Cap2015
- 1. Community-Acquired Pneumonia Eric Mortensen, MD, MSc, FACP
- 2. Community-Acquired Pneumonia (CAP) • Eighth leading cause of death in the U.S. • Leading infectious cause of death • Since 1950 mortality has been stable or increasing • Increased incidence with aging of the U.S. population
- 3. Impact of CAP • “More than 1.2 million Americans- roughly equivalent to the population of Dallas- were hospitalized for pneumonia in 2006, making this lung infection the most common reason for admission to the hospital other than for childbirth…” AHRQ News and Numbers July 2, 2008
- 4. Case Presentation • 72 year old male • C/O cough and fever/chills • Past medical history significant for – Stroke – Chronic kidney disease • Lives with wife at home
- 5. Physical Exam Findings • Pulse 110 • Respiratory rate 32 • Blood pressure 150/72 • Temperature 39.2o C • Confused
- 6. Labs • Lab results – BUN 45 – Partial pressure of arterial oxygen 58 mm Hg
- 8. Severity of Illness Scores • Pneumonia severity index (PSI) – 20 variables • CURB-65 – Confusion – Urea > 20 – Respiratory rate > 30 – Blood pressure, systolic < 90 or diastolic < 60 – Age > 65
- 9. Site of Care Decision • PSI – Broken into five classes – Classes I and II outpatient treatment unless other mitigating factors • CURB-65 – 0-1 factors outpatient treatment – 2 factors medicine wards – >3 consider ICU admission
- 10. Severity of Illness • Pneumonia severity index class – Class V • CURB-65 – Confusion – Urea > 20 – Respiratory rate > 30 – Blood pressure SBP < 90 or DBP <60 – Age > 65
- 11. Definition of Severe CAP • Minor criteria – Respiratory rate > 30/min – PaO2/FiO2 < 250 – Multilobar infiltrates – Confusion – BUN > 20 mg/dl – Platelet < 100k – Temp <36o C – Hypotension requiring fluid resuscitation • Major criteria – Invasive mechanical ventilation – Septic shock with need for vasopressors
- 12. CAP or HCAP? • HCAP = health care associated pneumonia • Very controversial!!! • Potential criteria include: – Hospitalization > 2 days in preceding 90 days – Nursing home residence – Home infusion therapy – Home wound care – Family member with drug resistant pathogen – Chronic dialysis – Immunosuppression
- 13. Etiology of CAP • CAP is not a homogeneous condition – True community-acquired versus healthcare acquired e.g. nursing home • Pathogens not found in > 50% of cases
- 14. Most Common Etiologies Ambulatory Hospital Ward ICU S. pneumoniae M. pneumoniae H. influenzae C. pneumoniae Viruses S. pneumoniae M. pneumoniae H. influenzae C. pneumoniae Legionella Aspiration Viruses S. pneumoniae Legionella H. influenzae Gram (-) bacilli S. Aureus Viruses File T et al. Lancet 2003
- 15. Community-Acquired MRSA • Increasing number of cases identified • Defined as community-acquired if no hospitalization or procedure < 1 year • Usually sensitive to numerous antibiotics – clindamycin, bactrim, and doxycycline • Severe necrotizing pneumonia – Panton-Valentine Leukocidin gene – Survival < 20%
- 16. What is the most likely organism? Streptococcus pneumoniae
- 17. Clinical Practice Guidelines for CAP • ATS- 1993 and 2001 • IDSA- 1998, 2000, and 2003 • BTS- 1993 and 2001 • CIDS/CTS- 1993 and 2000 • CDC- 2000 • ATS/IDSA- 2007 Mandell,Clin Infect Dis, 2007. 44 Suppl 2: p. S27
- 18. Guideline Recommendations Empiric Outpatient Therapy • No significant risk factors for drug resistant S. pneumoniae (DRSP) – Macrolide – Doxycycline
- 19. Guideline Recommendations Empiric Outpatient Therapy • Has risk factors for DRSP or significant comorbid conditions – Anti-pneumococcal fluoroquinolone β-lactam + macrolide/doxycycline • Preferred- high dose amoxicillin or amoxicillin/clavulanate • Alternates- ceftriaxone, cefpodoxime, or cefuroxime
- 20. Risk Factors for DRSP • Age > 65 years ∀β-lactam or macrolide therapy within the past 6 months • Alcoholism • Medical comorbidities • Immunosuppressive therapy • Exposure to a child in day care Cambell, Clin Infect Dis 1998;26: 1188
- 21. Guideline Recommendations Empiric Ward Therapy ∀β-lactam + macrolide/doxycycline – Cefotaxime, ceftriaxone, ampicillin, ertapenem • Anti-pneumococcal fluoroquinolone alone
- 22. Guideline Recommendations Empiric ICU/SCAP Therapy ∀β-lactam + azithromycin or respiratory fluoroquinolone – Cefotaxime, ceftriaxone, ampicillin-sulbactam • If penicillin allergic – Fluoroquinolone + aztreonam
- 23. Guideline Recommendations Risk Factors for Pseudomonas • Antipseudomonal β-lactam + high dose ciprofloxacin or levofloxacin – Piperacillin-tazobactam, cefepime, imipenem, meropenem • Antipseudomonal β-lactam+ aminoglycoside+ azithromycin • Antipseudomonal β-lactam+ aminoglycoside+ ciprofloxacin or levofloxacin
- 24. Guideline Recommendations CA-MRSA • Addition of vancomycin or linezolid to empiric antimicrobial regime
- 25. What empiric antibiotic regime(s) should this patient be given? β-lactam + macrolide β-lactam + fluoroquinolone or Fluoroquinolone + clindamycin
- 26. Guideline-Concordant Antimicrobial Therapy and Mortality • 420 subjects hospitalized at 2 tertiary hospitals – 20% were initially admitted to the ICU – 30-day mortality was 9.8% • After adjusting for potential confounders the use of non-guideline concordant antibiotics was associated with increased mortality – Odds ratio 5.7, 95% CI 2-16 Mortensen et al. AJM, 2004; 117:726
- 27. β-Lactam vs β-Lactam–Macrolide Combination Treatment in CAP: A Randomized Noninferiority Trial Gain N et al. JAMA Intern Med. 2014
- 28. Antibiotic Treatment Strategies for CAP Postma DF et al. N Engl J Med 2015
- 29. 90-day Mortality by Azithromycin Use Odds ratio 0.73, 95% CI 0.70-0.76 Mortensen et al. JAMA 2014
- 30. Time to First Cardiac Event by Azithromycin Use Outcome OR 95% CI MI 1.17 1.08-1.25 Arrhythmia 0.99 0.95-1.02 Heart failure 1.01 0.97-1.04 Any CV 1.01 0.98-1.05 Mortensen et al. JAMA 2014
- 31. Azithromycin and Pneumonia • Azithromycin use associated with lower mortality but higher rate of MI – NNT to prevent 1 death- 21 – NNH to cause 1 MI- 144 – Net benefit: 7 deaths averted for each non- fatal MI Mortensen et al. JAMA 2014
- 32. Switching Antimicrobial Therapy • Switch from IV to PO – Continuation of similar antimicrobial coverage • Clinical stability criteria • Ability to tolerate antibiotics by mouth • Afebrile (<100o F) on two occasions 8h apart • Decreasing white blood cell count • Improving symptoms: cough, dyspnea and fevers
- 33. Early Switch for Patients with Bacteremic Pneumococcal CAP • 75 patients • Intervention to promote early switch of IV to PO antibiotic therapy • Mean Duration of IV Therapy- 3 days • LOS reduced by 2 days in study patients – 4 days versus 6 days • Clinical cure reported in 99% of patients Ramirez, JA et al. Arch Intern Med. 2001;161:848
- 34. Duration of Therapy • Very few studies have examined length of therapy • At least 5 days of therapy recommended • Levofloxacin – 750mg of levofloxacin for 5 days equivalent to 500mg for 10 days Dunbar, LM et al. CID. 2003;37:752
- 35. Procalcitonin (PCT) • Stimulated by bacterial endotoxin • Viral and localized infection have lower PCT levels than systemic infections • Autoimmune and neoplastic disease do not induce • Available at VA
- 36. PCT and Diagnosis Nyamande Int J TB Lung Dz 2006; 10: 510 P=0.0004
- 37. PCT and Antibiotics • RCT to examine whether PCT guidance associated with less antibiotic use • PCT strata – <0.1 Antibiotics strongly discouraged – 0.1-0.25 Antibiotics discouraged – 0.25-0.5 Antibiotics advised – >0.5 Antibiotics strongly recommended Christ-Crain AJRCCM 2006 174: 84
- 38. PCT and Antibiotic Discontinuation
- 39. PCT and Antibiotic Duration
- 40. PCT/CRP and Treatment Failure • Prospective cohort of 453 CAP patients – 18% treatment failures • CRP & PCT higher in failures – Day 1 • CRP: 13.6 vs. 23.2 • PCT: 0.5 vs. 1.5 – Day 3 • CRP: 4.5 vs. 12.1 • PCT 0.3 vs. 0.5 Menendez Thorax 2008;
- 41. At Time of Discharge or Soon After • Pneumococcal vaccination • Influenza vaccination • Follow up chest imaging
- 42. Pulmonary Malignancy after Pneumonia Mortensen et al. Am J Med 2010
- 43. Summary • Use CURB-65 for admission decisions • Use guideline concordant antibiotics • Treat for at least 5-7 days (not only IV) • Consider using PCT (when available) in addition to clinical status to guide treatment decisions
Editor's Notes
- #36: Pro-calcitonin is an endogenous pre-cursor of calcitonin.