What is the initial treatment for pneumonia?

Initial Treatment for Pneumonia

For outpatients without comorbidities, start with amoxicillin 1g three times daily; for hospitalized non-ICU patients, use a β-lactam (such as ceftriaxone) plus a macrolide (such as azithromycin); and for severe ICU pneumonia, use a β-lactam plus either a macrolide or respiratory fluoroquinolone. 1, 2

Outpatient Treatment Algorithm

Previously healthy adults without risk factors:

• First-line: Amoxicillin 1g every 8 hours 1, 2
• Alternative: Doxycycline 100mg twice daily (consider 200mg first dose for rapid serum levels) 2
• For patients under 40 years: Macrolide monotherapy (azithromycin 500mg Day 1, then 250mg Days 2-5) is acceptable, particularly when atypical pathogens are suspected 2

Outpatients with comorbidities or recent antibiotic use:

• Preferred: Respiratory fluoroquinolone (levofloxacin or moxifloxacin) OR β-lactam plus macrolide 1, 2
• Comorbidities include chronic heart, lung, liver, or renal disease, diabetes, alcoholism, malignancy, or asplenia 3

Hospitalized Non-ICU Patients

Standard regimen options:

• β-lactam (ceftriaxone 1-2g every 24 hours) PLUS macrolide (azithromycin or clarithromycin) 1, 2, 4
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin or moxifloxacin) 1, 2
• Most patients can be adequately treated with oral antibiotics if no contraindications exist 5

The combination of β-lactam plus macrolide is preferred because it ensures coverage for both typical bacteria (S. pneumoniae, H. influenzae) and atypical pathogens (Mycoplasma, Chlamydophila, Legionella). 1, 2 A 2024 JAMA review confirms this approach reduces mortality in hospitalized patients. 4

Severe CAP/ICU Treatment

For patients WITHOUT Pseudomonas risk factors:

• β-lactam (non-antipseudomonal cephalosporin III such as ceftriaxone or cefotaxime) PLUS macrolide 1, 2
• Alternative: Respiratory fluoroquinolone (moxifloxacin or levofloxacin) with or without β-lactam 1, 2

For patients WITH Pseudomonas risk factors:

• Antipseudomonal β-lactam (cefepime, piperacillin-tazobactam, or carbapenem) PLUS ciprofloxacin OR levofloxacin 1, 2
• Alternative: Antipseudomonal β-lactam PLUS aminoglycoside (gentamicin, tobramycin, or amikacin) PLUS azithromycin 1, 2

Pseudomonas risk factors include structural lung disease (bronchiectasis), recent hospitalization, or recent broad-spectrum antibiotic use. 6

Timing and Duration of Therapy

Initiation:

• Antibiotics should be administered immediately after diagnosis, ideally while still in the emergency department 1, 2
• Delaying antibiotic administration increases mortality, particularly in severe pneumonia 2

Duration:

• Minimum 5 days for most patients responding to therapy 1, 2
• Patient must be afebrile for 48-72 hours and have no more than one sign of clinical instability before discontinuing 1, 2
• Generally should not exceed 8 days in a responding patient 1, 2
• A 2007 meta-analysis confirmed that short-course regimens (≤7 days) are as effective as extended courses for mild-to-moderate CAP 7

Extended duration (14-21 days) required for:

• Legionella pneumonia 5, 1
• Staphylococcal pneumonia 5, 1
• Gram-negative enteric bacilli pneumonia 5, 1

Switch to Oral Therapy

Criteria for IV-to-oral transition:

• Hemodynamically stable 3
• Clinically improving 3
• Able to take oral medications 3
• Normally functioning gastrointestinal tract 3
• Afebrile for 24 hours 2

Up to half of hospitalized patients meet criteria for oral switch by Day 3. 5 Early switch to oral therapy can reduce hospital length of stay without compromising outcomes. 5

Special Considerations and Pathogen-Specific Coverage

MRSA coverage (add vancomycin or linezolid) when:

• Prior MRSA infection 2
• Recent hospitalization 2
• Recent antibiotic use 2
• Cavitary infiltrates or necrotizing pneumonia 2

Atypical pathogen coverage:

• Macrolides, doxycycline, or respiratory fluoroquinolones provide coverage for Mycoplasma, Chlamydophila, and Legionella 1, 2
• For confirmed Legionella: levofloxacin, moxifloxacin, or azithromycin (with or without rifampin) 1

Testing recommendations:

• All patients should be tested for COVID-19 and influenza when these viruses are circulating in the community 4
• Only 38% of hospitalized CAP patients have a pathogen identified; of those, up to 40% have viral etiologies 4

Critical Pitfalls to Avoid

Fluoroquinolone overuse:

• Reserve respiratory fluoroquinolones for patients with β-lactam allergies or specific indications to prevent resistance development 2
• The FDA has issued warnings about increasing adverse events related to fluoroquinolone use, including QT prolongation, tendon rupture, and peripheral neuropathy 2, 8

Inadequate atypical coverage:

• S. pneumoniae resistance to macrolides ranges 30-40% and often co-exists with β-lactam resistance 2
• Consider local resistance patterns when selecting empiric therapy 2
• A 2013 study found that dual therapy improved the likelihood of adequate initial therapy, though it did not independently predict decreased mortality 9

Premature antibiotic changes:

• Do not change antibiotics within the first 72 hours unless there is marked clinical deterioration or bacteriologic data necessitate a change 5
• Radiographic progression in the first 24-48 hours may occur despite appropriate therapy and does not necessarily indicate treatment failure 5

Failure to reassess non-responders:

• For patients not improving by Day 3, conduct careful review of clinical history, examination, and all investigation results 5, 2
• Consider repeat chest radiograph, CRP, white cell count, and additional microbiological testing 5, 2
• Evaluate for complications (empyema, abscess), alternative diagnoses, or resistant pathogens 5, 2