What are the causative agents, pathological features, clinical features, diagnostic procedures, and treatment options for pneumonia?

Pneumonia: Comprehensive Disease Overview

Causative Agents

Streptococcus pneumoniae is the most common causative agent of community-acquired pneumonia, accounting for approximately two-thirds of all bacteremic pneumonia cases. 1

Bacterial Pathogens

• S. pneumoniae (most frequent, including multi-drug resistant strains) 1
• Haemophilus influenzae (mostly nontypeable strains, particularly in smokers and COPD patients) 1
• Staphylococcus aureus (especially post-influenza or methicillin-resistant strains) 1
• Mycoplasma pneumoniae (atypical pathogen) 1
• Chlamydophila pneumoniae (atypical pathogen) 1
• Legionella species (particularly L. pneumophila) 1
• Moraxella catarrhalis 1
• Gram-negative organisms: Klebsiella pneumoniae, Escherichia coli, Enterobacteriaceae, Pseudomonas aeruginosa (in bronchiectasis or nosocomial settings) 1
• Anaerobes (in aspiration pneumonia with poor dentition, neurologic illness, or impaired consciousness) 1

Other Pathogens

• Respiratory viruses: Influenza, respiratory syncytial virus, adenovirus, parainfluenza 1
• Endemic fungi: Histoplasmosis, blastomycosis, coccidioidomycosis 1
• Mycobacterium tuberculosis (especially in foreign-born individuals, alcoholics, nursing home residents) 1
• Rare pathogens: Coxiella burnetii (Q fever), Chlamydia psittaci (psittacosis), Francisella tularensis (tularemia), Nocardia, hantavirus 1

Important Diagnostic Limitation

In 40-60% of community-acquired pneumonia cases, no causative pathogen is identified despite extensive diagnostic evaluation. 1, 2

Pathological Features

Pneumonia causes inflammation in the alveoli and distal airways, with pathological changes largely dependent on the host immune response rather than pathogen characteristics. 3

Inflammatory Response

• Alveolar and interstitial inflammation with cellular infiltration 3
• Accumulation of inflammatory exudate in alveolar spaces 3
• Disruption of normal gas exchange mechanisms 3
• Potential for persistent dysregulated inflammatory response that can lead to cardiovascular complications post-infection 4

Radiographic Patterns

• Lobar consolidation (typical bacterial pneumonia) 1
• Interstitial or patchy infiltrates (atypical pathogens, viral) 1
• Cavitation (anaerobes, S. aureus, Klebsiella, tuberculosis) 1
• Pleural effusion or empyema (complication in up to 10% of bacteremic pneumococcal cases) 1

No roentgenographic pattern is sufficiently distinctive to allow classification of individual cases by etiology. 1

Clinical Features

Clinical features alone cannot reliably establish a specific etiologic diagnosis of community-acquired pneumonia, as host factors are often as important as pathogen identity in defining presentation. 1, 2

Common Presenting Symptoms

• Fever (may be absent in elderly) 1
• Cough (productive or nonproductive) 1
• Purulent sputum production 5
• Dyspnea 1
• Pleuritic chest pain 1
• Systemic symptoms: malaise, myalgias, headache 1

Physical Examination Findings

• Tachypnea and tachycardia 1
• Rales/crackles on auscultation 1
• Evidence of pulmonary consolidation (dullness to percussion, bronchial breath sounds, egophony) 1
• Hypoxemia (oxygen saturation <90% indicates severity) 1
• Altered mental status (stupor or coma in severe cases) 1

Special Populations

In elderly patients (>65 years), common clinical features are often atypical, obscured, or even absent, increasing mortality risk. 1

"Typical" vs "Atypical" Distinction

The traditional classification into "typical" and "atypical" pneumonia has limited clinical value, as these syndromes include diverse entities with significant overlap. 1, 2

Diagnostic Procedures

Initial Assessment (All Patients)

• Chest radiography (mandatory to substantiate diagnosis, assess severity, detect complications, and establish baseline) 1
• Pulse oximetry or arterial blood gas (if oxygen saturation <90% or respiratory distress) 1

Outpatient Management

• Sputum Gram stain and culture are optional for outpatients 1
• Most outpatients can be treated empirically without extensive microbiological workup 2

Hospitalized Patients (Non-ICU)

• Complete blood count with differential 1
• Serum creatinine, urea nitrogen, glucose, electrolytes, bilirubin, liver enzymes 1
• Blood cultures (×2 before antibiotic treatment) 1
• Sputum Gram stain and culture (deep-cough specimen obtained before antibiotics, interpreted by trained personnel) 1
• HIV serological testing for persons aged 15-54 years 1
• Tuberculosis testing (acid-fast bacilli staining and culture) for patients with cough >1 month, suggestive symptoms, or radiographic changes 1
• Legionella testing for seriously ill patients aged >40 years, immunocompromised, nonresponsive to β-lactams, or in outbreak settings 1
• Thoracentesis if pleural effusion present (with stain, culture, pH, and leukocyte count) 1

Severe Pneumonia/ICU Patients

• All above studies plus more aggressive microbiological evaluation 1
• Consider bronchoscopy for enigmatic cases or when sputum cannot be obtained 1
• CT scan if complications suspected (empyema, lung abscess) 1

Key Diagnostic Principles

Up to 50% of CAP patients will not have a responsible pathogen identified even with extensive evaluation, as no single test can identify all potential pathogens. 2

Gram stain and sputum culture may be discordant for S. pneumoniae and do not detect atypical pathogens like Mycoplasma, Chlamydophila, or Legionella. 2

Treatment

Outpatient Treatment (No Cardiopulmonary Disease, No Risk Factors)

For previously healthy outpatients, treat empirically with a macrolide (azithromycin or clarithromycin) or doxycycline targeting S. pneumoniae, H. influenzae, and atypical pathogens. 1

• Alternative: Antipneumococcal fluoroquinolone (levofloxacin, moxifloxacin) as monotherapy 1, 6
• Levofloxacin 750 mg daily for 5 days is FDA-approved for community-acquired pneumonia due to S. pneumoniae, H. influenzae, H. parainfluenzae, M. pneumoniae, or C. pneumoniae 6

Hospitalized Patients (Non-ICU) WITH Cardiopulmonary Disease or Risk Factors

Treat with intravenous β-lactam (cefotaxime, ceftriaxone, or ampicillin/sulbactam) PLUS intravenous or oral macrolide or doxycycline. 1

• Alternative: Antipneumococcal fluoroquinolone alone (levofloxacin 750 mg IV/PO daily) 1, 6
• This regimen covers S. pneumoniae (including DRSP), H. influenzae, atypical pathogens, enteric gram-negatives, and aspiration anaerobes 1

Hospitalized Patients (Non-ICU) WITHOUT Cardiopulmonary Disease or Risk Factors

Treat with intravenous azithromycin alone, or doxycycline plus a β-lactam if macrolide allergic/intolerant. 1

• Alternative: Antipneumococcal fluoroquinolone monotherapy 1
• Azithromycin is FDA-approved for community-acquired pneumonia due to C. pneumoniae, H. influenzae, M. pneumoniae, or S. pneumoniae 7

Severe Pneumonia/ICU Patients

For ICU admission, use combination therapy with broader coverage and consider Pseudomonas aeruginosa coverage if risk factors present (bronchiectasis, prior antibiotics). 1

• If P. aeruginosa suspected: Antipseudomonal β-lactam (cefepime, piperacillin/tazobactam, imipenem, meropenem) plus fluoroquinolone or aminoglycoside 6
• Add vancomycin empirically if methicillin-resistant S. aureus suspected 6

Multi-Drug Resistant S. pneumoniae (MDRSP)

Levofloxacin 500 mg daily for 7-14 days is highly effective for MDRSP (95% clinical and bacteriologic success), defined as resistance to ≥2 of: penicillin, 2nd generation cephalosporins, macrolides, tetracyclines, or TMP-SMX. 6

Duration of Therapy

• Standard regimen: 7-14 days 6
• High-dose short course: Levofloxacin 750 mg daily for 5 days (90.9% clinical success) 6
• Azithromycin: Typically 5 days for community-acquired pneumonia 7

Critical Treatment Principles

Penicillin G remains the drug of choice for penicillin-susceptible S. pneumoniae infections in the United States. 1

Erythromycin is the preferred treatment for Legionella infections and M. pneumoniae. 1

For aspiration pneumonia acquired in the community, penicillin G is the treatment of choice, usually without culture results; alternatives include lincosamides or penicillin/β-lactamase inhibitor combinations. 1

Important Warnings

Azithromycin carries risks of hepatotoxicity (including hepatic failure with fatalities), QT prolongation, torsades de pointes, and Clostridium difficile-associated diarrhea; it should not be used in patients with pneumonia judged inappropriate for oral therapy due to moderate-to-severe illness or risk factors. 7

Fluoroquinolones can cause QT prolongation and should be used cautiously in patients with known QT prolongation, electrolyte abnormalities, or concurrent use of other QT-prolonging drugs. 7

Nonresponse to Therapy

If clinical improvement does not occur within 72 hours, consider:

• Drug-resistant pathogens 1
• Unusual pathogens (tuberculosis, fungi, Nocardia) 1
• Complications (empyema, lung abscess, metastatic infection) 1
• Noninfectious mimics (pulmonary embolus, heart failure, malignancy, inflammatory lung diseases) 1
• Repeat chest radiograph or CT scan and sample any pleural fluid 1