community and hospital-acquired pneumonia

1. Community and Hospital-acquired Pneumonia David L. Paterson MD Division of Infectious Diseases

2. Contact details (412)-648-6478 patersond@dom.pitt.edu

3. Outline Classification of pneumonia Epidemiology – who gets pneumonia Pathogenesis Causative organisms Symptoms, signs and investigations Antibiotic treatment

4. Definition Pneumonia is infection of the gas exchanging (alveolar) compartment of the lung (that is, it is a lower respiratory tract infection) (Bronchitis is infection of the bronchial tree) (Tracheitis or pharyngitis are infections of the trachea or pharynx respectively)

5. Importance “Pneumonia is captain of the men of death” “Pneumonia is the old man’s friend” Industrialized countries – 3rd leading cause of death Estimated costs of $7 billion annually

6. Developing countries Pneumonia is a major cause of death in developing countries Neonatal pneumonia Pneumonia complicating childhood measles Pneumococcal pneumonia Pneumonia complicating HIV infection

7. Classification of pneumonia Why classify pneumonia? Different categories of pneumonia have different etiologies Pneumonia is usually treated empirically (that is, before the etiology is known) Different potential etiologies require different empiric treatments

8. Classification Pneumonia in immunocompetent patients Community-acquired pneumonia Hospital-acquired pneumonia (also called nosocomial pneumonia) Pneumonia in immunocompromised patients

9. Community-acquired pneumonia Frequently referred to as CAP CAP is pneumonia acquired outside of hospital in the immuno-competent host Does not include patients with aspiration pneumonia, bronchial obstruction or TB Nursing home patients Only 20% of patients with CAP require hospitalization

10. Hospital-acquired pneumonia Frequently referred to as HAP May also be referred to as nosocomial pneumonia HAP is pneumonia that occurs at least 48 hours after admission to hospital (earlier cases are initially misdiagnosed CAP) Is the second most common hospital-acquired infection

11. HAP in the ICU Pneumonia acquired in the intensive care unit (ICU) requires special consideration Many patients in ICU are mechnically ventilated These patients may develop ventilator-associated pneumonia (VAP)

12. Pneumonia in the immuno-compromised host Differentiated from CAP and HAP because the pathogens are different (however, immuno-compromised patients may also get the pathogens that occur in immuno-competent patients) Examples of immuno-compromise include HIV, iatrogenic immunosuppression (eg, in transplant recipients) and inherited disorders of the immune system

14. Pathogenesis of pneumonia Defense mechanisms for the lung How are these defense mechanisms affected?

15. Where is sterile, where is not Bacteria are found in the mouth, nose and pharynx (that is, above the vocal cords) Examples of the “normal respiratory flora” are viridans streptococci, “non-pathogenic” Neisseria and certain anaerobes The host defenses prevent these bacteria and others from invading the lower respiratory tree

16. Upper airway defenses Filtering via the nasopharynx Sneeze reflex Nasal secretions contain defensins, lysozyme and immunoglobulin A Glottic closure Cough reflex

17. Airway protection Mucus layer in trachea and bronchi Mucociliary escalator

18. Alveolar protection Surfactant proteins Alveolar macrophages Neutrophils recruited from vasculature

19. Defects in host defense Impaired cough reflex Neurologic impairment Impaired mucociliary function Smoking Impaired activity of alveolar macrophages Corticosteroid use

20. Hematogenous seeding Most infections in the lung are acquired via inhalation or aspiration Infection of the right sided heart valves (eg, tricuspid valve) can lead to septic pulmonary emboli

22. CAP - Etiology Streptococcus pneumoniae (“the pneumococcus”) is the most common organism causing CAP Gram positive coccus, often appearing in pairs (“diplococci”)

23. The father of the Gram stain? Christian Gram

24. CAP – Etiology (II) Other common organisms Haemophilus influenzae Moraxella catarrhalis

25. CAP – Etiology (III) “Atypical” organisms Will not grow on conventional culture media Mycoplasma pneumoniae Chlamydia pneumoniae Legionella pneumophila

26. CAP – Etiology (IV) Respiratory Viruses Metapneumovirus Influenza Adenovirus Parainfluenza viruses Respiratory syncytial viruses (RSV)

27. CAP- Etiology (V) Less common bacterial causes of CAP Staphylococcus aureus Particularly following influenza Enteric Gram negative bacilli Klebsiella pneumoniae was a classical cause of CAP but is now rarely seen in the U.S. Pseudomonas aeruginosa Usually in severe pneumonia in patients with underlying structural lung disease

28. Important notes In many patients, no etiology is discovered Prior antibiotic therapy Autolysis of the pneumococcus Insufficient testing – atypical agents, viruses etc

29. Clinical pointers to the etiology Young people with no comorbidities and mild disease Mycoplasma pneumoniae Young people with no comorbidities and severe disease Streptococcus pneumoniae Smokers Haemophilus influenzae

30. In every case of CAP Antibiotics need to cover: Streptococcus pneumoniae Atypical organisms

31. Symptoms of CAP Classical symptoms Cough (usually productive of purulent sputum) Fever Shortness of breath Pleuritic chest pain Pneumococcal pneumonia classically starts with shaking chills and patients end up with rusty colored sputum

32. Signs of CAP Patients typically appear short of breath at rest Vital signs – fever, increased heart rate and increased respiratory rate Chest exam – crackles over the affected area Signs of consolidation: ? vocal and tactile fremitus, dullness to percussion, bronchial breath sounds, whispering egophony

33. Investigations – to establish that a patient has CAP CXR Characteristically abnormal in CAP (some early disease may be an exception) White blood cell count - ? WBC with left shift (if bacterial) Sputum Gram stain

34. Severe lobar pneumonia

35. CAP - Sputum Gram Stain PRO Non-invasive, inexpensive Can establish the etiologic diagnosis CON At least one third of patients do not produce sputum May not change empiric therapy

36. CAP – Etiologic diagnosis For patients requiring hospitalization Sputum culture Blood cultures Legionella urinary antigen (Pneumococcal urinary antigen) (Serology for Legionella, Mycoplasma, Chlamydia etc)

37. CAP – Decision Pathway Once the diagnosis of CAP has been made, important decisions need to be made Does the patient require hospitalization? If yes, does the patient require ICU admission? What antibiotics should I prescribe?

38. CAP – the Hospitalization Decision Assessment of pre-existing conditions that compromise the safety of home care Calculation of the pneumonia severity index (PSI) Patients are stratified into 5 severity classes Factors such as age, comorbid conditions, vital signs, mental status Clinical judgment

39. CAP – antibiotic therapy (I) Need to cover both: Streptococcus pneumoniae Atypical organisms (Legionella, Mycoplasma, Chlamydia pneumoniae)

40. CAP – antibiotic therapy (II) Strep. Atypicals pneumoniae Penicillin Yes No Cephalosporins Yes No Macrolides Yes Yes Ketolides Yes Yes Quinolones Yes Yes Tetracyclines Yes Yes

41. CAP – Antibiotic Therapy (III) Why not monotherapy for everybody? Antibiotic resistance in Streptococcus pneumoniae “Collateral damage” inflicted by quinolones

42. Resistance in Streptococcus pneumoniae – Pittsburgh 2005 %R Macrolides 25% Doxycyline 20% Penicillin 10% Ceftriaxone <1% Levofloxacin <1%

43. CAP – how to choose a regimen? Consult most recent guidelines Consider whether therapy will be as an outpatient, inpatient or in ICU Consider prior antibiotic therapy (predicts resistance to itself)

44. CAP – example regimens Previously healthy patient, no comorbidities, no prior antibiotic use, Rx at home - Doxycycline PO alone Patient with comorbidities, prior azithromycin use, Rx at home - Moxifloxacin PO alone Patient admitted to medical ward, no prior antibiotic use - Azithromycin IV plus ceftriaxone IV

45. Special considerations Patients with severe CAP admitted to the ICU This is the only situation in CAP in which Pseudomonas is required to be covered Risks for Pseuodmonas in severe CAP include structural lung disease (eg, bronchiectasis, with prior antibiotic use)

47. Hospital-acquired pneumonia Etiologic organisms Diagnostic tests Antibiotic regimens

48. HAP – etiologic organisms Early-onset VAP S. pneumoniae, H. influenzae, S. aureus Late-onset VAP Pseudomonas aeruginosa, S. aureus, enteric Gram negative bacilli (Klebsiella, E. coli etc) HAP, not associated with ventilators Enteric Gram negative bacilli, H. influenzae, S. aureus

49. HAP – symptoms and signs Most patients with HAP are ventilated or neurologically impaired, so can not describe symptoms Nursing observations Fever Increased respiratory rate Increased oxygen requirement Suctioning of purulent respiratory secretions

50. HAP – laboratory findings WBC ? WBC with left shift CXR Alveolar infiltrate BUT - Could also be due to pulmonary edema, blood, ARDS etc

51. VAP – making the diagnosis Two approaches Standardized clinical approach Clinical pulmonary infection score (CPIS) Microbiologic approach Quantitative cultures of LOWER respiratory secretions obtained by bronchoalveolar lavage (BAL) or protected specimen brush (PSB)

52. Colonization versus pneumonia Ventilated patients routinely have colonization of the airways with potentially pathogenic bacteria There is no advantage in treating colonizing bacteria in the absence of pneumonia Excessive antibiotic use in the ICU leads to increased antibiotic resistance

53. Empiric antibiotic therapy – HAP (I) Early onset VAP Ampicillin/sulbactam Rationale: covers S. pneumoniae, H. influenzae, S. aureus

54. Empiric antibiotics – HAP (II) Late-onset VAP Combination of vancomycin, cefepime and gentamicin Rationale: Vancomycin in case there is MRSA, cefepime and gentamicin in case there is multiply resistant Pseudomonas

55. Late-onset VAP EMPIRIC therapy should usually consist of combination therapy because antibiotic resistance is common in bacteria in the ICU Therapy should then be narrowed when antibiotic susceptibilties are known

56. Empiric therapy – HAP (III) HAP in the non-ventilated patient Empiric therapy: Piperacillin/tazobactam Rationale – covers common Gram negative bacilli, anaerobes

57. SUMMARY Pneumonia can be subdivided into CAP, HAP and pneumonia in the immunocompromised The subdivisions are important because different organisms are responsible Pneumonia treatment is almost always empiric, therefore knowledge of the likely pathogens is essential

58. Practice question 1 Which of the following are not true with respect to CAP: Less than 50% of patients with CAP require admission to hospital Treatment of CAP with ceftriaxone and azithromycin is logical because it provides coverage of pneumococci and atypicals Knowledge of the prior antibiotic treatment of a patient with CAP is important because it will modify the empiric regimen chosen Coverage of MRSA and Pseudomonas are important in all cases of CAP

59. Practice question 2. With respect to VAP, which of the following is not true: Since patients with VAP are in the ICU, multidrug resistance is common Antibiotic treatment for VAP can not wait until the susceptibilties of the infecting organisms are known Pulmonary edema or ARDS may be hard to distinguish radiologically from VAP Pneumocystis carinii should always be covered in an antibiotic regimen for VAP