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

Community-Acquired Pneumonia: Empiric Antibiotic Therapy

Outpatient Treatment (Previously Healthy Adults)

Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy for previously healthy adults without comorbidities. 1, 2, 3

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative if amoxicillin cannot be tolerated 1, 2, 3
• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented <25%, as resistance rates now exceed this threshold in most regions 1, 2, 3

Outpatient Treatment (Adults with Comorbidities)

For patients with COPD, diabetes, chronic heart/liver/renal disease, malignancy, or recent antibiotic use within 3 months, use combination therapy: 1, 3

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1, 3
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) 1, 3

Hospitalized Non-ICU Patients

Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (IV or oral) is the standard regimen for hospitalized patients not requiring ICU admission. 1, 2, 3, 4

• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 1, 2
• Alternative regimen: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) for penicillin-allergic patients 1, 2, 3
• Administer the first antibiotic dose immediately in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1, 2, 3

The combination of β-lactam plus macrolide provides coverage for both typical bacterial pathogens (Streptococcus pneumoniae, Haemophilus influenzae) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1, 2 Multiple observational studies demonstrate that β-lactam plus macrolide combination therapy is associated with 26-68% relative reductions in short-term mortality compared to β-lactam monotherapy. 5

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate and associated with higher mortality. 1, 2, 3

• Ceftriaxone 2 g IV daily PLUS azithromycin 500 mg IV daily 1, 2, 3
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with either azithromycin OR respiratory fluoroquinolone 1, 2

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage ONLY when specific risk factors are present: 1, 2, 3

• Structural lung disease (bronchiectasis, cystic fibrosis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of P. aeruginosa

Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem 500 mg IV every 6 hours, OR meropenem 1 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) PLUS azithromycin 500 mg IV daily 1, 2

MRSA Risk Factors

Add MRSA coverage ONLY when specific risk factors are present: 1, 2, 3

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics
• Post-influenza pneumonia
• Cavitary infiltrates on imaging

Regimen: 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, 2

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, 2, 3, 4

• Typical duration for uncomplicated CAP: 5-7 days total 1, 2, 3
• Extended duration (14-21 days) required ONLY for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2, 3

Clinical stability criteria include: temperature ≤37.8°C, heart rate ≤100 beats/min, respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, oxygen saturation ≥90% on room air, ability to maintain oral intake, and normal mental status. 1

Transition to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal gastrointestinal function—typically by day 2-3 of hospitalization. 1, 2, 3

Oral step-down options: 1

• Amoxicillin 1 g orally three times daily
• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily
• Continue azithromycin 500 mg orally daily if part of initial regimen
• Levofloxacin 750 mg orally once daily for penicillin-allergic patients

Diagnostic Testing

Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy and de-escalation. 1, 2, 3

• 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
• Consider urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 2, 3

Critical Pitfalls to Avoid

• Never use macrolide monotherapy for hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1, 2, 3
• Do not add antipseudomonal or MRSA coverage routinely—only when specific risk factors are documented 1, 2, 3
• Do not extend therapy beyond 7 days in responding patients without specific indications (atypical pathogens, S. aureus, Gram-negative bacilli), as this increases antimicrobial resistance risk 1, 2
• Never delay antibiotic administration—delays beyond 8 hours increase 30-day mortality by 20-30% 1, 2, 3

Treatment Failure Management

If no clinical improvement by day 2-3: 1, 3

• Obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens
• Consider chest CT to evaluate for complications (pleural effusions, lung abscess, central airway obstruction)
• For non-severe pneumonia on combination therapy, switch to respiratory fluoroquinolone
• For severe pneumonia not responding to combination therapy, consider adding rifampicin

Follow-Up

• Schedule clinical review at 6 weeks for all hospitalized patients 1, 3
• Reserve chest radiograph for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1, 3