Pneumonia H2012 -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the pathogens—even if they are not killed—are eliminated via either the mucociliary elevator or the lymphatics and no longer represent an infectious challenge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

الهی ! ما را آن ده که ما را آن به !

Microbial Causes of Community-Acquired Pneumonia, by Site of Care Outpatients Non-ICU ICU S. pneumoniae S. pneumoniae S. pneumoniae M. pneumoniae M. pneumoniae S. aureus H. influenzae C. Pneumoniae Legionella C. pneumoniae H. influenzae Gram-negative Respiratory v. a Legionella H. influenzae Respiratory viruses a listed in descending order of frequency a Influenza 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 conditions Cavitation 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 therapy Mycobacterium 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 urine Only serogroup 1 Most community-acquired Sensitivity and Specificity high as 90% and 99%

Antigen Tests Pneumococcal Urine Antigen Sensitive 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 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 Macrolide a 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 -lactam c [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 macrolide d [oral Clarithromycin or Azithromycin (as listed above for previously healthy patients) or IV azithromycin (1 g once, then 500 mg qd)]

Inpatients, ICU A -lactam e [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 -lactams f plus an aminoglycoside plus an antipneumococcal fluoroquinolone If CA-MRSA is a consideration Add linezolid (600 mg IV q12h) or vancomycin (1 g IV q12h).

a Doxycycline (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 CAP Previously 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 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

با تشکر