Treatment for Pneumonia
Outpatient Management for Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily for 5–7 days is the first-line treatment for previously healthy adults with community-acquired pneumonia. 1, 2, 3, 4 This regimen provides superior pneumococcal coverage, retaining activity against 90–95% of Streptococcus pneumoniae isolates—including many penicillin-resistant strains—and represents the most cost-effective option with an excellent safety profile. 1, 2, 3
Alternative regimens:
- Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens. 1, 2, 3, 4 However, this carries a conditional recommendation with lower-quality evidence compared to amoxicillin. 1, 2
- Macrolide monotherapy (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%. 1, 2, 3 In most U.S. regions, resistance ranges from 20–30%, making macrolide monotherapy unsafe as first-line therapy due to increased risk of breakthrough bacteremia and treatment failure. 1, 2, 3
Outpatient Management for Adults With Comorbidities
For patients with chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; asplenia; or recent antibiotic use (within 90 days), combination therapy is mandatory. 1, 2, 3
Preferred combination regimen:
- Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg on day 1, then 250 mg daily for days 2–5, for a total of 5–7 days. 1, 2, 3, 4 This combination provides dual coverage against typical bacterial pathogens (S. pneumoniae, Haemophilus influenzae, β-lactamase producers) and atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila). 1, 2, 3
- Alternative β-lactams include cefpodoxime 200 mg twice daily or cefuroxime 500 mg twice daily, each combined with a macrolide. 1, 2
- Doxycycline 100 mg twice daily can substitute for the macrolide component if azithromycin is unavailable or contraindicated, though this represents lower-quality evidence. 1, 2
Alternative monotherapy:
- Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily) for 5–7 days is an acceptable alternative when β-lactams or macrolides are contraindicated. 1, 2, 3 However, fluoroquinolones should be reserved for specific situations due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1, 2, 3
Critical decision point: If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2, 3, 4
Inpatient Management for Non-ICU Hospitalized Patients
Two equally effective regimens exist with strong recommendations and high-quality evidence: 1, 2
Preferred regimen:
- Ceftriaxone 1–2 g IV once daily PLUS azithromycin 500 mg IV or orally daily. 1, 2, 3 This combination provides comprehensive coverage for typical pathogens (S. pneumoniae, H. influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1, 2
- Alternative β-lactams include cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, each combined with azithromycin. 1, 2
Alternative regimen:
- Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1, 2, 3 This is reserved for penicillin-allergic patients or when combination therapy is contraindicated. 1, 2
Transition to oral therapy: Switch from IV to oral antibiotics when the patient is hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm), clinically improving, afebrile for 48–72 hours, respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air, and able to take oral medications—typically by hospital day 2–3. 1, 2, 3
Oral step-down options:
- Amoxicillin 1 g three times daily plus azithromycin 500 mg daily. 1, 2, 3
- Amoxicillin-clavulanate 875 mg/125 mg twice daily plus azithromycin. 1, 2, 3
Severe CAP Requiring ICU Admission
Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with higher mortality. 1, 2, 3
Preferred ICU regimen:
- Ceftriaxone 2 g IV once daily (or cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours) PLUS azithromycin 500 mg IV daily OR a respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1, 2, 3 This regimen reduces mortality in critically ill patients with bacteremic pneumococcal pneumonia. 1, 2
Special Pathogen Coverage (Risk-Based)
Antipseudomonal coverage should be added ONLY when specific risk factors are present: 1, 2
- Structural lung disease (bronchiectasis, cystic fibrosis)
- Recent hospitalization with IV antibiotics within 90 days
- Prior respiratory isolation of Pseudomonas aeruginosa
- Chronic or prolonged broad-spectrum antibiotic exposure (≥7 days in the past month) 1, 2
Antipseudomonal regimen:
- Piperacillin-tazobactam 4.5 g IV every 6 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 Dual antipseudomonal coverage is required for severe infections. 1, 2
MRSA coverage should be added ONLY when specific risk factors are present: 1, 2
- Prior MRSA infection or colonization
- Recent hospitalization with IV antibiotics within 90 days
- Post-influenza pneumonia
- Cavitary infiltrates on imaging 1, 2
MRSA regimen:
- 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, 2
Duration of Therapy
Treat for a minimum of 5 days AND until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability. 1, 2, 3, 4 Typical duration for uncomplicated CAP is 5–7 days. 1, 2, 3, 4
Extended duration (14–21 days) is required ONLY for infections caused by: 1, 2, 3
Critical Timing and Diagnostic Considerations
Administer the first antibiotic dose immediately upon diagnosis, ideally in the emergency department. 1, 2, 3 Delays beyond 8 hours increase 30-day mortality by 20–30% in hospitalized patients. 1, 2, 3
Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation. 1, 2, 3
Common Pitfalls to Avoid
- Never use macrolide monotherapy in hospitalized patients because it fails to cover typical pathogens like S. pneumoniae and leads to treatment failure. 1, 2, 3
- Never use macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25% due to increased risk of breakthrough bacteremia. 1, 2, 3
- Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns. 1, 2, 3
- Do not add broad-spectrum antipseudomonal or MRSA agents routinely; restrict their use to patients with documented risk factors to prevent unnecessary resistance and adverse effects. 1, 2
- Do not extend therapy beyond 7–8 days in responding patients without specific indications (e.g., Legionella, S. aureus, Gram-negative bacilli), as longer courses increase antimicrobial resistance risk without improving outcomes. 1, 2, 3
Follow-Up and Monitoring
Outpatient review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1, 2, 3, 4
Signs of treatment failure warranting hospital referral: 1, 2, 3
- No clinical improvement by day 2–3
- Development of respiratory distress (respiratory rate >30/min, oxygen saturation <92%)
- Inability to tolerate oral antibiotics
- New complications such as pleural effusion 1, 2, 3
Escalation strategy for outpatient treatment failure: 1, 2, 3
- If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin or clarithromycin) to cover atypical pathogens. 1, 2, 3
- If combination therapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2, 3
Routine follow-up at 6 weeks for all patients; chest radiograph only for those with persistent symptoms, abnormal physical findings, or high risk for underlying malignancy (e.g., smokers >50 years). 1, 2, 3