• Information
  1. Epidemiology
  2. Normal Defenses
  3. Considerations in Assessment
  4. Presentation and Evaluation
  5. Etiology
  6. Viral Pneumonia
  7. Community Acquired Pneumonia
  8. Pneumococcal Pneumonia
  9. Hemophilus Pneumonia
  10. Mycoplasma Pneumonia
  11. Legionella Pneumonia
  12. Inpatient Treatment of Pneumonia
  13. Parapneumonic Effusions
  14. Ventilator Associated Pneumonia
  15. Pneumonia in Long-Term Care Facilities
  16. Hospital Discharge Parameters

A. Epidemiology

1. Pneumonia is the sixth leading cause of death in USA
2. About 12 cases per 1000 patients per year
3. About 20% of cases of community acquired pneumonia (CAP) are hospitalized
4. Risk of death is highly dependent on many factors and can be as high as 30% [1,5]

B. Normal Defenses

1. Upper airway mechanics
2. Alveolar macrophages
3. Complement mediated opsonization, alternative pathway, Ab mediated opsonization

C. Considerations in Assessment

1. Pneumonia Severity Index (PSI) is probably best overall tool for risk stratification [1,5]
2. Timing: chronic versus acute
3. Potential Organism - Community (CAP), Hospital, or Insitution Acquired
4. Immune Status of Host (underlying disease, including all chronic diseases)
5. Child versus Adult (age <50 or >50)
6. Hospitalization of patients with CAP should be based on [1,5]:
   1. Any patient with <90% oxygen saturation (oxygen <60mm Hg) on room air
   2. Hemodynamic instability
   3. Inability to tolerate oral medications
   4. Active coexisting condition requiring hospitalization
   5. PSI Class IV and V patients
   6. Consider brief hospitalization for Class III patients
   7. Frail physical condition, previous no response to oral therapy, consider hospitalization
7. Chest radiography (CXR) is absolutely required to rule in or rule out pneumonia [2,3]

D. Presentation and Evaluation

1. Cough
   1. Productive of sputum ? (color, tenaciousness)
   2. Hemoptysis ?
2. Time of Onset
3. Severity of Symptoms
   1. Fever (~80%) and Rigors
   2. Tachypnea at rest (>50%), shortness of breath, especially on exertion
   3. Pleuritic pain
4. Underlying disorders
   1. Smoking
   2. Chronic Disease
   3. Immunosuppression - HIV, glucocorticoids, neutropenia, congenital disease
   4. Level of consciousness (neurological) - reduced level is risk for aspiration pneumonia [4]
5. Chest Examination
   1. >80% of patients with CAP have rales (crackles) on exam
   2. The majority will have CXR changes (consolidation or interstitial pattern)
   3. Bronchophony, egophany, whispered pectoriloque are much less reliable
   4. Wheezing is occasionally appreciated
   5. Inspiratory squeeks suggest bronchiolitis
6. Risk Factors for Poor Outcome
   1. Scoring system to assess severity in CAP [1,5]
   2. Increased age
   3. Respiratory rate >30/minute
   4. Temperature >40°C
   5. Blood arterial pH <7.35
   6. Blood urea nitrogen (BUN) >30mg/dL
   7. Serum sodium <130mM
   8. Complete algorithm presented elsewhere
7. History and physical exam alone do not evaluate pneumonia reliably [2,5]
8. Pneumonia Patient Outcomes Research Severity Index may be helpful [1]

E. Etiology

1. Acute Viral
   1. Influenza A: usually protracted "flu-like" syndrome, rarely causes fulminant pneumonia
   2. Influenza B: more common in children; aspirin use with virus linked with Reye Syndrome
   3. Other: Adenovirus, Cocksackie Virus
   4. Immunocompromised: CMV, HSV
2. Acute Bacterial
   1. Streptococcus pneumoneae (pneumococcus)
   2. Haemophilus influenza
   3. Mycoplasma pneumoneae
   4. Klebsiella pneumoneae
   5. Chlamydophila (fomerly Chlamydia) pneumoniae
   6. Legionella pneumophila
   7. Staphylococcus aureus
   8. Moraxella cattharalis
   9. Anaerobic Oral Flora: aspiration pneumonia (± aspiration pneumonitis)
3. Subacute / Chronic Pneumonia
   1. Mycobacterial
   2. Fungi: Cryptococcus, Histoplasmosis, Aspergillus, Mucormyces, Candida
   3. Nocardiosis: more common in immunocompromised such as diabetics
   4. Pneumocystis carinii : immunocompromised patients, often severely hypoxemic
4. Chemical [4]
   1. Aspiration pneumonitis
   2. Inhalation
   3. Lipid accumulation - lipoid pneumonia usually due to mineral oil ingestion [15]
   4. Up to 15% of CAP is aspiration pneumonia [4]
5. Bronchiolitis Obliterans Organizing Pneumonia (BOOP) [23]
   1. Relatively rare, pneumonia-like disorder
   2. Clinicopathological syndrome including clinical, radiographic and pathologic features
   3. Usually occurs ages 40s through 50s, men slightly more than women
   4. May be caused by infections, neoplasms, inflammatory diseases, or drug reaction
   5. Also occurs with recurrent gastroesophageal reflux and occult aspiration
   6. Sjogren Syndrome should be considered with concommitant dry eyes, mouth
   7. However, true BOOP (versus BO) is probably most commonly a reaction to infection

F. Viral Pneumonia

1. Occurrence and Cause
   1. Most common CAP
   2. More commonly affects younger, healthier persons
   3. Adenovirus, Coxsackie viruses, Influenza virus
   4. Respiratory Syncitial Virus (RSV) - common bronchiolitis in <2 year olds
2. Presentation
   1. Gradual Onset
   2. Tachypnea and tachycardia are rare
   3. Patient moderately ill with little sputum production
   4. White Blood Count (WBC) may decrease
3. CXR
   1. Diffuse Interstitial infiltrate
   2. No consolidation unless bacterial superinfection
4. Treatment
   1. Mostly supportive therapy with careful watch for superinfection
   2. Monitor electrolytes and WBC
   3. Consider amantadine or rimantadine for influenza A infections

G. Community Acquired Pneumonia (CAP) [3,8,10]

1. Accounts for ~600,000 hospitalizations per year in USA
2. Risk Factors
   1. Underlying lung disease
   2. Smoking
   3. Increasing Age
   4. Exposure to organisms including initial viral infection
   5. Previous pneumonia
   6. Acid-suppression therapy (H2-blockers, proton-pump inhibitors) ~1.7X increased risk [24]
3. Organisms [14,28]
   1. S. pneumoniae (pneumococcus) is most common bacterium overall, ~30-60% of cases
   2. Mycoplasma pneumoniae is probably most common in younger (<40 years) persons (~25%)
   3. Haemophilus influenzae in ~10%, particularly elderly and/or COPD
   4. Chlamydophila pneumoniae (TWAR Agent) in ~10% (mainly younger persons)
   5. Legionella pneumophilia is very uncommon in most places
   6. Viral pneumonias are common in young, healthy persons, usually self limited
   7. Gram negative infections are relatively uncommon, but have very high mortality
   8. Aspiration pneumonia - up to 15% of CAP
4. Smokers and COPD
   1. S. pneumoniae is still the most common
   2. H. influenza is also common
   3. Moraxella catarrhalis (Brahnamella) is frequently found as well
5. Other Concerning Organisms (particularly in patients with underlying disease)
   1. Tuberculosis
   2. Pneumocystis
   3. Anaerobic Bacteria
   4. Nocardia
6. Assessment of Severity [3]
   1. Important for decision to hospitalize patient
   2. Generally based on severity of symptoms
   3. WBC > 15K/µL is particularly concerning
   4. Anemia suggests chronic disease, mycoplasma infection, or complex pneumonia
   5. Pneumonia severity index (PSI) is best overall scale for evaluating severity of CAP [1,3,5]
   6. PSI can be used for predicting which patients can be treated safely as outpatients [22]
   7. PSI risk classes II and III can be treated with oral levofloxacin (Levoquin®) 500mg qd [22]
7. Hospitalization and Clinical Stabilization [8,10,22]
   1. Hospitalization for conditions as described above and for patients in poor social conditions
   2. Patients should be clinically stable before consideration of discharge
   3. In addition, intravenous antibiotics should generally be continued until stability reached
   4. Double coverage with ceftriaxone or cefuroxime + macrolide or fluoroquinolone is recommended [19,20]
   5. Single agent anti-pneumococcal fluoroquinolone (levofloxacin, gatifloxacin, moxifloxacin) may be used in moderately severe patients
   6. Diagnosis of organism and suceptibility testing used to target antibiotics
   7. Most patients require 3-7 days for clinical stability after admission
   8. Severe patients may require longer stays, including ICU admission
   9. Discharge Parameters are provided below
   10. Once patients are clinically stable, complications occurred in <1% of cases
8. Empiric Outpatient Therapy in Non-Smokers [10,17,20,25,28]
   1. Macrolides or doxycycline recommended for <60 year healthy persons
   2. The macrolides clarithromycin or azithromycin much better tolerated than erythromycin
   3. Single dose extended release azithromycin (Zmax®, 2gm x 1 po) approved for CAP [25]
   4. "Respiratory" fluoroquinolones (levofloxacin, moxifloxacin, gatifloxacin) very effective
   5. For >60 years old, comorbidities or recent antibiotic therapy, anti-pneumococcal fluoroquinolone, ß-lactam + macrolide, or telithromycin are recommended
   6. Amoxicillin/clavulonate (Augmentin®) may be required for resistant pneumococcus
   7. Doxycycline 100mg po bid for 10-14 days also covers most pneumococcus and atypicals
   8. Increasing macrolide resistance may become a problem
9. Empiric Outpatient Therapy in Smokers [28]
   1. Second generation cephalosporin (cefuroxime axetil, Ceftin®, 500mg po bid x10days)
   2. Cefpodoxime (Vantin®) also active
   3. Enhanced second generation oral agents such as Cefixime (Suprax®, 400mg po qd x 10d)
   4. Amoxicillin-clavulanate Augmentin® or Ofloxacin (Oflox®) may be used also
   5. Ciprofloxacin has poor pneumococcal but good Haemophilis and Moraxella coverage
   6. Clarithromycin (Biaxin®, 10 days) or azithromycin (Zithromax®, 5 days) second line
10. Mortality of CAP
    1. Gram Negative Infections (Pseudomonas, Klebsiella, E. coli ) 35-60%
    2. Staphylococcus aureus ~30%
    3. Legionella pneumophila and L. micdadei ~15%
    4. S. pneumoniae (pneumococcus) ~12%
    5. Chlamydophila pneumoniae ~10%
    6. H. influenzae ~7%
    7. Mycoplasma pneumoniae <2%
    8. Coxiella burnetti <1%
    9. Chlamydia psittaci 0%

H. Pneumococcal Pneumonia

1. Predisposing Factors
   1. Splenectomy (Penicillin prophylaxis)
   2. Hypoglobulinemia; Myeloma
   3. Nephrotic syndrome
   4. HIV (5X increased risk)
   5. Sickle Cell Anemia (splenic infarction)
   6. Narcotics (?)
   7. Congestive Heart Failure
2. Presentation
   1. Acute onset
   2. Recent Viral Syndrome: myalgias, lethargy, sore throat, lymphadenopathy
   3. Frequent Pleuritic Pain
   4. High Fevers and frank Rigors
   5. Accounts for ~60% of CAP
3. CXR
   1. Usually Alveolar infiltrates, usually one lobe is involved
   2. Spread to multiple lobes possible
   3. Air Bronchograms common
4. Laboratory
   1. High WBC with left shift (immature forms)
   2. Sputum shows gram positive diplococci
   3. Blood Cultures - positive in ~10-20% of cases
5. Treatment
6. Vaccination

I. Hemophilus Pneumonia

1. Characteristics
   1. Second most common cause of bacterial pneumonia
   2. Frequently found in patients with COPD
   3. Common in children <6 years and in Elderly
   4. Overall ~10% of CAP
2. Symptoms
   1. Onset acute (children and elderly) or gradual (COPD)
   2. Moderate to high fever
   3. Sputum production
   4. Must rule out meningeal and bone (such as sinus) spread
   5. Acute epiglottitis
3. CXR
   1. Scattered or no infiltrates in COPD
   2. Children / Compromised adults may show rapid progression with consolidation
4. Treatment
   1. Standard therapies must cover H. influenza
   2. Cefuroxime covers H. influenza well
   3. Prophylaxis with Bactrim®
   4. Outpatient: Bactrim®, Cefuroxime axetil (Ceftin®), Clarithromycin, Augmentin®
5. Vaccinations - only serotype B vaccine is available

J. Mycoplasma Pneumonia

1. Atypical pneumonia with dry cough, intersitial infiltrates, multilobar
2. Most common form in young adults, 10-35% of ambulatory patients
3. May be accompanied by hemolytic anemia, cryglobulinemia, bullous myringitis
4. Pleurisy is common with pleural effusions in a small number of patients
5. Treatment
   1. Macrolides: Erythromycin, clarithromycin, azithromycin
   2. Doxycycline also effective
   3. Prolonged course, 2-4 weeks, usually required
   4. Disease may be self limited in many patients, though superinfections can occur

K. Legionella Pneumonia

1. Characteristics of Legionella pneumophila
   1. Ingested by Macrophages and PMNs, inhibits lysosomal fusion
   2. Intracellular pathogen
2. Symptoms
   1. Pleural effusion (~50%), pleuritic pain (~30%), hyponatremia (~45%)
   2. Usually multilobar, often without sputum production
   3. High incidence of GI upset, LFT abnormalities with this pneumonia
   4. Patients are often very sick and may require intubation for respiratory support
3. Treatment
   1. Azithromycin 500mg iv for 3 days, then switch to oral
   2. IV Second Generation Quinolones levofloxacin or alatrofloxacin highly effective
   3. High dose erythromycin IV is no longer recommended (very poorly tolerated)
   4. Consider addition of rifampin 300mg po bid in severe cases

L. Inpatient Treatment of Pneumonia [3,17]

1. Administration of antibiotics within 8 hours and obtaining blood cultures within 24 hours of hospital arrival were associated with 10-15% reduced 30-day mortality [7]
2. CAP Empiric Treatment [28]
   1. Antipneumococcal fluoroquinolones are highly effective and well tolerated initial therapy
   2. Advanced generation macrolides generally well tolerated, good coverage
   3. Cephalosporins must be combined with doxycycline or erythromycin for atypical coverage
   4. Smokers require good gram negative coverage as well as usual organisms
   5. Patients with severe pneumonia treated with parenteral antibiotics for 48 hours regardless of fevere status then switched to oral agents do well [12]
   6. Inpatients with less severe pneumonia may be treated initially with oral agents [12]
3. Resistant or Hospital Acquired
   1. Concern is for resistant Gram Negative Rods and Staphylococcus aureus ± Anaerobes
   2. Aminoglycoside + one of the following:
   3. Ceftriaxone, cefotaxime, cefepime, Timentin®, Zosyn®, meropenem, or imipenem
   4. If Pseudomonas is suspected, ceftazidime + aminoglycoside is recommended
   5. If methacillin resistant staphylococci are suspected, vancomycin is required
   6. Major concerns for patients on ventilators with pneumonia (see below)
4. Atypical Pneumonias (Mycoplasma, Legionella, Chlamydia, Chlamydophila) [28]
   1. Azithromycin 500mg IV qd is highly effective
   2. Levofloxacin (Levaquin®) or Alatrofloxacin (Trovan®) highly effective as well
   3. Note that azithromycin, levofloxacin, alatrofloxacin cover nearly all organisms very well
   4. Doxycycline is second line (100mg IV bid)
5. Aspiration pneumonia
   1. CAP: Penicillin or Clindamycin ± ceftriaxone
   2. Hospital Acquired: Clindamycin + Ceftazidime or triple antibiotics
   3. Ventilator associated pneumonia - antibiotics, recumbant (not supine) positioning
6. Staphylococcal Pneumonia
   1. IV: Oxacillin (or cefazolin) ± Gentamicin for methicillin sensitive
   2. PO: TMP/SMX (Bactrim®) or fluoroquinolone
   3. Staph A (methicillin resistant): IV Vancomycin ± Gentamicin
   4. PO Methicillin resistant: Ciprofloxacin ± Rifampin; check doxycycline sensitivities
7. Immunocompromised
   1. TMP/SMX (includes PCP)
   2. Prophylaxis with aerosolized Pentamidine or dapsone
   3. Pseudomonas coverage: ceftazidime, anti-pseudomonal aminoglycoside, penam, others
8. After Hospital Discharge
   1. TMP/SMX, Amoxicillin, Augmentin® (Amoxicillin / Clavulonate)
   2. Cefuroxime axetil (Ceftin): 250mg po bid-tid
   3. Erythromycin is no longer recommended because it is very poorly tolerated
   4. Clarithromycin (Biaxin®): 250-500mg po bid (especially if atypical suspected)
   5. Azithromycin (Zithromax®): 500mg bid x 1 day then 500mg qd
   6. Fluoroquinolones are all very effective

M. Parapneumonic Effusions

1. Present in ~40% of patients with CAP (severe in ~10%)
2. May be more common in patients with hospital acquired pneumonia
3. Large effusions should be evaluated with thoracocentesis
4. Moderate or smaller effusions may be evaluated in patients not responding to therapy
5. Pleural fluid analysis is based on pH and culture / gram stain
6. Pleural biopsy may be required for diagosis of tuberculosis

N. Ventilator Associated Pneumonia (VAP) [26]

1. Risk Factors [16]
   1. Situations contributing to failure to clear secretions properly
   2. Supine position and enteral nutrition increase risk considerably
   3. Incidence of pneumonia is reduced 6.8 fold for semi-recumbant versus supine position
   4. Mechanical ventilation >2-7days is another risk factor
   5. Glascow coma scale score <9 is also a risk factor
   6. Noninvasive positive pressure ventilation (NIPPV) had reduced incidence of nosocomial pneumonia and other infections in acute pulmonary edema [21]
2. Overall, increasing comorbid conditions predicts poor outcome in ventilated patients
3. Monitoring for VAP [26,27]
   1. Oxygenation and gas exchange parameters should be monitored frequently
   2. Continuous pulse oximetry
   3. In general, once patient has stabilized, dailyCXR in ventilated patients are only required if clinical condition (pulse oximetry, other parameters) has changed
   4. Physical exam is only minimally beneficial
   5. Changes in gas exchange parameters should always prompt evaluation
   6. Combination of new chest x-ray (CXR) infiltrate with at least 2 of fever, leukocytosis or purulent sputum increases VAP likelihood 2.8X [26]
   7. Absence of new infiltrate on CXR reduces VAP likelihood to 0.35X [26]
   8. Bronchial brushings and/or lavage should be used to make diagnosis [6]
   9. Early bronchoscopy with sampling for suspected VAP rather than expectant "clinical" management" reduces antibiotic use, organ dysfunction, and mortality [18]
   10. Bronchoalveolar lavage (BAL) with quantitative culture of BAL fluid or endotracheal aspiration with nonquantitative aspirate culture have similar clinical outcomes [27]
   11. <50% neutrophils on cell counts of lower pulmonary secretions makes VAP <10% likely [26]
   12. Levels of soluble triggering receptor expressed on monocytes (sTREM-1) in BAL fluid can be used to predict presence of VAP [18]
   13. Thus, either BAL or endotracheal aspiration are reasonable for diagnosis of VAP
4. Gram negative rods are most common in longer term ventilated patients
   1. Pseudomonas species are most common
   2. Highly resistant GNR are increasingly being isolated
   3. Duration of ventilation and use of antibiotics correlates with increasing resistance
5. Otherwise, classical hospital acquired infections are found

O. Pneumonia in Long-Term Care Facilities [11]

1. About 1 per 1,000 patient days
2. Similar risk factors as above
3. Agents vary widely
   1. S. pneumoniae 0-39%
   2. Gram negative bacilli 0-51%
   3. Staph. aureus 0-33%
   4. H. influenzae 0-22%
   5. Influenza and/or respiratory syncytial virus usually in outbreaks
4. Increased risk for aspiration pneumonitis and pneumonia with neurologic impairment [4]
5. Patients should be considered for oral treatment and/or prophylaxis
   1. Indications for oral therapy as above, with concern for comorbid conditions
   2. Drug interactions should also be considered carefully
6. Pneumococcus and influenza vaccines should be given to all residents

P. Hospital Discharge Parameters [5]

1. Vital signs stable for 24 hours
   1. Temperature <37.8°C (100°F)
   2. Respiratory rate <25/min
   3. Pulse <100/min
   4. SBP >90 mm Hg
   5. Oxgen saturation >90% breathing room air
2. Patient able to tolerate oral medications
   1. Tailored to infectious agent
   2. Antipneumococcal fluoroquinolone or advanced generation macrolide usually acceptable
3. Patient able to tolerate adequate hydration and nutrition
4. Normal or baseline mental status
5. No other active clinical or psychosocial problems requiring hospitalization

References

1. Fine MJ, Auble TE, Yealy DM, et al. 1997. NEJM. 336(4):243
2. Metlay JP, Kapoor WN, Fine MJ. 1997. JAMA. 278(17):1440
3. Metlay JP and Fine MJ. 2003. Ann Intern Med. 138(2):109
4. Marik PE. 2001. NEJM. 344(9):665
5. Halm EA and Teirstein AS. 2002. NEJM. 347(25):2039
6. Breeon F, Papazien L, Visconti A, et al. 1997. JAMA. 277(8):655
7. Meehan TP, Fine MJ, Krumholz HM, et al. 1997. JAMA. 277(24):2080
8. Halm EA, Fine MJ, Marrie TJ, et al. 1998. JAMA. 279(18):1452
9. Edelstein PH. 1998. Ann Intern Med. 129(4):328
10. File TM Jr. 2003. Lancet. 362(9400):1991
11. Muder RR. 1998. Am J Med. 105(4):319
12. Castro-Guardiola A, Viejo-Rodriguez AL, Soler-Simon S, et al. 2001. Am J Med. 111(5):367
13. Ailani RK, Agastya G, Ailani RK, et al. 1999. Arch Intern Med. 159(3):266
14. Ruiz-Gonzalez A, Falguera M, Nogues A, Rubio-Caballero M. 1999. Am J Med. 106(4):385
15. Pugatch RD and Mark EJ. 1999. NEJM. 341(18):1379
16. Drakulovic MB, Torres A, Bauer TT, et al. 1999. Lancet. 354(9193):1851
17. Choice of Antibacterial Drugs. 2001. Med Let. 43(1111):69
18. Fagon JY, Chastre J, Wolff M, et al. 2000. Ann Intern Med. 132(8):621
19. Gleason PP, Meehan TP, Fine JM, et al. 1999. Arch Intern Med. 159:2562
20. Bartlett JG. 2000. Ann Intern Med. 133(4):287
21. Girou E, Schortgen F, Delclaux C, et al. 2000. JAMA. 284(18):2361
22. Carratala J, Fernandez-Sabe N, Ortega L, et al. 2005. Ann Intern Med. 142(3):165
23. Fleming CM, Shepard JO, Mark EJ. 2003. NEJM. 348(20):2019 (Case Record)
24. Laheij RJF, Sturkenboom MCJM, Hassing RJ, et al. 2004. JAMA. 292(16):1955
25. Azithromycin Extended Release. 2005. Med Let. 47(1218):78
26. Klompas M. 2007. JAMA. 297(14):1583
27. Canadian Critical Care Trials Group. 2006. NEJM. 355(25):2619
28. Drugs for Community-Acquired Bacterial Pneumonia. 2007. Med Let. 49(1266):62