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 serumand 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 yield20 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

RiskRisk class

Recommended site of care

No predictors Low I Outpatient

≤ 70 Low II

Outpatient

71 to 90 Low III

Inpatient (briefly)

91 to 130 Moderate IV

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

AntibioticResistance (%)

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 DosageCost per course (generic) Common adverse reactions

Cefotaxime (Claforan)Cefpodoxime (Vantin)Cefprozil (Cefzil)Ceftriaxone (Rocephin)Cefuroxime (Ceftin)

1 g IV every six to eight hours200 mg orally twice per day500 mg orally twice per day1 g IV every 24 hours500 mg orally twice per day0.75 to 1.5 g IV every eight hours

$355 (330)124 (110)192392219 oral250 to 358 IV

Mild diarrheaRash

Clindamycin (Cleocin) 300 mg orally every six hours600 mg IV every eight hours

238 (148 to 168) oral250 IV

Mild diarrheaAbdominal painPseudomembranous colitisRash

Gatifloxacin (Tequin)Levofloxacin (Levaquin)Moxifloxacin (Avelox)

400 mg orally or IV once per day500 mg orally or IV once per day400 mg orally once per day

98 oral, 382 IV56 oral, 438 IV107

Mild diarrheaNauseaVomitingConstipationDizzinessHeadache

Azithromycin (Zithromax)

Clarithromycin (Biaxin)Erythromycin

500 mg orally for one dose, then250 mg once per day for four doses500 mg IV every 24 hours500 mg orally twice per day500 mg orally every six hours500 to 1,000 mg IV every six hours

49 to 60 oral

295 IV9617 (8 to 10) oral(167) IV

Mild diarrheaNauseaVomitingAbdominal painRash

AmoxicillinAmoxicillin/clavulanate (Augmentin)Penicillin GPenicillin V

500 mg orally every eight hours875 mg orally every 12 hours875 mg/125mg orally every 12 hours 1 to 3 mU IV every four hours500 mg orally four times per day

4 (4 to 8)20 (18 to 19)166 (110 to 115) (273)15 (9 to 15)

Mild diarrheaNauseaVomitingRash

Doxycycline (Vibramycin) 100 mg orally twice per day 102 (16 to 21) Mild diarrheaNauseaVomitingPhototoxicity

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