What are the first line antibiotics for community-acquired pneumonia?

First-Line Antibiotics for Community-Acquired Pneumonia

For healthy outpatients without comorbidities, amoxicillin 1 g three times daily is the first-line antibiotic of choice, with doxycycline 100 mg twice daily as an alternative. 1, 2

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

Preferred first-line therapy:

• Amoxicillin 1 g three times daily (strong recommendation, moderate quality evidence) 1, 2

Alternative options:

• Doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 1, 2
• Macrolide (azithromycin 500 mg day 1, then 250 mg daily; OR clarithromycin 500 mg twice daily; OR clarithromycin extended-release 1,000 mg daily) ONLY if local pneumococcal macrolide resistance is <25% (conditional recommendation, moderate quality evidence) 1

The rationale for prioritizing amoxicillin is its superior efficacy against Streptococcus pneumoniae, the most common bacterial pathogen in CAP, accounting for approximately 15% of identified cases. 2, 3

Adults With Comorbidities

Comorbidities include chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia. 1

Option 1 - Combination therapy (strong recommendation):

• Beta-lactam: amoxicillin/clavulanate 500 mg/125 mg three times daily, OR 875 mg/125 mg twice daily, OR 2,000 mg/125 mg twice daily; OR cefpodoxime 200 mg twice daily; OR cefuroxime 500 mg twice daily
• PLUS macrolide (azithromycin 500 mg day 1, then 250 mg daily; OR clarithromycin 500 mg twice daily or extended-release 1,000 mg daily) (strong recommendation, moderate quality evidence) 1, 2
• OR PLUS doxycycline 100 mg twice daily (conditional recommendation, low quality evidence) 1

Option 2 - Monotherapy (strong recommendation):

• Respiratory fluoroquinolone: levofloxacin 750 mg daily, OR moxifloxacin 400 mg daily, OR gemifloxacin 320 mg daily (strong recommendation, moderate quality evidence) 1, 2

Inpatient Treatment (Non-ICU)

Preferred regimens:

• Beta-lactam (ampicillin-sulbactam, cefotaxime, ceftriaxone, or ceftaroline) PLUS macrolide (azithromycin preferred) 2, 3
• OR respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 2, 4

For hospitalized patients, ceftriaxone combined with azithromycin is commonly used and should be continued for a minimum of 3 days. 3

Severe CAP (ICU Patients)

Standard treatment:

• Beta-lactam (ceftriaxone, cefotaxime, or ceftaroline) PLUS either macrolide OR respiratory fluoroquinolone 2

When Pseudomonas is suspected:

• Antipseudomonal beta-lactam (piperacillin/tazobactam, imipenem/cilastatin, meropenem, doripenem, or cefepime) PLUS either ciprofloxacin or aminoglycoside PLUS macrolide 2, 4

Treatment Duration

• Standard duration: 5-7 days for most antibiotics in uncomplicated cases 2
• Extended duration: 14-21 days for suspected Legionella, staphylococcal, or gram-negative enteric bacilli pneumonia 2

Critical Caveats and Pitfalls

Macrolide resistance considerations:

• Macrolides should only be used as monotherapy in healthy adults when local pneumococcal macrolide resistance is documented to be <25% 1
• In areas with higher resistance, avoid macrolide monotherapy 1

Recent antibiotic exposure:

• Choose a different antibiotic class than recently used to reduce resistance risk 2
• If antibiotics were used within the previous 3 months, escalate to combination therapy or fluoroquinolone even in otherwise healthy patients 4

Fluoroquinolone warnings:

• Reserve fluoroquinolones for patients with comorbidities or when other options cannot be used 2
• Significant adverse effects include tendinopathy, peripheral neuropathy, and CNS effects 2

Aspiration pneumonia:

• Use amoxicillin-clavulanate or clindamycin for suspected aspiration 2

Switching from IV to oral:

• Hospitalized patients can switch from intravenous to oral antibiotics after clinical improvement and ability to tolerate oral medications, typically within the first 3 days 4