Recommended Antibiotics for Community-Acquired Pneumonia
For outpatient treatment without comorbidities, amoxicillin 1 gram three times daily is the first-line antibiotic, while hospitalized patients require combination therapy with ceftriaxone 1-2 grams IV daily plus azithromycin 500 mg daily, or alternatively a respiratory fluoroquinolone (levofloxacin 750 mg or moxifloxacin 400 mg) as monotherapy. 1, 2
Outpatient Treatment Algorithm
Healthy Adults Without Comorbidities
Amoxicillin 1 gram orally three times daily for 5-7 days is the preferred first-line therapy, providing excellent coverage against Streptococcus pneumoniae (the most common pathogen) with strong recommendation and moderate quality evidence. 1, 2
Doxycycline 100 mg orally twice daily for 5-7 days serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries conditional recommendation with lower quality evidence. 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 to be <25%, as breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains. 1, 2
Adults With Comorbidities
Comorbidities include chronic heart/lung/liver/renal disease, diabetes mellitus, alcoholism, malignancies, asplenia, or immunosuppressing conditions. 2, 3
Combination therapy: Amoxicillin-clavulanate 875/125 mg twice daily (or 2000/125 mg twice daily for enhanced coverage) PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days total. 1, 2
Alternative combination: Beta-lactam (cefpodoxime or cefuroxime) plus macrolide or doxycycline 100 mg twice daily. 1, 2
Fluoroquinolone monotherapy: Levofloxacin 750 mg daily for 5 days, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily, though fluoroquinolones should be reserved for appropriate indications due to FDA warnings about serious adverse events. 1, 2
Inpatient Treatment Algorithm
Non-ICU Hospitalized Patients
Two equally effective regimens exist with strong recommendations and high-quality evidence: 1, 2
Beta-lactam plus macrolide: Ceftriaxone 1-2 grams IV once daily PLUS azithromycin 500 mg daily (IV initially, then oral when stable), providing coverage for both typical bacterial pathogens and atypical organisms. 1, 2, 4
Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily, with systematic reviews demonstrating fewer clinical failures compared to beta-lactam/macrolide combinations. 1, 2, 5
For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative. 1, 2
ICU-Level Severe Pneumonia
Mandatory combination therapy with beta-lactam (ceftriaxone 2 grams IV daily, cefotaxime 1-2 grams IV every 8 hours, or ampicillin-sulbactam 3 grams 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
This dual coverage is obligatory for all ICU patients regardless of other factors. 1, 2
Special Populations Requiring Broader Coverage
Pseudomonas Risk Factors
When structural lung disease, recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa exists: 1, 2
- Antipseudomonal beta-lactam (piperacillin-tazobactam 4.5 grams IV every 6 hours, cefepime 2 grams IV every 8 hours, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily). 1, 2
MRSA Risk Factors
When prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging exist: 1, 2
- Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours to the base regimen. 1, 2
Duration of Therapy
Treat for a minimum of 5 days and until afebrile for 48-72 hours with no more than one sign of clinical instability, with typical duration for uncomplicated CAP being 5-7 days. 1, 2
Extend to 14-21 days ONLY for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 2
Transition to Oral Therapy
Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 1, 2, 6
Preferred oral step-down: Amoxicillin 1 gram orally three times daily plus azithromycin 500 mg orally daily (or clarithromycin 500 mg twice daily as alternative macrolide). 2
Critical Pitfalls to Avoid
NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, in patients with any comorbidities, or in hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens and leads to treatment failure. 1, 2
NEVER delay antibiotic administration beyond 8 hours in hospitalized patients, as this increases 30-day mortality by 20-30%. The first dose should be given in the emergency department. 1, 2
AVOID using ceftriaxone 1 gram daily for suspected MSSA pneumonia, as this dose demonstrates poor clinical outcomes with 53% early clinical failure rates; use higher doses (2 grams daily) or alternative agents. 7
DO NOT automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors for Pseudomonas or MRSA, as this drives unnecessary resistance. 1, 2
If the patient received antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2
Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation when results become available. 1, 2