First-Line Treatment for Community-Acquired Pneumonia
For healthy outpatients without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, with doxycycline 100 mg twice daily as an acceptable alternative. 1
Outpatient Treatment Algorithm
Previously Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily is the first-line choice, providing excellent coverage against Streptococcus pneumoniae (the most common pathogen, accounting for 48% of identified cases) with activity against 90-95% of pneumococcal strains including many with intermediate penicillin resistance 1, 2
Doxycycline 100 mg orally twice daily serves as the preferred alternative, offering broad-spectrum coverage including atypical organisms (Mycoplasma, Chlamydophila, Legionella) 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 <25%, as breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains 1, 2
Standard duration is 5-7 days total for uncomplicated pneumonia 1
Adults With Comorbidities
Comorbidities include COPD, diabetes, chronic heart/lung/liver/renal disease, alcoholism, malignancy, asplenia, immunosuppression, or recent antibiotic use within 90 days 1
Two equally effective regimens exist:
Combination therapy: β-lactam PLUS macrolide or doxycycline 1, 2
- Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1
- Alternative β-lactams: cefpodoxime or cefuroxime (though these have inferior in vitro activity compared to high-dose amoxicillin) 1
- Doxycycline 100 mg twice daily can substitute for the macrolide component 1
Hospitalized Non-ICU Patients
Two equally effective regimens with strong recommendations and high-quality evidence: 1
For penicillin-allergic patients: respiratory fluoroquinolone is the preferred alternative 1
Minimum duration: 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1, 4
Switch to oral therapy when: hemodynamically stable, clinically improving, able to take oral medications, and normal GI function—typically by day 2-3 of hospitalization 1
Severe CAP Requiring ICU Admission
Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate for severe disease 1, 4
β-lactam PLUS either azithromycin OR respiratory fluoroquinolone 1, 4
For penicillin-allergic ICU patients: aztreonam 2 g IV every 8 hours PLUS respiratory fluoroquinolone 1
Duration: minimum 5 days, typical 7-10 days; extend to 14-21 days for Legionella, S. aureus, or Gram-negative enteric bacilli 1, 2
Special Pathogen Coverage
When to Add Antipseudomonal Coverage
ONLY add when specific risk factors are present: 1
- Structural lung disease (bronchiectasis)
- Recent hospitalization with IV antibiotics within 90 days
- Prior respiratory isolation of P. aeruginosa
Regimen: antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin or levofloxacin PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) 1
When to Add MRSA Coverage
ONLY add when specific risk factors are present: 1
- Prior MRSA infection or colonization
- Recent hospitalization with IV antibiotics
- Post-influenza pneumonia
- Cavitary infiltrates on imaging
Regimen: vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours added to base regimen 1
Critical Pitfalls to Avoid
Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% or in any patient with comorbidities 1, 2
Administer the first antibiotic dose in the emergency department immediately upon diagnosis—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1
Obtain blood cultures and sputum Gram stain/culture BEFORE initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy and de-escalation 1
Do NOT automatically add antipseudomonal or MRSA coverage without documented risk factors—this increases resistance and adverse events without improving outcomes 1
If patient used antibiotics within past 90 days, select an agent from a DIFFERENT antibiotic class to reduce resistance risk 1, 2
Do NOT extend therapy beyond 7-8 days in responding patients without specific indications (identified resistant pathogens)—longer courses increase antimicrobial resistance risk 1
Transition and Follow-Up
Clinical stability criteria before discharge or oral step-down: temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic BP ≥90 mmHg, oxygen saturation ≥90% on room air, ability to maintain oral intake, normal mental status 1
Oral step-down options: amoxicillin 1 g three times daily, amoxicillin-clavulanate 875/125 mg twice daily, doxycycline 100 mg twice daily, or continuation of fluoroquinolone 1
Clinical review at 48 hours for outpatients, 6-week follow-up for all hospitalized patients with chest radiograph reserved for persistent symptoms, smokers, or age >50 years 1