What is the initial treatment for community-acquired pneumonia (CAP)?

Initial Treatment for Community-Acquired Pneumonia

For outpatients without comorbidities, start amoxicillin 1g three times daily; for hospitalized non-ICU patients, use ceftriaxone 1-2g IV daily plus azithromycin 500mg daily; for ICU patients, use ceftriaxone 2g IV daily plus azithromycin 500mg daily or a respiratory fluoroquinolone. 1

Outpatient Treatment (Healthy Adults Without Comorbidities)

First-line therapy:

• Amoxicillin 1g orally three times daily is the preferred first-line treatment, supported by moderate quality evidence for effectiveness against common CAP pathogens 2, 1
• Doxycycline 100mg twice daily serves as an acceptable alternative (conditional recommendation, low quality evidence) 2, 1

Macrolide considerations:

• Azithromycin (500mg day 1, then 250mg daily) or clarithromycin (500mg twice daily) should only be used in areas where pneumococcal macrolide resistance is <25% 2, 1
• Macrolide monotherapy has been downgraded from strong to conditional recommendation due to rising resistance patterns 1

Outpatient Treatment (Adults With Comorbidities)

Combination therapy is required:

• β-lactam (amoxicillin-clavulanate, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 1
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750mg daily, moxifloxacin 400mg daily, or gemifloxacin) 1

Hospitalized Non-ICU Patients

Two equally effective regimens with strong evidence:

• β-lactam (ceftriaxone 1-2g IV daily, cefotaxime 1-2g IV every 8 hours, or ampicillin-sulbactam 3g IV every 6 hours) PLUS azithromycin 500mg daily (strong recommendation, high quality evidence) 2, 1, 3
• Respiratory fluoroquinolone monotherapy (levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily) (strong recommendation, high quality evidence) 2, 1

Rationale for combination therapy:

• β-lactams provide excellent coverage for Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 1
• Macrolides or fluoroquinolones add coverage for atypical pathogens (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila) 2, 1
• Combination β-lactam/macrolide therapy may reduce mortality compared to monotherapy 3

Severe CAP/ICU Patients

Mandatory combination therapy:

• β-lactam (ceftriaxone 2g IV daily, cefotaxime 1-2g IV every 8 hours, or ampicillin-sulbactam 3g IV every 6 hours) PLUS either azithromycin 500mg daily OR respiratory fluoroquinolone (levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily) (strong recommendation) 2, 1
• Parenteral antibiotics should be administered immediately after diagnosis 2

Special considerations for ICU patients:

• Systemic corticosteroids within 24 hours of severe CAP development may reduce 28-day mortality 3
• Consider broader coverage if specific risk factors present (see below)

Coverage for Drug-Resistant Pathogens

Pseudomonas aeruginosa coverage (add if risk factors present):

• Risk factors: structural lung disease, recent hospitalization with IV antibiotics within 90 days, prior P. aeruginosa isolation 1
• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin 400mg IV every 8 hours OR levofloxacin 750mg IV daily 1
• Alternative: Add aminoglycoside (gentamicin 5-7mg/kg IV daily or tobramycin 5-7mg/kg IV daily) 1

MRSA coverage (add if risk factors present):

• Risk factors: post-influenza pneumonia, cavitary infiltrates, prior MRSA infection/colonization, recent hospitalization with IV antibiotics 1
• Add vancomycin 15mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600mg IV every 12 hours 1

Penicillin-Allergic Patients

Non-ICU setting:

• Respiratory fluoroquinolone monotherapy (levofloxacin 750mg IV daily or moxifloxacin 400mg IV daily) 1

ICU setting:

• Respiratory fluoroquinolone PLUS aztreonam 2g IV every 8 hours 1

Duration of Therapy

Standard duration:

• Minimum 5 days for uncomplicated CAP, with patient required to be afebrile for 48-72 hours and have no more than one sign of clinical instability before discontinuing 2, 1, 3
• Typical duration: 5-7 days for most patients once clinical stability achieved 2, 1

Extended duration (14-21 days) required for:

• Legionella pneumophila 2, 1
• Staphylococcus aureus 2, 1
• Gram-negative enteric bacilli 2, 1

Transition to Oral Therapy

Criteria for IV-to-oral switch:

• Patient is hemodynamically stable 1
• Clinically improving 1
• Able to ingest oral medications 1
• Normal gastrointestinal function 1
• Typically occurs by day 2-3 of hospitalization 1

Recommended oral step-down regimens:

• Amoxicillin 1g orally three times daily PLUS azithromycin 500mg orally daily 1
• Alternative macrolide: clarithromycin 500mg orally twice daily 1
• Avoid macrolide monotherapy for step-down as it provides inadequate coverage for typical bacterial pathogens 1

Timing of Antibiotic Administration

For hospitalized patients:

• Administer first antibiotic dose while still in the emergency department 1
• While older studies suggested 4-hour thresholds, recent evidence shows no significant mortality benefit from strict 4-hour administration in all patients 4
• Prioritize patients based on age, comorbidities, clinical condition, and pneumonia severity rather than applying universal time thresholds 4

Diagnostic Testing

Obtain before initiating antibiotics:

• Blood cultures and sputum cultures for all hospitalized patients 1
• Test for COVID-19 and influenza when these viruses are common in the community, as diagnosis affects treatment and infection prevention strategies 3

Critical Pitfalls to Avoid

Antibiotic selection errors:

• Avoid macrolide monotherapy in areas with >25% pneumococcal macrolide resistance to prevent treatment failure 2, 1
• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 1
• Overreliance on fluoroquinolones can lead to resistance; reserve for patients with β-lactam allergies or specific indications 2

Coverage gaps:

• Ensure adequate coverage for atypical pathogens (Mycoplasma, Chlamydophila, Legionella) by using combination therapy or fluoroquinolones 2
• For patients failing to improve, consider adding or substituting a macrolide if initially treated with amoxicillin monotherapy 2

Duration errors:

• Avoid extending therapy beyond 7 days in responding patients without specific indications, as this increases antimicrobial resistance risk 1
• Do not discontinue antibiotics before patient is afebrile for 48-72 hours 2, 1

Clinical assessment:

• If no clinical improvement by day 2-3, repeat chest radiograph, CRP, white cell count, and obtain additional microbiological specimens 2
• Consider alternative diagnoses or resistant pathogens 2