New Developments in Community Onset Pneumonia
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This document discusses new developments in the treatment of community-onset pneumonia. It notes that mortality from pneumonia has declined due to pneumococcal vaccines, timely administration of appropriate antibiotics, and avoiding overtreatment in low-risk patients. Viruses are now recognized as a common cause of adult pneumonia. Procalcitonin levels may help identify patients at low risk of deterioration who need only extremely short courses of antibiotics. While healthcare-associated pneumonia is associated with drug-resistant pathogens and worse outcomes, inappropriate antibiotics alone do not fully explain increased mortality.
New Developments in Community Onset Pneumonia
- 1. New Developments in Community- Onset Pneumonia Richard G. Wunderink MD Northwestern University Feinberg School of Medicine Chicago, IL, USA
- 2. Conflicts of Interest • bioMerieux – investigator-initiated grant • Pfizer – data safety monitoring board • Accelerate Diagnostics • Curetis • Genmark • Nabriva • Arsanis Diagnostics companies
- 3. US Causes of Death 1 10 100 1000 Deathsper100,000population Pneumonia Tuberculosis Sepsis AIDS 20/100K Pediatric Conjugate Vaccine Clinical use of penicillin starts Effective anti-TB drugs
- 4. US Causes of Death 1 10 100 1000 Deathsper100,000population Pneumonia Tuberculosis Sepsis AIDS 20/100K CMS Public reporting/Pediatric ConjugateVaccine Clinical use of penicillin starts Effective anti-TB drugs
- 5. Paradigm change #1: Outcome of many critical illnesses, including CAP, is determined by the timely provision of appropriate antibiotic(s)
- 6. Time to First Antibiotic Dose in Septic Shock Kumar, Crit Care Med, 2006 7.6%/hr increase in mortality
- 7. ARDS Prevention Strategies: Appropriate Antibiotics Levitt JE and Matthay MA. Critical Care 2012;1:223 Septic Shock Pneumonia Iscimen et al, Crit Care Med 2008;36:151 8- 1522 Kojicic et al Crit Care 2012;16:R46
- 9. What is (are) the correct antibiotic(s)?
- 10. What is (are) the correct antibiotic(s) in the era of antibiotic stewardship?
- 11. JAMA, 2014
- 12. JAMA, 2014
- 14. July 14, 2015
- 15. CDC Etiology of Pneumonia in the Community (EPIC) Study Both children (< 18 years) and adults 4 sites: Chicago, Nashville, Memphis, Salt Lake City January 1, 2010 – June 30, 2012 2320 adults with radiographic pneumonia Objective: Determine US population-based incidence and etiology of CAP
- 17. Am J Respir Crit Care Med, 2015 319 patients with clinically suspected CAP in 4 EDs
- 18. 87% prior to antibiotics CDC EPIC Diagnostic Algorithm
- 19. CDC-EPIC Etiology of CAP: Etiology Results 77 27 10 11 18 64 0 10 20 30 40 50 60 70 80 90 Pediatric Adult Percentofpatients Viral Bacterial None
- 20. Only 52/2320 (2%) of adults enrolled in EPIC died Slightly higher in eligible, un- enrolled patients (4% at most)
- 21. Trends in Adult Community- Acquired Pneumonia Smith et al, JAMA Int Med, 2014 EPIC
- 23. 3rd Gen Cephalo Aminoglycoside B-lactam+Macro Cephalo+Macro Quinolone Treatment Outcomes Data Gleason, Arch Intern Med, 1999
- 24. Macrolide Combination Therapy 0 2 4 6 8 10 Ceftriaxone Other Ceph Penicilln Quinolone 6.31 5.11 8.15 4.94 2.76 2.16 2.46 2.91 Mortality(%) Monotherapy Macrolide Combination p < 0.0001 p < 0.05 Brown, Chest, 2003 18,500 16,000 4,500 1800
- 25. Presumption of proponents of narrow-spectrum therapy e.g. β-lactam monotherapy, is that S. pneumoniae is the overwhelming cause of CAP
- 26. EPIC – Adult Pathogen Detections 0 20 40 60 80 100 120 140 160 180 200 HRV Flu S. pn. HMPV RSV PIV G. ng.* CoV M. pn. S. au. AdV Leg. Strep sp. Other† 115/2320 (5%) S. pneumoniae
- 27. Changing Etiology of CAP PCV7
- 29. CAP-START Postma et al, NEJM, 2015
- 30. CAP-START Primary Endpoint : 90 Day Mortality Postma et al, NEJM, 2015
- 31. CAP-START Endpoints 9 8.8 11.1 6.1 8.8 3.7 0 2 4 6 8 10 12 90-DayMortality Add Abs for failure % B-Lactam BL/Macro Quinolone Postma et al, NEJM, 2015
- 32. JAMA Intern Med 2014 TCS difference at 7 days – 7.6% (95%CI:-0.8 to 16, p = .07) HR PSI IV = 0.81 (0.59-1.10) HR CURB65 >2 = 0.80 (0.61-1.06) ICU transfer: 3 (Legionella) vs. 0 Death 2 (Mycoplasma) vs. 0 Significantly more readmissions
- 33. Viruses are a common cause of adult CAP Paradigm Change #2
- 34. EPIC – Pathogen Detections 0 20 40 60 80 100 120 140 160 180 200 HRV Flu S. pn. HMPV RSV PIV G. ng.* CoV M. pn. S. au. AdV Leg. Strep sp. Other†
- 36. RCT of PCT in LRTI Christ-Crain, Lancet, 2004
- 37. Admission Procalcitonin in EPIC < .25 ng/dl, 1042, 59% > .25 ng/dl, 728, 41%
- 38. Admission Procalcitonin in EPIC Viral 18% Unknown 36% Atypical 2% Bacterial 2% Bacterial 7% Atypical 2% Unknown 25% Viral 8% < .25 ng/dl> .25 ng/dl
- 39. Antibiotics in CHF Admissions Maisel et al, Eur J Heart Fail, 2011
- 40. Antibiotics in CHF Admissions Maisel et al, Eur J Heart Fail, 2011
- 41. Phase III RCT of Daptomycin vs. Ceftriaxone in CAP • Daptomycin subsequently found to be inactivated by pulmonary surfactant • Essentially placebo- controlled study of ceftriaxone • Re-analyzed based on whether received prior antibiotic dose – usually cephalosporin 60 65 70 75 80 85 90 95 All Prior No Prior 79.4 90.7 75.4 87.9 88 87.8 ClinicalSuccess(%) Daptomycin Ceftriaxone Pertel, Clin Infect Dis, 2008 Clinically Evaluable
- 42. It is OK to avoid or use ultra-short course antibiotics for some suspected CAPs Paradigm Change #3
- 43. 10 days 5 days • Antibiotic of physician’s choice • Placebo after 5 days 10 days 5 days Higher readmissions in 10-day treatment also Sept 2016
- 45. Epidemiology Of HCAP Culture-positive cases from large database 0 5 10 15 20 25 30 MRSA Pseudomonas Acinetobacter Enterics 8.9 17.1 1.6 21.3 26.5 25.3 2.6 25.8 22.9 18.4 2 19.8 14.6 21.2 3 26.6 CAP HCAP HAP VAP Kollef, Chest, 2005 %ofisolates
- 46. 7 22.6 37.8 4 9.9 19.8 5 20.1 32.7 0 5 10 15 20 25 30 35 40 LOS 30-Day 90-Day GC-HCAP GC-CAP Non-GC Mortality p = 0.001 p = 0.001 p = 0.001
- 47. EPIC Adult Exclusions Recent hospitalization 30 days for immunocompetant 90 days for immunosuppressed Functionally dependent nursing home patients Tracheostomy or PEG Cystic Fibrosis Severe immunosuppression Language barrier to consent
- 48. EPIC: Severe Immunosuppression Cancer with neutropenia Solid organ or stem cell transplant within 90 days Graft vs. Host Disease or Bronchiolitis obliterans HIV with CD4 < 200 mm3
- 49. EPIC – Pathogen Detections 0 20 40 60 80 100 120 140 160 180 200 HRV Flu S. pn. HMPV RSV PIV G. ng.* CoV M. pn. S. au. AdV Leg. Strep sp. Other† 7/2320 (0.3%) Pseudomonas 38/2320 (1.6%) S. aureus 115/2320 (5%) S. pneumoniae
- 50. CAP-Drug Resistant Pathogens 618 36% 219 57120 162 74 286 14 79 5% 22 77 Unknown S. pneumoniae Other Strep MSSA H. flu/Morax Atypicals GNB - sens GNB - resist Pseudo Other Nonferm MRSA Shindo, Am J Respir Crit Care Med, 2013
- 51. Independent Risk Factors for Pneumonia Secondary to: CAP-DRP MRSA Hospitalization > 2 days in previous 90 days Hospitalization > 2 days in previous 90 days Use of antibiotics in previous 90 days Use of antibiotics in previous 90 days Immunosuppression Chronic hemodialysis in previous 30 days* Non-ambulatory status Prior MRSA colonization* Tube feedings Congestive heart failure* Gastric acid suppression Gastric acid suppression * MRSA- specific risk factors Shindo, Am J Respir Crit Care Med, 2013
- 52. 2/12
- 53. Gross Findings: The Lung
- 54. Wunderink RG, Waterer GW. N Engl J Med 2014;370:543-551.
- 55. Risk for CAP-Drug Resistant Pathogens 439 122 57 20 25 32 12 9 32 0 50 100 150 200 250 300 350 400 450 500 <=1 2 >=3 CAP-DRP Risk Factors Negative MRSA Other CAP-DRPs Shindo, Am J Respir Crit Care Med, 2013
- 56. Treatment Response for Patients with < 1 Risk for CAP-DRPs 2.1 10.2 13.2 9.7 0 2 4 6 8 10 12 14 CAP Mono β-lactam Broad Spec Inappropriate Mortality Empirical Treatment p = 0.00001 284 380 266 72 Shindo, Am J Respir Crit Care Med, 2013
- 57. Paradigm Change #4: Should have good reasons to not treat with traditional CAP drugs CAP-DRG make up 13.6% of all CAP Increased mortality in HCAP is likely not due to inappropriate antibiotics alone
- 58. Summary Falling CAP mortality rates can result from: Pneumococcal conjugate vaccine Early traditional CAP antibiotics Avoiding overtreatment of patients at low risk for DRPs Viral CAP is much more common than previously believed Greater availability of multiplex RVPs Procalcitonin may identify patients at low risk for deterioration with extremely short course antibiotics
- 59. “Not everything that counts can be measured and not everything that can be measured counts.” Albert Einstein