Evidence-based Treatment of

Community Acquired Pneumonia

Stephen A. Wilson, MD, MPH

Director, University of Pittsburgh Family

Medicine Faculty Development Fellowship
Clinical Associate Professor, University of
Pittsburgh School of Medicine
Objectives
 Identify common causes of CAP
 Select appropriate antibiotics for CAP
 Be aware of CAP Quality Measures
 Rethink antibiotic timing
What is pneumonia?
 Infection / Inflammatory illness of the
lungs
 Bacteria
 Virus
 Fungus
 Parasites
 Lung parenchyma/alveolar
inflammation and abnormal alveolar
filling with fluid consolidation and
exudation
Consolidation
What is pneumonia consolidation?
 Alveolar space that now contains the fluid
instead of air
 Area of lung that was collapsible that is
now filled with a fluid
 Pulmonary edema
 Inflammatory exudate
 Pus
 Inhaled water
 Blood (from bronchial tree or a pulmonary
artery)
What is CAP?
 Acute infection/inflammation of the
pulmonary parenchyma not acquired
in the hospital or a long-term care
facility
 Not
 Nursing-home acquired
 Ventilator-acquired
 Nosocomial
How is CAP described
radiographically?
 Lobar pneumonia
 Multilobar pneumonia is more severe
 Bronchial pneumonia
 Interstitial pneumonia
Lobar Pneumonia
 Bronchial Pneumonia
http://www.lakeridgehealth.on.ca/patient_care/interventional_radiology/presentations/radiology/pneumo
nia.jpg
 Interstitial Pneumonia

http://www.mevis-research.de/~hhj/Lunge/ima/InfInt_zu_AlvThA15_8.JPG
 Bronchitis vs. Pneumonia

http://www.medtogo.com/bronchitis-pneumonia.html
 CAP Facts & Epidemiology
 ~5.6 million cases/yr in the United States
 1.1 million  hospitalization
 ~ $8.4 billion annual cost for CAP
 92% of cost with inpatient therapy
 60% of adults 65 years and over received a
pneumococcal vaccination (2008)
 Hospital discharges annually: 1.2 million
 Average length of stay: 5.1 days

Early Release of Selected Estimates from the National Health Interview Survey,data table
for figure 5.1
2006 National Hospital Discharge Survey, tables 2,4
CAP Facts & Epidemiology
 Mortality
 Number of deaths: 55,477a
 Deaths rate: 18.5 per 100,000
populationa
 Percent of hospital inpatient deaths from
pneumonia: 5.4%b

a) Deaths: Final Data for 2006, tables 10, 11

b) National Hospital Discharge Survey: 2004 Annual Summary With Detailed
Diagnosis and Procedure Data, table 25
Why some and not others?
 Genetic predisposition?
 Predisposing factors in old age may be
 Impaired cough reflex
 Neurological diseases  impaired functioning of
the pharynx and susceptibility to aspiration
 Obstructive pulmonary diseases
 Immobilization
 Heart failure
 Malnourished or undernourished
 Cigarette smoking

Riquelme-R et al. Community-acquired pneumonia in the elderly: A multivariate analysis of risk and
prognostic factors. Am J Respir Crit Care Med 1996;154:1450-5
 How is CAP described by causative
pathogen?
 Typical: 60-70%
 Usually Streptococcus pneumonia 40-60%
 H. influenzae 3-10%
 Atypical: 30-40%
 Mycoplasma pneumoniae
 Legionella pneumophila
 Chlamydia pneumoniae
 Viruses: Influenza, Adenovirus
 Gram-negative bacteria up to ~5-10%
 Staphylococcal up to 5-10%
 IV drug abuse (with right-sided endocarditis),
immunocompromised, chronic lung disease, post-op
 more common after an episode of influenza
CAP symptoms
 Cough, fever, chills, fatigue, dyspnea,
rigors, and pleuritic chest pain
 May include headache and myalgia
 Depending on the pathogen, cough
may be persistent and dry, or it may
produce sputum
 Legionella may produce
gastrointestinal symptoms
CAP Signs & Symptoms

http://upload.wikimedia.org/wikipedia/commons/0/07/Main_symptoms_of_infectious_pneumonia.png
CAP Physical Exam
 Dullness to percussion of chest, crackles on
auscultation, bronchial breath sounds,
tactile fremitus, egophony, whispered
pectoriloquy, bronchophony
 Tachypnea may be present
 Patients with typical pneumonia are more
likely to present with dyspnea and
bronchial breath sounds on auscultation
Exam
Traditional chest physical
examination not sufficiently
accurate to confirm or exclude
diagnosis of pneumonia
 48-71% positive predictive value
 55-72% negative predictive value
 Unknown if inclusion of history would
improve accuracy of clinical diagnosis

Arch Intern Med 1999 May 24;159(10):1082

Lab Tests
 Sputum culture
 Blood culture
 Procalcitonin
Lab Test: Sputum Culture
 Sputum samples are adequate in
52% of CAP, and only 44 % of those
samples contain pathogens  22/100
Lab Test: Blood culture
 Positive blood cultures in only 5-10%
of patients, including those with
severe disease
 Do not correlate with severity of illness
or outcome
 Lab Test: Blood Cultures
 Prompted a change in antibiotic
therapy in 2% of patients, but in only
0.4% of them was this change likely
to have improved the patient's
outcome.
 May still be prudent to order them in
cases where patients have a higher
disease severity (Fine class III - V).

Campbell SG, Marrie TJ, Anstey R, et al. The contribution of blood cultures to the clinical management of
adult patients admitted to the hospital with community-acquired pneumonia. Chest 2003; 123:1142-50.
Lab Test: Blood cultures
 Do not seem necessary for patients
with routine community-acquired
pneumonia and no underlying risk
factors
 Blood cultures and sputum studies do
not seem warranted in patients with
mild pneumonia and no co-morbid
conditions

Ann Emerg Med 2005 Nov;46(5):393

Chest 2001 Jan;119;181 in Am Fam Physician 2001 Aug 15;64(4):665
 Lab Test: Procalcitonin
 Elevated in the presence of severe bacterial
conditions
 not viral or nonspecific inflammatory conditions
 Reduced antibiotic use by half in patients
with lower respiratory tract without adverse
effects on the patients. LOE-2B (Single
blind but used ITT)

Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of procalcitonin-guided treatment on antibiotic

use and outcome in lower respiratory tract infections: cluster-randomised, single-blinded intervention trial.
Lancet 2004; 363:600-07.
What about CXR?
 Useful in helping make diagnosis
 Maybe normal early on
 May not affect M&M of outpatient CAP
47-year-old smoker presented a few hours of rigors and
productive cough
Despite clinical signs of right upper zone consolidation, chest x-
ray showed only minor abnormalities
Empirical therapy for CAP was begun
•12 hours later
•Chest x-ray showed consolidation in the right upper lobe
consistent with the earlier clinical signs
CXR in Outpatients with LRI

 Adults
 trial involving 1502 adults attending an
emergency department found no significant
difference in length of illness, the single
outcome prespecified for this review (mean
of 16.9 days in radiograph group versus
17.0 days in control group, P > 0.05).

Swingler, George H; Zwarenstein, Merrick; Swingler, George H. Chest radiograph in acute respiratory
infections (Cochrane Review). In: The Cochrane Library 2009 Issue 2. Chichester, UK: John Wiley and
Sons, Ltd.
Management
 Inpatient ($7,000 - $8,000)
 Outpatient ($150 - $300)
CAP Prognosis
Pneumonia Severity CURB 65
Index Risk of mortality
30-day mortality  0 points 0.7%
based on risk class  1 point 3.2%
 I - 0-0.4%  2 points 3%
 II - 0.4-0.9%  3 points 17%
 III - 0-2.8%  4 points 41.5%
 IV - 8.2-12.5%  5 points 57%
 V - 0.6-10.6%

Fine MJ, et al. N Engl J Med 1997; 336: 243-50. Aujesky D, Auble TE, Yealy DM, et al.
Prospective comparison of three validated prediction rules for prognosis in
community-acquired pneumonia. Am J Med 2005; 118: 384-92.
Aujesky D, Auble TE, Yealy DM, et al. Prospective comparison of three validated prediction rules for
prognosis in community-acquired pneumonia. Am J Med 2005; 118: 384-92.
 FACTORS THAT INCREASE THE RISK OF
INFECTION WITH SPECIFIC PATHOGENS
Penicillin-resistant and drug-resistant pneumococci
 Age > 65 yr
 Beta-Lactam therapy within the past 3 mo
 Alcoholism
 Immune-suppressive illness (including therapy with corticosteroids)
 Multiple medical co-morbidities
 Exposure to a child in a day care center

Enteric gram-negatives
 Residence in a nursing home
 Underlying cardiopulmonary disease
 Multiple medical co-morbidities
 Recent antibiotic therapy

Pseudomonas aeruginosa
 Structural lung disease (bronchiectasis)
 Corticosteroid therapy (>10 mg of prednisone per day)
 Broad-spectrum antibiotic therapy for >7 d in the past month
 Malnutrition
 Outpatients: without cardiopulmonary
disease and no modifying factor
Organisms Therapy
 Streptococcus Advanced generation
pneumoniae
macrolide:
 Mycoplasma pneumoniae
azithromycin or
 Chlamydia pneumoniae
(alone or as mixed clarithromycin
infection)
 Hemophilus influenzae or
 Respiratory viruses
 Miscellaneous
 Legionella spp. Doxycycline
 Mycobacterium
tuberculosis
 Endemic fungus
<8 days Abx same as >8 days

Dutch study: mild-mod CAP

with PSI <110  3d =8d if
significant improvement
after 3rd day
Outpatient WITH Cardiopulmonary Ds
AND/OR Other Modifying Factors
Organisms Therapy
 Streptococcus pneumoniae Beta-Lactam (oral
(including DRSP) cefpodoxime, cefuroxime,
 Mycoplasma pneumoniae high-dose amoxicillin,
 Chlamydia pneumoniae amoxicillin/clavulanate;
 Mixed infection (bacteria or parenteral ceftriaxone
plus followed by oral
atypical pathogen or cefpodoxime)
virus
 Hemophilus influenzae
plus
 Enteric gram-negatives Macrolide or doxycycline
 Respiratory viruses
 Miscellaneous or
 Moraxella catarrhalis,
Legionella spp., aspiration Antipneumococcal
(anaerobes),
Mycobacterium fluoroquinolone (used
tuberculosis, endemic fungi alone)
 Inpatient NOT in ICU
NO Cardiopulmonary Disease, No Modifying Factors

Organism Therapy
 S. Pneumoniae IV azithromycin alone
 H. influenzae If macrolide allergy or
 M. pneumoniae intolerant:
 C. pneumoniae Doxycycline + Beta-lactam
 Mixed infection
(bacteria plus atypical or
pathogen)
 Viruses Monotherapy with an
 Legionella spp. antipneumococcal
 Miscellaneous fluoroquinolone
 M. tuberculosis
 endemic fungi
 P. carinii
 Inpatient NOT in ICU
WITH Cardiopulmonary Ds and/or Modifying
Factors (Incl. from Nursing Home)

Organism Therapy
 S. Pneumoniae IV Beta-lactam (cefotaxime,
 H. influenzae ceftriaxone,ampicillin/sulba
 M. pneumoniae ctam, high-dose
ampicillin) plus
 C. pneumoniae macrolide or doxycycline
 Mixed infection
(bacteria plus atypical or
pathogen)
 Viruses IV antipneumococcal
 Legionella spp. fluoroquinolone alone
 Miscellaneous
 M. tuberculosis
 endemic fungi
 P. carinii
 Inpatient in ICU
No Risks for Pseudomonas
aeruginosa

IV Beta-lactam (cefotaxime,
ceftriaxone) plus
either IV macrolide (azithromycin)
or IV fluoroquinolone
 Inpatient in ICU
Risks for Pseudomonas aeruginosa

Selected IV antipseudomonal Beta-lactam

(cefepime, imipenem, meropenem,
piperacillin/tazobactam)
plus IV antipseudomonal quinolone (ciprofloxacin)
or
Selected IV antipseudomonal Beta-lactam
(cefepime, imipenem, meropenem,
piperacillin/tazobactam)
plus IV aminoglycoside
plus either IV macrolide (azithromycin) or
intravenous nonpseudomonal fluoroquinolone
What if Tx is not working?
 Expectation = stable by Day 3
 If not and if pt has factors associated
with a delayed response  no Abx
change.
 If no explanation for a slow to no
response after 7 d of therapy, or if
there is clinical deterioration after
24 h of therapy
 re-evaluate
4 Main Reasons for Failure or Lack
of Improvement
 Inadequate antimicrobial selection
 Unusual pathogens
 Complications of pneumonia
 Up to 10% with bacteremic pneumococcal
pneumonia can have metastatic infections
 Meningitis
 Arthritis
 Endocarditis
 Pericarditis
 Peritonitis
 Empyema
 Noninfectious pulmonary illness
Antibiotic timing – Old thinking

Antibiotics within 4 hours of hospital

arrival associated with lower mortality
 Retrospective cohort study
 Antibiotics within 4 hours of arrival was
associated with lower in-hospital mortality
(6.8% vs. 7.4%), lower 30-day mortality
(11.6% vs. 12.7%), and shorter length of
stay (by 0.4 days)

Arch Intern Med 2004 Mar 22;164(6):637

Antibiotic timing – Evolving
Rapid delivery of appropriate antibiotics associated
with reduced length of hospital stay
 Observational cohort study
 Factors associated with length of stay < 9 days
included
 Initial antibiotic treatment in emergency department
instead of hospital floor (odds ratio [OR] 0.31, 95%
confidence interval [CI] 0.19-0.48)
 Appropriate antibiotic selection (OR 0.55, 95% CI
0.35-0.88)
 Shorter door-to-needle time (OR 1.75 per each
additional 8 hours, 95% CI 1.34-2.29)

Arch Intern Med 2002 Mar 25;162(6):682

Antibiotic timing – New thinking
4-hour rule as quality indicator for
receiving antibiotics has been
questioned
 Delay in receiving antibiotics > 4 hours
from hospital admission not independently
associated with mortality
 Prospective study of 451 immunocompetent
adults admitted for community-acquired
pneumonia

Chest 2006 Jul;130(1):11

Antibiotic timing – New thinking
 Retrospective before-and-after study
 4-hour rule may reduce accuracy of
diagnosis and may not reduce time to
antibiotic treatment for community-
acquired pneumonia in emergency
department

Arch Intern Med 2008 Feb25;168(4):351

Antibiotic Duration
 Levofloxacin 750 mg/day for 5 days as
effective as 500 mg/day for 10 days

 Randomized trial without intention-to-treat analysis

 No significant differences in clinical response rates (92.4% vs.
91.1%), microbiologic eradication rates, relapse rates or
adverse events
 750 mg group had more patients with resolution of fever at 3
days (67.4% vs. 54.6%) and trend toward more rapid
resolution of dyspnea and purulent sputum

Clin Infect Dis 2003 Sep 15;37(6):752

Antibiotic Duration
 Amoxicillin for 3 days may be as effective as
amoxicillin for 8 days for adults hospitalized
with pneumonia who improved at 3 days

 Randomized trial with wide confidence intervals

 Comparing 3 days vs. 8 days of amoxicillin in

intention-to-treat analysis
 clinical success rate at 10 days 88% vs. 87.5%
 clinical success rate at 28 days 82% vs. 77%
 adverse events in 11% vs. 21% (p = 0.1)

BMJ 2006 Jun 10;332(7554):1355

Oral vs. IV Abx
Oral antibiotics appear as effective as IV
antibiotics in inpatients with non-severe
pneumonia

 Meta-analysis of 7 studies comparing oral vs. IV antibiotics in

1,366 patients hospitalized with non-severe community-
acquired pneumonia
 No significant differences in mortality at end of treatment or at
follow-up
 Mean length of hospital stay shorter with oral antibiotics (6.1
days vs. 7.8 days)

Am J Med 2004 Mar 15;116(6):385

Transition from Oral  IV Abx
 Early switch (day 3 vs. day 7) from IVoral
appears safe and shortens hospital stay in
severe community-acquired pneumonia
 Early switch from IV  oral antibiotics and
early discharge strategies may reduce
hospital length of stay
 In-hospital observation may be
unnecessary after switch from intravenous
to oral antibiotics
Which elderly with CAP get
bacteremia?

Metersky ML, Ma A, Bratzler DW, Houck PM. Predicting bacteremia in patients with community-
acquired pneumonia. Am J Respir Crit Care Med 2004; 169:342-47.
Does all this matter?
 Yes
 Using Abx empirically per guidelines in
hospitalized patients
 less CAP deaths at 48-96 hrs
 less overall death
 shorter hospital stay
 shorter time to oral abx

http://firstwatch.jwatch.org/cgi/content/full/2006/1010/3
Medicare/Joint Commission National
Hospital Inpatient Quality Measures

http://dynaweb.ebscohost.com/Detail.as
px?docid=/dynamed/Blankmisc207&si
d=446993f2-d2b2-4af0-b068-
e82c8bcd7d55@sessionmgr14
More to Pneumonia than CAP
 Chronic  Eosinophilic
 Nursing-home Not pneumonia
so fast…
acquired  Chemical pneumonia
 Ventilator-acquired  Aspiration
 Nosocomial pneumonia
 Chronic  Dust pneumonia
 Severe acute  Necrotizing
respiratory syndrome pneumonia
(SARS)
 Opportunistic
 Bronchiolitis
obliterans organizing pneumonia
pneumonia (BOOP)
Objectives
 Identify common causes of CAP
 Select appropriate antibiotics for CAP
 Be aware of CAP Quality Measures
 Rethink antibiotic timing
 References
 http://dynaweb.ebscohost.com
 www.essentialevidenceplus.com
 http://en.wikipedia.org/wiki/Pneumonia
 http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?p
g=/ppdocs/us/common/dorlands/dorland/six/000084139.htm
 http://www2.merriam-webster.com/cgi-
bin/mwmednlm?book=Medical&va=consolidation
 http://www.lakeridgehealth.on.ca/patient_care/interventional_radiol
ogy/presentations/radiology/pneumonia.jpg
 http://www.medtogo.com/bronchitis-pneumonia.html
 http://www.mevis-
research.de/~hhj/Lunge/ima/InfInt_zu_AlvThA15_8.JPG
 Valenzuela, Peter. Community Acquired Pneumonia. www.fmdrl.org
 Harrison, Bradley K. Community Acquired Pneumonia (CAP).
www.fmdrl.org
 http://www.cdc.gov/nchs/FASTATS/pneumonia.htm
 http://upload.wikimedia.org/wikipedia/commons/0/07/Main_sympto
ms_of_infectious_pneumonia.png
References
 Early Release of Selected Estimates from the National Health
Interview Survey, data table for figure 5.1
 2006 National Hospital Discharge Survey, tables 2,4
 Deaths: Final Data for 2006, tables 10, 11
 National Hospital Discharge Survey: 2004 Annual Summary
With Detailed Diagnosis and Procedure Data, table 25
 Riquelme-R et al. Community-acquired pneumonia in the
elderly: A multivariate analysis of risk and prognostic factors.
Am J Respir Crit Care Med 1996;154:1450-5
 Arch Intern Med 1999 May 24;159(10):1082
 Christ-Crain M, Jaccard-Stolz D, Bingisser R, et al. Effect of
procalcitonin-guided treatment on antibiotic use and outcome
in lower respiratory tract infections: cluster-randomised,
single-blinded intervention trial. Lancet 2004; 363:600-07.
 References
 Campbell SG, Marrie TJ, Anstey R, et al. The contribution of blood
cultures to the clinical management of adult patients admitted to the
hospital with community-acquired pneumonia. Chest 2003; 123:1142-
50.
 Swingler, George H; Zwarenstein, Merrick; Swingler, George H. Chest
radiograph in acute respiratory infections (Cochrane Review). In: The
Cochrane Library 2009 Issue 2. Chichester, UK: John Wiley and Sons,
Ltd.
 Ann Emerg Med 2005 Nov;46(5):393
 Chest 2001 Jan;119;181 in Am Fam Physician 2001 Aug 15;64(4):665
 Fine MJ, et al. N Engl J Med 1997; 336: 243-50. Aujesky D, Auble TE,
Yealy DM, et al. Prospective comparison of three validated prediction
rules for prognosis in community-acquired pneumonia. Am J Med 2005;
118: 384-92.
 Aujesky D, Auble TE, Yealy DM, et al. Prospective comparison of three
validated prediction rules for prognosis in community-acquired
pneumonia. Am J Med 2005; 118: 384-92.
 Am. J. Respir. Crit. Care Med., Volume 163, Number 7, June 2001,
1730-1754