1. Community Acquired Pneumonia (CAP) by
Paras Patel MD.
Assistant Professor of Internal Medicine, Division of Infectious disease. ETSU

2. Alphabet Soup for Pneumonia
HAP: Hospital-acquired pneumonia
≥ 48 h from admission
VAP: Ventilator-associated pneumonia
≥ 48 h from endotracheal intubation
HCAP: Healthcare-associated pneumonia
Long-term care facility (NH), hemodialysis, outpatient chemo, wound care, etc.
CAP: Community-acquired pneumonia
Outside of hospital or extended-care facility 2

3. Community Acquired Pneumonia
Definition:
… an acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, accompanied by the presence of an acute infiltrate on a chest radiograph, or auscultatory findings consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for > 14 days before onset of symptoms.
Bartlett. Clin Infect Dis 2000;31:

4. Community Acquired Pneumonia
Epidemiology:
4-5 million cases annually
~500,000 hospitalizations
~45,000 deaths
Mortality 2-30%
<1% for those not requiring hospitalization
Cdc.gov/data 2007.

5. Community Acquired Pneumonia
Epidemiology: (contd)
fewest cases in yr group
probably highest incidence in <5 and >65 yrs
mortality disproportionately high in >65 yrs

6. Community Acquired Pneumonia
Mortality
# in 1000s
NCHS Data:

7. Age-specific Rates of Hospital Admission by Pathogen
Marsten. Community-based pneumonia incidence study group.
Arch Intern Med 1997;157: 7

8. CAP – Pathogenesis
Inhalation, aspiration and hematogenous spread are the 3 main mechanisms by which bacteria reaches the lungs
Inhalation
Aspiration
Hematogenous
Infectious agents gain entry to the lower respiratory tract through aspiration of upper airway resident flora, inhalation of of aerosolized materal and less frequently metastatic seeding of the lung from blood.

9. Pathogenesis
Primary inhalation: when organisms bypass normal respiratory defense mechanisms or when the Pt inhales aerobic GN organisms that colonize the upper respiratory tract or respiratory support equipment
Aspiration: occurs when the Pt aspirates colonized upper respiratory tract secretions
Stomach: reservoir of GNR that can ascend, colonizing the respiratory tract.
Hematogenous: originate from a distant source and reach the lungs via the blood stream.
Microaspiration: S. pneumo
Inhalation: TB, viruses, Legionella
Aspiration: anaerobes
Bloodborne: Staph endocarditis, septic emboli
Direct extension: Amebiasis, trauma

10. Community Acquired Pneumonia
Risk Factors for pneumonia
age
smoking
asthma
immunosuppression
institutionalization
COPD
PVD
Dementia
HIV/AIDS
Pneumonia has been noted to occur with increased frequency in patients with a variety of underlying diseases as above. The incidence of invasive pneumococcal pneumonia is 100 to 300 times higher in HIV infected patients. And the incidence of H. influenzae infection may be up to 100 fold higher in this population.
ID Clinics 1998;12: Am J Med 1994;96:313

11. Community Acquired Pneumonia
Risk Factors in Patients Requiring Hospitalization
older, unemployed
common cold in the previous year
asthma, COPD; steroid or bronchodilator use
Chronic disease
amount of smoking
Farr BM. Respir Med 2000;94:954-63
Farr BM. Respir Med 2000;94:

12. Community Acquired Pneumonia
Risk Factors for Mortality
age
bacteremia (for S. pneumoniae)
extent of radiographic changes
degree of immunosuppression
amount of alcohol
Fine. JAMA 1996;275:

13. Community Acquired Pneumonia
Microbiology
Legionella spp %
S. aureus: 3-5%
Gram negative bacilli: 3-5%
Viruses: 2-13%
S. pneumoniae: 20-60%
H. influenzae: 3-10%
Chlamydia pneumoniae: 4-6%
Mycoplasma pneumonaie: 1-6%
Bartlett. NEJM 1995;333:
40-60% - NO CAUSE IDENTIFIED
2-5% - TWO OR MORE CAUSES
Bartlett. NEJM 1995;333:

14. Streptococcus pneumonia (Pneumococcus)
Most common cause of CAP
About 2/3 of CAP are due to S.pneumoniae
These are gram positive diplococci
Typical symptoms (e.g. malaise, shaking chills fever, rusty sputum, pleuritic chest pain, cough)
Lobar infiltrate on CXR
May be Immuno suppressed host
25% will have bacteremia – serious effects
Predisposing factors: anorexia, ETOH, HIV, sickle cell disease, splenectomy, hematologic diseases

15. Atypical Pneumonia Pneumonia
#2 cause (especially in younger population)
Commonly associated with milder Sx’s: subacute onset, non-productive cough, no focal infiltrate on CXR
Mycoplasma: younger Pts, extra-pulm Sx’s (anemia, rashes), headache, sore throat
Chlamydia: year round, URI Sx, sore throat
Legionella: higher mortality rate, water-borne outbreaks, hyponatremia, diarrhea

16. Viruses and Pneumonia Pneumonia in the normal host Adults or Children
Influenza A and B, RSV, Adenovirus, Para Influenza
Pneumonia in the immuno-compromised
Measles, HSV, CMV, HHV-6, Influenza viruses
Can cause a primary viral pneumonia. Cause partial paralysis of “mucociliary escalator” - increased risk of secondary bacterial LRTI. S.aureus pneumonia is a known complication following influenza infection.

17. Other bacteria Anaerobes
Aspiration-prone Pt, putrid sputum, dental disease
Gram negative
Klebsiella - alcoholics
Branhamella catarrhalis - sinus disease, otitis, COPD
H. influenza

18. S. aureus CAP – Dangerous
This CAP is not common; Multi lobar Involvement
Post Influenza complication, Class IV or V
Compromised host, Co-morbidities, Elderly
CA MRSA – A Problem; CA MSSA also occurs
Empyema and Necrosis of lung with cavitations
Multiple Pyemic abscesses, Septic Arthritis
Hypoxemia, Hypoventilation, Hypotension common
Vancomycin, Linezolid are the drugs for MRSA

19. Diagnosis and Management

20. Clinical Diagnosis Suggestive signs and symptoms
CXR or other imaging technique
Microbiologic testing

21. Signs and Symptoms Fever or hypothermia
Cough with or without sputum, hemoptysis
Pleuritic chest pain
Myalgia, malaise, fatigue
GI symptoms
Dyspnea
Rales, rhonchi, wheezing
Egophony, bronchial breath sounds
Dullness to percussion
Atypical Sx’s in older patients

22. Clinical Diagnosis: CXR
Demonstrable infiltrate by CXR or other imaging technique
Establish Dx and presence of complications (pleural effusion, multilobar disease)
May not be possible in some outpatient settings
CXR: classically thought of as the gold standard

23. May show hyper-expansion, atelectasis or infiltrates
Chest Radiograph
May show hyper-expansion, atelectasis or infiltrates
Normal
Pneumonia 23

24. Infiltrate Patterns Pattern Possible Diagnosis Lobar
S. pneumo, Kleb, H. flu, GN
Patchy
Atypicals, viral, Legionella
Interstitial
Viral, PCP, Legionella
Cavitary
Anaerobes, Kleb, TB, S. aureus, fungi
Large effusion
Staph, anaerobes, Kleb

25. Clinical Diagnosis: Recommended testing
Outpatient: CXR, sputum Cx and Gram stain not required
Inpatient: CXR, Pox or ABG, chemistry, CBC, two sets of blood Cx’s
If suspect drug-resistant pathogen or organism not covered by usual empiric abx, obtain sputum Cx and Gram stain.
Severe CAP: Legionella urinary antigen, consider bronchoscopy to identify pathogen
In general, sputum gram stain cannot be used to focus initial empiric antibioic therapy, but could be used to broaden initial antibiotic therapy.
IDSA consensus group believes that a properly collected and examined Gram’s stain of expectorated sputum is helpful for focusing initial empiric therapy in CAP. A lower respiratory tract sample that is not heavily contaminated by oral secretions will typically have fewer than 10 squamous epithelial cells and > 25 neutrophils per LPF.
Limitations: not all Pts can provide an adequate sample, interpretation-observer dependent, etc.

26. Community Acquired Pneumonia
Who should be hospitalized?

27. To Admit or Not? Pneumonia Severity & Deciding Site of Care
Using objective criteria to risk stratify & assist in decision re outpatient vs inpatient management
PSI
CURB-65
Caveats
Other reasons to admit apart from risk of death
Not validated for ward vs ICU
Labs/vitals dynamic 27

28. Pneumonia Severity Index
Class
Points
Mortality*
Site of Care I
<51
0.1%
OutPatient II
51-70
0.6%
III
71-90
2.8%
In or OutPatient IV
91-130
9.5%
Inpatient V
>130
26.7%

29. CURB 65 Rule – Management of CAP
BP SBP <90
DBP <60
RR > 30
BUN > 30
Confusion
Age > 65
CURB 0 or 1
Home Rx
CURB 2
Short Hosp
CURB 3
Medical Ward
CURB 4 or 5
ICU care

30. Who Should be Hospitalized?
Class I and II Usually do not require hospitalization Class III May require brief hospitalization Class IV and V Usually do require hospitalization
Severity of CAP with poor prognosis
RR > 30; PaO2/FiO2 < 250, or PO2 < 60 on room air
Need for mechanical ventilation; Multi lobar involvement
Hypotension; Need for vasopressors
Oliguria; Altered mental status

31. CAP – Criteria for ICU Admission
Major criteria
Invasive mechanical ventilation required
Septic shock with the need of vasopressors
Minor criteria (least 3)
Confusion/disorientation
Blood urea nitrogen ≥ 20 mg%
Respiratory rate ≥ 30 / min; Core temperature < 36ºC
Severe hypotension; PaO2/FiO2 ratio ≤ 250
Multi-lobar infiltrates
WBC < 4000 cells; Platelets <100,000

32. Traditional Treatment Paradigm
Conservative start with ‘workhorse’ antibiotics
Reserve more potent drugs for non-responders

33. New Treatment Paradigm
Hit hard early with appropriate antibiotic(s)
Short Rx. Duration; De-escalate where possible

34. The Effect of the Traditional Approach50
Inappropriate therapy (%) 45 40 34 30 17 20 10
CAP
HAP
HAP on CAP
Kollef, et al. Chest 1999;115:462–474

35. New data – Don’t Wait for Results !
Switching after susceptibility results
p<0.001
Adequate treatment within ‘a few hours’
Mortality (%)
n=75
For the subgroup of patients whose inadequate initial treatment was corrected based on in vitro susceptibility data, the 21-day mortality rate was 52% (39 of 75), compared with only 18% in the subgroup that received adequate treatment within a few hours of BSI onset (OR 2.18; 95% CI 1.58, 3.01; p<0.001).
Inadequate antimicrobial therapy within the first 72 h of infection is a predictor of mortality (OR 6.28; 95% CI 3.18, 12.42; p<0.001).
21-day mortality rate was highest among the 16 patients treated from the start with fluoroquinolones (44.4% OR 4.05; 95% CI 1.89, 8.65; p<0.001).
21-day mortality rate was lowest in patients treated from the start with carbapenems (5.5%; OR 0.14; 95% CI 0.02, 1.03; p=0.01).
Tumbarello, et al. Antimicrob Agents Chemother 2007;51:1987–1994 35

36. New data – The Speed of Delay ! (Class 4,5)
Delay in treatment (hours) from hypotension onset
Survival (%)
Each hour of delay carries 7.6% reduction in survival
Kumar, et al. Crit Care Med 2006;34:1589–1596

37. CAP – Complications Hypotension and septic shock
3-5% Pleural effusion; Clear fluid + pus cells
1% Empyema thoracis pus in the pleural space
Lung abscess – destruction of lung .
Single (aspiration) anaerobes, Pseudomonas
Multiple (metastatic) Staphylococcus aureus
Septicemia – Brain abscess, Liver Abscess
Multiple Pyemic Abscesses

38. IDSA: Outpt Management in Previously Healthy Pt
Organisms: S. pneumo, Mycoplasma, viral, Chlamydia pneumo, H. flu
Recommended abx:
Advanced generation macrolide (azithro or clarithro) or doxycycline
If abx within past 3 months:
Respiratory quinolone (moxi-, levo-, gemi-), OR
Advanced macrolide + amoxicillin, OR
Advanced macrolide + amoxicillin-clavulanate

39. IDSA: Outpt Management in Pt with comorbidities
Comorbidities: cardiopulmonary dz or immunocompromised state
Organisms: S. pneumo, viral, H. flu, aerobic GN rods, S. aureus
Recommended Abx:
Respiratory quinolone, OR advanced macrolide
Recent Abx:
Respiratory quinolone OR
Advanced macrolide + beta-lactam

40. IDSA: Inpt Management-Medical Ward
Organisms: all of the above plus polymicrobial infections (+/- anaerobes), Legionella
Recommended Parenteral Abx:
Respiratory fluoroquinolone, OR
Advanced macrolide plus a beta-lactam
Recent Abx:
As above. Regimen selected will depend on nature of recent antibiotic therapy.

41. IDSA: Inpt Management-Severe/ICU
One of two major criteria:
Mechanical ventilation
Septic shock, OR
Two of three minor criteria:
SBP≤90mmHg,
Multilobar disease
PaO2/FIO2 ratio < 250
Organisms: S. pneumo, Legionella, GN, Mycoplasma, viral, ?Pseudomonas
PIF ratio: index of severity of hypoxemia. Used as part of the definition of ALI (acute lung injury) and ARDS. ALI, PIF=
ARDS, PIF <200

42. IDSA: Inpt Management: Severe/ICU
No risk for Pseudomonas
IV beta-lactam plus either
IV macrolide, OR IV fluoroquinolone
Risk for Pseudomonas
Double therapy: selected IV antipseudomonal beta-lactam (cefepine, imipenem, meropenem, piperacillin/tazobactam), plus
IV antipseudomonal quinolone
-OR-
Triple therapy: selected IV antipseudomonal beta-lactam plus
IV aminoglycoside plus either
IV macrolide, OR IV antipseudomonal quinolone

43. Switch to Oral Therapy Four criteria:
Improvement in cough and dyspnea
Afebrile on two occasions 8 h apart
WBC decreasing
Functioning GI tract with adequate oral intake
If overall clinical picture is otherwise favorable, can can switch to oral therapy while still febrile.

44. Duration of Therapy Minimum of 5 days Afebrile for at least 48 to 72 h
No > 1 CAP-associated sign of clinical instability
Longer duration of therapy
If initial therapy was not active against the identified pathogen or complicated by extra pulmonary infection

45. Prevention Smoking cessation Vaccination per ACIP recommendations
Influenza
Inactivated vaccine for people >50 yo, those at risk for influenza compolications, household contacts of high-risk persons and healthcare workers
Intranasal live, attenuated vaccine: 5-49yo without chronic underlying dz
Pneumococcal
Immunocompetent ≥ 65 yo, chronic illness and immunocompromised ≤ 64 yo
Vaccination may be done either at hospital discharge or during outpatient treatment
ACIP: Advisory Committee on Immunization Practices

47. Epidemiology of Pneumococcal Infection in Immunocompromised Adults
Streptococcus pneumoniae remains a leading cause of serious illness, including bacteremia, meningitis, and pneumonia among adults in the United States.
An estimated 4,000 deaths occur annually in USA primarily among adults.
For adults aged 18–64 years with hematologic cancer, the rate of IPD in 2010 was 186 per 100,000, and for persons with human immunodeficiency virus (HIV) the rate was 173 per 100,000 (CDC, unpublished data, 2012).
The disease rates for adults in these groups can be more than 20 times those for adults without high-risk medical conditions.

48. PCV13 has been used for children since 2010, when it replaced an earlier version targeting seven serotypes (PCV7; Prevnar, Pfizer) that had been in use since 2000.
The routine use of PCV7 in infants and young children resulted in significant reductions in IPD caused by vaccine serotypes in children, and because of indirect effects, also in adults.
Rates of IPD caused by vaccine serotypes in adults aged 18–64 years without HIV decreased from six cases to one case per 100,000 during 2000–2007.
However, even after indirect effects of the pediatric immunization had been realized fully, the incidence of IPD caused by the serotypes included in PCV7 remained high in HIV-infected persons aged 18–64 years at 64 cases per 100,000 persons with acquired immunodeficiency syndrome (AIDS) .
Moreover, 50% of IPD cases among immunocompromised adults in 2010 were caused by serotypes contained in PCV13; an additional 21% were caused by serotypes only contained in PPSV23.

49. In two randomized, multicenter immunogenicity studies conducted in the United States and Europe, immunocompetent adults aged ≥50 years received a single dose of PCV13 or PPSV23.
In adults aged 60–64 years and aged >70 years, PCV13 elicited opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) that were comparable with, or higher than, responses elicited by PPSV23.
OPA GMTs elicited by PCV13 in adults aged 50–59 years for all 13 serotypes were comparable with the corresponding GMTs elicited by administration of PCV13 in adults aged 60–64 years.

50. PCV13 Vaccine in Adults
PCV13 was licensed by the Food and Drug Administration (FDA) for prevention of IPD and otitis media in infants and young children in February 2010, supplanting PCV7
One dose of PCV13 is recommended by ACIP for children aged 6–18 years with high-risk conditions such as functional or anatomic asplenia, immunocompromising conditions, cochlear implants, or CSF leaks.
In December 2011, FDA licensed PCV13 for prevention of pneumonia and IPD in adults aged ≥50 years .
Approval of PCV13 for adults was based on immunogenicity studies that compared antibody responses to PCV13 with antibody responses to PPSV23

51. ACIP Recommendations for PCV13 and PPSV23 Use
Pneumococcal vaccine-naïve persons.
ACIP recommends that adults aged ≥19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, and who have not previously received PCV13 or PPSV23, should receive a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later (Table).
Subsequent doses of PPSV23 should follow current PPSV23 recommendations 5 years after the first PPSV23 dose for persons aged 19–64 years with functional or anatomic asplenia and for persons with immunocompromising conditions.

52. Previous vaccination with PPSV23.
Adults aged ≥19 years with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, who previously have received ≥1 doses of PPSV23 should be given a PCV13 dose ≥1 year after the last PPSV23 dose was received.
For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23

54. CAP – So How Best to Win the War?
Early antibiotic administration within 4-6 hours
Empiric antibiotic Rx. as per guidelines (IDSA / ATS)
PORT – PSI scoring and Classification of cases
Early hospitalization in Class IV and V
Decrease smoking cessation - advice / counseling
Arterial oxygenation assessment in the first 24 h
Blood culture collection in the first 24 h prior to Abx.
Pneumococcal & Influenza vaccination; Smoking X

55. Thank you