Antibiotic Regimen for Community-Acquired Pneumonia in Previously Healthy Adults
For previously healthy adults with community-acquired pneumonia treated as outpatients, amoxicillin 1 gram orally three times daily for 5-7 days is the preferred first-line therapy. 1
Outpatient Treatment Algorithm
First-Line Therapy for Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily for 5-7 days is the preferred regimen, providing excellent coverage against Streptococcus pneumoniae (the most common pathogen, accounting for 48% of identified CAP cases) with activity against 90-95% of pneumococcal strains including many with intermediate penicillin resistance 1, 2
Doxycycline 100 mg orally twice daily for 5-7 days serves as an acceptable alternative, offering broad-spectrum coverage including atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila) with comparable efficacy to fluoroquinolones at significantly lower cost 1, 2, 3, 4
Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5, 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 macrolide-resistant strains 1, 2
Critical Decision Points
If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk—for example, if recently treated with a β-lactam, use doxycycline instead of amoxicillin 1, 2
Avoid fluoroquinolones (levofloxacin, moxifloxacin) as first-line therapy in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendinopathy, peripheral neuropathy, CNS effects) and concerns about resistance development—reserve these agents for patients with comorbidities or treatment failures 1, 2
Inpatient Treatment for Non-ICU Patients
For hospitalized patients not requiring ICU admission, use either β-lactam plus macrolide combination therapy OR respiratory fluoroquinolone monotherapy 1, 5
Preferred Regimens (Both Equally Effective)
Ceftriaxone 1-2 g IV once daily PLUS azithromycin 500 mg IV or oral daily, providing coverage for both typical bacterial pathogens and atypical organisms 1, 6, 7
Levofloxacin 750 mg IV once daily OR moxifloxacin 400 mg IV once daily as monotherapy, with systematic reviews demonstrating fewer clinical failures compared to β-lactam/macrolide combinations 1, 6
Transition to Oral Therapy
Switch from IV to oral antibiotics when the patient is hemodynamically stable (systolic BP >90 mmHg, heart rate <100, respiratory rate <24), clinically improving, afebrile for 48-72 hours, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization 1, 5
Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily, OR levofloxacin 750 mg once daily 1, 5
Severe CAP Requiring ICU Admission
Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease 1, 2
Use ceftriaxone 2 g IV once daily (or cefotaxime 1-2 g IV every 8 hours) PLUS either azithromycin 500 mg IV daily OR a respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 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—typical duration for uncomplicated CAP is 5-7 days 1, 2, 3
Extend duration to 14-21 days ONLY if Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli are identified 1, 2
Do not extend therapy beyond 7-8 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1, 2
Special Populations Requiring Modified Regimens
Adults With Comorbidities (COPD, Diabetes, Heart/Liver/Renal Disease, Malignancy)
Use combination therapy with amoxicillin-clavulanate 875 mg/125 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days 1, 2
Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily OR moxifloxacin 400 mg daily) 1, 2, 8
Risk Factors for Pseudomonas aeruginosa
Add antipseudomonal coverage if the patient has structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa 1, 5
Use antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin or levofloxacin PLUS aminoglycoside 1, 5
Risk Factors for MRSA
Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours if the patient has prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 1
Critical Pitfalls to Avoid
Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and is associated with higher treatment failure rates 1, 2
Never delay antibiotic administration beyond 8 hours in hospitalized patients—delayed administration increases 30-day mortality by 20-30% 1
Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation 1
Avoid using cefuroxime or ciprofloxacin as first-line monotherapy for hospitalized CAP—cefuroxime has less reliable coverage against drug-resistant S. pneumoniae, and ciprofloxacin lacks adequate activity against S. pneumoniae 5