What are the recommended antibiotic regimens and treatment durations for community‑acquired pneumonia in (1) a healthy adult outpatient, (2) an outpatient with chronic heart, lung, liver, renal disease, diabetes, immunosuppression, or recent antibiotic use, (3) a non‑ICU hospitalized patient, and (4) an ICU patient, including adjustments for macrolide resistance, β‑lactam allergy, MRSA risk, and Pseudomonas risk?

Community-Acquired Pneumonia Antibiotic Guidelines

Healthy Adult Outpatients (No Comorbidities)

Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line therapy for previously healthy adults with community-acquired pneumonia. 1

• Amoxicillin retains activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, and provides superior pneumococcal coverage compared with oral cephalosporins. 1
• Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens. 1
• Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is documented to be <25%. 1
• In most U.S. regions, macrolide resistance among S. pneumoniae is 20–30%, making macrolide monotherapy unsafe as first-line therapy. 1
• Oral cephalosporins (cefuroxime, cefpodoxime) should not be used as first-line agents due to inferior in-vitro activity against S. pneumoniae, lack of atypical coverage, and higher cost without demonstrated clinical superiority. 1

Outpatients with Comorbidities or Recent Antibiotic Use

For adults with chronic heart, lung, liver, renal disease, diabetes, immunosuppression, or antibiotic use within 90 days, combination therapy is required. 1

• Option 1 – Combination therapy: Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin (500 mg day 1, then 250 mg daily) or doxycycline 100 mg twice daily for 5–7 days. 1
• Alternative β-lactams (cefpodoxime or cefuroxime) must be combined with a macrolide or doxycycline to achieve similar spectrum. 1
• Option 2 – Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily for 5–7 days. 1
• Fluoroquinolones should be reserved for patients with β-lactam allergy or contraindications to macrolides due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1
• If the patient received antibiotics within the previous 90 days, select an agent from a different class to minimize resistance. 1

Hospitalized Non-ICU Patients

For hospitalized patients not requiring ICU admission, ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily is the preferred regimen. 1

• This combination provides comprehensive coverage for typical pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1
• 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. 1
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is an equally effective alternative with strong recommendation and high-quality evidence. 1
• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative. 1
• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation. 1
• Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30%. 1

ICU Patients (Severe CAP)

Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with higher mortality in critically ill patients. 1

• Preferred ICU regimen: Ceftriaxone 2 g IV once daily (or cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours) plus azithromycin 500 mg IV daily or a respiratory fluoroquinolone (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 a respiratory fluoroquinolone. 1

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

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 P. aeruginosa. 1

• Antipseudomonal regimen: Piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 hours or carbapenem plus ciprofloxacin 400 mg IV every 8 hours or levofloxacin 750 mg IV daily plus an aminoglycoside (gentamicin or tobramycin 5–7 mg/kg IV daily) for dual coverage. 1

MRSA Risk Factors

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

• MRSA regimen: Vancomycin 15 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL) or linezolid 600 mg IV every 12 hours, added to the base regimen. 1

β-Lactam Allergy Adjustments

• For outpatients with β-lactam allergy and comorbidities, use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily). 1
• For hospitalized non-ICU patients with β-lactam allergy, use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1
• For ICU patients with β-lactam allergy, use aztreonam 2 g IV every 8 hours plus a respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1

Macrolide Resistance Adjustments

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% (most of the United States). 1
• In hospitalized patients, macrolide monotherapy is inadequate and should never be used; combination therapy with a β-lactam plus macrolide or fluoroquinolone monotherapy is required. 1

Duration of Therapy

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. 1

• Typical duration for uncomplicated CAP is 5–7 days. 1
• Extended duration (14–21 days) is required only for infections caused by 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, clinically improving, afebrile for 48–72 hours, able to take oral medications, and has normal GI function—typically by hospital day 2–3. 1

• Clinical stability criteria include: 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, and normal mental status. 1
• Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily, or continuation of respiratory fluoroquinolone orally. 1

Critical Pitfalls to Avoid

• Never delay antibiotic administration beyond 8 hours in hospitalized patients; this increases 30-day mortality by 20–30%. 1
• Avoid macrolide monotherapy in hospitalized patients; it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and leads to treatment failure. 1
• 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
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns. 1
• Do not extend therapy beyond 7 days in responding patients without specific indications; longer courses increase antimicrobial resistance risk without improving outcomes. 1