Management of Serious MRSA Infections. DNA Staphylococcus aureus MRSA mecA gene Cell Membrane...

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Management of Serious Management of Serious MRSA Infections MRSA Infections
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Transcript of Management of Serious MRSA Infections. DNA Staphylococcus aureus MRSA mecA gene Cell Membrane...

  • Slide 1
  • Management of Serious MRSA Infections
  • Slide 2
  • DNA Staphylococcus aureus MRSA mecA gene Cell Membrane Enzymes: Abnormal Penicillin Binding Protein (PBP2a) -Lactam AntibioticsPenicillins,(Methicillin)Cephalosporins,Monobactams,Carbapenems, Staphylococcal Cassette Chromosome (SCC) MSSA
  • Slide 3
  • Chambers HF. Clin Microbiol Rev. 1997;10:781-791 MSSA MRSA PBP2a encoded by a mecA gene Located in a mobile genetic element, the Staphylococcal Cassette Chromosome mec SCCmec types I, II, III, IV, V SCCmec types II, III MSSA MRSA 1990s SCCmec type IV HA-MRSA CA-MRSA Genetics of Resistance Vandenesch F et al. EID.2003; 9:978 Jevons MP. Br Med J. 1961;1:124-125 Gillet Y et al. Lancet. 2002;359:753-759 Different genetic backgrounds PFGE: USA 300 PFGE: USA 100 1960s MRSA MRSA: Resistance
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  • PVL exotoxin MSSA MRSA 1960s MSSA MRSA 1990s HA-MRSA CA-MRSA Genetics of Virulence Vandenesch F et al. EID.2003; 9:978 Labandeira-Rey M et al. Science. 2007;315:1130-1133 MRSA: Virulence DNA LukSPV and LukFPV genes mecA gene PVL (+) strains More virulent strains Genes that encode for Panton-Valentin leukocidin toxin (PVL)
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  • Catheter Related Bacteremia Endocarditis Bone & Joint Infections Hospital-Acquired Pneumonia HA-MRSA Klevens M et al. JAMA. 2007;298:1763-1771 MRSA: Clinical Manifestations CA-MRSA Cellulitis Abscess Necrotizing fasciitis Necrotizing skin infection Septic thrombosis Necrotizing pneumonia Ventilator-Associated Pneumonia MRSA Infections Moellering RC Jr. Ann Intern Med 144:368, 2006 Bone & Joint InfectionsCatheter Related UTI
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  • UofL Guidelines for HAP/VAP 4. UofL Treatment Pathway 4. UofL Treatment Pathway 2. De-escalation of Therapy 2. De-escalation of Therapy 1. Selection of Empiric Therapy 1. Selection of Empiric Therapy 3. Duration of Therapy 3. Duration of Therapy
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  • Hospital-Acquired Infections Hospital-Acquired Infections Percent Mortality 0 20 40 60 80 100 Study 1 Study 2 Study 3 Study 4 4. Ibrahim EH et al. Chest. 2000;118:146-155 2.Rello J et al. Am J Respr Crit Care Med. 1997;156:196-200 3. Kollef MH et al. Chest. 1998;113:412-420 1.Luna C et al. Chest. 1997;111:676-685 Appropriate Empiric Therapy Inappropriate Empiric Therapy HAP/VAP: Empiric Therapy
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  • * Appropriate empiric therapy on day one * Empiric therapy based on likely organisms * Appropriate empiric therapy on day one * Empiric therapy based on likely organisms Correlation of Empiric Therapy with Patient Outcome Correlation of Empiric Therapy with Patient Outcome HAP/VAP: Empiric Therapy
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  • Alveolar Space Space 3. Aspiration of gastric content 3. Aspiration of gastric content 2. Inhalation 4. Hematogenous spread 4. Hematogenous spread 5. Inoculation 1. Microaspiration The etiology of VAP is closely related to the microbiology of the patients oropharynx The etiology of VAP is closely related to the microbiology of the patients oropharynx Likely Organisms HAP/VAP: Etiology
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  • Microbiology of the Oropharynx Normal Community Flora Resistant Nosocomial Flora 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Days after hospitalization Shift HAP/VAP: Etiology
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  • Normal Community Flora Resistant Nosocomial Flora 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Days after hospitalization Shift HAP/VAP: Etiology ATS/IDSA. Am J Respr Crit Care Med. 2005;171:388 HAP/VAP: Likely Organisms Group 1 Core Organisms Group 2 Core Plus Resistant Organisms
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  • HAP/VAP: Etiology ATS/IDSA. Am J Respr Crit Care Med. 2005;171:388 HAP/VAP: Likely Organisms Group 1 Core Organisms Group 2 Core Plus Resistant Organisms *Streptococcus pneumoniae *Methicillin-sensitive Staphylococcus aureus *Haemophilus influenzae *Moraxella catarrhalis *Escherichia coli *Klebsiella pneumoniae *Pseudomonas aeruginosa *Acinetobacter species *Citrobacter freundii *Enterobacter cloacae *Morganella morganii * Methicillin-resistant Staphylococcus aureus
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  • Normal Community Flora Resistant Nosocomial Flora Shift 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 Days after hospitalization Microbiology of the Oropharynx HAP/VAP: Etiology Late OnsetEarly Onset Risk Factors for Resistant Organisms
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  • Group 1: Core Organisms Group 1: Core Organisms Group 2: Core plus MDR Group 2: Core plus MDR 2. Prolonged Hospitalization ( > 7 days) Risk Factors for Resistant Organisms 3. Prolonged Ventilation (> 3 days) 4. Prior Antibiotic Use ( > 3 days) 5. Immunosuppression 1. Documented MDR colonization No Yes No Yes ATS/IDSA. Am J Respr Crit Care Med. 2005;171:388 HAP/VAP: Etiology
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  • Group 1: Patient with no RFRO Focus Antibiotic Therapy HAP/VAP: Empiric Therapy *Streptococcus pneumoniae *Methicillin-sensitive Staphylococcus aureus *Haemophilus influenzae *Moraxella catarrhalis *Escherichia coli *Klebsiella pneumoniae * Cephalosporins 3 rd Generation: Ceftriaxone * Penicillin/B-lactamase inhibitor: Ampicillin-sulbactam
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  • Group 2: Patient with RFRO ATS/IDSA. Am J Respr Crit Care Med. 2005;171:388 Broad Spectrum Antibiotic Therapy Vancomycin vs Linezolid Monotherapy vs Combination HAP/VAP: Empiric Therapy *Pseudomonas aeruginosa *Acinetobacter species *Citrobacter freundii *Enterobacter cloacae *Morganella morganii * Methicillin-resistant Staphylococcus aureus
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  • Days 0 10 20 30 40 50 NAP due to S. aureus: Kaplan-Meier Survival Curve NAP due to S. aureus: Kaplan-Meier Survival Curve Survival (percentage of patients) Survival (percentage of patients) 100 % 0 % Vancomycin Linezolid ITT S. aureus (n = 339) P = 0.131 Wunderink R et al. Chest. 2003;124:1789-1797 VAP: Empiric Therapy OR (95% CI) Age < 65 yr APACHE II score < 20 Single-lobe NAP 1.7 (1.0-2.9) 3.7 (2.0-6.9) 1.7 (1.0-2.9) 0.081 0.001 0.072 Predictors P value Linezolid therapy 1.7 (1.0-2.9) 0.068 Logistic Regression Analysis for Survival Logistic Regression Analysis for Survival
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  • Days 0 10 20 30 40 50 Survival (percentage of patients) Survival (percentage of patients) 100 % 0 % Vancomycin Linezolid ITT MRSA (n = 160) P = 0.025 Wunderink R et al. Chest. 2003;124:1789-1797 NAP due to MRSA: Kaplan-Meier Survival Curve NAP due to MRSA: Kaplan-Meier Survival Curve VAP: Empiric Therapy Predictors OR (95% CI) P value Logistic Regression Analysis for Survival Logistic Regression Analysis for Survival Linezolid therapy 2.2 (1.0-4.8) 0.050
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  • Clinical Cure (Percent of Patients) Linezolid Linezolid VancomycinVancomycin Patient Population VAP (n=434) 45 37 62 21 Clinical Cure Rates for Patients with VAP Clinical Cure Rates for Patients with VAP 0 20 40 60 80 Kollef MH et al. Intensive Care Med. 2004;30:388-394 G+ VAP (n=214) Sa VAP (n=179) MRSA VAP (n=70) P = 0.07 54 38 P = 0.02 49 35 P = 0.06 P = 0.001 HAP/VAP: Empiric Therapy
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  • Vancomycin & MRSA: S I R MRSA: Treatment Considerations MRSA: Treatment Considerations Moise-Broder PA et al. Clin Infect Dis. 2004;38:1700-1705. Clinical and Laboratory Standards Institute (CLSI); 2006. MIC 2 MIC 4-8 MIC 16 Susceptible (VS-MRSA) Intermediate (VISA or GISA) Resistant (VRSA) Vancomycin Susceptibility
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  • Vancomycin & MRSA: S I R MRSA: Treatment Considerations MRSA: Treatment Considerations R VRSA I VISA (GISA) S hVISA S MIC 2 ug/ml S MIC 1 ug/ml S MIC 0.5 ug/ml MIC 16 MIC 4-8 Allen M et al. IDSA Meeting 2008. HA-MRSA 124 21% 75% CA-MRSA 65% 124 35% 4%
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  • Vancomycin & MRSA: S I R MRSA: Treatment Considerations MRSA: Treatment Considerations R VRSA I VISA (GISA) S hVISA S MIC 2 ug/ml S MIC 1 ug/ml S MIC 0.5 ug/ml Vancomycin MIC 0.512 Treatment Failure 22% 37% 63% MIC 16 MIC 4-8 MRSA HAP/VAP Zervos M et al. IDSA Meeting 2008.
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  • Group 2: Patient with RFRO ATS/IDSA. Am J Respr Crit Care Med. 2005;171:388 Broad Spectrum Antibiotic Therapy Vancomycin vs Linezolid Monotherapy vs Combination HAP/VAP: Empiric Therapy *Pseudomonas aeruginosa *Acinetobacter species *Citrobacter freundii *Enterobacter cloacae *Morganella morganii * Methicillin-resistant Staphylococcus aureus
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  • Gram (-) rods: Combination Therapy To obtain synergy To prevent development of resistance To provide a broad-spectrum empiric regimen HAP/VAP: Empiric Therapy *Anti-Pseudomonal Beta-lactam: Cefepime, Piperacillin-tazobactam, * Aminoglycoside: Tobramycin *Quinolone: Cipro/Levo PLUS 2 nd Antipseudomonal Agent OR Meta-analysis: Monotherapy is not inferior to combination therapy in the empirical treatment of VAP Aarts MA. Crit Care Med. 2008 Jan;36(1):108-17
  • Slide 25
  • Group 2: Patient with RFRO *Anti-Pseudomonal Beta-lactam: Cefepime, Piperacillin-tazobactam, *Glycopeptide: Vancomycin *Oxazolidins: Linezolid PLUS Anti-MRSA Therapy * Aminoglycoside: Tobramycin *Quinolone: Cipro/Levo (+/-) 2 nd Antipseudomonal Agent OR HAP/VAP: Empiric Therapy Broad Spectrum Antibiotic Therapy
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  • UofL Guidelines for HAP/VAP 4. UofL Treatment Pathway 4. UofL Treatment Pathway 2. De-escalation of Therapy 2. De-escalation of Therapy 1. Selection of Empiric Therapy 1. Selection of Empiric Therapy 3. Duration of Therapy 3. Duration of Therapy
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  • De-escalation of Therapy Initial Empiric Therapy De-Escalation of Therapy De-Escalation of Therapy Positive Culture 1. Pathogen directed therapy according to C&S Negative Culture 2. No MRSA: Discontinuation of anti-MRSA therapy 3. No Pseudomonas: Discontinuation of combination therapy 5. Switch to oral antibiotic therapy 4. Discontinuation of combination anti-pseudomonal therapy Clinical Improvement
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  • De-escalation of Therapy Initial Empiric Therapy De-Escalation of Therapy De-Escalation of Therapy 280 Patients Patients treated for HAP/VAP 233 Patients Empiric therapy for HAP/VAP 198 Patients Candidates for de-escalation 85%
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  • UofL Guidelines for HAP/VAP 4. UofL Treatment Pathway 4. UofL Treatment Pathway 2. De-escalation of Therapy 2. De-escalation of Therapy 1. Selection of Empiric Therapy 1. Selection of Empiric Therapy 3. Duration of Therapy 3. Duration of Therapy
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  • Hospital-Acquired Pneumonia Short-course empiric antibiotic therapy for patients with pulmonary infiltrates in the intensive care unit Singh N et al. Am J Respr Crit Care Med. 2000;162:505-511 Duration of Therapy Clinical pulmonary infection score (CPIS)
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  • Clinical Pulmonary Infection Score (CPIS) NAP: Short Course Therapy 1. Temperature: 0 to 2 points 2. Blood Leukocytes: 0 to 1 point 3. Tracheal secretions: 0 to 2 points 4. Oxygenation, PaO 2 /FIO 2 : 0 to 2 points 5. Pulmonary radiography: 0 to 2 points 6. Progression of pulmonary infiltrate: 0 to 2 points 7. Culture of tracheal aspirate: 0 to 2 points
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  • Clinical Pulmonary Infection Score (CPIS) CPIS equal or < 6 ATB x 3 days CPIS > 6 CPIS 6 Singh N et al. Am J Respr Crit Care Med. 2000;162:505-511 NAP: Short Course Therapy ATB Use/Cost Superinfection LOS in ICU Mortality 3 days / $259 10 days / $640 9 days 15 days 14 % 38 % 13 % (30 days) 31 % (30 days).0001.04.01.06 Short Course Standard Care
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  • Candidate for Short Course Therapy Candidate for Short Course Therapy CPIS < 6 on day 0 and day 3 Short Course Therapy No severe sepsis or shock No immunosuppression Yes HAP: Duration of Therapy No bacteremia No other site of infection 16 Patients 280 Patients
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  • HAP: Duration of Therapy 8 days? 14 days? 21 days? 10 days? 4 days? For other patients consider discontinuation of antibiotics once documented clinical improvement Total duration of therapy of +/- 14 days for HAP/VAP due to Pseudomonas or Acinetobacter or MRSA Total duration of therapy of 4 days for patients that are candidates for short course therapy Recommendations
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  • UofL Guidelines for HAP/VAP 5. UofL Treatment Pathway 5. UofL Treatment Pathway 3. De-escalation of Therapy 3. De-escalation of Therapy 2. Selection of Empiric Therapy 2. Selection of Empiric Therapy 4. Duration of Therapy 4. Duration of Therapy 1. Clinical Diagnosis 1. Clinical Diagnosis
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  • Day 2/3: Evaluation for De-escalation of Therapy Results of cultures and sensitivity Discontinue MRSA therapy if cultures (-) for MRSA Discontinue combination therapy if cultures are (-) for Pseudomonas Day 0: Evaluation for Empiric Therapy Cultures Calculate CPIS Evaluate RFRO Start ATB: Group 1 Focus therapy vs Group 2 broad spectrum Day 4: Evaluation for Duration of Therapy Pathogen directed therapy according to C&S Candidate for short course therapy: 4 days Pseudomonas, MRSA, Acinetobacter: +/- 14 days Other patients: duration of therapy based on clinical response HAP/VAP: UofL Treatment Pathway