PNEUMONIA

Etiology

     Pneumonia is a common infection.  Multiple pathogens to include bacteria, viruses and fungi may invade and infect the pulmonary parenchyma.  Pneumonia may also be classified by the conditions under which infection occurred in a particular patient (community acquired versus nosocomial versus nursing home-acquired).

     Community acquired pneumonia (CAP) is an acute infection of the pulmonary parenchyma with associated symptoms and findings that occurs in patients who have not been hospitalized and have not been residents of a chronic care facility for the past 14 days.  Pneumonia is the most common lethal infection in the United States, and it is the sixth most common cause of death.  Associated symptoms include fever or hypothermia, rigors, sweats, cough with or without sputum production, dyspnea, and pleuritis.  Physical findings include abnormal breath sounds on pulmonary auscultation, the use of accessory respiratory muscles, and sputum production.  Certain infections especially mycoplasma pneumonia may be associated with erythema multiforme and the Stevens-Johnson syndrome.  Chest radiography often reveals an infiltrate but there may also be an associated pleural effusion.  Elderly patients with signs of dehydration should have a repeat chest radiograph taken after adequate fluid resuscitation because many times, infiltrates that were undetectable in the dehydrated state will become detectable after the patient becomes euvolemic.  Leukocytosis with a left shift (bandemia) and arterial hypoxemia with an elevated A-a gradient are common associated laboratory abnormalities that may occur in patients with pneumonia.

     Almost any infectious agent may be involved; however, certain pathogens are commonly associated with CAP.  Streptococcus pneumonia is the most common etiologic agent identified in cases of pneumonia.  Other common pathogens include Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, Staphylococcus aureus, Streptococcus pyogenes, Neisseria meningitidis, Moraxella catarrhalis, Klebsiella pneumoniae, and Legionella species.  Viral pathogens include influenza virus, respiratory syncytial virus, adenovirus, and parainfluenza virus.  Fungal etiologies include histoplasmosis, blastomycosis, and coccidiomycosis.  Less common pathogens include Chlamydia psittaci (psittacosis), Coxiella burnettii (Q fever), and Fracisella tularensis (tularemia).  Tuberculous pneumonia is caused by Mycobacteria tuberculosis and should be considered in appropriate cases.  In cases where an anaerobic etiology is identified, aspiration pneumonia should be suspected and these pathogens may lead to the formation of a pulmonary abscess.

     Nosocomial pneumonias occur in seriously ill hospitalized patients and are associated with invasive procedures and a variety of pathogens.  Gram-negative bacilli and S. aureus are common with nosocomial pneumonias.  Intubated patients are at a greatly increased risk for developing nosocomial pneumonia.  Nursing home-acquired pneumonias are commonly secondary to S. pneumonia, H. infuluenzae, S. aureus, and gram-negative bacilli.  Common disorders seen in nursing homes (cardiopulmonary disease, neurologic disorders, diabetes mellitus, cirrhosis, malignancy, and poor nutritional status) increase the risk of pneumonia as they either affect immune system function or the ability to protect the airway.  Aspiration of oropharyngeal organisms is a common cause of nursing home-acquired pneumonias.  Institutionalized patients are subject to influenza epidemics from December through March, and therefore should undergo aggressive vaccination and prophylactic therapy when appropriate.  Nursing home patients should also undergo pneumococcal vaccination.

     The diagnosis of pneumonia is usually made in patients with characteristic symptoms (cough, sputum production, and fever) who display an infiltrate on chest radiography and leukocytosis with a leftward shift.  Blood cultures (two cultures taken from two separate sites) and a sputum gram stain may aid in establishing which etiologic agent is responsible.  If the gram stain is consistent with an adequate specimen, then it should be subjected to aerobic culturing techniques.  Specific tests which may help diagnose or implicate a particular etiologic agent include urinary Legionella antigen assay (Legionella serogroup 1) and cold agglutinins (Mycoplasma pneumoniae).  However, cold agglutinins are not specific nor are they sensitive.  In appropriate cases, the patient’s HIV status should be determined.  Bacterial pneumonias are extremely common in HIV positive patients; however, Pneumocystis carinii pneumoniae (PCP) and tuberculosis should be aggressively pursued as possible etiologic agents in HIV positive patients.  PCP should also be strongly considered in patients on long term corticosteroid therapy.

     Abnormalities associated with Legionella include hyponatremia, transaminasemia, an increased LDH, hypophosphatemia, and abnormal renal function studies (elevated BUN and creatinine, proteinuria, and microscopic hematuria).  Sputum gram stain may suggest the etiology to be Legionella when it demonstrates sheets of leukocytes without evidence of any organism.  The organism may be cultured on Mueller-Hinton or charcoal-yeast extract agar medium.  Serologic testing includes Legionella titers of acute and convalescent sera.  An acute titer of 1:256 or greater is very suggestive.  Direct fluorescent antibody staining of respiratory secretions is a rapid test to establish the diagnosis; however, it is not commonly available at most facilities.

     Initially, therapy is empiric.  Once an etiologic agent is identified, culture sensitivity testing may guide the choice of therapy.  High-level resistance (MIC>2 microgm/mL) S. pneumoniae should be treated according to susceptibility studies.  Therapeutic options for penicillin-resistant pneumococci include carbapenems (imipenem-cilastatin or meropenem), rifampin, the newer fluoroquinolones, and vancomycin since resistance to beta lactam antibiotics and many non-beta-lactam antibiotics (macrolides, clindamycin, tetracyclines, chloramphenicol, and trimethoprim-sulfamethoxazole) is also common in these organisms.  Intermediate level (MIC 0.12-1.0 microgm/mL) resistant strains may still be treated with penicillin or amoxicillin.  Multiple therapeutic options are available for empiric therapy when community rates of resistant organisms is low.  Outpatient therapy may include a macrolide, doxycycline, or a fluoroquinolone with good coverage for S pneumoniae.  Hospitalized patients should be treated with a beta-lactam, beta-lactam with a macrolide, or a fluoroquinolone with antipneumococcal activity.  Of course, regional practices based on the prevalence of certain pathogens and their resistance profiles should be employed when appropriate.  When anaerobic bacteria are suspected (lung abscess or aspiration pneumonia) clindamycin, metronidazole plus penicillin, or amoxicillin/clavulanate are potential therapeutic interventions.  Patients with repeated pneumonia or patients considered at high risk for pneumonia should undergo vaccination.

     Symptoms of pneumonia generally resolve within days after starting appropriate antibiotics.  Radiographic features of pneumonia often take longer to resolve (radiographic lag).  Pneumonia symptoms which persist after appropriate therapy are often secondary to noncompliance with therapy, infection of multiple lobes, postobstructive pneumonia secondary to endobronchial tumors, dysfunctional host immune function which is often the result of an underlying illness (diabetes mellitus, congestive heart failure, and renal failure), age greater than 50 years, or chronic alcohol abuse.  Another cause of slowly resolving or nonresolving pneumonia is when a radiographic abnormality is incorrectly diagnosed as pneumonia.  Noninfectious conditions which may mimic nonresolving pneumonia include: malignancy, pulmonary emboli, Wegener’s granulomatosis, allergic bronchopulmonary aspergillosis, bronchiolitis obliterans with organizing pneumonia, idiopathic pulmonary fibrosis, eosinophilic pneumonia, bronchocentric granulomatosis, congestive heart failure, drug toxicity (bleomycin sulfate, methotrexate and amiodarone), foreign bodies, sarcoidosis, alveolar hemorrhage syndromes, lupus pneumonitis, Goodpasture syndrome, pulmonary alveolar proteinosis, lipoid pneumonia, and atelectasis.

     Patients with nonresolving pneumonia require further evaluation.  A thorough evaluation includes ventilation-perfusion lung scanning, pulmonary angiography, chest CT scanning, antineutrophil cytoplasmic antibody assay, bronchoscopy and lung biopsy.  Patients who suffer frequent recurrent pneumonia or other infections of the upper (otitis or sinusitis) or lower (bronchitis) respiratory tract without an identifiable etiology should be evaluated further for primary hypogammaglobulinemia (common variable immune deficiency or selective IgA deficiency)