What are the recommended treatments for community-acquired pneumonia?

Common Organisms and Treatment of Community-Acquired Pneumonia

The most common bacterial pathogen in community-acquired pneumonia is Streptococcus pneumoniae, identified in approximately 15% of cases where a pathogen is found, though up to 40% of identified cases are viral in etiology. 1

Most Common Pathogens

Bacterial Organisms

• Streptococcus pneumoniae remains the predominant bacterial cause, including drug-resistant strains (DRSP) 2, 1
• Haemophilus influenzae and Haemophilus parainfluenzae are frequently identified 3
• Moraxella catarrhalis is a common pathogen, particularly in patients with underlying lung disease 3
• Mycoplasma pneumoniae and Chlamydophila pneumoniae are important atypical pathogens 3
• Legionella pneumophila should be considered, especially in severe cases 3

Viral Pathogens

• Up to 40% of identified CAP cases have viral etiologies 1
• COVID-19 and influenza testing should be performed when these viruses are circulating in the community 1
• Secondary bacterial pneumonia with S. pneumoniae and S. aureus commonly complicates influenza 2

Special Circumstances

• Methicillin-resistant Staphylococcus aureus (MRSA) should be considered in severe CAP or post-influenza pneumonia 2
• Pseudomonas aeruginosa is relevant in patients with structural lung disease or specific risk factors 2

Empirical Treatment Recommendations

Outpatient Treatment (Previously Healthy, No Comorbidities)

• A macrolide (azithromycin, clarithromycin, or erythromycin) is first-line 2
• Doxycycline is an alternative option 2

Outpatient Treatment (With Comorbidities or Risk Factors for DRSP)

Comorbidities include chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancies; asplenia; immunosuppression; or recent antibiotic use within 3 months 2

• Respiratory fluoroquinolone (levofloxacin 750 mg, moxifloxacin, or gemifloxacin) is strongly recommended 2
• β-lactam plus macrolide combination: High-dose amoxicillin (1 g three times daily) or amoxicillin-clavulanate (2 g twice daily) PLUS a macrolide 2
• Alternative β-lactams include ceftriaxone, cefpodoxime, or cefuroxime (500 mg twice daily) 2

Important caveat: In regions with high macrolide resistance (≥25% with MIC ≥16 mcg/mL), use alternative agents even in patients without comorbidities 2

Inpatient Non-ICU Treatment

• Respiratory fluoroquinolone (levofloxacin 750 mg or moxifloxacin) as monotherapy 2
• β-lactam plus macrolide combination: Cefotaxime, ceftriaxone, or ampicillin PLUS azithromycin or clarithromycin 2
• Ertapenem is acceptable for patients with risk factors for gram-negative pathogens (excluding Pseudomonas) 2
• Doxycycline can substitute for the macrolide 2

Recent evidence strongly favors azithromycin over doxycycline: A 2025 matched cohort study of 8,492 hospitalized patients demonstrated that azithromycin combined with β-lactams resulted in significantly lower in-hospital mortality (OR 0.71) and 90-day mortality (HR 0.83) compared to doxycycline combinations 4

Inpatient ICU Treatment

• β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) PLUS either azithromycin OR a fluoroquinolone 2
• For penicillin-allergic patients: respiratory fluoroquinolone plus aztreonam 2

For Pseudomonas risk factors (structural lung disease, bronchiectasis, recent hospitalization):

• Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin or levofloxacin 750 mg 2
• Alternative: Antipseudomonal β-lactam PLUS aminoglycoside PLUS azithromycin or fluoroquinolone 2

For suspected MRSA (post-influenza, necrotizing pneumonia, severe sepsis):

• Add vancomycin or linezolid to the above regimens 2

Treatment Duration and Monitoring

Duration

• Minimum 5 days of therapy for uncomplicated CAP 2
• Patient must be afebrile for 48-72 hours and have no more than one sign of clinical instability before discontinuation 2
• 7 days total is recommended for most non-severe cases 2
• 10 days for severe pneumonia 2
• 14-21 days for Legionella, Staphylococcus, or gram-negative enteric bacilli 2

IV to Oral Switch

• Switch when hemodynamically stable, clinically improving, able to ingest medications, and have functioning GI tract 2, 5
• Patients should be afebrile for 24 hours before switching 2
• Inpatient observation while on oral therapy is unnecessary; discharge when clinically stable 2

Critical Clinical Pearls

Pathogen identification is uncommon: Only 38% of hospitalized CAP patients have a pathogen identified, making empirical therapy essential 1

First antibiotic dose timing: For ED admissions, administer the first dose while still in the ED 2

Fluoroquinolone stewardship: Reserve new fluoroquinolones for treatment failures, β-lactam allergies, or documented highly resistant pneumococci (penicillin MIC ≥4 mcg/mL) to limit resistance emergence 6

Combination therapy superiority: For severe CAP, combination empirical therapy (β-lactam plus macrolide or fluoroquinolone) has strengthened evidence over monotherapy 2

Corticosteroids in severe CAP: Systemic corticosteroids administered within 24 hours may reduce 28-day mortality in severe cases 1