Community-Acquired Pneumonia Treatment Recommendations
Healthy Outpatient Without Comorbidities
Prescribe amoxicillin 1 g orally three times daily for 5–7 days as first-line therapy. This regimen retains activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, and provides superior pneumococcal coverage compared with oral cephalosporins. 1
Alternative: Doxycycline 100 mg orally twice daily for 5–7 days is acceptable when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens. 1
Macrolides (azithromycin or clarithromycin) should only be used when local pneumococcal macrolide resistance is documented to be <25%. In most U.S. regions, resistance is 20–30%, making macrolide monotherapy unsafe as first-line therapy. 1, 2
Treat for a minimum of 5 days and continue until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability; typical total duration is 5–7 days. 1
Outpatient With Comorbidities
Use combination therapy: amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin (500 mg day 1, then 250 mg daily for days 2–5) for 5–7 days. This regimen achieves approximately 91.5% favorable clinical outcomes by covering typical bacteria (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical pathogens (Mycoplasma, Chlamydophila, Legionella). 1
Comorbidities requiring combination therapy include COPD, diabetes, chronic heart/liver/renal disease, alcoholism, malignancy, asplenia, immunosuppression, or antibiotic use within the past 90 days. 1
Alternative monotherapy: Respiratory fluoroquinolone (levofloxacin 750 mg daily OR moxifloxacin 400 mg daily) for 5–7 days is reserved for patients with β-lactam allergy or when combination therapy is contraindicated, due to FDA safety warnings (tendon rupture, peripheral neuropathy, aortic dissection). 1, 2
If the patient received antibiotics within the previous 90 days, select an agent from a different class to minimize resistance. 1
Hospitalized Non-ICU Patient
Administer ceftriaxone 1–2 g IV once daily PLUS azithromycin 500 mg IV or orally daily as the standard empiric regimen. This combination provides coverage for typical pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella), with strong recommendation and high-quality (Level I) evidence. 1, 3
Alternative regimen: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) is equally effective and preferred for penicillin-allergic patients. 1, 3
Timing is critical: Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30%. 1, 2
Obtain blood cultures and sputum Gram stain/culture before the first antibiotic dose to enable pathogen-directed therapy and safe de-escalation. 1, 3
Switch to oral therapy when the patient is hemodynamically stable (SBP ≥90 mmHg, HR ≤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 medication—typically by hospital day 2–3. 1, 4
Oral step-down options include amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily (or azithromycin alone after 2–3 days of IV therapy). 1
Treat for a minimum of 5 days and until afebrile for 48–72 hours with no more than one sign of clinical instability; typical total duration is 5–7 days. 1, 3
ICU Patient (Severe CAP)
Combination therapy is mandatory for all ICU patients: 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). β-lactam monotherapy is associated with higher mortality in critically ill patients with bacteremic pneumococcal pneumonia. 1, 3
For penicillin-allergic ICU patients: Use aztreonam 2 g IV every 8 hours PLUS levofloxacin 750 mg IV daily. 1
Add antipseudomonal coverage ONLY when specific risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of Pseudomonas aeruginosa. 1, 2
Add MRSA coverage ONLY when specific risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1, 2
Treat for a minimum of 5 days and until afebrile for 48–72 hours with no more than one sign of clinical instability; typical duration for uncomplicated severe CAP is 7–10 days. 1, 3
Extended courses (14–21 days) are required ONLY for infections caused by Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 5
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, 5
Never delay antibiotic administration beyond 8 hours—this increases 30-day mortality by 20–30% in hospitalized patients. 1, 2
Do not add broad-spectrum antipseudomonal or MRSA agents routinely—restrict their use to patients with documented risk factors to prevent resistance, adverse effects, and unnecessary cost. 1, 5
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP—reserve for patients with comorbidities or β-lactam allergy due to FDA warnings about serious adverse events and rising resistance. 1, 2
Do not extend therapy beyond 7–8 days in responding patients without specific indications—longer courses increase antimicrobial resistance risk without improving outcomes. 1