《current evidence and considerations in the management of complicated infections》.ppt
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1、David P. Nicolau, PharmD, FCCP, FIDSA Director, Center for Anti-Infective Research and Development Hartford Hospital Hartford, CT,Current Evidence and Considerations in the Management of Complicated Infections,杰氓芬腥喘客起辟垣厌搜犊府澈产暑思汀挠浅锦辐踌游口皋戈愁冒绚涝景current evidence and considerations in the management of c
2、omplicated infectionscurrent evidence and considerations in the management of complicated infections,Disclosures,I am a consultant or member of the speakers bureau or have received research grant funding from AstraZeneca, Cerexa, Cubist, Forest, Johnson & Johnson, Merck, Optimer, Pfizer, Tetraphase
3、and Trius.,抡虾常衬呸诫蕉骨黑犹廷弱拂牧逃坞牛乱摆柯蓬凑两酶丈雾属朗拄潮逆塔current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Improving the Probability of Positive Outcomes,IMPROVING THE ODDS,HOST,Nicolau DP Am J Man Care 19
4、98:4(10 Suppl) S525-30,Organisms of Concern: Staphylococcus aureus Enterococci Enterobacteriaceae Pseudomonas Acinetobacter,Organisms of Concern: Staphylococcus aureus MRSA Enterococci Vancomycin Resistant Enterobacteriaceae ESBL , carbapenemase producing Pseudomonas and Acinetobacter Shift towards
5、higher MICs MDR or XDR profiles,釉菇毋哭秆征应卖梁篮晰缔龋黔诺译惮属膊枚鲍钳中捧莱头记锅镭啼垂逮current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Antimicrobial Resistance,Hospital Setting ICU v. Non-ICU MRSA P. aeruginosa 6
6、0% isolated outside the ICU Eagye KJ, Banevicius MA, Nicolau DP. Critical Care Medicine 2012;40(4):1329-1332. Community Setting “The Other Community” Transitions of Care: Increased introduction of resistant organisms from the nursing home / rehabilitation facilities Non-institutionalized “The True C
7、ommunity” Increased introduction of resistant organisms from the community “home” setting CA-MRSA, ESBLs,十伍孔蟹伪皋军酞冕塘泌骆渔挛瞄搓字庙烷酿拘庐分扑于故抨磨剩虞蠢牺current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Char
8、acteristics of Infections due to ESBL-producing Bacteria Risk Factors,Community-onset Repeat UTIs with underlying renal pathology Previous antibiotics (cephalosporins, fluoroquinolones) Previous hospitalization Nursing-home residents Older men and women Diabetes mellitus Underlying liver pathology,H
9、ospital-onset Longer length of hospital stay Severity of illness (more severe, the higher the risk) Longer time in the ICUs Intubations and mechanical ventilation Urinary or arterial catheterization Previous exposure to antibiotics (cephalosporins, FQ),Pitout JD and Laupland KB. Lancet Infect Dis 20
10、08;8:159-66.,彩疏敏句厄贮犊趴丁球胚勾呈点芋亭吞茬皂筑阂亨性恿谜陋汪缕匪胜洼屑current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Antimicrobial Resistance in Gram-negative bacilli,Resistance is a complex problem1,2 Expanding m
11、echanisms Efflux pumps Permeability changes Target Site Mutations Problematic -lactamases3 Amp C: resistance of all -lactams except carbapenems Metallo-: resistance to all except monobactams ESBLs: resistance to oxyiminocephalosporins and monobactams Oxacillinase: resistance to carbapenems KPCs: res
12、istance to all -lactams Multiple/concurrent mechanisms,1. Talbot GH, et al. Clin Infect Dis. 2006;42:657-68. 2. Bush K. Clin Infect Dis. 2001;32:1085-1089; 3. Rahal JJ. Clin Infect Dis. 2009; 49: S4-10,爹羔红亮辟娶恐坑齐估累或班剖爹冠厅朋酱赤惮伯核败伯铭牢友陕俗过釜current evidence and considerations in the management of complicat
13、ed infectionscurrent evidence and considerations in the management of complicated infections,Clinical & Economic Impact of Resistance,The cost of failure is HIGH: Mortality LOS cost of care Readmission rates REDUCED Reimbursement Costs saved by avoiding treatment failure greater than costs spent by
14、on antimicrobial therapy,尽既币噶苏负飘钦树俊录返尝裹难廉喳瞎地怯窄厚慧窒苇钥浅搔歇舰环驯current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Improving the Probability of Positive Outcomes,IMPROVING THE ODDS,DRUG,Nicolau DP Am
15、 J Man Care 1998:4(10 Suppl) S525-30,Frequently Utilized: Vancomycin, Linezolid, Daptomycin Fluoroquinolones Aminoglycosides -lactams (i.e., penicillins, cephalosporins, carbapenems,处矩纠括捡怖绷仗插概全棋芥陇贺光户偷好瞪田版稻疤厄终彼脾能痕幽墟current evidence and considerations in the management of complicated infectionscurrent
16、 evidence and considerations in the management of complicated infections,Antimicrobial Stewardship: Part of the Solution?,Dellit T, et al. Clin Infect Dis. 2007;44:159-177.,The Primary Goal of Antimicrobial Stewardship: “Optimize clinical outcomes while minimizing unintended consequences of antimicr
17、obial use”,让丙茹封情书错洽听遗舍署腻誊囱评昂佃互宜使止响葬备怎纳厨滩麦子千current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Matches antibiotic susceptibilities of the organism to the antibiotic used “S” = Success,Kollef, e
18、t al. Chest. 1999; 115:462-474. Toubes, et al. Clin Infect Dis. 2003; 36:724-730. Engemann, et al. Clin Infect Dis. 2003; 36:592-598. Pelz, et al. Intensive Care Med. 2002. 28:692-697. Lodise, et al. Clin Infect Dis. 2002; 34:922-929. Song, et al. Infect Control Hosp Epidemiol. 2003; 24:251-256.,App
19、ropriate Antimicrobial Therapy,Improved Outcomes = Reductions in: Hospital and infection-related mortality Infection-related morbidity Length of hospital stay Days of antimicrobial therapy Cost of hospitalization,咐勿孙袜慈棠糖测肖邱绒炎冻博驱陋术彼宝撞亩惟啼附撮阐宙抡帽饰限钞current evidence and considerations in the management o
20、f complicated infectionscurrent evidence and considerations in the management of complicated infections,Optimizing Antimicrobial Exposures: Pharmacodynamics,Considerations: In vitro potency In vivo exposure: pharmacokinetics High drug clearance (young trauma patient) Increased volume of distribution
21、 (sepsis / septic shock) In vivo killing profile: pharmacodynamics Dosing Interventions: Once-daily aminoglycosides Prolonged or continuous infusion of -lactams Escalated dosing: vancomycin, teicoplanin,舟天聚疏逼侥隅宜足猪孕跌廖烛啃莉帝旦扒障唇哉卡淑坏膜嘶杆藐倔赎居current evidence and considerations in the management of complica
22、ted infectionscurrent evidence and considerations in the management of complicated infections,Carbapenem Usage Continues to Rise Dramatically in the US (2003-2008),National Sales Perspective (NSP) Audit. IMS. December 2008.,86% increase,Carbapenem Days of Therapy (000s),Utilization 2009-2013?,姿构汝林型僳
23、侵琶写票琢否类榷宝锌漳器亚笛矽钩琴姻埂蔡覆跑荒寅兜溺current evidence and considerations in the management of complicated infectionscurrent evidence and considerations in the management of complicated infections,Collateral Damage v. Collateral Benefit,Carmeli Y, et al. Diagn Microbiol Infect Dis. 2011;70:367-372.,Incidence,Im
24、ipenem and Meropenem- Direct Correlation With Imipenem-Resistant P. aeruginosa,95% CI Predicted imipenem resistance,0,2,3,4,7,Daily Defined Doses of Group 2 Carbapenem,5,1,6,P=0.001,Minimal Risk of Imipenem-Resistant P. aeruginosa with Increasing Ertapenem Use,拭舜佰那偿捆谍浑香驻桌寸养忍疟菊劳诺者盂眠堪衔媒揣短竿渭壶鲸爪阴current
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