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

Treatment of Community-Acquired Pneumonia

For hospitalized patients with community-acquired pneumonia without ICU-level severity, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily as first-line therapy, or alternatively, respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2

Outpatient Treatment Algorithm

For previously healthy outpatients without comorbidities:

• First-line: Amoxicillin 1 g orally three times daily provides optimal coverage against Streptococcus pneumoniae and other common bacterial pathogens 1, 2
• Alternative: Doxycycline 100 mg twice daily if amoxicillin cannot be tolerated 1, 2
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented <25% 1, 2

For outpatients with comorbidities (COPD, diabetes, renal/heart failure, malignancy) or recent antibiotic use:

• Combination therapy: β-lactam (amoxicillin-clavulanate 2 g twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) or doxycycline 1, 2
• Monotherapy alternative: Respiratory fluoroquinolone (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) 1, 2, 3

Inpatient Non-ICU Treatment

Two equally effective regimens exist with strong evidence:

Regimen 1 (Preferred):

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily 1, 2, 4
• This combination provides coverage for typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 5, 2

Regimen 2 (Alternative):

• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2, 3
• Systematic reviews demonstrate fewer clinical failures with fluoroquinolones compared to β-lactam/macrolide combinations 2

For penicillin/cephalosporin-allergic patients:

• Respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is the preferred alternative 2
• Alternative: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 2

ICU-Level Severe CAP

Combination therapy is MANDATORY for all ICU patients:

• β-lactam (ceftriaxone 2 g IV daily, cefotaxime 1-2 g IV every 8 hours, or ampicillin-sulbactam 3 g IV every 6 hours) PLUS either azithromycin 500 mg daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2, 5

Add antipseudomonal coverage when risk factors present:

• Risk factors: structural lung disease, recent hospitalization with IV antibiotics within 90 days, prior P. aeruginosa isolation 2, 5
• Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) 2, 5

Add MRSA coverage when risk factors present:

• Risk factors: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates on imaging 2, 5
• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 2, 5

Duration of Therapy

Minimum treatment duration:

• Treat for a minimum of 5 days AND until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability 1, 2, 4
• Typical duration for uncomplicated CAP: 5-7 days total 1, 2

Extended duration required for specific pathogens:

• Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli: 14-21 days 1, 2
• Severe microbiologically undefined pneumonia: 10 days 2

Transition to Oral Therapy

Switch from IV to oral antibiotics when ALL criteria met:

• Hemodynamically stable 1, 2
• Clinically improving 1, 2
• Able to take oral medications 1, 2
• Normal gastrointestinal function 1, 2
• Typically occurs by day 2-3 of hospitalization 2

Recommended oral step-down regimens:

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 2
• Alternative macrolide: clarithromycin 500 mg orally twice daily can substitute for azithromycin 2

Critical Pitfalls to Avoid

Timing of antibiotic administration:

• Administer the first antibiotic dose in the emergency department immediately upon diagnosis 2
• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 2, 4

Macrolide resistance:

• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% 1, 2
• Macrolide-resistant S. pneumoniae may also be resistant to doxycycline 2

Inappropriate β-lactam selection:

• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 2
• Ceftriaxone, cefotaxime, and ampicillin-sulbactam are the preferred β-lactams for standard CAP treatment 2

Fluoroquinolone overuse:

• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns 2
• Reserve fluoroquinolones for patients with comorbidities, recent antibiotic use, or penicillin allergy 2

Unnecessary broad-spectrum coverage:

• Do NOT automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for resistant organisms 2
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow targeted de-escalation 2, 5

Excessive treatment duration:

• Avoid extending therapy beyond 7 days in responding patients without specific indications, as this increases antimicrobial resistance risk 2

Diagnostic Testing

Obtain blood and sputum cultures before antibiotics when:

• All inpatients empirically treated for MRSA or P. aeruginosa 2
• Concern for multidrug-resistant pathogens 5
• ICU admission 2

Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis may affect treatment and infection prevention strategies 4