First-Line Antibiotic Therapy for Hospitalized Adults with Community-Acquired Pneumonia
For adults admitted to the hospital with community-acquired pneumonia, initiate ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV daily immediately upon diagnosis—this combination reduces mortality compared with β-lactam monotherapy and provides comprehensive coverage of typical and atypical pathogens. 1
Standard Empiric Regimen for Non-ICU Hospitalized Patients
Ceftriaxone 1–2 g IV once daily PLUS azithromycin 500 mg IV daily is the guideline-recommended first-line regimen, supported by strong evidence (Level I) demonstrating superior clinical outcomes and mortality reduction. 1
This combination covers typical bacterial pathogens (Streptococcus pneumoniae including penicillin-resistant strains with MIC ≤2 mg/L, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila). 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 azithromycin. 1
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) is equally effective but should be reserved for penicillin-allergic patients due to FDA safety warnings about tendon rupture, peripheral neuropathy, and aortic dissection. 1, 2
ICU-Level Severe Pneumonia
Escalate to ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily (or a respiratory fluoroquinolone) for patients requiring ICU admission—combination therapy is mandatory as β-lactam monotherapy is linked to significantly higher mortality in critically ill patients. 1
ICU admission criteria include 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
Critical Timing and Diagnostic Sampling
Administer the first antibiotic dose in the emergency department immediately—delays beyond 8 hours increase 30-day mortality by 20–30%. 1
Obtain blood cultures and sputum Gram stain/culture BEFORE the first antibiotic dose in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation. 1
Duration of Therapy and Transition to Oral Antibiotics
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 (temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic BP ≥90 mmHg, oxygen saturation ≥90% on room air, able to maintain oral intake, normal mental status). 1
Typical duration for uncomplicated CAP is 5–7 days; extend to 14–21 days only for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1
Switch from IV to oral therapy when all clinical stability criteria are met—typically by hospital day 2–3. Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily. 1
Special Pathogen Coverage (Risk-Based Only)
Pseudomonas aeruginosa Coverage
Add antipseudomonal therapy only when documented risk factors exist: 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
Regimen: piperacillin-tazobactam 4.5 g IV every 6 hours 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 antipseudomonal coverage. 1
MRSA Coverage
Add MRSA therapy only when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1
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
Common Pitfalls to Avoid
Never use β-lactam monotherapy in hospitalized patients—it fails to cover atypical pathogens (which account for 10–40% of CAP cases) and is associated with higher mortality compared with combination therapy. 1, 3
Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and leads to treatment failure. 1
Do not routinely add vancomycin or piperacillin-tazobactam without documented risk factors—indiscriminate use promotes antimicrobial resistance without clinical benefit. 1, 4
Avoid fluoroquinolone monotherapy as first-line unless the patient has a documented penicillin allergy—reserve these agents to limit resistance and adverse effects. 1
Monitoring and Reassessment
Monitor vital signs (temperature, respiratory rate, pulse, blood pressure, oxygen saturation) at least twice daily to detect early deterioration. 5
If no clinical improvement by day 2–3, obtain repeat chest radiograph, inflammatory markers (CRP, white blood cell count), and additional microbiologic specimens to assess for complications (pleural effusion, empyema, resistant organisms). 5, 1
For non-severe pneumonia initially treated with β-lactam monotherapy that fails, add or substitute a macrolide to cover atypical pathogens. 5