What is the recommended management and antimicrobial regimen for community‑acquired pneumonia (CAP) based on severity and care setting (outpatient low‑risk, outpatient with comorbidities, inpatient non‑ICU, inpatient intensive care unit) and for hospital‑acquired or ventilator‑associated pneumonia (HAP/VAP)?

Pneumonia Treatment: Evidence-Based Management by Severity and Setting

Outpatient Management – Previously Healthy Adults

For previously healthy adults without comorbidities, prescribe amoxicillin 1 g orally three times daily for 5–7 days as first-line therapy. This regimen 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 serves as an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens 1.
• Avoid macrolide monotherapy (azithromycin, clarithromycin) in most U.S. regions where pneumococcal macrolide resistance is 20–30%, exceeding the 25% threshold at which macrolides become unsafe as first-line agents 1.
• 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; typical duration is 5–7 days 1, 2.

Outpatient Management – Adults with Comorbidities

For patients with COPD, diabetes, chronic heart/lung/liver/renal disease, malignancy, or recent antibiotic use (within 90 days), prescribe combination therapy: amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin 500 mg on day 1, then 250 mg daily for days 2–5. This regimen achieves 91.5% favorable clinical outcomes by covering typical bacteria and atypical pathogens 1.

• Alternative: respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) for 5–7 days, reserved for β-lactam allergy or when combination therapy is contraindicated due to FDA safety warnings 1, 3.
• If the patient received antibiotics within the past 90 days, select an agent from a different class to minimize resistance 1.

Hospitalized Patients (Non-ICU)

Administer ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily immediately upon diagnosis in the emergency department. This combination provides comprehensive coverage for typical pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) with strong recommendation and high-quality (Level I) evidence 1, 2.

• Alternative β-lactams: cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, each combined with azithromycin 1.
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is reserved for penicillin-allergic patients due to FDA warnings about tendon rupture, peripheral neuropathy, and aortic dissection 1, 3.
• Critical timing: delays beyond 8 hours increase 30-day mortality by 20–30% 1, 2.
• Obtain blood cultures and sputum Gram stain/culture before the first antibiotic dose to enable pathogen-directed therapy 1, 2.

Transition to Oral Therapy

• Switch from IV to oral antibiotics when the patient is hemodynamically stable (SBP ≥90 mmHg, HR ≤100 bpm), clinically improving, afebrile for 48–72 hours, respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air, and able to take oral medication—typically by hospital day 2–3 1, 2.
• Oral step-down options: amoxicillin 1 g three times daily plus azithromycin 500 mg daily 1.

Severe CAP Requiring ICU Admission

For ICU patients, mandatory combination therapy consists of ceftriaxone 2 g IV once daily plus azithromycin 500 mg IV daily (or a respiratory fluoroquinolone: levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). β-lactam monotherapy is linked to significantly higher mortality in critically ill patients with bacteremic pneumococcal pneumonia 1, 2.

• Alternative β-lactams for ICU: cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1.
• For penicillin-allergic ICU patients: aztreonam 2 g IV every 8 hours plus a respiratory fluoroquinolone 1.
• ICU admission criteria: any one major criterion (septic shock requiring vasopressors or respiratory failure requiring mechanical ventilation) OR ≥3 minor criteria (confusion, respiratory rate ≥30/min, systolic BP <90 mmHg, multilobar infiltrates, PaO₂/FiO₂ <250) 1.

Special Pathogen Coverage (Risk Factor–Based)

Pseudomonas aeruginosa Coverage

Add antipseudomonal therapy ONLY when specific risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, prior respiratory isolation of P. aeruginosa, or chronic broad-spectrum antibiotic exposure (≥7 days in the past month) 1, 2.

• Regimen: antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours OR imipenem OR meropenem) 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, 2.

MRSA Coverage

Add MRSA therapy ONLY when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics within 90 days, post-influenza pneumonia, or cavitary infiltrates on imaging 1, 2.

• 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 CAP regimen 1, 2.

Duration of Therapy

• Minimum duration: 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability 1, 2.
• Typical duration for uncomplicated CAP: 5–7 days 1, 2.
• Extended duration (14–21 days) ONLY for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2.
• Do not extend therapy beyond 7–8 days in responding patients without specific indications—this increases antimicrobial resistance risk without improving outcomes 1, 2.

Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

For early-onset HAP/VAP without risk of multidrug resistance, use ceftriaxone, ampicillin-sulbactam, ertapenem, or a respiratory fluoroquinolone. For late-onset HAP/VAP or when multidrug-resistant organisms are suspected, broader antipseudomonal and anti-MRSA coverage is required 3, 4.

• The 2019 IDSA/ATS guidelines eliminated the healthcare-associated pneumonia (HCAP) category, which had led to overuse of broad-spectrum agents without improving outcomes 1.
• Not all HAP patients need antipseudomonal therapy—use risk factors to guide therapy selection rather than empiric broad-spectrum coverage for all 4.

Critical Pitfalls to Avoid

• Never delay antibiotics beyond 8 hours in hospitalized patients—mortality increases by 20–30% 1, 2.
• Never use macrolide monotherapy in hospitalized patients—it fails to cover typical pathogens like S. pneumoniae and leads to treatment failure 1, 2.
• Never use macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25% (the situation in most U.S. regions) 1.
• Never use β-lactam monotherapy in ICU patients—combination therapy is mandatory and reduces mortality 1, 2.
• Never add antipseudomonal or MRSA coverage without documented risk factors—this promotes resistance, increases adverse events, and adds unnecessary cost 1, 2.
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance 1.

Monitoring and Follow-Up

• Monitor temperature, respiratory rate, pulse, blood pressure, mental status, and oxygen saturation at least twice daily in hospitalized patients 5.
• If no clinical improvement by day 2–3, obtain repeat chest radiograph, CRP, white blood cell count, and additional microbiologic specimens to assess for complications such as pleural effusion, empyema, or resistant organisms 5, 1.
• For outpatients, clinical review at 48 hours (or sooner if symptoms worsen) to assess response, oral intake, and adherence 5, 1.
• Routine follow-up at 6 weeks for all patients; chest radiograph only if symptoms persist, physical signs remain, or high risk for underlying malignancy (smokers >50 years) 5, 1.

Prevention

• Offer pneumococcal polysaccharide vaccine to all adults ≥65 years and those with high-risk conditions 1.
• Recommend annual influenza vaccination for all patients 1.
• Provide smoking-cessation counseling to all current smokers 1.