Community-Acquired Pneumonia: Guideline-Recommended Antibiotic Regimens and Treatment Durations
(1) Otherwise Healthy Adult Outpatient (No Comorbidities)
Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line therapy for previously healthy adults with community-acquired pneumonia. 1
- Amoxicillin retains activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, making it the most effective oral agent for the predominant CAP pathogen. 1
- Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative when amoxicillin is contraindicated, providing coverage of both typical and atypical organisms. 1, 2
- Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily days 2–5; or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is documented to be <25%. 1, 2 In most U.S. regions, macrolide resistance among S. pneumoniae is 20–30%, rendering macrolide monotherapy unsafe as first-line. 1, 3
- Treat for a minimum of 5 days and continue until afebrile for 48–72 hours with no more than one sign of clinical instability; typical duration is 5–7 days for uncomplicated CAP. 1, 2
(2) Patients ≥65 Years or With Comorbidities
For outpatients aged ≥65 years or with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; immunosuppression; recent antibiotic use; or drug-resistant S. pneumoniae risk), combination therapy with a β-lactam plus macrolide or respiratory fluoroquinolone monotherapy is required. 1, 2
Preferred Combination Regimen:
- Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5–7 days total. 1, 2
- Alternative β-lactams (cefpodoxime or cefuroxime) can be substituted but must be combined with a macrolide or doxycycline. 1, 2
- Doxycycline 100 mg twice daily can replace the macrolide component if azithromycin is contraindicated. 1, 2
Alternative Monotherapy:
- Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily for 5–7 days. 1, 2, 4
- Fluoroquinolones should be reserved for patients with β-lactam allergy or when combination therapy is contraindicated, given FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection). 1, 2
Critical Considerations:
- If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2
- Never use macrolide monotherapy in patients with comorbidities; breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains. 1, 2
- Treat for a minimum of 5 days and until afebrile for 48–72 hours with ≤1 sign of clinical instability; typical duration is 5–7 days. 1, 2
(3) Hospitalized Non-ICU Patients
For hospitalized patients not requiring ICU admission, two equally effective regimens exist with strong recommendations and high-quality evidence: β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy. 1, 5
Preferred Combination Regimen:
- Ceftriaxone 1–2 g IV once daily PLUS azithromycin 500 mg IV or orally daily. 1, 5
- Alternative β-lactams: cefotaxime 1–2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin. 1
- Clarithromycin 500 mg twice daily can substitute for azithromycin. 1
Alternative Monotherapy:
- Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily. 1, 5
- Fluoroquinolone monotherapy is reserved for penicillin-allergic patients. 1
Duration and Transition:
- Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30%. 1
- Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients. 1
- Treat for a minimum of 5 days and until afebrile for 48–72 hours with ≤1 sign of clinical instability; typical duration is 5–7 days. 1
- Switch from IV to oral therapy when hemodynamically stable (SBP ≥90 mmHg, HR ≤100 bpm), clinically improving, afebrile 48–72 hours, RR ≤24 breaths/min, SpO₂ ≥90% on room air, and able to take oral medication—typically by hospital day 2–3. 1
Renal/Hepatic Adjustments:
- Ceftriaxone requires no dose adjustment in renal or hepatic impairment. 1
- Azithromycin requires no renal dose adjustment. 1
- Levofloxacin dose should be reduced to 750 mg loading dose, then 500 mg every 48 hours if CrCl 20–49 mL/min. 1
(4) ICU Patients (Severe CAP)
For patients requiring ICU admission, combination therapy is mandatory; β-lactam monotherapy is associated with higher mortality. 1, 5
Standard ICU Regimen:
- Ceftriaxone 2 g IV once daily PLUS azithromycin 500 mg IV daily OR a respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1, 5
- Alternative β-lactams: cefotaxime 1–2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours. 1
Duration:
- Treat for a minimum of 5 days and until afebrile for 48–72 hours with ≤1 sign of clinical instability; typical duration for uncomplicated severe CAP is 7–10 days. 1
- Extend therapy to 14–21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 2
Special Pathogen Coverage
Methicillin-Resistant Staphylococcus aureus (MRSA):
- Add MRSA coverage ONLY when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics (≤90 days), post-influenza pneumonia, or cavitary infiltrates on imaging. 1
- Vancomycin 15 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL) OR linezolid 600 mg IV every 12 hours, added to the base regimen. 1
Pseudomonas aeruginosa:
- Add antipseudomonal coverage ONLY when risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics (≤90 days), or prior respiratory isolation of P. aeruginosa. 1, 2
- Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS an aminoglycoside (gentamicin or tobramycin 5–7 mg/kg IV daily). 1, 2
Macrolide Contraindication Alternatives
For patients with macrolide contraindication (e.g., QT prolongation, drug interactions), use β-lactam plus doxycycline OR respiratory fluoroquinolone monotherapy. 1
Non-ICU Hospitalized Patients:
- Ceftriaxone 1–2 g IV daily PLUS doxycycline 100 mg IV or orally twice daily. 1
- Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily as monotherapy. 1
ICU Patients:
- Ceftriaxone 2 g IV daily PLUS levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily. 1
Critical Pitfalls to Avoid
- Never use macrolide monotherapy in hospitalized patients; it fails to cover typical pathogens such as S. pneumoniae and leads to treatment failure. 1, 2
- Never use macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25% (the situation in most of the United States). 1, 3
- Do not add broad-spectrum antipseudomonal or MRSA agents routinely; restrict to patients with documented risk factors to prevent resistance, adverse effects, and unnecessary cost. 1
- Do not delay antibiotic administration beyond 8 hours; this increases 30-day mortality by 20–30% in hospitalized patients. 1
- Do not extend therapy beyond 7–8 days in responding patients without specific indications (e.g., Legionella, S. aureus, Gram-negative bacilli); longer courses increase antimicrobial resistance risk without improving outcomes. 1, 6