Antibiotic Treatment for Community-Acquired Pneumonia
Direct Recommendation by Clinical Setting
For outpatients without comorbidities, use amoxicillin 1 g orally three times daily for 5-7 days as first-line therapy; for outpatients with COPD, heart disease, or other comorbidities, use combination therapy with amoxicillin-clavulanate plus a macrolide (azithromycin or clarithromycin) or respiratory fluoroquinolone monotherapy (levofloxacin 750 mg or moxifloxacin 400 mg daily); for hospitalized non-ICU patients, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily; and for severe CAP requiring ICU admission, use ceftriaxone 2 g IV daily plus either azithromycin 500 mg daily or levofloxacin 750 mg IV daily. 1, 2
Outpatient Treatment Algorithm
Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line agent, providing excellent coverage against Streptococcus pneumoniae, the most common CAP pathogen, with strong recommendation and moderate quality evidence. 1, 2
Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries conditional recommendation with lower quality evidence. 1
Macrolides (azithromycin 500 mg on 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%, as higher resistance rates lead to treatment failure. 1, 3
Adults with Comorbidities (COPD, Heart Disease, Diabetes, etc.)
Combination therapy is mandatory for patients with underlying conditions: use amoxicillin-clavulanate 875/125 mg twice daily (or 2 g twice daily for high-dose regimen) plus either azithromycin 500 mg daily or clarithromycin 500 mg twice daily. 1, 2, 4
Alternative monotherapy option: respiratory fluoroquinolone—levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily—provides equivalent efficacy with strong evidence, though fluoroquinolone use should be reserved for specific indications due to FDA warnings about serious adverse events. 1, 5, 6
The rationale for combination therapy in comorbid patients is that underlying conditions increase risk for both typical bacterial pathogens and atypical organisms (Mycoplasma, Chlamydophila, Legionella), necessitating broader coverage. 1, 7
Hospitalized Non-ICU Patients
Standard Regimen
Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily is the preferred regimen, providing coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms, with strong recommendation and high-quality evidence. 1, 2, 4
Alternative β-lactams include cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, always combined with a macrolide. 8, 1
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is equally effective as β-lactam/macrolide combination therapy, with systematic reviews demonstrating fewer clinical failures and treatment discontinuations. 1, 5, 6
Penicillin-Allergic Patients
Use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) as the preferred alternative, with strong recommendation and level I evidence. 1
Alternative for patients with contraindications to both β-lactams and fluoroquinolones: aztreonam 2 g IV every 8 hours plus azithromycin 500 mg IV daily. 1
Severe CAP Requiring ICU Admission
Mandatory Combination Therapy
All ICU patients require combination therapy with a β-lactam plus either azithromycin or a respiratory fluoroquinolone, as monotherapy is inadequate for severe disease. 1, 2
Preferred regimen: ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours) plus azithromycin 500 mg IV daily, with strong recommendation. 8, 1, 2
Alternative regimen: ceftriaxone 2 g IV daily plus levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily, providing equivalent efficacy. 1, 5
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, 3
Antipseudomonal regimen: piperacillin-tazobactam 4.5 g IV every 6 hours (or cefepime 2 g IV every 8 hours, or meropenem 1 g IV every 8 hours) plus ciprofloxacin 400 mg IV every 8 hours or levofloxacin 750 mg IV daily, plus aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) and azithromycin 500 mg IV daily. 8, 1
Risk Factors for MRSA
Add MRSA coverage if the patient has: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1, 3
MRSA regimen: add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) or linezolid 600 mg IV every 12 hours to the base regimen. 1
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, with typical duration for uncomplicated CAP being 5-7 days. 8, 1, 2
Extend duration to 14-21 days for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 2
Treatment duration should generally not exceed 8 days in a responding patient, as longer courses increase antimicrobial resistance risk without improving outcomes. 8
Transition from IV 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 (decreased fever, respiratory rate, oxygen requirement), able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 8, 1, 2
Oral step-down regimen: amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily (or clarithromycin 500 mg orally twice daily), continuing the same total duration as planned for IV therapy. 1, 2
For patients initially treated with respiratory fluoroquinolone IV, continue the same fluoroquinolone orally at the same dose, as oral bioavailability is equivalent to IV formulation. 5, 6
Critical Timing Considerations
Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients. 1, 2
In patients with CAP and septic shock, immediate antibiotic administration is essential and takes priority over diagnostic testing. 8, 2
Common Pitfalls to Avoid
Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and increased mortality. 1, 3
Never use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 1
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and resistance concerns; reserve fluoroquinolones for patients with comorbidities, recent antibiotic exposure, or penicillin allergy. 1
Do not automatically escalate to broad-spectrum antibiotics (antipseudomonal agents, anti-MRSA agents) without documented risk factors, as this increases resistance risk and adverse events without improving outcomes. 1
Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for P. aeruginosa or MRSA are present, as third-generation cephalosporins (ceftriaxone, cefotaxime) have superior outcomes for standard CAP. 1
Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients, as this allows pathogen-directed therapy and de-escalation once culture results are available. 1, 3
Do not extend therapy beyond 7 days in responding patients without specific indications (such as Legionella, S. aureus, or Gram-negative bacilli), as this increases antimicrobial resistance risk without improving outcomes. 8, 1