Community acquired pneumonia

1. Community acquired pneumonia Bharat Awsare MD FCCP Division of Pulmonary and Critical Care Medicine Assistant Professor of Medicine Director, Medical Intensive Care Unit Thomas Jefferson University Hospital

2. Pneumonias – Classification -Acute infection of parenchyma -Symptoms of infection -Acute infiltrate or auscultatory findings consistent with pneumonia Nosocomial Pneumonias

3. Atypical Classical Sudden onset of CAP High fever, shaking chills Pleuritic chest pain, SOB Productive cough Rusty sputum, blood tinge Poor general condition High mortality up to 20% in patients with bacteremia S.pneumoniae causative • Gradual & insidious onset • Low grade fever • Dry cough, No blood tinge • Walking CAP • Low mortality 1-2%; except in cases of Legionellosis • Mycoplasma, Chlamydiae, Legionella, Ricketessiae, Viruses are causative CAP – Two Types of Presentations

4. Scope of the problem • 5 million cases/year • 10 million office visits • 1 million admissions/year • 100,000 ICU admissions • Estimated cost: $12 billion* • Inpatient (20%) $10 billion • Outpatient (80%) $2 billion *Colice GL et al. Am J Resp Crit Care Med (2006)176:913-920.

5. Incidence of CAP per age (in 1000’s)

6. CAP mortality per age (in 1000’s)

7. Mortality in CAP • Most common cause of severe sepsis • 6th leading cause of death • Leading cause of death from infection • Mortality has not changed in 4 decades • Outpatient 1% • Inpatient 5-10% • ICU 20-40%

8. Age adjusted death rates www.cdc.gov/mmwr

10. Risk factors • Major • COPD/smoking • Alcoholism • Chronic heart disease • Diabetes • 1/3 patients previously healthy • Other risk factors • Poor dentition • Renal failure • Hepatic disease • CVA • Immunodeficiency • Malnutrition

11. Microbiology • * • Influenza A and B • Adenovirus • Respiratory syncitial virus • Parainfluenza 40-70% of patients with CAP have no organism identified (fastidious growth of S. pneumoniae, H. influenzae)

12. Modern methods to determine etiology of CAP • Adults admitted with CAP over 1 year • Microbiologic testing • Sputum culture • Blood culture • Nasopharyngeal sampling • Sputum samples analyzed by PCR • Nasal samples analyzed by PCR • Serologic testing for M pneumoniaeandChlamydophilapneumoniae, and viruses • Urine antigen assay for S pneumoniae, Legionella

13. Results • N = 184 • Organism identified in 124 (67%) • 35% of these had 2+ organisms • For complete sampling, organism identified in 89% • Sputum PCR increased yield over traditional methods

14. Bacterial and viral yields

15. Incidence of co-infections

16. Etiology in special situations • Alcohol, poor dental hygiene: anaerobes • Sick hunting dogs: blastomycosis • Bats, bird droppings: histoplasmosis • Travel to SW US: coccidiomycosis • Birds: Chlamydia psittaci • Rabbits: Francisellatularensis • Farm animals, parturient cats: Coxiellaburnetii(Q fever) • Post-influenza: S. aureus, S. pneumoniae, S. pyogenes, H. influenzae

17. H1N1 outbreak April 2009 • 61 million affected • 13,000 deaths • 90% hospitalizations, 87% deaths occurred in patients less than 65 • Obesity • Pregnancy • Asthma • Young age

18. Community acquired MRSA • New strain of MRSA (USA 300 strain) • Not traditional risk factors for MRSA • Often follow influenza viral infection • Influenza with bilateral cavitary pneumonia • Skin/soft tissue infection • Risk factors • Young age • Close living conditions • Skin contact, cuts/abrasions

19. Necrotizing pneumonia (CA-MRSA) Eur Respir J 2009; 34: 1470–1476

20. CA-MRSA virulence factors • Panton-Valentine leukocidin (PVL) gene • Skin/soft tissue infections • Severe cavitary pneumonia • Type IV mecA gene • Resistance to beta lactams/methicillin

21. CA-MRSA therapy • Antibiotics • Vancomycin (reports of poor outcomes with monotherapy*) • Linezolid • Anti-toxin • Clindamycin • Linezolid *Micek et al. Chest 2005(128):2732.

22. Assessment of severity • Physicians overestimate risk of death • Unnecessary admissions • Increased cost • Potential for morbidity related to hospitalization • Multiple tools available • PORT/Pneumonia Severity Index • CURB-65 • ATS/IDSA

23. PORT Pneumonia Severity Index

25. ED’s using PSI reduced rate of hospitalization in low risk groups NO DIFFERENCES IN MORTALITY

26. CURB-65 algorithm

27. CRB-65 algorithm

30. ATS/IDSA: site of care decisions • Severity scores should be used to identify patients for outpatient therapy • CURB-65 • PSI • Scores should always be supplemented by physician determination of other factors • Psychosocial factors • Support resources • Compliance • Ability to tolerate oral therapy • Failure of outpatient therapy

31. Laboratory testing (hospitalization) • Chest X-ray • CBC with differential • Electrolytes • BUN/creatinine • Glucose • Liver enzymes • Oxygen saturation • Gram stain/cultures of sputum (??) • Blood cultures (??)

32. Chest x-ray • Radiology + clinical scenario are gold standard for diagnosis • Not mandatory (outpatient) • Information provided • Extent of disease • Cavitation • Complications (effusion) • Alternate or co-existing diagnosis (neoplasm) • Information not provided • Causative organism

34. Chest Xray in CAP

35. Cavitary pneumonia

36. Parapneumonic effusion

37. CXR – PA and Lateral Views Lateral - RML PA - RML

38. Round Pneumonic Consolidation RLL, LLL RUL

39. Special Forms of Pneumonia PCP/ CMV

40. Empyema CT Empyema Empyema R Split pleura sign

41. Microbiologic testing • Utility for all CAP uncertain • False negatives • Not cost effective • Diagnosis may not affect outcome • IDSA/ATS recommendations • Severe CAP (ICU) • Optional for outpatient • Diagnosis uncertain • Structural lung disease • Pleural effusion

43. Biomarkers for CAP • Procalcitonin (available) • C-reactive protein (available) • Pro-adrenomedullin • Co-peptin • Natriuretic peptides • Cortisol • Pro-atrial natriuretic peptide • Coagulation markers Brar NK and Niederman MS, Ther Adv Respir Dis (2011) 61-78

44. Procalcitonin • Precursor of calcitonin • No hormonal effects • Increased with bacterial infection • Toxin mediated (lipopolysaccaride) • Cytokine mediated (IL-6, IL-1, TNF) • Cell mediated response mediated • Decreased with viral infection • Cytokine mediated (IFN-gamma) • Also increased with trauma, burns

45. Procalcitonin: Pros/cons • Pros • Helps reduce antibiotic duration • Helps antibiotic exposure • Helps convert to oral therapy • May help with early discharge • Cons • Inadequate accuracy to discriminate bacterial vs. viral infection • Accuracy too low to withhold therapy

46. Timing of antibiotics • Multiple studies show delayed antibiotics associated with increased mortality (Houck et al 2004, Meehan et al 1997) • 4 hour antibiotic was adopted as quality core measure • Implementation of 4 hours had problems: • Misdiagnosis of CAP* • Inappropriate antibiotics* • Antibiotic toxicity including C difficile *Kanwar et al. Chest 2007:1865-1869.

47. Timing of antibiotics • IDSA/ATS guidelines recommendation • First dose of antibiotics in ED (6-8 hrs) • Earlier antibiotics probably better with severe sepsis

48. Factors influencing antibiotics • Setting • Outpatient • Inpatient • ICU • Comorbidities • Risk factors for certain pathogens • Resistant pneumococcus • Resistant gram negatives • Pseudomonas • Community acquired MRSA

50. Monotherapy vs. combination therapy • Multiple recent studies show improved outcomes with combination therapy1-5 • Odds ratio of death with monotherapy ranged from 1.5-6x adjusted for severity • Benefit most in those with severe CAP • Benefit only seen when macrolides used6 1Waterer et al. Arch Int Med 2001(161):1837. 2Baddour et al. Am J Respir Crit Care Med 2004(170):440. 3Tessmer et al. J Antimicrob Chemother 2009(63):1025. 4Rodriguez et al. Crit Care Med 2007(35):1493. 5Restrepo et al.Eur Respir J 2009(33):153. 6Martin-Loeches et al. Intensive Care Med 2010(36):612.