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Community Acquired
Pneumonia (CAP)
Bradley K. Harrison, M.D.
CAP defined
• Pneumonia not acquired in a hospital or a
long-term care facility
– Hospital acquired pneumonia
– Healthcare associated pneumonia: other
healthcare facilities such as nursing homes,
dialysis centers, and outpatient clinics
Introduction
• Estimated 5.6 million cases of CAP occur
annually in the United States
• Estimated total annual cost for CAP in the
United States is $8.4 billion
– 92% of cost with inpatient therapy
• Because CAP is the only acute respiratory tract
infection in which there is increased mortality if
antibiotic therapy is delayed, diagnostic and
treatment decisions need to be made accurately
and efficiently
• Mortality rate among hospitalized patients with
CAP varies each year and can reach 35%
Epidemiology
• Unclear because few population-based statistics
for CAP alone are available
• Center for Disease Control and Prevention
(CDC) combines pneumonia with influenza
when collecting data on morbidity and mortality
• In 2001, influenza and pneumonia combined
were the 7th
leading cases of death in the U.S.
– Down from 6th
in previous years
• Death rate of 21.8 per 100,000 patients
Clinical Presentation
• Pneumonia is an inflammation or
infection of the lungs that causes them to
function abnormally
• Classified as typical or atypical, although
the clinical presentations are often similar
• Several symptoms commonly present in
patients with pneumonia
• Approximately 20-33% of episodes result
in hospitalization
Etiology
• Typical: up to 70%
– Usually caused by Streptococcus pneumoniae
• Atypical: 30-40%
– “My Lungs Contain Viruses”
• Mycoplasma pneumoniae
• Legionella pneumophila
• Chlamydia pneumoniae
• Viruses: Influenza, Adenovirus
– May be co-pathogens in other cases
Symptoms
• Cough, fever, chills, fatigue, dyspnea, rigors, and
pleuritic chest pain
• Depending on the pathogen, cough may be
persistent and dry, or it may produce sputum
• Other presentations may include headache and
myalgia
• Certain etiologies, such as legionella, also may
produce gastrointestinal symptoms
– Symptoms at presentation are not useful in
distinguishing CAP from respiratory illnesses with
other causes
Diagnosis: Physical Examination
• Dullness to percussion of chest, crackles
or rales on auscultation, bronchial breath
sounds, tactile fremitus, and egophany
(“E” to “A” changes)
• Patient may also be tachypneic
• Patients with typical pneumonia are more
likely to present with dyspnea and
bronchial breath sounds on auscultation
Diagnosis: Radiography
• CXR (PA and Lateral):
– American Thoracic Society (ATS) guidelines, “all patients with
suspected CAP should have a chest radiograph to establish the
diagnosis and identify complications (pleural effusions,
multilobar disease)”
– Lobar consolidation – more common in typical pneumonia
– Bilateral, diffuse infiltrates – commonly seen in atypical
pneumonia
• However, radiologists cannot reliably differentiate bacterial from
nonbacterial pneumonia on the basis of the radiographic
appearance
– If performed early in the course of the disease, may be negative
• The sensitivity of chest radiography depends greatly on pretest
probability
•47-year-old smoker presented after just 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 community-acquired pneumonia was begun
•12 hours later
•Chest x-ray showed consolidation in the right upper lobe consistent with the
earlier clinical signs
•S. pneumoniae was isolated from blood cultures
•The patient recovered fully
Diagnosis: Radiography (cont.)
• CT
– CT scan could be performed in patients with a negative chest
radiograph when there is a high clinical suspicion for
pneumonia
– CT scan, especially high resolution CT (HRCT), is more
sensitive than plain films for the evaluation of interstitial
disease, bilateral disease, cavitation, empyema, and hilar
adenopathy
– This technology is not generally recommended for routine use
because the data for its use in CAP are limited, the cost is high,
and there is no evidence that this improves outcome
– Thus, a chest radiograph is the preferred method for initial
imaging, with CT scan or MRI reserved for further anatomical
definition
Diagnosis: Laboratory Tests
• Historically: WBC, sputum cultures, two sets of blood
cultures, and urine antigens
– Sputum samples are adequate in only 52% of patients with
CAP, and only 44 % of those samples contain pathogens
• Likely due to problems with retrieving samples from lower
respiratory tract, previous antibiotics, contamination from upper
airways, or viral etiology
– Positive blood cultures obtained in only 5-10% of patients,
including those with severe disease
• Positive blood culture has no correlation with severity of illness or
outcome
– Current ATS guidelines recommend that patients hospitalized
for suspected CAP receive 2 sets of blood cultures
Sensitivity and Specificity of Diagnostic Tests for CAP
Diagnostic tests by pathogen Sensitivity (%) Specificity (%)
Chlamydia
Rapid PCR (sputum, BAL fluid) 30 to 95 > 95
Serology (fourfold rise in serum
and convalescent titers)
10 to 100 -
Sputum culture 10 to 80 > 95
Gram-negative rods
Sputum Gram stain 15 to 100 11 to 100
Haemophilus influenzae, Moraxella catarrhalis,
Pneumoniae
Sputum culture Diagnostic yield 20 to
79*
Diagnostic yield 20 to
79*
Influenza
Rapid DFA (sputum, BAL fluid) 22 to 75 90
Legionella pneumophila
DFA (sputum, BAL fluid) 22 to 75 90
PCR (sputum, BAL fluid) 83 to 100 > 95
Serum acute titer 10 to 27 > 85
Urinary antigen 55 to 90 > 95
Mycoplasma pneumoniae
Antibiotic titers 75 to 95 > 90
Cold agglutinins 50 to 60 -
PCR (sputum, BAL fluid) 30 to 95 > 95
Pneumococcal pneumoniae
Chest radiography (lobar infiltrate) 40† -
Sputum culture Diagnostic yield
20 to 79*
Diagnostic yield 20 to
79*
Sputum Gram stain 15 to 100 11 to 100
Diagnosis and treatment of community-acquired pneumonia: Am Fam
Physician. 2006 Feb 1;73(3):442-50.
Treatment
• Initial treatment of CAP is based on physical
examination findings, laboratory results, and patient
characteristics
– Age, chronic illnesses, smoking history, history of the illness
• Therapy for pneumonia is empiric because specific
pathogens usually are not identified at the time treatment
is initiated
• Physicians should begin their treatment decisions by
assessing the need for hospitalization using a prediction
tool for increased mortality, combined with clinical
judgment
– Pneumonia Severity Index
Pneumonia Severity Index (PSI)
• PSI was derived and validated as part of the Pneumonia
Patient Outcomes Research Team (PORT) prospective
cohort study for the purpose of identifying patients with
CAP at low risk for mortality
– The Pneumonia PORT prediction rule used a derivation cohort
of 14,199 inpatients with CAP; it was independently validated
in 38,039 inpatients with CAP and in 2,287 inpatients and
outpatients prospectively
– The PSI rule stratified adults with radiographic evidence of
pneumonia into five classes for risk of death from all causes
within 30 days of presentation
• One limitation in the derivation of this rule was that it
included mostly patients seen in a hospital emergency
department, and included few outpatients who were
evaluated in a physician's office and sent home
Demographics
Male Age (years)
Female Age (years) − 10
Nursing home resident + 10
Comorbid illness
Neoplastic disease + 30
Liver disease + 20
Congestive heart failure + 10
Cerebrovascular disease + 10
Renal disease + 10
Physical examination findings
Altered mental status + 20
Respiratory rate > 30 breaths per minute + 20
Systolic blood pressure < 90 mm Hg + 20
Temperature < 35˚C (95˚F) or > 40˚C (104˚F) + 15
Pulse rate > 125 beats per minute + 10
Laboratory and radiographic findings
Arterial pH < 7.35 + 30
Blood urea nitrogen > 64 mg per dL (22.85 mmol
per L)
+ 20
Sodium < 130 mEq per L (130 mmol per L) + 20
Glucose > 250 mg per dL (13.87 mmol per L) + 10
Hematocrit < 30 percent + 10
Partial pressure of arterial oxygen < 60 mm Hg or
oxygen percent saturation < 90 percent
+ 10
Pleural effusion + 10
Pneumonia Severity Index (PSI)
Point total
Risk
R
i
s
k
c
l
a
s
s
Recommended site
of care
No predictors Low I Outpatient
≤ 70 Low I
I
Outpatient
71 to 90 Low I
I
I
Inpatient (briefly)
91 to 130 Moderate I
V
Inpatient
> 130 High V Inpatient
Treatment: Outpatient vs. Inpatient
• Choosing between outpatient and inpatient
treatment is a crucial decision because of the
possible risk of death
• Decision influences diagnostic testing and
medication choices, as well as a psychological
impact on patients and families
• Average cost
– Inpatient: $7,500
– Outpatient: $150-350
• Based on age, co-morbidities, and the severity of
presenting disease
Treatment: Outpatient vs. Inpatient
(cont.)
• Physicians tend to overestimate a patient’s risk
of death; many low-risk patients could be treated
safely as outpatients
• By using Pneumonia Severity Index (PSI), 26-
31% of hospitalized patients were good
outpatient candidates
– An additional 13-19% only needed brief hospital
observation
• PSI can serve as a general guideline, clinical
judgment should always supersede prognostic
score
Pharmacotherapy: Outpatient
• Consensus guidelines
– ATS, Infectious Disease Society of America, and Canadian Guidelines
for the Initial Management of Community-Acquired Pneumonia
• Empiric oral therapy with macrolides, doxycycline, or an
oral beta lactam (amoxicillin, cefuroxime [ceftin], or
amoxicillin/clavulanate [augmentin]), or a
flouroquinolone
– Therapeutic Working Group of the CDC
• Use flouroquinolones sparingly because of resistance concerns
• Duration of therapy
– S. pneumoniae: 7-10 days or until afebrile 3 days
• Bacteremic: 10-14 days
– Mycoplasma/Chlamydia pneumoniae: 10-14 days, up to 21 days
– Legionella: 10-21 days
Pharmacotherapy: Outpatient
(cont.)
• Several classes of antibiotics are effective against atypical
pathogens
• C. pneumoniae and Legionella species are intracellular
organisms and M. pneumoniae lacks a cell wall, beta
lactams are not effective
– Erythromycin and tetracycline have been traditional choices for
atypical CAP
– Newer macrolides (azithromycin [zithromax] and
clarithromycin [biaxin]) have good atypical activity and are
generally are better tolerated than erythromycin
– Doxycycline (Vibramcyin) is effective, associated with fewer
gastrointestinal side effects, and is a less expensive alternative
– Flouroquinolones have demonstrated excellent activity against
atypicals and have one-daily dosing and excellent bioavailability
Pharmacotherapy: Outpatient
(cont.)
• The Sanford Guide to Antimicrobial
Therapy 2006 – 36th
Ed.
– CAP, not hospitalized, no comorbidities*
• Azithro 0.5g PO x 1, then 0.25g PO QD
• Azithro-ER 2g x 1 (2g /60mL single dose bottle)
• Clarithro 500mg PO BID
• Clarithro-ER 1g PO Q24h
• Doxy 100mg PO BID
* Alcoholism, bronchiectasis, COPD, IVDU, Post-
CVA aspiration, post-obstruction of bronchi,
post-viral
Pharmacotherapy: Outpatient
(cont.)
• The Sanford Guide to Antimicrobial
Therapy 2006 – 36th
Ed.
– CAP, not hospitalized, with comorbidities
• Respiratory flouroquinolone
– Gati 400mg PO q24h, Gemi 320mg PO q24h, Levo
750mg PO q24h, Moxi 400mg PO q24h
• Telithro 800mg PO q24h
• Azithro/Clarithro + HD Amox, HD AM-CL,
cefdinir, cefpodoxime, cefprozil
Pharmacotherapy: Inpatient
• Antibiotic therapy should be initiated within 4
hours of hospitalization
• Intravenous beta lactam (cefotaxime [claforan]
or ceftriaxone [rocephin]) plus a macrolide or a
combination of ampicillin/sulbactam (unasyn)
plus a macrolide or a fluoroquinolone alone
• After clinically stable (T<100.0, HR<100,
RR<24, SBP>90, O2 sat>90%) and able to
tolerate oral intake, may be switched to oral
antibiotics for remainder of therapy
– Save money, earlier discharge, minimizes risk of
nosocomial infections
Pharmacotherapy: Inpatient (cont.)
• The Sanford Guide to Antimicrobial
Therapy 2006 – 36th
Ed.
– CAP, hospitalized, NOT in ICU, no
comorbidities
• Ceftriaxone 2g IV q24h + Azithro 500mg IV
q24h
– Age >65: Ceftriaxone 1g IV q24h
– CAP, hospitalized, NOT in ICU,
comorbidities
• Gati 400mg IV q24h, Levo 750mg IV q24h, Moxi
400mg IV q24h
Flouroquinolones
• Conservative use is recommended to
minimize resistance patterns
• New flouroquinolones (levofloxacin,
gatifloxacin, moxifloxacin) should be used
only when patients have failed
recommended first-line regimens, are
allergic to alternative agents, or have a
documented infection with highly drug-
resistant pneumococci
Pneumococcal Resistance
• S. pneumoniae accounts for 60-70% of all bacterial
CAP
– Affects all patient groups and can be fatal
• Alarming rate of resistance to many commonly
used antibiotics
– PCN uncommon before 1990
• Resistance classified as intermediate or high-
level
– Intermediate: 28%
– High-level: 16%
• Nation-wide
Patterns of Resistance to Antibiotics in North America
Antibiotic
Resistance
(%)
Penicillins
Amoxicillin/clavulanate (Augmentin) 4.1
Penicillin 21.3
Cephalosporins
Cefepime (Maxipime) 0.4
Cefprozil (Cefzil) 23.9
Ceftriaxone (Rocephin) 1.9
Cefuroxime (Ceftin) 24.7
Macrolides
Azithromycin (Zithromax) 23.0
Clarithromycin (Biaxin) 26.6
Erythromycin 28.3
Fluoroquinolones
Gatifloxacin (Tequin) 0.7
Levofloxacin (Levaquin) 0.7
Moxifloxacin (Avelox) 0.4
Miscellaneous
Clindamycin (Cleocin) 9.2
Tetracycline 18.8
Trimethoprim/sulfamethoxazole (Bactrim,
Septra)
29.9
Vancomycin (Vancocin) 0.0
•Antibiotics tested against
Streptococcus pneumoniae
isolates
•Resistance rates averaged
across all patient groups
Cost-effective Care
• When choosing a treatment, it is essential
to compare costs and outcomes of all
recommended drug therapies
• Evaluation should lead to a decision that
will maximize the value of health care
services, not simply reduce the costs of
drug therapy
– Overall cost of each therapy should be
obtained by comparing the end cost with the
probability of achieving a positive outcome
Antimicrobial Therapies for CAP
Agent Dosage
Cost per course
(generic) Common adverse reactions
Cefotaxime (Claforan)
Cefpodoxime (Vantin)
Cefprozil (Cefzil)
Ceftriaxone (Rocephin)
Cefuroxime (Ceftin)
1 g IV every six to eight hours
200 mg orally twice per day
500 mg orally twice per day
1 g IV every 24 hours
500 mg orally twice per day
0.75 to 1.5 g IV every eight hours
$355 (330)
124 (110)
192
392
219 oral
250 to 358 IV
Mild diarrhea
Rash
Clindamycin (Cleocin) 300 mg orally every six hours
600 mg IV every eight hours
238 (148 to 168) oral
250 IV
Mild diarrhea
Abdominal pain
Pseudomembranous colitis
Rash
Gatifloxacin (Tequin)
Levofloxacin (Levaquin)
Moxifloxacin (Avelox)
400 mg orally or IV once per day
500 mg orally or IV once per day
400 mg orally once per day
98 oral, 382 IV
56 oral, 438 IV
107
Mild diarrhea
Nausea
Vomiting
Constipation
Dizziness
Headache
Azithromycin (Zithromax)
Clarithromycin (Biaxin)
Erythromycin
500 mg orally for one dose, then
250 mg once per day for four doses
500 mg IV every 24 hours
500 mg orally twice per day
500 mg orally every six hours
500 to 1,000 mg IV every six hours
49 to 60 oral
295 IV
96
17 (8 to 10) oral
(167) IV
Mild diarrhea
Nausea
Vomiting
Abdominal pain
Rash
Amoxicillin
Amoxicillin/clavulanate
(Augmentin)
Penicillin G
Penicillin V
500 mg orally every eight hours
875 mg orally every 12 hours
875 mg/125mg orally every 12
hours
1 to 3 mU IV every four hours
500 mg orally four times per day
4 (4 to 8)
20 (18 to 19)
166 (110 to 115)
(273)
15 (9 to 15)
Mild diarrhea
Nausea
Vomiting
Rash
Doxycycline (Vibramycin) 100 mg orally twice per day 102 (16 to 21) Mild diarrhea
Nausea
Vomiting
Phototoxicity
Prevention
• More people die from pneumococcal infections (an
estimated 40,000 annually in the United States) than
from any other vaccine preventable disease
• PPV23 is recommended for all adults ≥65 years of age
and in younger patients with a number of conditions
that increase the risk of invasive pneumococcal disease
– Adults who have been diagnosed with invasive pneumococcal
disease should also be vaccinated because infection with one
serotype does not necessarily provide protection against other
serotypes
• A single revaccination is recommended in adults ≥65
years of age if they were vaccinated more than 5 years
previously at a time when they were <65 years of age,
and in immunocompromised patients five years or more
after the first dose

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Community acquired pneumonia (cap)

  • 2. CAP defined • Pneumonia not acquired in a hospital or a long-term care facility – Hospital acquired pneumonia – Healthcare associated pneumonia: other healthcare facilities such as nursing homes, dialysis centers, and outpatient clinics
  • 3. Introduction • Estimated 5.6 million cases of CAP occur annually in the United States • Estimated total annual cost for CAP in the United States is $8.4 billion – 92% of cost with inpatient therapy • Because CAP is the only acute respiratory tract infection in which there is increased mortality if antibiotic therapy is delayed, diagnostic and treatment decisions need to be made accurately and efficiently • Mortality rate among hospitalized patients with CAP varies each year and can reach 35%
  • 4. Epidemiology • Unclear because few population-based statistics for CAP alone are available • Center for Disease Control and Prevention (CDC) combines pneumonia with influenza when collecting data on morbidity and mortality • In 2001, influenza and pneumonia combined were the 7th leading cases of death in the U.S. – Down from 6th in previous years • Death rate of 21.8 per 100,000 patients
  • 5. Clinical Presentation • Pneumonia is an inflammation or infection of the lungs that causes them to function abnormally • Classified as typical or atypical, although the clinical presentations are often similar • Several symptoms commonly present in patients with pneumonia • Approximately 20-33% of episodes result in hospitalization
  • 6. Etiology • Typical: up to 70% – Usually caused by Streptococcus pneumoniae • Atypical: 30-40% – “My Lungs Contain Viruses” • Mycoplasma pneumoniae • Legionella pneumophila • Chlamydia pneumoniae • Viruses: Influenza, Adenovirus – May be co-pathogens in other cases
  • 7. Symptoms • Cough, fever, chills, fatigue, dyspnea, rigors, and pleuritic chest pain • Depending on the pathogen, cough may be persistent and dry, or it may produce sputum • Other presentations may include headache and myalgia • Certain etiologies, such as legionella, also may produce gastrointestinal symptoms – Symptoms at presentation are not useful in distinguishing CAP from respiratory illnesses with other causes
  • 8. Diagnosis: Physical Examination • Dullness to percussion of chest, crackles or rales on auscultation, bronchial breath sounds, tactile fremitus, and egophany (“E” to “A” changes) • Patient may also be tachypneic • Patients with typical pneumonia are more likely to present with dyspnea and bronchial breath sounds on auscultation
  • 9. Diagnosis: Radiography • CXR (PA and Lateral): – American Thoracic Society (ATS) guidelines, “all patients with suspected CAP should have a chest radiograph to establish the diagnosis and identify complications (pleural effusions, multilobar disease)” – Lobar consolidation – more common in typical pneumonia – Bilateral, diffuse infiltrates – commonly seen in atypical pneumonia • However, radiologists cannot reliably differentiate bacterial from nonbacterial pneumonia on the basis of the radiographic appearance – If performed early in the course of the disease, may be negative • The sensitivity of chest radiography depends greatly on pretest probability
  • 10. •47-year-old smoker presented after just 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 community-acquired pneumonia was begun
  • 11. •12 hours later •Chest x-ray showed consolidation in the right upper lobe consistent with the earlier clinical signs •S. pneumoniae was isolated from blood cultures •The patient recovered fully
  • 12. Diagnosis: Radiography (cont.) • CT – CT scan could be performed in patients with a negative chest radiograph when there is a high clinical suspicion for pneumonia – CT scan, especially high resolution CT (HRCT), is more sensitive than plain films for the evaluation of interstitial disease, bilateral disease, cavitation, empyema, and hilar adenopathy – This technology is not generally recommended for routine use because the data for its use in CAP are limited, the cost is high, and there is no evidence that this improves outcome – Thus, a chest radiograph is the preferred method for initial imaging, with CT scan or MRI reserved for further anatomical definition
  • 13. Diagnosis: Laboratory Tests • Historically: WBC, sputum cultures, two sets of blood cultures, and urine antigens – Sputum samples are adequate in only 52% of patients with CAP, and only 44 % of those samples contain pathogens • Likely due to problems with retrieving samples from lower respiratory tract, previous antibiotics, contamination from upper airways, or viral etiology – Positive blood cultures obtained in only 5-10% of patients, including those with severe disease • Positive blood culture has no correlation with severity of illness or outcome – Current ATS guidelines recommend that patients hospitalized for suspected CAP receive 2 sets of blood cultures
  • 14. Sensitivity and Specificity of Diagnostic Tests for CAP Diagnostic tests by pathogen Sensitivity (%) Specificity (%) Chlamydia Rapid PCR (sputum, BAL fluid) 30 to 95 > 95 Serology (fourfold rise in serum and convalescent titers) 10 to 100 - Sputum culture 10 to 80 > 95 Gram-negative rods Sputum Gram stain 15 to 100 11 to 100 Haemophilus influenzae, Moraxella catarrhalis, Pneumoniae Sputum culture Diagnostic yield 20 to 79* Diagnostic yield 20 to 79* Influenza Rapid DFA (sputum, BAL fluid) 22 to 75 90 Legionella pneumophila DFA (sputum, BAL fluid) 22 to 75 90 PCR (sputum, BAL fluid) 83 to 100 > 95 Serum acute titer 10 to 27 > 85 Urinary antigen 55 to 90 > 95 Mycoplasma pneumoniae Antibiotic titers 75 to 95 > 90 Cold agglutinins 50 to 60 - PCR (sputum, BAL fluid) 30 to 95 > 95 Pneumococcal pneumoniae Chest radiography (lobar infiltrate) 40† - Sputum culture Diagnostic yield 20 to 79* Diagnostic yield 20 to 79* Sputum Gram stain 15 to 100 11 to 100 Diagnosis and treatment of community-acquired pneumonia: Am Fam Physician. 2006 Feb 1;73(3):442-50.
  • 15. Treatment • Initial treatment of CAP is based on physical examination findings, laboratory results, and patient characteristics – Age, chronic illnesses, smoking history, history of the illness • Therapy for pneumonia is empiric because specific pathogens usually are not identified at the time treatment is initiated • Physicians should begin their treatment decisions by assessing the need for hospitalization using a prediction tool for increased mortality, combined with clinical judgment – Pneumonia Severity Index
  • 16. Pneumonia Severity Index (PSI) • PSI was derived and validated as part of the Pneumonia Patient Outcomes Research Team (PORT) prospective cohort study for the purpose of identifying patients with CAP at low risk for mortality – The Pneumonia PORT prediction rule used a derivation cohort of 14,199 inpatients with CAP; it was independently validated in 38,039 inpatients with CAP and in 2,287 inpatients and outpatients prospectively – The PSI rule stratified adults with radiographic evidence of pneumonia into five classes for risk of death from all causes within 30 days of presentation • One limitation in the derivation of this rule was that it included mostly patients seen in a hospital emergency department, and included few outpatients who were evaluated in a physician's office and sent home
  • 17. Demographics Male Age (years) Female Age (years) − 10 Nursing home resident + 10 Comorbid illness Neoplastic disease + 30 Liver disease + 20 Congestive heart failure + 10 Cerebrovascular disease + 10 Renal disease + 10 Physical examination findings Altered mental status + 20 Respiratory rate > 30 breaths per minute + 20 Systolic blood pressure < 90 mm Hg + 20 Temperature < 35˚C (95˚F) or > 40˚C (104˚F) + 15 Pulse rate > 125 beats per minute + 10 Laboratory and radiographic findings Arterial pH < 7.35 + 30 Blood urea nitrogen > 64 mg per dL (22.85 mmol per L) + 20 Sodium < 130 mEq per L (130 mmol per L) + 20 Glucose > 250 mg per dL (13.87 mmol per L) + 10 Hematocrit < 30 percent + 10 Partial pressure of arterial oxygen < 60 mm Hg or oxygen percent saturation < 90 percent + 10 Pleural effusion + 10 Pneumonia Severity Index (PSI) Point total Risk R i s k c l a s s Recommended site of care No predictors Low I Outpatient ≤ 70 Low I I Outpatient 71 to 90 Low I I I Inpatient (briefly) 91 to 130 Moderate I V Inpatient > 130 High V Inpatient
  • 18. Treatment: Outpatient vs. Inpatient • Choosing between outpatient and inpatient treatment is a crucial decision because of the possible risk of death • Decision influences diagnostic testing and medication choices, as well as a psychological impact on patients and families • Average cost – Inpatient: $7,500 – Outpatient: $150-350 • Based on age, co-morbidities, and the severity of presenting disease
  • 19. Treatment: Outpatient vs. Inpatient (cont.) • Physicians tend to overestimate a patient’s risk of death; many low-risk patients could be treated safely as outpatients • By using Pneumonia Severity Index (PSI), 26- 31% of hospitalized patients were good outpatient candidates – An additional 13-19% only needed brief hospital observation • PSI can serve as a general guideline, clinical judgment should always supersede prognostic score
  • 20. Pharmacotherapy: Outpatient • Consensus guidelines – ATS, Infectious Disease Society of America, and Canadian Guidelines for the Initial Management of Community-Acquired Pneumonia • Empiric oral therapy with macrolides, doxycycline, or an oral beta lactam (amoxicillin, cefuroxime [ceftin], or amoxicillin/clavulanate [augmentin]), or a flouroquinolone – Therapeutic Working Group of the CDC • Use flouroquinolones sparingly because of resistance concerns • Duration of therapy – S. pneumoniae: 7-10 days or until afebrile 3 days • Bacteremic: 10-14 days – Mycoplasma/Chlamydia pneumoniae: 10-14 days, up to 21 days – Legionella: 10-21 days
  • 21. Pharmacotherapy: Outpatient (cont.) • Several classes of antibiotics are effective against atypical pathogens • C. pneumoniae and Legionella species are intracellular organisms and M. pneumoniae lacks a cell wall, beta lactams are not effective – Erythromycin and tetracycline have been traditional choices for atypical CAP – Newer macrolides (azithromycin [zithromax] and clarithromycin [biaxin]) have good atypical activity and are generally are better tolerated than erythromycin – Doxycycline (Vibramcyin) is effective, associated with fewer gastrointestinal side effects, and is a less expensive alternative – Flouroquinolones have demonstrated excellent activity against atypicals and have one-daily dosing and excellent bioavailability
  • 22. Pharmacotherapy: Outpatient (cont.) • The Sanford Guide to Antimicrobial Therapy 2006 – 36th Ed. – CAP, not hospitalized, no comorbidities* • Azithro 0.5g PO x 1, then 0.25g PO QD • Azithro-ER 2g x 1 (2g /60mL single dose bottle) • Clarithro 500mg PO BID • Clarithro-ER 1g PO Q24h • Doxy 100mg PO BID * Alcoholism, bronchiectasis, COPD, IVDU, Post- CVA aspiration, post-obstruction of bronchi, post-viral
  • 23. Pharmacotherapy: Outpatient (cont.) • The Sanford Guide to Antimicrobial Therapy 2006 – 36th Ed. – CAP, not hospitalized, with comorbidities • Respiratory flouroquinolone – Gati 400mg PO q24h, Gemi 320mg PO q24h, Levo 750mg PO q24h, Moxi 400mg PO q24h • Telithro 800mg PO q24h • Azithro/Clarithro + HD Amox, HD AM-CL, cefdinir, cefpodoxime, cefprozil
  • 24. Pharmacotherapy: Inpatient • Antibiotic therapy should be initiated within 4 hours of hospitalization • Intravenous beta lactam (cefotaxime [claforan] or ceftriaxone [rocephin]) plus a macrolide or a combination of ampicillin/sulbactam (unasyn) plus a macrolide or a fluoroquinolone alone • After clinically stable (T<100.0, HR<100, RR<24, SBP>90, O2 sat>90%) and able to tolerate oral intake, may be switched to oral antibiotics for remainder of therapy – Save money, earlier discharge, minimizes risk of nosocomial infections
  • 25. Pharmacotherapy: Inpatient (cont.) • The Sanford Guide to Antimicrobial Therapy 2006 – 36th Ed. – CAP, hospitalized, NOT in ICU, no comorbidities • Ceftriaxone 2g IV q24h + Azithro 500mg IV q24h – Age >65: Ceftriaxone 1g IV q24h – CAP, hospitalized, NOT in ICU, comorbidities • Gati 400mg IV q24h, Levo 750mg IV q24h, Moxi 400mg IV q24h
  • 26.
  • 27. Flouroquinolones • Conservative use is recommended to minimize resistance patterns • New flouroquinolones (levofloxacin, gatifloxacin, moxifloxacin) should be used only when patients have failed recommended first-line regimens, are allergic to alternative agents, or have a documented infection with highly drug- resistant pneumococci
  • 28. Pneumococcal Resistance • S. pneumoniae accounts for 60-70% of all bacterial CAP – Affects all patient groups and can be fatal • Alarming rate of resistance to many commonly used antibiotics – PCN uncommon before 1990 • Resistance classified as intermediate or high- level – Intermediate: 28% – High-level: 16% • Nation-wide
  • 29. Patterns of Resistance to Antibiotics in North America Antibiotic Resistance (%) Penicillins Amoxicillin/clavulanate (Augmentin) 4.1 Penicillin 21.3 Cephalosporins Cefepime (Maxipime) 0.4 Cefprozil (Cefzil) 23.9 Ceftriaxone (Rocephin) 1.9 Cefuroxime (Ceftin) 24.7 Macrolides Azithromycin (Zithromax) 23.0 Clarithromycin (Biaxin) 26.6 Erythromycin 28.3 Fluoroquinolones Gatifloxacin (Tequin) 0.7 Levofloxacin (Levaquin) 0.7 Moxifloxacin (Avelox) 0.4 Miscellaneous Clindamycin (Cleocin) 9.2 Tetracycline 18.8 Trimethoprim/sulfamethoxazole (Bactrim, Septra) 29.9 Vancomycin (Vancocin) 0.0 •Antibiotics tested against Streptococcus pneumoniae isolates •Resistance rates averaged across all patient groups
  • 30. Cost-effective Care • When choosing a treatment, it is essential to compare costs and outcomes of all recommended drug therapies • Evaluation should lead to a decision that will maximize the value of health care services, not simply reduce the costs of drug therapy – Overall cost of each therapy should be obtained by comparing the end cost with the probability of achieving a positive outcome
  • 31. Antimicrobial Therapies for CAP Agent Dosage Cost per course (generic) Common adverse reactions Cefotaxime (Claforan) Cefpodoxime (Vantin) Cefprozil (Cefzil) Ceftriaxone (Rocephin) Cefuroxime (Ceftin) 1 g IV every six to eight hours 200 mg orally twice per day 500 mg orally twice per day 1 g IV every 24 hours 500 mg orally twice per day 0.75 to 1.5 g IV every eight hours $355 (330) 124 (110) 192 392 219 oral 250 to 358 IV Mild diarrhea Rash Clindamycin (Cleocin) 300 mg orally every six hours 600 mg IV every eight hours 238 (148 to 168) oral 250 IV Mild diarrhea Abdominal pain Pseudomembranous colitis Rash Gatifloxacin (Tequin) Levofloxacin (Levaquin) Moxifloxacin (Avelox) 400 mg orally or IV once per day 500 mg orally or IV once per day 400 mg orally once per day 98 oral, 382 IV 56 oral, 438 IV 107 Mild diarrhea Nausea Vomiting Constipation Dizziness Headache Azithromycin (Zithromax) Clarithromycin (Biaxin) Erythromycin 500 mg orally for one dose, then 250 mg once per day for four doses 500 mg IV every 24 hours 500 mg orally twice per day 500 mg orally every six hours 500 to 1,000 mg IV every six hours 49 to 60 oral 295 IV 96 17 (8 to 10) oral (167) IV Mild diarrhea Nausea Vomiting Abdominal pain Rash Amoxicillin Amoxicillin/clavulanate (Augmentin) Penicillin G Penicillin V 500 mg orally every eight hours 875 mg orally every 12 hours 875 mg/125mg orally every 12 hours 1 to 3 mU IV every four hours 500 mg orally four times per day 4 (4 to 8) 20 (18 to 19) 166 (110 to 115) (273) 15 (9 to 15) Mild diarrhea Nausea Vomiting Rash Doxycycline (Vibramycin) 100 mg orally twice per day 102 (16 to 21) Mild diarrhea Nausea Vomiting Phototoxicity
  • 32. Prevention • More people die from pneumococcal infections (an estimated 40,000 annually in the United States) than from any other vaccine preventable disease • PPV23 is recommended for all adults ≥65 years of age and in younger patients with a number of conditions that increase the risk of invasive pneumococcal disease – Adults who have been diagnosed with invasive pneumococcal disease should also be vaccinated because infection with one serotype does not necessarily provide protection against other serotypes • A single revaccination is recommended in adults ≥65 years of age if they were vaccinated more than 5 years previously at a time when they were <65 years of age, and in immunocompromised patients five years or more after the first dose