Potential Conflicts of Interests

Transcription

1 Potential Conflicts of Interests Research Grants Agency for Healthcare Research and Quality Akers Bioscience, Inc. Pfizer, Inc. Scientific Advisory Boards Pfizer, Inc. Cadence Pharmaceuticals Kimberly Clark Consult Pfizer, Inc.

2 Dong HE et al. Arch Intern Med. 2011;171(1):18-22 Khan AR et al. Clin Infect Dis Nov 15;51(10):

3 Summary of Findings Most recommendations are based on level III evidence Such as expert opinion, clinical experience, descriptive studies, or reports of expert committees Recommendations based on data from at least 1 randomized controlled trial Range 16 to 23% Conclusions These findings highlight the limitations of current clinical infectious diseases research that can provide high-quality evidence. Until more data from well-designed controlled clinical trials become available, physicians should remain cautious when using current guidelines as the sole source guiding patient care decisions.

4 96 recommendations and findings, 29 pages, 294 references, 13 authors Key points Hospital-acquired, ventilator-associated, and health-care associated pneumonias (HAP, VAP, and HCAP) all carry similar and significant risk for multidrug resistant pathogens. (Think Pseudomonas and MRSA.) Initial treatment should therefore be very broad spectrum to ensure that all pathogens are covered. Once a pathogen is identified and the patient is improving, antibiotics should be de-escalated.

5 Do Guidelines Need Testing? They are, after all, Evidence Based!

6 Do Guidelines Need Testing? They are, after all, Evidence Based!

7 Do Guidelines Need Testing? They are, after all,. evidence graded Criteria for not evidence Evidence grades for ATS/IDSA pneumonia guidelines: Level I 24 (25%) of recommendations or findings Level II 58 (60%) of recommendations or findings Level III 14 (15%) of recommendations or findings

8 ATS/IDSA Pneumonia Guidelines Level I Recommendations 1. Routine use of effective infection control procedures. 2. Avoid intubation, as it increases the risk of ventilator-associated pneumonia. 3. Use non-invasive ventilation whenever possible. 4. Use an ET tube with continuous suction of subglottic secretions. 5. Keep head of bed elevated. 6. Enteral nutrition is preferred over parenteral nutrition. 7. Use a restrictive transfusion policy and leukocyte depleted red cells. 8. Keep blood glucose between 80 and 110 mg/dl. 9. Dose antibiotics correctly. 10. Monotherapy can be used if no resistant pathogens are identified. 11. Antibiotic courses can be shortened to as little as 7 days if the patient is doing well and the pathogen is not pseudomonas.

9 ATS/IDSA Pneumonia Guidelines Controversial Level I Recommendations 1. Routine use of effective infection control procedures. 2. Avoid intubation, as it increases the risk of ventilator-associated pneumonia. 3. Use non-invasive ventilation whenever possible. 4. Use an ET tube with continuous suction of subglottic secretions. 5. Keep head of bed elevated. 6. Enteral nutrition is preferred over parenteral nutrition. 7. Use a restrictive transfusion policy and leukocyte depleted red cells. 8. Keep blood glucose between 80 and 110 mg/dl. 9. Dose antibiotics correctly. 10. Monotherapy can be used if no resistant pathogens are identified. 11. Antibiotic courses can be shortened to as little as 7 days if the patient is doing well and the pathogen is not pseudomonas.

10 ATS/IDSA Pneumonia Guidelines Uninformative Level I Recommendations 1. Routine use of effective infection control procedures. 2. Avoid intubation, as it increases the risk of ventilator-associated pneumonia. 3. Use non-invasive ventilation whenever possible. 4. Use an ET tube with continuous suction of subglottic secretions. 5. Keep head of bed elevated. 6. Enteral nutrition is preferred over parenteral nutrition. 7. Use a restrictive transfusion policy and leukocyte depleted red cells. 8. Keep blood glucose between 80 and 110 mg/dl. 9. Dose antibiotics correctly. 10. Monotherapy can be used if no resistant pathogens are identified. 11. Antibiotic courses can be shortened to as little as 7 days if the patient is doing well and the pathogen is not pseudomonas.

11 ATS/IDSA Pneumonia Guidelines Unrelated Level I Recommendations 1. Routine use of effective infection control procedures. 2. Avoid intubation, as it increases the risk of ventilator-associated pneumonia. 3. Use non-invasive ventilation whenever possible. 4. Use an ET tube with continuous suction of subglottic secretions. 5. Keep head of bed elevated. 6. Enteral nutrition is preferred over parenteral nutrition. 7. Use a restrictive transfusion policy and leukocyte depleted red cells. 8. Keep blood glucose between 80 and 110 mg/dl. 9. Dose antibiotics correctly. 10. Monotherapy can be used if no resistant pathogens are identified. 11. Antibiotic courses can be shortened to as little as 7 days if the patient is doing well and the pathogen is not pseudomonas.

12 ATS/IDSA Pneumonia Guidelines Surviving Level I Recommendations 3. Use non-invasive ventilation whenever possible. 10. Monotherapy can be used if no resistant pathogens are identified. 11. Antibiotic courses can be shortened to as little as 7 days if the patient is doing well and the pathogen is not pseudomonas.

13 ATS/IDSA Pneumonia Guidelines Example of a Level II Recommendation The responding patient should have de-escalation of antibiotics, narrowing therapy to the most focused regimen possible on the basis of culture data.

14 ATS/IDSA Pneumonia Guidelines Example of a Level III Recommendation Initial empiric therapy for hospital-acquired, ventilatorassociated, and high risk healthcare-associated pneumonias should include: Antipseudomonal cephalosporin or Antipseudomonal carbapenem or b-lactam/b-lactamase inhibitor combination Antipseudomonal fluoroquinolone or Aminoglycoside Vancomycin or Linezolid

15 ATS/IDSA Pneumonia Guidelines Example of a Level III Recommendation Initial empiric therapy for hospital-acquired, ventilatorassociated, and high risk healthcare-associated pneumonias should include: Antipseudomonal cephalosporin or Antipseudomonal carbapenem or b-lactam/b-lactamase inhibitor combination Noncompliance is common... Antipseudomonal fluoroquinolone or Aminoglycoside Vancomycin or Linezolid

16 Improving Medicine through Pathway Assessment of Critical Therapy in Healthcare Associated Pneumonia (IMPACT-HAP)

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18 IMPACT HAP Kett DH et al. Lancet Infect Dis. 2011: 11;

19 Factors Associated with Guideline Compliance: Understanding Prescribing Patterns Parameter Regression Coefficient Odds Ratio Exponential 95% Confidence Limit [Lower, Upper] Intercept [0.015, 0.192] Pre versus Post rollout of the education program (Yes/No) [1.122, 3.286] Previous antibiotic therapy (Yes/No) [1.201, 3.548] Presence of severe sepsis (Yes/No) [1.496, 6.384] Age (in years) [0.996, 1.027] Days already spent in ICU* (days) [0.999, 1.052] History of end stage liver disease (Yes/No) [0.069, 0.956] Kett DH et al. Lancet Infect Dis. 2011: 11;

20 IMPACT HAP: Primary and Secondary outcomes Compliant treatment (n=129) Non-compliant treatment (n=174) P value Survival through day 28 65% (3) 79% (4) Resource use, after pneumonia [days median (IQR)] Mechanical ventilation support 8 (3 15) 9 (2 18) 0.44 Length of stay in ICU 12 (7 22) 13 (5 20) 0.57 Length of stay in hospital 16 (9 28) 17 (10 26) 0.52 Kett DH et al. Lancet Infect Dis. 2011: 11;

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22 Guideline-compliant empirical treatment 28-day mortality Kett DH et al. Lancet Infect Dis. 2011: 11;

23 Conclusions Clinicians should critically review guidelines Our results further question the need for combination Gramnegative empirical treatment This study highlights that guidelines need to be validated Especially when elements that have, in large part, been based on expert opinion and retrospective studies Guidelines cannot replace sound clinical judgment and decisions individualized to the unique patient Clinicians individualize therapeutic decisions on factors such as the patient s clinical status, medical history and knowledge of the local antibiogram Because adherence with empirical treatment was associated with increased mortality, there should be a commitment to perform a randomized trial of future guidelines