1. Pneumonia Charles B. Lehman, MD College of Community Health Sciences
University of Alabama

2. Diagnosing pneumonia Clinical evaluation
Chest x-ray with or without microbial testing

3. Clinical evaluation Common clinical features: Cough Fever
Pleuritic chest pain
Dyspnea
Sputum production
GI: nausea, vomiting, diarrhea
Mental status changes

4. Clinical evaluation Physical exam: Lab findings: 80% will be febrile
Tachypnea, especially in elderly patients
Tachycardia
Audible crackles
Evidence of consolidation
Lab findings:
Leukocytosis with left shift
Leukopenia can occur and is an ominous sign

5. Clinical evaluation: chest x-ray
Radiologic evaluation
Presence of infiltrate on plain chest x-ray is gold standard for diagnosis
Should be obtained whenever diagnosis is suspected
Recommendations less clear when viral infection suspected but should be obtained in patients with an abnormal vital sign, especially tachypnea.

6. Lobar consolidation
Left lower lobe opacity in patient with pneumococcal pneumonia.

7. Interstitial infiltrates
Nodular opacities in the right lower lobe in patient with mycoplasma pneumonia.

9. Cavitation
Lung abscess with air-fluid level in right lung in first image. Next image is of necrotizing pneumonia in the left lung

10. Clinical evaluation: chest x-ray
Considerable variation in reading between different radiologists
Even more between ED physicians and radiologists
High-resolution CT is a much better test but generally not necessary to make a diagnosis.

11. Clinical evaluation: chest x-ray
Other causes for chest x-ray which can look like pneumonia
Malignancy
Hemorrhage
Pulmonary edema
Pulmonary embolism with infarction
Inflammation due to non-infectious causes
CT can be used to clarify cases when clinical picture is consistent with pneumonia but chest x-ray is negative.

12. Clinical evaluation: microbial testing
Outpatients: testing is optional
Hospitalized patients with specific indications should have blood cultures and sputum Gram stain and culture.
Severe CAP requiring ICU admission should have blood cultures, Legionella and pneumococcus urinary antigen tests and sputum culture.
Other tests indicated with specific findings

14. Clinical evaluation: microbial testing Blood cultures
Blood cultures are positive in 7 to 16% of hospitalized patients with S. pneumococcus accounting for 2/3 of positive cultures.
Arguments to obtain blood cultures:
Establishes a diagnosis when likely pathogen found
In many cases is the only test done and is primary source for microbiologic data for many hospitals
Isolates are an important resource for tracking resistance patterns in S. pneumoniae which provide data for evaluating vaccines.
Arguments against:
Relatively low rate of positives
Rarely lead to modification of therapy

15. Clinical evaluation: microbial testing Sputum cultures
ICU admission
Failure of antibiotic therapy
Cavitary lesions
Active alcohol abuse
Severe obstructive of structural lung disease
Immunocompromised host
Pleural effusion
Epidemic pneumonia

16. Clinical evaluation Predisposing conditions
Altered mental status which can lead to micro/macro aspiration (stroke, seizure, intoxication, anesthesia)
Smoking
Alcohol
Hypoxemia
Acidosis
Toxic inhalations
Pulmonary edema
Uremia
Malnutrition

17. Clinical evaluation: predisposing conditions
Immunosuppresive agents
Mechanical obstruction of a bronchus
Advanced age
Cystic fibrosis
Bronchiectasis
COPD
HIV
Viral respiratory tract infection, especially influenza
Lung cancer

18. Microbiology: bacteria
S. pneumoniae: most common cause
H. influenzae: more common in elderly and patients with underlying pulmonary disease (COPD, cystic fibrosis)
M. pneumoniae: most common atypical cause, highest rates in school-aged children, military recruits and college students.
C. pneumoniae
Legionella: transmitted by aerosols containing the bacteria such as showers, grocery store misters, cooling towers, whirlpool spas and fountains.

19. Microbiology: bacteria
Gram negative bacilli
E. coli
Serratia
K. pneumoniae
Acinetobacter
P. aeruginosa
Enterobacter
Uncommon in CAP except in patients with severe disease requiring ICU admission

20. Microbiology: bacteria
S. aureus
Usually in older adults or younger patients who are recovering from influenza
Associated with severe necrotizing pneumonia
Group A streptococcus
Can cause fulminant pneumonia with early empyema even in young competent hosts.
Anaerobes (aspiration and lung abscess)
Neisseria meningitidis
M. tuberculosis

21. Microbiology: viruses
Influenza
Can cause primary pneumonia, more likely to cause secondary bacterial pneumonia
Parainfluenza viruses
RSV
Adenovirus
Human metapneumovirus
Severe acute respiratory syndrome (SARS)
Middle East respiratory syndrome coronavirus (MERS-CoV)
Other coronaviruses

22. Microbiology: viruses
Hantavirus (ARDS)
Avian influenza: considered a possible source for next global influenza pandemic.
Varicella

23. Microbiology: fungi Usually occur in immunocompromised hosts
Neutropenia
Immunosuppressive therapy
HIV
Usually endemic to particular areas

24. Microbiology: fungi Cryptococcus Histoplasma
Found world-wide
Infection often asymptomatic in immunocompetent hosts
Histoplasma
Most common in Ohio and Mississippi River valleys
Less than 5% develop symptoms with low-level exposure
Coccidioides (Sonoran desert regions)
Aspergillosis
P. jirovecii

25. Microbiology: bioterrorism
Bacillus anthracis (anthrax)
Yersinia pestis (plague)
Francisella tularensis (tularemia)
C. burnetti (Q fever)

26. Inpatient vs. outpatient treatment
Hospital admission rates vary widely
Rates often are not related to local disease severity
Physicians often overestimate patient risk of short-term mortality
Many unnecessary admissions as a result

27. Inpatient vs. outpatient treatment Pneumonia Severity Index
Step 1 risk factors:
Age > 50
Coexisting conditions: cancer, CHF, cerebrovascular disease, renal disease or liver disease
Physical exam: AMS, heart rate >= 125, respiratory rate >= 30, SBP < 90, temperature < 35 (95) or > 40 (104)
If one or more Step 1 risk factors are present then evaluation proceeds to Step 2.

29. Inpatient vs. outpatient treatment Pneumonia Severity Index
Class I: no predictors
Class II: <= 70
Class III: 71–90
Class IV:
Class V: > 130

30. PSI and mortality by class
Points
Mortality I
No predictors
0.1 II
<= 70
0.6
III
71-90
0.9 IV
91-130
9.3 V
> 130
27.0

31. Inpatient vs. outpatient treatment Pneumonia Severity Index
Measuring impact using Pneumonia PORT cohort
Strategy 1: outpatient therapy for class I or II, brief observation for class III and admission for class IV or V:
31% fewer admissions
19% more would have been assigned to observation
4.3% admitted to ICU
< 1% mortality

32. Inpatient vs. outpatient treatment Pneumonia Severity Index
Measuring impact using Pneumonia PORT cohort
Strategy 2: same as strategy 1 except that all patients with hypoxemia were admitted:
26% reduction in admissions
13% assigned to observation
1.6% admitted to ICU
Mortality < 1%
Either set of recommendations would have recommended inpatient therapy for 5 of the 6 patients who died following an initial course of outpatient therapy.

33. Inpatient vs. outpatient treatment Pneumonia Severity Index
CAPITAL trial (Canada)
Admission rate for low risk (class I, II or III) patients dropped from 49 to 31%
No negative effects on patient quality of life or adverse medical outcomes (ICU admission, mortality, readmission or complications).
EDCAP (US)
Increased proportion of low-risk patients treated in outpatient setting
No statistically significant difference in safety outcomes

34. Inpatient vs. outpatient treatment CURB-65 score
Confusion
Urea (BUN > 20)
Respiratory rate (>30)
Blood pressure (SBP < 90 or DBP < 60)
Age > 65
0-1: outpatient treatment
2: admission
>= 3 should be assessed for ICU admission

35. Inpatient vs. outpatient treatment Severe CAP score
Major criteria:
pH < 7.30 (13 points)
SBP < 90 (11 points)
Minor criteria:
RR > 30 (9)
PaO2/FiO2 < 250 (6)
BUN > 30 (5)
Age > 80 (5)
Multilobar/bilateral infiltrates (5)
Score > 10 predicts progression to severe CAP

36. CAP: outpatient treatment Empiric therapy
Chest x-ray which demonstrates pneumonia
Risk stratification with CURB-65 or PSI
Distinguish CAP from HCAP
Microbiologic testing is optional
Blood cultures
Sputum if quality sample can be obtained

37. CAP: outpatient treatment Empiric therapy
Co-morbidity
Alcoholism
COPD
Post-CVA aspiration
Post-obstruction of bronchi
Influenza
Local resistance of S. pneumoniae to macrolides > 25%

38. CAP: outpatient treatment Empiric therapy
No co-morbidities, local macrolide resistance < 25%
Azithromycin 500 x 1 dose then 250 mg/day
Clarithromycin 500 mg BID for 7 days
If patient had antibiotics within 3 months:
Above plus amoxicillin 1 gm TID or Augmentin 1000/ tabs BID
Levofloxacin 750 mg qD
If co-morbidity present:
Levofloxacin 750 mg qD x 5 days

39. CAP: inpatient treatment Non-ICU patients
S. pneumoniae most common pathogen
Respiratory viruses
Less common:
M. pneumoniae
H. influenzae
C. pneumoniae
Legionella

40. CAP: inpatient treatment Non-ICU patients
Primary regimens:
Ceftriaxone 1 gm q24 + azithromycin 500 mg q24
Ertapenem 1 gm q24 + azithromycin 500 mg q24
Alternative regimens:
Levofloxacin 750 mg q24
Moxifloxacin 400 mg q24

41. CAP: inpatient treatment Non-ICU patients with COPD
Primary regimens:
Levofloxacin 750 mg q24
Moxifloxacin 400 mg q24
Alternative regimens:
Ceftriaxone 1 gm q24 + azithromycin 500 mg q24
Ertapenem 1 gm q24 + azithromycin 500 mg q24

42. CAP: inpatient treatment Empiric therapy, ICU patients
Patients admitted to an ICU are more likely to have resistant pathogens including community-associated MRSA and Legionella
Suspicion for P. aeruginosa
Chronic or structural lung disease
Known prior colonization
Suspicion for CA-MRSA
Post-influenza
IV drug use
Gram (+) cocci in clusters on Gram stain

43. CAP: inpatient treatment Empiric therapy, ICU patients
Primary regimens:
(Ceftriaxone 1-2 gm q24 or Unasyn 3 gm q6) + azithromycin 500 q24
Levofloxacin 750 mg q24
Moxifloxacin 400 q24
If CA-MRSA suspected add:
Vancomycin mg/kg q8-12
Linezolid 600 IV q12

44. CAP: inpatient treatment Empiric therapy, ICU patients
If P. aeruginosa suspected:
Beta-lactam (Cefepime 2 gm q12 or Zosyn gm q4 or ceftazidime 2 gm q8 or meropenem 1 gm q8)
Fluoroquinolone (levofloxacin 750 q24 or ciprofloxacin 400 q8) or tobramycin 5 mg/kg q24 and azithromycin 500 q24

45. CAP: inpatient treatment Response to therapy
Some improvement usually seen within 48 to 72 hours
Resolution of symptoms and radiographic findings takes longer
Crackles can persist for weeks
As many as 87% of patients continue to report at least one symptom at 39 days
Takes 6-8 weeks for a chest x-ray to clear and can take up to 12 weeks in patients with underlying lung disease

46. CAP: inpatient treatment Change to oral therapy
Clinical improvement
Hemodynamically stable
Normally functioning GI tract

47. CAP: inpatient treatment Choice of oral therapy
Base on culture results if possible
Use oral medications from same drug class
No need to cover for S. aureus or gram (-) bacilli unless isolated from a good quality sputum specimen
Choice depends on risk of resistant S. pneumoniae and the initial IV regimen

48. CAP: inpatient treatment Duration of hospitalization
Can go home when:
On oral medications
No other active medical problems
Appropriate environment for discharge
Not necessary to keep patient for observation after changing to oral antibiotics.

49. CAP: inpatient treatment Duration of therapy
Minimum of 5 days
Should be afebrile for 48 hours
No more than 1 clinical instability factor
Heart rate > 100
Respiratory rate > 24
SBP < 90

50. CAP: inpatient treatment Duration of therapy
Longer duration needed if:
Initial therapy was not active against a subsequently identified pathogen
Extrapulmonary infection identified (meningitis, endocarditis)
P. aeruginosa, S. aureus or Legionella infections
Necrotizing pneumonia, empyema or lung abscess

51. CAP: inpatient treatment Non-responding patients
Progressive pneumonia or clinical deterioration
Requirement of ventilator support
Development of septic shock
Absence of delay of achieving clinical stability after 72 hours

52. CAP: inpatient treatment Non-responding patients
Unusual organisms not covered by empiric therapy
Patient-related factors
Severity of illness
Neoplasia
Aspiration pneumonia
Neurologic disease
Infectious complications
Empyema
Superimposed nosocomial pneumonia

53. HAP, VAP and HCAP Hospital-acquired (nosocomial) pneumonia
48 hours or more after admission, did not appear present on admission
Ventilator-associated pneumonia
48-72 hours after endotracheal intubation
Healthcare-associated pneumonia
IV therapy, wound care or IV chemotherapy within 30 days
Residence in a nursing home or other long-term care facility
Hospitalization in an acute care hospital for 2 or more days within the last 90 days
Attendance at a hospital or hemodialysis clinic within 30 days

54. HAP, VAP and HCAP
Drug selection should be based on risk factors for multi-drug resistant organisms
Recent antibiotic therapy
Resident flora in the hospital or ICU
Presence of underlying diseases
Available culture data

55. HAP, VAP and HCAP MRSA Vancomycin or linezolid should be added
Should be discontinued if not isolated in cultures
If MSSA later isolated should replace above with nafcillin or oxacillin

56. HAP, VAP and HCAP Other considerations
Combination therapy for Gram (-) organisms often used but no conclusive evidence to support this practice
Legionella should be covered, especially if known to be present in the hospital water supply
Anaerobes in patients with recent abdominal surgery or aspiration

57. HCAP Etiologies S. aureus (often MRSA)
Gram (-) enterics which may be MDR (E. coli, K. pneumoniae, enterobacter, Serratia)
P. aeruginosa
Acinetobacter

58. HCAP Empiric treatment
Vancomycin mg/kg q8-12
Cefepime 2 gm 12 or Zosyn 4.5 gm q6 or meropenem 1 gm q8
Doripenem should not be used
Linezolid 600 IV q12 can be substituted for vancomycin
If Legionella suspected should use a fluoroquinolone or add azithromycin 500 mg q24

59. HCAP Empiric treatment
Controversy exists regarding uniqueness of HCAP
Duration of therapy is not well-defined
Therapy should be streamlined once culture results area available

60. HAP/VAP Subtypes
Early-onset: no other risk factors for MDR, < 5 days in the hospital
S. pneumoniae, S. aureus, H. influenzae, enteric Gram (-) bacilli
Late onset: >= 5 days in the hospital, risk factors for MDR organisms
S. aureus, often MRSA
Gram (-) enterics
ESKAPE organisms (E. coli, Serratia, Klebsiella, acinetobacter, pseudomonas and enterobacter) etiology in about 80% of patients

61. HAP/VAP Early-onset Ceftriaxone 1 gm q24 or Unasyn 3 gm q6 or
Ertapenem 1 gm q24 or
Levofloxacin 750 q 24

62. HAP/VAP Late-onset
Meropenem 1 gm q8, Zosyn 4.5 gm q6 or cefepime 2 gm q12
Add vancomycin mg q8-12 if MRSA suspected
Imipenem preferred over meropenem if acinetobacter is suspected
Add levofloxacin if Legionella suspected