Community-Acquired Pneumonia: Assessment and Empiric Antibiotic Management
Initial Assessment and Site-of-Care Decision
Use severity scoring to determine treatment location immediately upon diagnosis. Apply the CURB-65 score (Confusion, Urea >7 mmol/L, Respiratory rate ≥30, Blood pressure <90/60, age ≥65) or Pneumonia Severity Index (PSI) to stratify patients 1. A CURB-65 score ≥2 or PSI class IV-V mandates hospitalization 1, 2. Outpatient management is appropriate for PSI classes I-III 1.
ICU admission is required when any one major criterion (septic shock requiring vasopressors or respiratory failure requiring mechanical ventilation) or at least three minor criteria are present 1, 3. Minor criteria include respiratory rate >30/min, PaO₂/FiO₂ ratio ≤250, multilobar infiltrates, confusion, uremia, leukopenia, thrombocytopenia, hypothermia, or hypotension requiring aggressive fluid resuscitation 1.
Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and de-escalation 1, 4.
Outpatient Management
Previously Healthy Adults Without Comorbidities
Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy because it retains activity against 90-95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains 1, 4. This recommendation carries strong evidence from multiple high-quality studies 1.
Doxycycline 100 mg orally twice daily serves as an acceptable alternative, providing coverage of both typical and atypical organisms 1, 4.
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 <25% 1, 4. In most U.S. regions, resistance ranges from 20-30%, making macrolide monotherapy unsafe as first-line therapy 1.
Patients With Comorbidities or Recent Antibiotic Use
Combination therapy is required for patients with COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within 90 days 1, 4.
Option 1: β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline 100 mg twice daily 1, 4.
Option 2: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 1, 4. However, fluoroquinolones should be reserved for patients with β-lactam allergies or macrolide contraindications due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) 1.
Inpatient Non-ICU Management
For hospitalized patients not requiring ICU admission, two equally effective regimens exist with strong recommendations and high-quality evidence 1, 4:
Regimen 1 (Preferred): Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily 1, 4. This combination provides comprehensive coverage for typical bacterial pathogens (S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1.
Regimen 2: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 4. Reserve this for penicillin-allergic patients 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.
Critical timing: Administer the first antibiotic dose in the emergency department immediately upon diagnosis 1, 4. Delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1, 4.
ICU Management for Severe CAP
Combination therapy is mandatory for all ICU patients; β-lactam monotherapy is associated with higher mortality 1, 4, 5.
Preferred ICU regimen: Ceftriaxone 2 g IV 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 respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 4.
For penicillin-allergic ICU patients, use aztreonam 2 g IV every 8 hours plus levofloxacin 750 mg IV daily 1.
Special Pathogen Coverage (Only When Risk Factors Present)
Antipseudomonal Coverage
Add antipseudomonal therapy only when specific risk factors are present 1, 4:
- Structural lung disease (bronchiectasis, cystic fibrosis)
- Recent hospitalization with IV antibiotics within 90 days
- Prior respiratory isolation of Pseudomonas aeruginosa
Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 hours) plus ciprofloxacin 400 mg IV every 8 hours or levofloxacin 750 mg IV daily plus aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) 1, 4.
MRSA Coverage
Add MRSA therapy only when risk factors are present 1, 4:
- Prior MRSA infection/colonization
- Recent hospitalization with IV antibiotics
- Post-influenza pneumonia
- Cavitary infiltrates on imaging
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, 4.
Duration of Therapy and Transition to Oral Treatment
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, 4. Typical duration for uncomplicated CAP is 5-7 days 1, 4.
Extended duration (14-21 days) is required only for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 4.
Switch from IV to oral therapy when all clinical stability criteria are met 1, 4:
- Hemodynamically stable (SBP ≥90 mmHg, HR ≤100 bpm)
- Clinically improving (afebrile 48-72 hours, RR ≤24 breaths/min)
- Oxygen saturation ≥90% on room air
- Able to take oral medications
- Normal GI function
This transition typically occurs by hospital day 2-3 1, 4.
Treatment Failure Management
If no clinical improvement by day 2-3, obtain repeat chest radiograph, CRP, white blood cell count, and additional microbiological specimens 1, 4. Consider chest CT to evaluate for complications such as pleural effusion, lung abscess, or central airway obstruction 1, 4.
For non-severe pneumonia initially treated with amoxicillin monotherapy, add or substitute a macrolide 1, 6. For non-severe pneumonia on combination therapy, switch to a respiratory fluoroquinolone 1, 6. For severe pneumonia not responding to combination therapy, consider adding rifampicin 1.
Follow-Up
Schedule clinical review at 6 weeks for all patients 1, 4. Chest radiograph is reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers >50 years) 1, 4.
Outpatients require clinical review at 48 hours or sooner if clinically deteriorating 6, 4.
Critical Pitfalls to Avoid
Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1.
Avoid macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25%—this increases risk of breakthrough bacteremia and treatment failure 1.
Do not add broad-spectrum antipseudomonal or MRSA agents automatically—restrict to patients with documented risk factors to prevent resistance, adverse effects, and unnecessary cost 1, 4.
Never delay antibiotic administration beyond 8 hours—this significantly increases mortality 1, 4.