What is the recommended antibiotic regimen for a patient with community-acquired pneumonia (CAP)?

Antibiotic Treatment for Community-Acquired Pneumonia

For outpatient CAP without comorbidities, use amoxicillin 1 g orally three times daily for 5-7 days as first-line therapy; for hospitalized non-ICU patients, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily; for ICU patients, use ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily. 1

Outpatient Treatment Algorithm

Previously 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 including penicillin-resistant strains. 1

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries lower quality evidence. 1

• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented to be <25%, as resistance rates now exceed this threshold in most U.S. regions. 1

Adults With Comorbidities (COPD, Diabetes, Heart/Liver/Renal Disease, Malignancy)

• Use combination therapy with amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg on day 1, then 250 mg daily for days 2-5, providing coverage for both typical bacterial pathogens and atypical organisms. 1, 2

• Alternative regimens include cefpodoxime or cefuroxime plus macrolide or doxycycline. 1

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) is equally effective but should be reserved for patients with contraindications to β-lactams or macrolides due to FDA warnings about serious adverse events. 1, 3

Hospitalized Non-ICU Patients

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily is the preferred regimen, with strong recommendation and high-quality evidence supporting 91.5% favorable clinical outcomes. 1, 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 azithromycin. 1

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is equally effective as combination therapy with systematic reviews demonstrating fewer clinical failures. 1, 5

• For penicillin-allergic patients, use respiratory fluoroquinolone as the preferred alternative. 1

Severe CAP Requiring ICU Admission

• Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 1

• Use ceftriaxone 2 g IV daily PLUS azithromycin 500 mg IV daily as the preferred regimen. 1, 4

• Alternative: ceftriaxone 2 g IV daily PLUS levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. 1

• For penicillin-allergic ICU patients, use aztreonam 2 g IV every 8 hours PLUS levofloxacin 750 mg IV daily. 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. 1, 6, 4

• Typical duration for uncomplicated CAP is 5-7 days—do not extend therapy beyond 7 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes. 1, 6

• For patients stabilized at day 3, three days of antibiotic treatment is sufficient for non-severe or moderate CAP. 6

• Extend duration to 14-21 days only for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1

Transition from IV to Oral Therapy

• Switch from IV to oral antibiotics when the patient is hemodynamically stable (systolic BP >90 mmHg), 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

• Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily, or transition to amoxicillin-clavulanate 875/125 mg twice daily plus azithromycin. 1

Special Populations Requiring Broader Coverage

Risk Factors for Pseudomonas aeruginosa

• Add antipseudomonal coverage only when specific risk factors are present: structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 1

• Use antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily. 1

• For septic shock or high mortality risk, add aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) for dual antipseudomonal coverage. 1

Risk Factors for MRSA

• Add MRSA coverage when specific risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1

• 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

Critical Timing Considerations

• Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients. 1, 4

• For severe CAP, systemic corticosteroid administration within 24 hours may reduce 28-day mortality. 4

Diagnostic Testing for Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 1

• Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis may affect treatment and infection prevention strategies. 4

• Urinary antigen testing for Legionella pneumophila serogroup 1 should be considered in severe CAP or ICU patients. 1

Common Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and leads to treatment failure in areas where resistance exceeds 25%. 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. 1

• Do not automatically escalate to broad-spectrum antibiotics (antipseudomonal agents, MRSA coverage) based solely on severity or comorbidities—only add when documented risk factors are present. 1

• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present, as these agents have inferior outcomes compared to ceftriaxone/cefotaxime. 1

• If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1