或者敏感的氟喹诺酮 (C-III)ESR 和/或CRP 可能对治疗应答有帮助(B-III),MRSA 指南: 骨和关节感染的治疗 骨髓炎和脓毒性关节炎1,Clinical Topics Addressed,皮肤及软组织感染周期性复发的皮肤及软组织感染MRSA血流感染以及心内膜炎MRSA 肺炎MRSA 骨和关节感染MRSA 中枢神经感染,联合治疗或辅助治疗万古霉素的剂量和检测万古霉素的敏感性试验持续性血流感染以及万古霉素治疗失败的管理MRSA 新生儿感染,万古霉素注射治疗2 周 (B-II)一些专家建议增加利福平600 mg/天或者300-450 mg 每天2次 (B-III)替代治疗利奈唑胺 600 mg PO/IV twice daily (B-II) or TMP/SMX 5 mg/kg/dose IV every 8-12 hours (C-III)If shunt infection, removal recommendedDo not replace until CSF cultures repeatedly negative (A-II),MRSA 指南: MRSA脑膜炎的治疗,神经外科评估开颅引流(A-II)抗感染治疗,MRSA 指南: MRSA 脑脓肿,硬膜下积脓及硬膜下脓肿的治疗,*Classification of the strength of recommendation and quality of evidence,Note：也有一些个案报告达托霉素成功治疗 MRSA CNS 感染,Clinical Topics Addressed,皮肤及软组织感染周期性复发的皮肤及软组织感染MRSA血流感染以及心内膜炎MRSA 肺炎MRSA 骨和关节感染MRSA 中枢神经感染,联合治疗或辅助治疗万古霉素的剂量和检测万古霉素的敏感性试验持续性血流感染以及万古霉素治疗失败的管理MRSA 新生儿感染,MRSA Guidelines: How Should Vancomycin MICs be Used to Guide Therapy?1,如果万古霉素的MIC 2 g/ml (eg, VISA or VRSA), 必须使用万古霉素的替代治疗 (A-III),MRSA=methicillin-resistant Staphylococcus aureus,1. Liu C, Bayer A, Cosgrove SE et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Jan 4 Epub ahead of print,37,Clinical Topics Addressed,皮肤及软组织感染周期性复发的皮肤及软组织感染MRSA血流感染以及心内膜炎MRSA 肺炎MRSA 骨和关节感染MRSA 中枢神经感染,联合治疗或辅助治疗万古霉素的剂量和检测万古霉素的敏感性试验持续性血流感染以及万古霉素治疗失败的管理MRSA 新生儿感染,MRSA Guidelines: 持续的菌血症& 万古霉素治疗失败的治疗策略1,由于MRSA菌血症的细菌清除中位时间是7-9 天, 大多数专家建议考虑在7天左右根据临床表现决定是否改变治疗：改变治疗的考虑因素:总体的临床反应万古霉素的谷浓度药敏结果感染病灶是否可以移除在以下情况下可以更早换药尽管已经做了足够的清创或者感染病灶的移除，患者的临床反应很糟万古霉素的MIC是 2 g/ml,MRSA=methicillin-resistant Staphylococcus aureus,1. Liu C, Bayer A, Cosgrove SE et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Jan 4 Epub ahead of print,MRSA Guidelines:持续的菌血症& 万古霉素治疗失败的治疗策略(continued)1,40,MRSA=methicillin-resistant Staphylococcus aureus,1. Liu C, Bayer A, Cosgrove SE et al. Clinical practice guidelines by the Infectious Diseases Society of America for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis. 2011 Jan 4 Epub ahead of print,专家组建议改变治疗而非在万古霉素的基础上增加其它药物,Research Gaps,血流感染与心内膜炎 心动超声图起到什么样的作用，对于治疗结果的改善是否有作用?How extensive should the work-up be to identify occult foci of metastatic infection?What is the optimal initial therapyWhat is the optimal therapy once susceptibility results are available?What regimens should be used in treating persistent or relapsing infection?What is the optimal duration of therapy?,骨髓炎What is optimal therapy?Importance of bactericidal therapy?Importance of bone penetration?Oral vs. parenteral therapy?What is optimal management of hardware-associated infectionsWhat is the optimal duration?,Research Gaps,皮肤及软组织感染What is optimal management of nonpurulent cellulitis?What is the optimal management of abscesses?What s optimal management of recurrent infection?,Research Gaps,Thank you!,Back up slides,MRSA Guidelines: Recommendations for the Management of 脓肿1,皮肤脓肿 Primary treatment is I&D (A-II)Simple abscess or boilsI&D alone is likely adequate Benefit of antibiotics is marginalhigh cure rates (85-90%) whether or not an active antibiotic is usedPossible short-term prevention of new lesions/improved cure ratesAntibiotics recommended after I&D, due to CA-MRSA, for (A-III):Severe or extensive disease (e.g., involves multiple sites) or rapid progression in presence of associated cellulitisSigns & symptoms of systemic illnessAssociated with comorbidities or immunosupression (DM, HIV/AIDS, neoplasm)Extremes of ageAbscess in area difficult to drain completely (e.g., face, hand, genitalia)Associated septic phlebitisLack of response to I&D alone,MRSA=methicillin-resistant Staphylococcus aureus; I CA-MRSA=community-associated MRSA,Liu C, et al. Clin Infect Dis. 2011;52:1-38,Purulent Cellulitis (eg, cellulitis with purulent drainage or exudate in the absence of a drainable abscess) empiric coverage of CA-MRSA,MRSA Guidelines: Recommendations for the Outpatient Management of Cellulitis,5-10 days of therapy is recommended, individualized based on response,Strength of recommendation and quality of evidence is A-II for all the above,Nonpurulent cellulitis (eg, cellulitis associated with no purulent drainage or exudate and no associated abscess) empiric coverage of -hemolytic streptococci,MRSA Guidelines: Recommendations for the Outpatient Management of Cellulitis,Strength of recommendation and quality of evidence is A-II for all the above,5-10 days of therapy is recommended, individualized based on response,Personal hygiene and appropriate wound care:Keep draining wounds covered, clean with dry bandages (A-III)Maintain good personal hygiene (Bathing, hand washing) (A-III)Avoid reusing/sharing personal items that have contacted infected skin (A-III)Environmental hygieneFocus on high-touch surfaces (counters, door knobs, toilet seats) that come into contact with bare skin (C-III)Commercial cleaners/detergents used according to instructions on label for that surface (C-III),MRSA Guidelines: Recommendations for management of recurrent MRSA SSTIs,Consider decolonization if:Recurrent SSTI despite optimizing wound care and hygiene measures (C-III)Ongoing transmission among close contacts despite optimizing wound care/hygiene measures (C-III)Decolonization should be in conjunction with ongoing reinforcement of hygiene measures,MRSA Guidelines: Recommendations for management of recurrent MRSA SSTIs (Con,Decolonization optionsNasal decolonization with mupiricin BID for 5-10 days (C-III)Mupiricin as above and topical body decolonization with skin antiseptic (chlorhexidine) 5-14 days or dilute bleach baths (1 teaspoon per gallon of water or cup per tub or 13 gallons of water) given for 15 minutes twice weekly for 3 months (C-III),MRSA Guidelines: Recommendations for management of recurrent MRSA SSTIs (cont),Note: Oral antimicrobial therapy for active infection only, not decolonization (A-III)Oral agent plus rifampin (if susceptible) may be considered for decolonization if infections recur despite measures mentioned aboveSurveillance cultures following decolonization regimen not routinely recommended in absence of active infection (B-III),MRSA Guidelines: Recommendations for management of recurrent MRSA SSTIs (cont),MRSA Guidelines: Adults with Infective Endocarditis, Prosthetic Valve,Early evaluation for v