What is the definition, epidemiology, etiology, pathogenesis, clinical presentation, diagnosis, scoring systems, differential diagnosis, treatment, and complications of Community-Acquired Pneumonia (CAP), including the role of steroids in treatment?

Community-Acquired Pneumonia: Comprehensive Overview

Definition

Community-acquired pneumonia (CAP) is an acute infection of the pulmonary parenchyma acquired outside the hospital or healthcare settings, characterized by new radiological shadowing (consolidation) with no other explanation for the illness, occurring in previously healthy individuals. 1, 2

• CAP specifically excludes infections acquired in hospitals, nursing homes, or other healthcare facilities 1
• The diagnosis requires both clinical features (signs and symptoms of pneumonia) AND radiological confirmation of consolidation 2
• These guidelines do NOT apply to non-pneumonic lower respiratory tract infections, including acute bronchitis or acute exacerbations of COPD 1

Epidemiology

CAP remains the sixth leading cause of death in the United States and the number one cause of death from infectious diseases, with approximately 5.6 million cases annually and 1.1 million requiring hospitalization. 1

Incidence and Mortality Rates

• Outpatient mortality: 1-5% 1
• Hospitalized patients (overall): 12% mortality 1
• Bacteremic pneumonia: higher mortality rates 1
• ICU-admitted patients: up to 40-50% mortality 1, 3
• Long-term mortality (within 1 year): up to 50% in severe cases 3

Age-Related Patterns

• Elderly patients (≥65 years) are at particularly high risk for mortality from bacteremic pneumococcal disease 1
• Mycoplasma and Chlamydia psittaci infections are less frequent in the elderly 1
• Elderly patients more frequently present with non-specific symptoms and are less likely to have fever than younger patients 1

Risk Factors

• Age (particularly ≥65 years) 1
• Smoking 1, 4
• Chronic comorbidities: COPD, diabetes mellitus, renal insufficiency, congestive heart failure, coronary artery disease, malignancy, chronic neurologic disease, chronic liver disease 1
• Previous antibiotic therapy 1
• Nursing home residence 1

Etiology

Streptococcus pneumoniae is the most frequent pathogen causing CAP across all settings, age groups, and regardless of comorbidities, accounting for 9-20% of identified cases. 1, 2, 5, 4

Common Bacterial Pathogens

• Streptococcus pneumoniae: Most common bacterial cause (9-20% of cases) 2
• Haemophilus influenzae: 3-10% of cases, especially in smokers 2
• Staphylococcus aureus: More common in severe CAP and ICU patients 1
• Enteric gram-negative bacilli: Up to 10% in non-ICU hospitalized patients, 22% in ICU patients 1
• Legionella species: Important cause of severe CAP 1

Atypical Pathogens

• Mycoplasma pneumoniae: 13-37% of cases 2
• Chlamydophila pneumoniae: Common across all age groups 1
• Legionella pneumophila: Particularly in severe CAP 1

Viral Pathogens

• Respiratory syncytial virus (RSV): Predominant viral cause 1
• Influenza A: Major viral pathogen 6
• Other viruses: parainfluenza, adenovirus, rhinovirus 1
• Recent evidence indicates respiratory viruses are a common cause of CAP 5

Special Considerations

• Drug-resistant Streptococcus pneumoniae (DRSP): More than 40% of pneumococci fall into this category, defined as resistance to two or more antibiotics (penicillin MIC ≥2 mcg/mL, 2nd generation cephalosporins, macrolides, tetracyclines, trimethoprim/sulfamethoxazole) 1, 7
• Pseudomonas aeruginosa: 1.5-5% of severe CAP, requires specific risk factors (chronic/prolonged broad-spectrum antibiotic therapy ≥7 days, bronchiectasis) 1
• Mixed infections: 8-40% of cases represent viral-bacterial or dual infections 1
• No pathogen identified: 20-60% of cases despite comprehensive testing 1, 6

Pathogenesis

The pathogenesis of severe CAP involves three key factors: pathogen virulence, presence of comorbidities, and host immune response, which may be dysregulated and compartmentalized in severe cases. 3

Mechanisms of Infection

• Microaspiration of oropharyngeal secretions containing pathogenic bacteria is the primary route 3
• The lung microbiome (diverse communities of microbes within alveoli) may play a role in pneumonia development 4
• Host factors are often as important as pathogen identity in determining disease severity 1

Host Response

• In severe CAP, the host response may be dysregulated and compartmentalized 3
• Acute cardiovascular diseases significantly impact clinical outcomes 3
• Pneumonia has an enduring, independent effect on long-term outcomes 3

Clinical Presentation

The likely etiological agent causing CAP cannot be accurately predicted from clinical or radiological features alone, and the term "atypical" pneumonia should be abandoned as it incorrectly implies a characteristic clinical presentation. 1

Common Symptoms and Signs

• Cough (productive or non-productive) 1
• Dyspnea 1
• Fever (though less common in elderly) 1
• Pleuritic chest pain 1
• Tachypnea 1
• Crackles on auscultation 1

Age-Related Presentations

• Elderly patients: More frequently present with non-specific symptoms, less likely to have fever, atypical or obscured presentations 1
• Younger patients: More typical presentations with fever and respiratory symptoms 1

Clinical Syndromes

• No roentgenographic pattern is sufficiently distinctive to classify individual cases by etiology 1
• Clinical features, history, physical examination, and routine laboratory/radiographic evaluation cannot reliably make a specific etiologic diagnosis 1
• Legionella infection cannot be diagnosed on clinical grounds alone despite common clinical practice 1

Diagnosis

The diagnosis of CAP requires demonstration of a new infiltrate on chest imaging in a patient with symptoms and signs of pneumonia. 2, 4

Imaging

• Chest radiography: Essential when symptoms and physical examination suggest pneumonia 2
• Helps differentiate pneumonia from other conditions 2
• Can suggest specific etiologies and identify coexisting conditions like pleural effusion 2
• Radiological resolution often lags behind clinical improvement, particularly following Legionella and bacteremic pneumococcal infection 1
• Radiographic changes from atypical pathogens clear more quickly than bacterial infections 1
• Resolution is slower in elderly and with multilobe involvement 1

Microbiological Testing

Appropriate culture and susceptibility tests should be performed before treatment to isolate and identify organisms and determine their susceptibility to levofloxacin, though therapy may be initiated before results are available. 7

• Blood cultures: Positive in only 5-10% of CAP cases for S. pneumoniae 1
• Sputum culture: Limited by inability to distinguish colonization from infection, especially for gram-negatives 1
• Molecular testing: Respiratory pathogen PCR panels play a significant role in evaluating respiratory viruses 4
• Procalcitonin: Useful as an adjunct to clinical judgment for determining appropriate duration of therapy 4

Diagnostic Limitations

• Pathogen not identified in 20-60% of cases despite comprehensive testing 1
• Some studies achieve etiologic diagnosis in 43-85% of cases with comprehensive investigations 1
• Serological testing for atypical pathogens is not standardized 1

Severity Assessment and Scoring Systems

Mortality prediction rules should be used to support, but not replace, physician decision-making, as the admission decision is the single most important clinical decision affecting intensity of testing, treatment, and costs. 1

CURB-65 Score (British Thoracic Society)

The CURB-65 score is recommended for assessing CAP severity, including five variables: Confusion, Urea nitrogen, Respiratory rate, Blood pressure, and age ≥65 years. 2

• Each variable scores 1 point 2
• Score 0-1: Low risk, consider outpatient treatment 1
• Score 2: Intermediate risk, consider hospitalization 1
• Score ≥3: High risk, requires hospitalization 1

Pneumonia Severity Index (PORT/PSI) - American Guidelines

• Heavily weights age and comorbidities 1
• Assigns patients to risk classes I-V 1
• May oversimplify severity by using thresholds (e.g., diastolic BP 56 vs 30 mmHg treated equally) 1
• Requires more severe physiologic abnormalities in young patients compared to older patients to warrant admission 1

Severe CAP Criteria (ICU Admission)

Severe CAP is defined by ICU admission requirements, with modified criteria including minor and major criteria to improve specificity. 1

Minor Criteria (present on admission):

• Respiratory rate ≥30/min 1
• PaO2/FiO2 ≤250 1
• Bilateral or multilobar pneumonia 1
• Systolic BP ≤90 mmHg 1
• Diastolic BP ≤60 mmHg 1

Major Criteria (on admission or during hospitalization):

• Need for mechanical ventilation 1
• Increase in infiltrate size by ≥50% within 48 hours 1
• Septic shock or need for pressors ≥4 hours 1
• Acute renal failure (urine output ≤80 mL in 4 hours or creatinine ≥2 mg/dL without chronic renal failure) 1

Limitations of Prediction Rules

• Do not account for rare conditions (severe neuromuscular disease, prior splenectomy) 1
• Neglect patient preferences for site of care 1
• Must consider ability to maintain oral intake, substance abuse history, cognitive impairment, and activities of daily living 1
• Low-risk patients may have medical and psychosocial contraindications to outpatient care 1

Cost Considerations

• Average inpatient care cost: $7,500 1
• Average outpatient care cost: $150-$350 1

Differential Diagnosis

CAP must be distinguished from non-pneumonic lower respiratory tract infections and other pulmonary conditions. 1

Conditions to Exclude

• Acute exacerbation of COPD: Does not show new infiltrate on imaging 1
• Acute bronchitis: No radiological consolidation 1
• "Chest infections": Non-specific term without pneumonia criteria 1
• Pulmonary embolus: Can mimic pneumonia presentation 1
• Inflammatory diseases: Non-infectious causes of infiltrates 1
• Complicated parapneumonic effusions: Requires specific management 6

Special Populations to Exclude from Standard Guidelines

• Patients with cancer or immunosuppression admitted to specialist units (oncology, hematology, palliative care, infectious diseases, AIDS units) 1
• Hospital-acquired or healthcare-associated pneumonia 1

Treatment

Outpatient Treatment (No Cardiopulmonary Disease, No Modifying Factors)

For outpatients without cardiopulmonary disease or modifying factors, oral macrolide (azithromycin) alone is the recommended first-line treatment. 1, 2

• First-line: Oral macrolide (azithromycin) alone 1, 2
• Alternative if macrolide allergic/intolerant: Doxycycline 1
• Alternative: Antipneumococcal fluoroquinolone monotherapy 1

Outpatient Treatment (With Cardiopulmonary Disease or Modifying Factors)

• Preferred: β-lactam PLUS macrolide or doxycycline 1
• Alternative: Antipneumococcal fluoroquinolone alone 1
• Selected β-lactams for DRSP coverage: Cefpodoxime, amoxicillin/clavulanate, high-dose amoxicillin, or cefuroxime 1

Hospitalized Non-ICU Patients

For hospitalized non-ICU patients, intravenous β-lactam (cefotaxime or ceftriaxone) plus intravenous or oral macrolide or doxycycline is recommended. 1, 2

• Preferred: IV β-lactam (ceftriaxone, cefotaxime) PLUS IV/oral macrolide or doxycycline 1, 2
• Alternative: IV azithromycin alone 1
• Alternative: Antipneumococcal fluoroquinolone monotherapy 1

ICU-Admitted Patients (No Pseudomonas Risk)

For ICU patients without Pseudomonas risk factors, IV β-lactam (cefotaxime or ceftriaxone) plus either IV macrolide (azithromycin) or IV fluoroquinolone is recommended. 1

• Preferred: IV β-lactam (cefotaxime, ceftriaxone) PLUS either IV macrolide (azithromycin) OR IV fluoroquinolone 1
• Antipseudomonal agents (cefepime, piperacillin/tazobactam, imipenem, meropenem) are active against DRSP but not recommended for routine use unless Pseudomonas risk factors present 1

ICU-Admitted Patients (With Pseudomonas Risk)

For ICU patients with Pseudomonas risk factors, combination therapy with an antipseudomonal β-lactam plus an antipseudomonal quinolone is required. 1

• Option 1: Selected IV antipseudomonal β-lactam (cefepime, imipenem, meropenem, piperacillin/tazobactam) PLUS IV antipseudomonal quinolone (ciprofloxacin) 1
• Option 2: Selected IV antipseudomonal β-lactam PLUS IV aminoglycoside PLUS either IV macrolide (azithromycin) OR IV nonpseudomonal fluoroquinolone 1
• Combination therapy with two antipseudomonal agents is required 1

Specific Antibiotic Considerations

Levofloxacin is FDA-approved for CAP treatment with proven efficacy against common pathogens including multi-drug resistant Streptococcus pneumoniae. 7

• Levofloxacin 500 mg: Once daily for 7-14 days (95% clinical success) 7
• Levofloxacin 750 mg: Once daily for 5 days (90.9% clinical success, non-inferior to 10-day regimen) 7
• Effective against MDRSP (95% clinical and bacteriologic success) 7
• Success rates for atypical pathogens: C. pneumoniae 96%, M. pneumoniae 96%, L. pneumophila 70% 7

Pediatric Treatment (Previously Healthy Children)

For previously healthy children with mild-moderate CAP who are immunized against H. influenzae type b, amoxicillin 90 mg/kg/day divided in three doses is first-line treatment. 8

• First-line (immunized children): Amoxicillin 90 mg/kg/day in 3 doses 8
• Unimmunized/incomplete immunization: Amoxicillin-clavulanate or 2nd/3rd generation cephalosporins 8
• Children >5 years with persistent symptoms: Add macrolide to amoxicillin after 48 hours if symptoms persist but clinical condition remains good 8
• Duration: 5 days recommended with clinical reassessment at 72 hours 8

Duration of Therapy

The recommended duration for antimicrobial therapy is 3-5 days if there is good clinical improvement by day 2 or 3. 4

• Most patients: 3-5 days with good clinical response 4
• Pediatric patients: 5 days with reassessment at 72 hours 8
• Procalcitonin levels can guide duration as adjunct to clinical judgment 4

Switch to Oral Therapy and Discharge

Switch to oral therapy should occur when the patient shows improvement in cough and dyspnea, is afebrile (<100°F) on two occasions 8 hours apart, has decreasing white blood cell count, and has functioning GI tract with adequate oral intake. 1

• Criteria for switch: improved cough/dyspnea, afebrile (<100°F) twice 8 hours apart, decreasing WBC, functioning GI tract 1
• Switch can occur even if febrile if other clinical features favorable 1
• Patient can be discharged same day as oral switch if medical and social factors permit 1

Treatment Failure

Initial antibiotic therapy should not be changed in the first 72 hours unless there is marked clinical deterioration; up to 10% of CAP patients will not respond to initial therapy. 1

• Evaluate for: drug-resistant/unusual pathogen, non-pneumonia diagnosis (inflammatory disease, pulmonary embolus), pneumonia complication 1
• Careful requestioning about epidemiologic factors predisposing to specific pathogens 1

General Management

• Start preferred antibiotic immediately 1
• Arrange clinical review 1
• Consider hospital referral if failure to improve 1
• Refer to hospital without delay if cannot be managed at home 1
• Consider starting antibiotics if patient severely ill or delay in hospital transfer 1

Complications

Radiological resolution often lags behind clinical improvement, particularly following Legionella and bacteremic pneumococcal infection, and is slower in elderly patients and those with multilobe involvement. 1

Common Complications

• Complicated parapneumonic effusions: Increasing incidence, requires specific management 6
• Requirement for ICU admission: Up to 10% of admitted patients 1
• Respiratory failure requiring mechanical ventilation: Major criterion for severe CAP 1
• Septic shock: Requiring pressors ≥4 hours 1
• Acute renal failure: Urine output ≤80 mL in 4 hours or creatinine ≥2 mg/dL 1
• Rapid infiltrate progression: ≥50% increase within 48 hours 1

Long-term Outcomes

• Pneumonia has enduring, independent effect on long-term outcomes 3
• Long-term mortality up to 50% within 1 year in severe cases 3
• Acute cardiovascular diseases significantly impact clinical outcomes 3

Delayed Resolution

• Radiological resolution slower in elderly 1
• Slower resolution with multilobe involvement 1
• Atypical pathogen-related changes clear more quickly than bacterial infections 1

Trials on Steroids in CAP

Current guidelines from the Infectious Diseases Society of America and American Thoracic Society do not include N-acetylcysteine or other immunomodulating therapies as part of standard treatment protocols for community-acquired pneumonia. 9

Current Guideline Position

• The American College of Physicians suggests that immunomodulating therapies, such as N-acetylcysteine, are not currently recommended as adjunct treatments for patients with pneumonia based on available evidence 9
• IDSA recommends appropriate and timely antibiotic therapy as the primary treatment for severe CAP 9
• ATS/IDSA do not include adjunctive immunomodulatory therapies in standard protocols 9

Evidence Status

• No high-quality evidence from the provided guidelines supports routine corticosteroid use in CAP 9
• Focus remains on appropriate antibiotic therapy, risk stratification, oxygenation/ventilation support, and obtaining cultures before antibiotics 9

Prevention

Pneumonia can be prevented by the use of pneumococcal and influenza vaccines in appropriate at-risk populations, and smoking cessation should be promoted in all patients. 1, 2, 4

Vaccination

• Pneumococcal vaccination: Recommended for adults ≥65 years and those with chronic medical conditions 2
• Influenza vaccination: Recommended annually for all persons ≥6 months of age 2
• Vaccination has decreased the incidence of pneumococcal CAP 4

Lifestyle Modifications

• Smoking cessation: Significantly reduces risk and severity of CAP 1, 2, 4
• Smoking is a dominant risk factor for CAP 6