2. Definition
Community-acquired pneumonia (CAP) is
defined as an acute infection of the lung
parenchyma accompanied by symptoms of
acute illness, which is not acquired in
hospitals or other long-term care facilities.
-Clin. infect Dis. 2000;31:347-82
4. 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
5. Epidemiology
8th leading cause of
death in US in 2007
4-5 million cases per
year in US
25% require
hospitalization
Almost 916,000 cases
annually in pts >65 yo
Case fatality rate has
not changed
substantially since
penicillin www.cdc.gov/mmwr
cdc.gov/nchs/data/hestat
6. Microbiology
Causative organism established in 60% CAP in
research setting, 20% in clinical setting
“Typical”:
S. pneumoniae, Haemophilus influenzae,
Staphylococcus aureus, Group A streptococci, Moraxella
catarrhalis, anaerobes, and aerobic gram-negative
bacteria
“Atypical” - 20-28% CAP worldwide
Legionella spp, Mycoplasma pneumoniae,
Chlamydophila (formerly Chlamydia) pneumoniae, and
C. psittaci
Mainly distinguished from typical by not being detectable
on Gram stain or cultivable on standard media
7. Microbiology of CAP among
hospitalized patients
Outpatient Streptococcus pneumoniae
Mycoplasma pneumoniae
Haemophilus influenzae
Chlamydophila pneumoniae
Respiratory viruses
Inpatient (Ward) S. pneumoniae
M. pneumoniae
H. influenzae
C. Pneumoniae
Legionella species
Respiratory viruses
Aspiration
Inpatient (ICU) S. pneumoniae
Legionella spp.
Staphylococcus aureus
Gram-negative bacilli
9. Typical vs
Atypical CAP
CXR patterns
Bronchopneumonia: 88%
C. pneumo vs 77%
Pneumococcal, P=0.67
Lobar or air-space: 29%
C. pneumo vs 54%
Pneumococcal
Kauppinen et al. Arch Intern Med 1996; 156: 1851.
13. Exposures & Associated Pathogens
Hotel or cruise ship Legionella spp
Travel or residence in US Coccidioides spp
Hantavirus
Travel or residence in Asia Burkolderia pseudomallei
Staph aureus
H.influenzae
Avian influenza A (H5N1)
Influenza active in community Influenza
S. pneumonae
Staph aureus (MRSA)
H. influenzae
Cough >2 wks with whoop or Bordetella pertussis
posttussive vomitting
14. Diagnosis: Cultures
Pretx Blood Cultures
Yield 5-15%
Stronger indication for severe CAP
Host factors: cirrhosis, asplenia, complement
deficiencies, leukopenia
Pretx expectorated sputum Gs & Cx
Yield can be variable
Depends on multiple factors: specimen collection,
transport, speed of processing, use of cytologic criteria
Predominant morphotype seen in only 14% of 1669
hospitalized CAP pts (Garcia-Vasquez, Arch Intern Med
2004)
Pretx endotracheal aspirate Gs & Cx
Pleural effusions >5 cm on lateral upright CXR
15. Diagnosis: Other testing
Urinary antigen tests
S. pneumoniae & L.
pneumophila
serogroup 1
50-80% sensitive,
>90% specific in adults
Pros: rapid (15 min),
simple, can detect
Pneumococcus after
abx started
Cons: cost, no
susceptibility data, not
helpful in patients with
recent CAP (prior 3
months)
16. Diagnosis: Other testing
Acute-phase serologies
C. pneumoniae, Mycoplasma, Legionella spp
Not practical given slow turnaround & single acute-phase
result unreliable
Influenza testing
Hospitalized patients: Severe respiratory illness (T> 37.8°C
with SOB, hypoxia, or radiographic evidence of pneumonia)
without other explanation and suggestive of infectious
etiology should get screened during season
NP swab or nasal wash/aspirate
Rapid flu test (15 min)
Distinguishes A vs B
Sensitivity 50-70%; specificity >90%
Respiratory virus DFA & culture - reflex subtyping for A
Respiratory viral PCR panel - reflex subtyping for A
Influenza A PCR panel
18. 2009-2010 Influenza Surveillance
Seattle - King County
www.kingcounty.gov/healthservices/health/communicable/immunization/fluactivity.aspx
19. 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
21. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Site-of-Care Decisions
• Hospital admission decision
- Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia,
respiratory rate, low blood pressure, age 65 years or greater), or prognostic models,
such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP
who may be candidates for outpatient treatment (Strong recommendation; Level I
evidence)
- Objective criteria or scores should always be supplemented with physician
determination of subjective factors, including the ability to safely and reliably take
oral medication and the availability of outpatient support resources (Strong
recommendation; Level II evidence)
- For patients with CURB-65 scores ≥ 2, more-intensive treatement – that is,
hospitalization or, where appropriate and available, intensive in-home health care
services – is usually warranted (Moderate recommendation; Level III evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
22. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Site-of-Care Decisions
• ICU admission decision
- Direct admission to an ICU is required for patients with septic shock requiring
vasopressors or with acute respiratory failure requiring intubation and mechanical
ventilation (Strong recommmendation; Level II evidence)
- Direct admission to an ICU or high-level monitoring unit is recommended for
patients with 3 of the minor criteria for severe CAP listed in table 4 (Moderate
recommendation; Level II evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
23. Criteria for Severe CAP
Minor criteria
Respiratory rate ≥30 breaths/min
PaO2/FiO2 ratio ≥ 250
Multilobar infiltrates
Confusion/disorientation
Uremia (BUN ≥20 mg/dL)
Leukopenia (WBC <4000 cells/mm3)
Thrombocytopenia (platelets <100,000 cells/mm3)
Hypothermia (core T <36°C)
Hypotension requiring aggressive fluid resuscitation
Major criteria
Invasive mechanical ventilation
Septic shock with the need for vasopressors
24. Consensus Guidelines on the Management of Community-Acquired
Pneumonia
Table 5: Clinical Indications for More Extensive Diagnostic Testing
Indication Blood culture Sputum culture Legionella UAT Pneumococcal UAT Other
Intensive care unit X X X X Xa
admission
Failure of outpatient X X X
antibiotic therapy
Cavitary infiltrates X X Xb
Leukopenia X X
Active alcohol abuse X X X X
Chronic severe liver X X
disease
Severe X
obstructive/structural
lung disease
Asplenia (anatomic or X X
functional
Recent travel (within X Xc
past 2 weeks)
Positive Legionella UAT Xd NA
result
Positive pneumococcal X X NA
UAT result
NOTE. NA, not
Pleural effusionapplication; UAT urinaryXantigen test X X X Xe
a Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage.
b Fungal and tuberculosis cultures.
c See table 8 for details
d Special media for Legionella
e Thoracentesis and pleural fluid cultures
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
25. Outpatient Empiric CAP Abx
Healthy; no abx x past 3 months
Macrolide e.g. azithromycin
2nd choice: doxycycline
Comorbidities; abx x past 3 mon (use alternative
abx)
Respiratory fluoroquinolone: Moxifloxacin, levofloxacin
750 mg, gemifloxacin
Beta-lactam + macrolide
Regions with >25% high-level macrolide-resistant
S. pneumo, consider alternative agents
2007 IDSA/ATS Guidelines for CAP in Adults.
26. Inpatient Empiric CAP Abx
Inpatients in ward
Respiratory fluoroquinolone
ß-lactam + macrolide
Inpatients in ICU
ß-lactam (cefotaxime/ceftriaxone or ampicillin/sulbactam) +
macrolide
Respiratory fluoroquinolone for PCN-allergic pts
Pseudomonas
Anti-pneumococcal & anti-pseudomonal ß-lactam +
azithromycin + cipro/levofloxacin
Can substitute quinolone for aminoglycoside
PCN-allergic: can substitute aztreonam
CA-MRSA: Add vanco or linezolid
2007 IDSA/ATS Guidelines for CAP in Adults.
27. Influenza pneumonia
Some things to keep in mind…
Antiviral treatment within 48 hrs
Reduce likelihood of lower tract complications
& antibacterial use in outpatients
Impact on hospitalized pts less clear
Possible exceptions to <48 h rule:
Immunocompromised patients
To reduce viral shedding for infection control in
hospitalized patients
28. Influenza pneumonia
Some things to keep in mind…
Influenza B
Oseltamavir 75 mg PO BID x 5 days
Zanamavir 2 INH BID x 5 days
Influenza A
H3N2 - general seasonal
Resistant to adamantane antivirals
H1N1 - general seasonal
High rate of oseltamavir resistance in 2008-2009
Still susceptible to zanamavir
Novel H1N1 (Swine flu)
Sensitive to neuraminidase inhibitors
Resistant to adamantanes
29. Drug-resistant Strep pneumoniae
ß-lactam resistance
Risk factors
Age >65 yrs
ß-lactam x previous 3 mon
Medical comorbidities
Exposure to child in day care
Current levels of ß-lactam resistance do not
generally result in treatment failure with
amoxicillin, ceftriaxone or cefotaxime
As opposed to macrolide or fluoroquinolone resistance
Clinically relevant threshold - MIC 4?
30. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Time to First Antibiotic Dose
• For patients admitted through the emergency department (ED),
the first antibiotic dose should be administered while still in the ED
(Moderate recommendation; Level III evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
31. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Switch from Intravenous to Oral Therapy
• Patients should be switched from intravenous to oral therapy
when they are hemodynamically stable and improving
clinically, are able to ingest medications, and have a normally
functioning gastrointestinal tract (Strong recommendation;
Level II evidence)
• Patients should be discharged as soon as they are clinically
stable, have no other active medical problems, and have a safe
environment for continued care. Inpatient observation while
receiving oral therapy is not necessary (Moderate
recommendation; Level II evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
32. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Duration of Antibiotic Therapy
• Patients with CAP should be treated for a minimum of 5 days (Level I
evidence), should be afebrile for 48-72 h, and should have no more than one
CAP-associated sign of clinical instability (Table 10) before discontinuation
of therapy (Moderate recommendation; Level II evidence)
• A longer duration of therapy may be needed if initial therapy was not active
against the identified pathogen or if it was complicated by extrapulmonary
infection, such as meningitis or endocarditis (Weak recommendation ; Level III
evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
33. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Table 10. Criteria for clinical stability
Temperature ≤ 37.8oC
Heart rate ≤ 100 beats/min
Respiratory rate ≤ 24 breaths/min
Systolic blood pressure ≥ 90 mmHg
Arterial oxygen saturation ≥ 90% or pO2 ≥ 60 mmHg on room air
Ability to maintain oral intakea
Normal mental statusa
NOTE. Critera are from [268, 274, 294]. pO2 oxygen partial pressure.
a
Important for discharge or oral switch decision but not necessarily for determination of nonresponse
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
34. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Other Treatment Considerations I
• Patients with CAP who have persistent septic shock despite
adequate fluid resuscitation should be considered for treatment
with drotrecogin alfa activated within 24h of admission (Weak
recommendation; Level II evidence)
• Hypotensive, fluid-resuscitated patients with severe CAP should
be screened for occult adrenal insufficiency (Moderate
recommendation; Level II evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
35. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Other Treatment Considerations II
• Patients with hypoxemia or respiratory distress should receive a
cautious trial of noninvasive ventilation unless they require
immediate intubation because of severe hypoxemia (PaO2/FiO2
ratio, <150) and bilateral alveolar infiltrates (Moderate
recommendation; Level I evidence)
• Low-tidal-volume ventilation (6 cm3/kg of ideal body weight)
should be used for patients undergoing ventilation who have
diffuse bilateral pneumonia or acute respiratory distress
syndrome (Strong recommendation; Level I evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
36. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Table 11. Patterns and Etiologies of Types of Failure to Respond
Failure to Improve
Early (<72h of treatment)
• Normal response
Delayed
• Resistant microorganism
- Uncovered pathogen
- Inappropriate by sensitivity
• Paraneumonic effusion/empyema
• Nosocomial superinfection
- Nosocomial pneumonia
- Extrapulmonary
• Noninfectious
- Complication of pneumonia (e.g., BOOP)
- Misdiagnosis: PE, CHF, vasculitis
- Drug fever
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
37. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Management of Non-responding Pneumonia
• The use of systematic classification of possible
causes of failure to respond, based on time of
onset and type of failure (Table 11), is
recommended. (Moderate recommendation;
Level II evidence)
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
38. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Table 11. Patterns and Etiologies of Types of Failure to Respond
Deterioration or Progression
Early (<72h of treatment)
• Severity of illness at presentation
• Resistant microorganism
- Uncovered pathogen
- Inappropriate by sensitivity
• Metastatic infection
- Empyema/parapneumonic
- Endocarditis, meningitis, arthritis
• Inaccurate diagnosis
- PE, aspiration, ARDS
- Vasculitis (e.g. SLE)
Delayed
• Nosocomial superinfection
- Nosocomial pneumonia
- Extrapulmonary
• Exacerbation of comorbid illness
• Intercurrent noninfectious disease
- PE
- Myocardial infarction
- Renal failure
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
39. Consensus Guidelines on the Management
of Community-Acquired Pneumonia
Table 12 Factors Associated with Non-responding Pneumonia
Overall Failure a Early failure b
Risk Factor Decreased Risk Increased Risk Decreased Risk Increased Risk
Older Age(>65 years) ... ... 0.35 ...
COPD 0.60 ... ... ...
Liver disease ... 2.0 ... ...
Vaccination 0.30 .... ... ...
Pleural effusion ... 2.7 ... ...
Multilobar infiltrates ... 2.1 ... 1.81
Cavitation ... 4.1 ... …
Leukopenia ... 3.7 ... ...
PSI class ... 1.3 ... 2.75
…
Legionella pneumonia ... ... ... 2.71
Gram-negative pneumonia ... ... ... 4.34
Fluoroquinolone therapy 0.50 ... .... ...
Concordant therapy ... ... 0.61 ...
Discordant therapy ... .... ... 2.51
NOTE. Data are relative risk values. COPD, chronic obstructive pulmonary disease; PSI, Pneumonia Severity Index
a
From [84]. b From [81].
Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
40. Case-control study from Canada - review of fluoroquinolone
(FLQ) use among Cx-proven TB cases.
Of 148 isolates of M. TB, 3 were FLQ resistant.
Patients who had received multiple FLQ prescriptions were more
likely than patients who had received a single FLQ prescription to
be infected with FLQ-resistant M. tuberculosis (15.0% vs. 0.0%;
odds ratio, 11.4; P<.04)
Long, Clin Infect Dis 2009. May 15; 48: 1355.
41. Follow-up Response
Expected improvement?
Clinical improvement w/ effective abx: 48-72 hrs
Fever can last 2-5 days with Pneumococcus,
longer with other etiologies, esp Staph aureus
CXR clearing
If healthy & <50 yo, 60% have clear CXR x 4 wks
If older, COPD, bacteremic, alcoholic, etc. only 25%
with clear CXR x 4 wks
Switch from IV to PO
Hemodynamically stable, improving clinically
Able to ingest meds with working GI tract
42. Question…
What is far & away the most common reason
for non-response to antibiotics in CAP?
1. Cavitation
2. Pleural effusion
3. Multilobar involvement
4. Discordant antibiotic/etiology
5. None of the above
43. Inadequate Response to Therapy
What to consider
Consider S. aureus, virus, resistant organism, TB, endemic fungi,
Pneumocystis
More unusual pathogens, atypical mycobacteria, higher bacteria
(Nocardia, actinomycetes), fungi
Noninfectious illness:
Lung neoplasms with bronchial obstruction
Lymphoma
Systemic autoimmune disorders
PE w/ infarct, pulm edema, ARDS
Consider other testing:
Lower tract sampling (bronch)
CT chest
PE work-up?
Serologic testing
Open lung biopsy