What is the treatment approach for Community-Acquired Pneumonia (CAP) based on disease severity and likely causative pathogens?

Community-Acquired Pneumonia: Classification, Epidemiology, and Treatment

Classification by Severity

CAP is classified into four treatment groups based on severity and location of care: outpatients without comorbidities (Group I), outpatients with comorbidities (Group II), hospitalized non-ICU patients (Group III), and ICU-admitted patients (Group IV), with Group IV further subdivided based on Pseudomonas risk factors. 1

Group I: Outpatient, No Comorbidities

• Previously healthy patients under 60 years without modifying factors 1
• Lowest mortality risk, suitable for oral outpatient therapy 1

Group II: Outpatient with Comorbidities

• Patients with cardiopulmonary disease, diabetes, renal/hepatic failure, malignancy, immunosuppression, or recent antibiotic use 1
• Nursing home residents included in this category 1

Group III: Hospitalized, Non-ICU

• Subdivided into those with and without cardiopulmonary disease or modifying factors 1
• Admission decisions guided by PORT scoring but remain a clinical judgment 1

Group IV: ICU-Admitted (Severe CAP)

• Group IVa: No Pseudomonas risk factors 1
• Group IVb: Pseudomonas risk factors present (chronic/prolonged broad-spectrum antibiotic therapy ≥7 days within past month, structural lung disease, bronchiectasis) 1
• Mortality rates up to 50% 1

Epidemiology and Causative Pathogens

Universal Pathogens (All Groups)

Streptococcus pneumoniae remains the most common pathogen across all severity groups, accounting for pneumonia even when no pathogen is identified by routine testing. 1, 2

• S. pneumoniae identified in approximately 15% of patients with confirmed etiology 2
• All patients potentially infected with atypical pathogens (Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella spp.) either alone or as mixed infection 1
• Drug-resistant S. pneumoniae (DRSP) adversely affects mortality only when MIC to penicillin ≥4 mg/L 1

Group-Specific Pathogens

Outpatients (Groups I-II):

• S. pneumoniae, H. influenzae, M. pneumoniae, C. pneumoniae, respiratory viruses 1
• Mixed infections (bacteria plus atypical pathogen) 1

Hospitalized Non-ICU (Group III):

• Same as outpatients plus enteric gram-negatives and aspiration anaerobes in those with modifying factors 1

ICU-Admitted (Group IV):

• S. pneumoniae, Legionella spp., H. influenzae, enteric gram-negative bacilli, S. aureus 1
• M. pneumoniae, respiratory viruses, C. pneumoniae 1
• P. aeruginosa only in Group IVb with specific risk factors (1.5-5% of severe CAP) 1

Epidemiologic Data

• Approximately 1.4 million ED visits, 740,000 hospitalizations, 41,000 deaths annually in the US 2
• Only 38% of hospitalized patients have pathogen identified 2
• Up to 40% of identified pathogens are viruses 2
• Up to 10% of CAP patients require hospitalization; 1 in 5 hospitalized patients require ICU 2

Treatment Recommendations

Group I: Outpatient, No Comorbidities

First-line therapy is a macrolide (azithromycin or clarithromycin) or doxycycline for previously healthy adults. 3

• Azithromycin 500 mg Day 1, then 250 mg Days 2-5 3
• Doxycycline 100 mg twice daily (first dose 200 mg for rapid serum levels) 3
• Amoxicillin 1 g every 8 hours as alternative first-line 3
• Respiratory fluoroquinolone (levofloxacin or moxifloxacin) reserved for β-lactam allergies 3

Group II: Outpatient with Comorbidities

Combination therapy with β-lactam plus macrolide OR respiratory fluoroquinolone monotherapy is recommended. 3

• Amoxicillin 3 g/day PLUS macrolide 3
• OR Respiratory fluoroquinolone alone (levofloxacin or moxifloxacin) 3, 4
• Patients with recent antibiotic exposure should receive different antibiotic class 3

Group III: Hospitalized Non-ICU

β-lactam (ceftriaxone, cefotaxime, or ampicillin/sulbactam) PLUS macrolide (azithromycin) is the standard regimen. 1, 2

With Cardiopulmonary Disease/Modifying Factors:

• IV ceftriaxone 1-2 g every 24 hours PLUS azithromycin 500 mg IV/oral daily 1, 3
• OR IV cefotaxime PLUS macrolide 1
• OR Respiratory fluoroquinolone alone (levofloxacin or moxifloxacin) 1, 3

Without Cardiopulmonary Disease/Modifying Factors:

• IV azithromycin alone 1
• OR Doxycycline plus β-lactam 1
• OR Antipneumococcal fluoroquinolone monotherapy 1

Group IV: ICU-Admitted (Severe CAP)

Group IVa: No Pseudomonas Risk

IV β-lactam (cefotaxime or ceftriaxone) PLUS either IV macrolide (azithromycin) OR IV fluoroquinolone is mandatory. 1

• Ceftriaxone 2 g IV daily PLUS azithromycin 500 mg IV daily 1
• OR Ceftriaxone 2 g IV daily PLUS levofloxacin 750 mg IV daily 1
• Legionella urinary antigen testing required 1

Group IVb: Pseudomonas Risk Present

Antipseudomonal β-lactam PLUS antipseudomonal quinolone OR aminoglycoside-based triple therapy is required. 1

• Cefepime, imipenem, meropenem, or piperacillin/tazobactam PLUS ciprofloxacin 1
• OR Antipseudomonal β-lactam PLUS aminoglycoside (gentamicin, tobramycin, or amikacin) PLUS azithromycin 1
• OR Antipseudomonal β-lactam PLUS aminoglycoside PLUS antipneumococcal fluoroquinolone 1

Special Considerations

Community-Acquired MRSA:

• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours when MRSA suspected 5
• Risk factors: prior MRSA infection, recent hospitalization, post-influenza pneumonia, cavitary infiltrates 5

Duration of Therapy:

• Minimum 5 days for most patients, requiring afebrile 48-72 hours with no more than one clinical instability sign 3
• 7-10 days for uncomplicated S. pneumoniae pneumonia 3
• 14-21 days for Legionella, staphylococcal, or gram-negative enteric bacilli 3

Route Transition:

• Switch to oral therapy when clinically improved and afebrile for 24 hours 3
• First antibiotic dose must be administered in emergency department 3

Diagnostic Testing by Severity

Outpatients (Groups I-II)

• Chest radiograph to confirm diagnosis 1
• Sputum culture and Gram stain NOT required 1
• Severity assessment mandatory 1

Hospitalized Non-ICU (Group III)

• Two sets of blood cultures before antibiotics 1
• Oximetry or arterial blood gas 1
• Routine blood chemistry and complete blood count 1
• Sputum culture if drug-resistant pathogen suspected 1
• Gram stain to guide interpretation, not initial therapy 1

ICU-Admitted (Group IV)

• All Group III tests PLUS Legionella urinary antigen 1
• Aggressive etiologic diagnosis including bronchoscopic samples in selected patients 1
• Paired serological tests for severe CAP 1
• Pneumococcal antigen tests if available 1

Critical Pitfalls to Avoid

Antibiotic Timing:

• Never delay antibiotic administration beyond 8 hours in hospitalized patients—increases 30-day mortality by 20-30% 5

Coverage Gaps:

• Never use macrolide monotherapy for hospitalized CAP—inadequate coverage for typical bacterial pathogens 5
• All patients require atypical pathogen coverage (M. pneumoniae, C. pneumoniae, Legionella) 1
• Macrolide resistance in S. pneumoniae ranges 30-40%, often co-exists with β-lactam resistance 3

Fluoroquinolone Overuse:

• Reserve for patients with β-lactam allergies or specific indications to prevent resistance 3
• Despite FDA warnings about adverse events, justified for comorbid outpatients due to performance, low resistance, and convenience 3

Pseudomonas Coverage:

• Only cover P. aeruginosa when specific risk factors present—avoid unnecessary broad-spectrum therapy 1

Clinical Reassessment:

• Regular severity reassessment mandatory throughout illness course 1
• Failure to improve at 48-72 hours requires repeat chest radiograph, CRP, white cell count, and additional microbiological testing 3