PneumoniaH2012 -Chapter 257

Infection of the pulmonary parenchyma

Proliferation of microbial pathogens at the alveolar level and the host's

response to those pathogens

Most common :aspiration from the oropharynx

Many inhaled as contaminated droplets

Rarely, hematogenous spread (tricuspid endocarditis)

Contiguous extension from an infected pleural or mediastinal space.

Mechanical factors

Hairs and turbinates of the nares

Branching architecture of the tracheobronchial tree(where mucociliary clearance and local antibacterial factors

either clear or kill)

Gag reflex and Cough

Normal flora of the oropharynx, components are remarkably constant

Macrophages are extremely efficient at clearing and killing pathogens.

Local proteins (e.g., surfactant proteins A and D) have intrinsic opsonizing properties

or antibacterial or antiviral activity

Once engulfed by the macrophage, the pathogens—even if they are not killed—are

eliminated via either the mucociliary elevator or the lymphatics and no longer

represent an infectious challenge

The host inflammatory response, rather than the

proliferation of microorganisms, triggers the clinical syndrome of

pneumonia

Community-Acquired Pneumonia

Bacteria, Fungi, Viruses, Protozoa

Newly :

Hantaviruses, Metapneumoviruses, Coronavirus responsible for severe acute respiratory syndrome (SARS), and community-acquired strains of

methicillin-resistant Staphylococcus aureus (MRSA)

Most Common

Streptococcus Pneumoniae

Typical

Streptococcus Pneumoniae

Haemophilus Influenzae

S. Aureus

Klebsiella Pneumoniae

Pseudomonas Aeruginosa

Atypical(in outpatients)

Mycoplasma pneumoniae

Chlamydia pneumoniae(in inpatients)

Legionella spp

Influenza viruses

Adenoviruses

Respiratory Syncytial Viruses

Atypical organisms

Cannot be cultured on standard media, nor can they be seen on

Gram's stain.

Intrinsically resistant to all β-lactam agents and must be treated with a

Macrolide, Fluoroquinolone, Tetracycline

Virus may be responsible for up to 18% of cases of CAP that require

admission to the hospital

10–15% of CAP

Polymicrobial

often Typical + Atypical

ما ! که ده آن را ما الهیبه آن ! را

Microbial Causes of Community-Acquired Pneumonia, by Site of Care

Outpatients Non-ICU ICUS. pneumoniae S. pneumoniae S. pneumoniae M. pneumoniae M. pneumoniae S. aureus H. influenzae C. Pneumoniae Legionella

C. pneumoniae H. influenzae Gram-negativeRespiratory v.a Legionella H. influenzae

Respiratory virusesa

listed in descending order of frequency

aInfluenza A and B viruses, adenoviruses, respiratory syncytial viruses, parainfluenza viruses

Anaerobes

Only when an episode of aspiration

days to weeks before presentation pneumonia

Alcohol

Drug Overdose

Seizure

Gingivitis

often complicated by abscess formation and significant empyemas or parapneumonic

effusions.

S. aureus

Complicate influenza infection

MRSA reported as the primary etiologic agent of CAP

still relatively uncommon, necrotizing pneumonia

MRSA from hospital to the community

Genetically distinct strains of MRSA in the community

Despite a careful history , physical examination and routine radiographic, the

causative pathogen in a case of CAP is difficult to predict

In more than One-Half of cases, a specific etiology is never determined

Epidemiologic and risk factors may suggest the involvement of certain pathogens

Epidemiologic Factors Suggesting Possible Causes of Community-

Acquired Pneumonia

Alcoholism

Streptococcus pneumoniae

Oral anaerobes

Klebsiella pneumoniae

Acinetobacter spp

Mycobacterium tuberculosis 

COPD and/or smoking

Haemophilus influenzae Pseudomonas

aeruginosa

Legionella spp.

S. Pneumoniae

Moraxella catarrhalis

Chlamydia pneumoniae

Risk factors for CAP

Alcoholism

Asthma

Immunosuppression

Institutionalization

≥70 years

Risk factors for pneumococcal pneumonia

Dementia

Seizure disorders

Heart failure

Cerebrovascular disease

Alcoholism

Tobacco smoking

COPD

CA-MRSA Pneumonia

Skin colonization

Infection with CA-MRSA

P. aeruginosa

Bronchiectasis

Cystic fibrosis

Severe COPD

Legionella

Diabetes

Hematologicmalignancy

Cancer

Severe renal disease

HIV infection

Smoking Male

Recent Hotel stay or Ship cruise

Clinical Manifestations

Indolent to Fulminant

Mild to Fatal

Frequently Febrile with Tachycardia

Chills

Sweats

Cough

Nonproductive or Productive

Mucoid, Purulent, Blood-tinged

If the pleura is involved, : Pleuritic Chest Pain

20% : Gastrointestinal symptoms

Nausea, Vomiting, Diarrhea

Other symptoms may include

Fatigue, Headache, Myalgias, Arthralgias

Auscultation

Crackles

Bronchial breath sounds

Pleural friction rub

Diagnosis

1:Is this pneumonia?

Clinical and Radiographic methods

2:what is the likely etiology?

aid of Laboratory techniques

Clinical Diagnosis

Acute bronchitis

Acute exacerbations of chronic bronchitis

Heart failure

Pulmonary embolism

Radiation pneumonitis.

Physical Examination

Sensitivity and Specificity

58% and 67%

Chest radiography is often necessary to differentiate CAP from other

conditionsCavitation or Multilobar

Occasionally, CXR suggest an etiologic diagnosis.

Pneumatoceles :S. aureus

Upper-lobe cavitating :Tuberculosis

CT is rarely necessary

suspected postobstructive pneumonia caused by a Tumor or

Foreign body

Outpatients

Clinical and Radiologic

usually all that is done before treatment for CAP

since most laboratory results are not available soon enough to influence initial management significantly

Rapid Diagnostic Tests

Influenza virus infection can prompt specific anti-influenza drug treatment and secondary prevention

Etiologic Diagnosis

Exposure to birds

Chlamydia psittaci 

Exposure to rabbits

Francisella tularensis 

Local influenza activity

Influenza virus

S. pneumoniae

S. aureus 

Travel to southwestern United States

Hantavirus

Coccidioides spp.

Dementia, stroke, decreased level of consciousness

Oral anaerobes

Gram-negative enteric bacteria

Severity

Cavitation

Multilobar

Etiologic Diagnosis

Pneumatoceles : S. Aureus

Upper-lobe cavitating : Tuberculosis

CT

Rarely necessary

Postobstructive pneumonia

Tumor or Foreign body

Etiologic Diagnosis

Except for the 2% of CAP patients who are admitted to the ICU

no data exist to show that treatment directed at a specific pathogen is statistically superior to empirical

therapyMycobacterium tuberculosis and influenza

Gram's stain

main purpose of the sputum Gram's stain is to ensure that a sample is suitable for culture

S. pneumoniae, S. aureus, Gram-negative bacteria

Adequate for Culture

>25 Neutrophils

<10 Squamous epithelial cells

per low-power field

Bacteremic Pneumococcal Pneumonia

positive cultures from sputum samples is 50%.

Blood Cultures

Only ~5–14% of cultures of blood from patients hospitalized with CAP are positive, and the

most frequently isolated pathogen is S. pneumoniae

Blood cultures are no longer considered for all hospitalized CAP

patients.

Neutropenia secondary to pneumonia, Asplenia, or Complement deficiencies; Chronic liver disease; or Severe CAP—

should have blood cultured

Antigen Tests

Legionella antigens in urineOnly serogroup 1

Most community-acquiredSensitivity and Specificity

high as 90% and 99%

Antigen Tests

Pneumococcal Urine AntigenSensitive and Specific

80% and >90%False-positive results can be obtained with

samples from pneumococcus-colonized Children

Both tests can detect antigen even after the initiation of appropriate antibiotic therapy

Rapid test for Influenza virus and direct fluorescent antibody tests for

influenza

Respiratory Syncytial Virus; the latter tests are only poorly sensitive

PCR

DNA or RNA

L. Pneumophila

Mycobacteria

M. Pneumoniae

C. Pneumoniae

PCR is generally limited to research studies

Pneumococcal Pneumonia

increased bacterial load documented by PCR is associated with an increased

risk of septic shock, need for mechanical ventilation, and death. Such a test could conceivably help identify patients suitable for ICU

admission.

Serology

A fourfold rise in specific IgM between acute- and convalescent-phase serum is

generally considered diagnostic

Coxiella burnetii

Recently, however, they have fallen out of favor because of the time required to

obtain a final result for the convalescent-phase sample.

Treatment: CAP

Certain patients clearly can be managed at Home, and others clearly require treatment in the

Hospital

S. Pneumoniae

Risk factors for penicillin-resistant :Recent antimicrobial therapy, Age of <2 or >65 years, Attendance at

day-care centers, recent Hospitalization, and HIV

Resistant to Three or more antimicrobial classes with different mechanisms considered MDR

Penicillin ,Macrolides, Tetracyclines, Trimethoprim-sulfamethoxazole

Initial Antibiotic Management

Macrolide + Cephalosporin

or

a Fluoroquinolone alone

Outpatients 

Previously healthy and no antibiotics in past 3 months

A macrolide [Clarithromycin (500 mg PO bid) or Azithromycin (500 mg PO once, then 250 mg qd)] or 

 Doxycycline (100 mg PO bid)

Comorbidities or antibiotics in past 3 months: select an alternative from a different class

A respiratory fluoroquinolone [Moxifloxacin (400 mg PO qd), Gemifloxacin (320 mg PO qd), Levofloxacin (750 mg PO qd)] or 

A -lactam [preferred: high-dose Amoxicillin (1 g tid) or Amoxicillin/clavulanate (2 g bid); alternatives: Ceftriaxone (1–2 g IV qd), Cefpodoxime (200 mg PO bid), Cefuroxime (500 mg PO bid)] plus a Macrolidea 

In regions with a high rate of "high-level" pneumococcal macrolide resistance,b consider alternatives listed above for patients with comorbidities. 

Inpatients, Non-ICU 

A respiratory fluoroquinolone [Moxifloxacin (400 mg PO or IV qd), Gemifloxacin (320 mg PO qd), Levofloxacin (750 mg PO or IV qd)]

A -lactamc [Cefotaxime (1–2 g IV q8h), Ceftriaxone (1–2 g IV qd), Ampicillin (1–2 g IV q4–6h), Ertapenem (1 g IV qd in selected patients)] plus a macrolided [oral Clarithromycin or Azithromycin (as listed above for previously healthy patients) or IV azithromycin (1 g once, then 500 mg qd)]

Inpatients, ICU 

A -lactame [cefotaxime (1–2 g IV q8h), ceftriaxone (2 g IV qd), ampicillin-sulbactam (2 g IV q8h)] plus 

 Azithromycin or a fluoroquinolone (as listed above for inpatients, non-ICU)

Special Concerns 

If Pseudomonas is a consideration 

An antipneumococcal, antipseudomonal -lactam [piperacillin/tazobactam (4.5 g IV q6h), cefepime (1–2 g IV q12h), imipenem (500 mg IV q6h), meropenem (1 g IV q8h)] plus either ciprofloxacin (400 mg IV q12h) or levofloxacin (750 mg IV qd)

The above -lactams plus an aminoglycoside [amikacin (15 mg/kg qd) or tobramycin (1.7 mg/kg qd) and azithromycin]

The above -lactamsfplus an aminoglycoside plus an antipneumococcal fluoroquinolone

If CA-MRSA is a consideration

Add linezolid (600 mg IV q12h) or vancomycin (1 g IV q12h).

aDoxycycline (100 mg PO bid) is an alternative to the macrolide

Management of bacteremic pneumococcal pneumonia

Controversial: nonrandomized studies suggest that combination therapy (especially with a macrolide and a -lactam) is associated with a lower mortality rate than monotherapy, particularly in severely ill

patients. The exact reason is unknown, but possible explanations include an Additive or Synergistic antibacterial effect, Antimicrobial tolerance,

Atypical co-infection, or the Immunomodulatory effects of the macrolides

Duration of treatment for CAPPreviously treated for 10–14 days

Fluoroquinolones and Telithromycin : 5-day course is sufficient for otherwise uncomplicated

CAP.

Even a Single dose of Ceftriaxone has been associated with a significant cure rate.

A longer course is required for patients with bacteremia, metastatic infection, or infection with a

virulent pathogen such as P. aeruginosa or CA-MRSA.

General Considerations

Adequate hydration, oxygen therapy for hypoxemia, and assisted ventilation

severe CAP who remain Hypotensive despite fluid resuscitation may have

adrenal insufficiency and may respond to Glucocorticoid treatment

Immunomodulatory therapy in the form of drotrecogin alfa (activated) should be considered for CAP patients with persistent septic shock and APACHE II scores of

25, particularly if the infection is caused by S. pneumoniae

Failure to Improve

Slow to respond to therapy reevaluated at about day 3 (sooner if is worsening)

Pulmonary edema, Pulmonary embolism, Lung carcinoma, Radiation , Hypersensitivity pneumonitis,

, Connective tissue disease involving the lungs

Resistant to the drug selected, or a sequestered focus (e.g., a lung abscess or empyema)

Also possible that CAP is the correct diagnosis but that an unsuspected pathogen (e.g., CA-MRSA, M.

tuberculosis, or a fungus) is the cause

Complications

Respiratory failure, Shock and Multiorgan failure, Coagulopathy

Metastatic infection, Lung abscess, and complicated Pleural Effusion. Metastatic

infection (e.g., Brain abscess or Endocarditis)

Pleural Effusion

should be tapped for both Diagnostic and Therapeutic purposes.

PH of <7, a Glucose level of <2.2 mmol/L, and a LDH >1000 U/L or if bacteria are seen or cultured, then the

fluid should be drained; a Chest Tube is usually required.

Follow-Up

Fever and Leukocytosis usually resolve 2–4 days

Physical findings may persist longer

CXR may require 4–12 weeks to clear

Age and Underlying lung disease

particularly for elderly patients follow-up radiograph can be done ~4–6 weeks later

relapse or recurrence :particularly in the same lung segment, underlying neoplasm must be considered.

Prognosis

Age, Comorbidities, and site of treatment (inpatient or outpatient)

Young well and usually recover fully after ~2 weeks

Older patients and those with comorbid conditions can take several weeks longer to recover fully

Mortality rate for the outpatient group is <1%

For patients requiring hospitalization, the overall mortality rate is estimated at 10%, with ~50% of

deaths directly attributable to pneumonia.

Prevention

Main preventive measure is Vaccination

Influenza and Pneumococcal

influenza outbreak, vaccinated immediately and given

chemoprophylaxis with either Oseltamivir or Zanamivir for 2 weeks—i.e., until vaccine-induced antibody

levels are sufficiently high

Nosocomial superinfections—both pulmonary and

extrapulmonary—are possible explanations for failure to

improve or worsening

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