MDR-西班牙讲稿.ppt

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Click to Edit Master Title Style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,Haga clic para cambiar el estilo de ttulo,Haga clic para modificar el estilo de texto del patrn,Segundo nivel,Tercer nivel,Cuarto nivel,Quinto nivel,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Clique para editar o estilo do ttulo mestre,Clique para editar os estilos do texto mestre,Segundo nvel,Terceiro nvel,Quarto nvel,Quinto nvel,*,MDR Gram positives in VAP/HAP,What do you expect to hear?,Is,ORSA VAP,an,important,challenge,?,Whats,new,on,ORSA,microbial,diagnosis?,How,therapy,&,organisms,affect,outcomes,?,Considerations,regarding,optimal,therapy,New,paradigm,S.aureus,The Most Frequent Isolate in EPIC Study,Vincent JL,et al.JAMA 1995;274:639-644.,Vincent JL.,Int,Care Med,2000;26:S3-S8.,MRSA prevalence is a serious problem in Europe,Rates of hospital Staphylococcus aureus isolates that are methicillin-resistant,based on samples from inpatient,outpatient,and ICU patients.,Adapted from European Antimicrobial Resistance Surveillance System EARSS interactive database results(2),ETIOLOGY OF VAP:Results of EU-VAP/CAP Study*,*,Endorsed by ESICM,PATHOGENS BY COUNTRY,Golan Y,et al.,abstract,44,th,Annual Meeting of the IDSA.Toronto.October 12-15,2006.,MIC(,g/mL,),%Isolates,MIC Creep Among Vancomycin-sensitive Strains of MRSA,In vitro,comparison of vancomycin MICs between 2002 and 2005 at New England Medical Center,A dramatic increase in MICs for MRSA bloodstream isolates,0,10,20,30,40,50,60,0.25,0.5,1,2,2002,2005,Vancomycin MICs and MRSA Bacteremia,414 cases bacteremia,Mortality,Vanco,Tx,with MIC2=6.39,Inappropriate Initial Empiric Therapy(IIET)=3.62,Shock=7.38,High(,incl,Pneumo,)=3.6 or Intermediate Risk=2.18,Steroids=1.85,Ultimately=10.2 or rapidly fatal underlying disease=1.81,Age=1.02/year,Soriano,Clin,Infect,Dis,2008,Vancomycin MIC and Clinical Cure of MRSA Infections,Renal insufficiency also significant risk for clinical failure,Success decreased approx 20%for every 10 ml/min decrease in,CrCl,Moise-Broder,CID,2004,MRSA bloodstream infection respond poorly to,vancomycin,Susceptibility breakpoint lowered to 15 mcg/,mL,did not improve outcomes troughs,Vancomycin,MIC=1.5 mg/L associated with Failure(RR 2.4),p,=0.05,Lodise,et al,Antimicrob,Ag,Chemother,2008;52:3315,Inadequate Antimicrobial Therapy Associated With Higher Mortality,Bloodstream infections,NP/VAP,1.,Ibrahim EH et al.,Chest.,2000;118:146-155.,2.,Alvarez-,Lerma,F et al.,Intensive Care Med.,1996;22:387-394.,3.,Rello,J et al.,Am J,Respir,Crit,Care Med.,1997;156:196-200.,1,2,3,Distribution,of S.,aureus,in VAP,Class 1-MV 7d,No Abs*,Class 2-MV,7d,+Abs,Class 3-MV,7d,No Abs,Class 4-MV,7d,+Abs,Rello,J,et al.Am J,Respir,Crit,Care Med 1999;160:608-613.,*,Antibiotics in previous 15 days,Ventilator“Bundles”and MRSA VAP,Primary focus of bundles is on,stomach,as source of pneumonia,Elevating Head of Bed(HOB),GI prophylaxis,Unlikely to play a role in MRSA VAP because source is,nasal,(?skin)colonization,*P,250,MRSA,Pseudomonas with initially,inappropriate,Tx,H.influenzae,MSSA,Pseudomonas with,Appropriate initial,Tx,Effect of Microorganism and Initially,Appropriate Antibiotics on VAP Resolution,Vidaur,Chest 2008,Treatment Decision Tree for VAP,Suspected VAP,Microbiological,investigation,Empiric antibiotics,based on risk factors,Cultures and Gram stain,G+stain if MRSA,start anti-MRSA coverage,G-stain if Acinetobacter,start carbapenem,if Pseudomonas,start 2 anti-Ps agents,If none of above,start antibiotics and consider local epidemiology,Rello J and E Diaz.,Crit Care Med,.2003:31;2544-2551.,Re-assess 48,-72,hours,Glycopeptides,in VAP&,Mortality,Matched,Cohort,Study,Rello,et al.CCM 2005;33:1983-1987,High Dose Vancomycin in MRSA VAP,All patients dosed at 15 mg/kg bid,Actual,extrapolated,or calculated troughs,2/3 had troughs 20,g/ml for all(RR 2.82),Only duration of,vanco,14 days if vasopressor use excluded(RR 3.33),p,=0.002,Jeffres,et al,Clin,Ther,2007,Continuous Infusion Vancomycin,RCT 119 patients,48%pneumonias,10%less pneumonia in continuous group,20%CNS,60%with MIC=2,Trough 10-15 in intermittent,AUC,24,685 in failures,20%,nephrotoxicity,Only with other,nephrotoxins,Wysocki,AAC,2001,Vancomycin Treatment of MRSA VAP,Initiation,Dosing,Rello,CCM 2005;33:1983,OR=0.22,(CI 0.05-0.8)p=0.03,22.7%,N=16,N=53,RELLO J et al.AJRCCM 1994;150:1545 GONZALEZ C et al.CID 1999;29:1171,OSSA+CLOXA,ORSA+VANCO,ORSA+VANCO,OSSA+VANCO,OSSA+CLOXA,50,25,%MORTALLITY,2.6,54.5,50,47,0,RELLO 94,GONZALEZ 99,EFFECTS OF LUNG PENETRATION,OSSA AND ORSA,Failure of Vancomycin Therapy in MRSA Pneumonia,Penetration,Inadequate serum levels,Bacterial clearance,Rising MICs,AgrII,polymorphism,Toxin production,Never proven to be an adequate pneumonia drug,Linezolid Versus Teicoplanin for Gram-Positive Infections in Critical Care,MRSA,methicillin-resistant,Staphylococcus aureus,.,Adapted from Cepeda JA,et al.,J Antimicrob Chemother.,2004;53:345-355.,P,=NS,P,=NS,P,=0.002,(71/90),(67/92),(49/70),(45/68),(23/45),(8/43),VAP,ventilator-associated pneumonia.,Adapted from,Kollef,MH,Rello,J,et al.,Intensive Care Med.,2004;30:388-394.,Clinical Cure Rate in VAP Patients,:Linezolid Versus Vancomycin,Vancomycin,Linezolid,P,=0.07,P,=0.02,P,=0.06,(n=434),(n=214),(n=179),(n=70),P,=0.01,Retrospective analysis of 2 randomized,double-blind studies,Linezolid in VAP subgroup,(n=340),Population,P=0.028,Kollef M,Rello J,et al,.Intensive Care Med 2004;30:388-394.,Clinical cure(%),P=0.05,NS,HAP MRSA Pneumonia,:Linezolid Versus Vancomycin,Adapted from,Wunderink,R,Rello,J,et al.,Chest.,2003;124:1789-1797.,Retrospective analysis of 2 randomized,double-blind studies,Linezolid,is,very,cost-effective,versus Vancomycin,The cost per QALY of,linezolid,versus vancomycin is well below the most stringent limit of cost-effectiveness ratio,In higher risk patients Linezolid is even more cost-effective,*,Quality,adjusted,Life,Year,saved,20 000 per QALY,Grau S,et,al.,J,Chemother,.2005;17:455.,Athanassa,et,al.,Eur,Respir,J 2008;31:625-32,Methicilin,Resistance,Impact,on,Mortality,in,S.,aureus,VAP,New Paradigm-Tarragona StrategyKey points for adequate therapy,Getting Right First Time Local,Anticipation:Immediate Start,Hard:Adequate Dose,Excellence:Good Penetration,Bodi,et al,.,Clin,Microbiol,Infect 2001;7:32-33.,Sandiumenge,et al.Intensive Care Med 2003;29:873,NEW PARADIGM on MANAGEMENT of VAP-When S.,aureus,is a consideration,2 Main Risk Factors for MRSA(,5 day in hospital+Prior Antibiotics)?,or,Documented,MRSA,Colonization,CULTURE,S,MSSA,OXACILLIN(if not,betalactam,allerg,y,),MRSA,OK,Continue,Renal impairment or,Nephrotoxics,use,Severe,Sepsis o,r Age 65 years,YES,EMPIRIC THERAPY for MRSA,VANCO/TEICO,NO,LINEZOLID,YES,CLINICAL RESPONSE,NO,If VANCO,-switch to LINEZOLID,If LINEZOLID-,add RIFAMPIN,?,add,VANCO,Continuous,infusion,?,Culture negative:,Stop RX,Discontinue VANCO,/,Use LINEZOLID,Conclusions,Inadequate,empiric,Rx,of ORSA NP&,bacteremia,increases,mortality,risk,;,other,sequela,include,increase,in,morbidity,LOS,and,cost,.,The,rising,incidence,of ORSA,requires,adequate,initial,Rx,to,avoid,severe,clinical,implications,.,Take-home messages,Empiric use of the most effective therapy for ORSA in todays ICU should be the standard of care,Optimal therapy for ORSA HAP is still not available.,Linezolid,should be used as first line therapy in patients with ORSA pneumonia.,Thank you,