What are the recommended antibiotic regimens for community-acquired pneumonia (CAP) in patients with varying risk levels and comorbidities?

Antibiotic Guidelines for Community-Acquired Pneumonia

Outpatient Treatment (Healthy Adults Without Comorbidities)

Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy for previously healthy outpatients with community-acquired pneumonia. 1, 2

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin 1, 2
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily) should only be used when local pneumococcal macrolide resistance is documented to be <25% 1, 2
• Never use macrolide monotherapy in areas where pneumococcal resistance exceeds 25%, as this leads to treatment failure and breakthrough bacteremia 1

Outpatient Treatment (Adults With Comorbidities)

For patients with comorbidities (COPD, diabetes, chronic heart/liver/renal disease, malignancy) or recent antibiotic use within 3 months, use combination therapy or respiratory fluoroquinolone monotherapy. 3, 1, 4

Combination Therapy Option:

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1, 4
• Alternative β-lactams: cefpodoxime, cefuroxime, or high-dose amoxicillin (1 g three times daily) 3, 1

Fluoroquinolone Monotherapy Option:

• Levofloxacin 750 mg orally daily for 5 days 1, 2, 5
• Moxifloxacin 400 mg orally daily for 5 days 1, 2
• Gemifloxacin 320 mg orally daily for 5 days 1

Critical: If the patient received antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 3, 1

Inpatient Treatment (Non-ICU Hospitalized Patients)

Two equally effective regimens exist with strong evidence: β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy. 3, 1

Preferred Combination Therapy:

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily 3, 1
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours, ampicillin-sulbactam 3 g IV every 6 hours, or ceftaroline 600 mg IV every 12 hours 1, 2

Alternative Fluoroquinolone Monotherapy:

• Levofloxacin 750 mg IV daily 3, 1, 5
• Moxifloxacin 400 mg IV daily 3, 1

For Penicillin-Allergic Patients:

• Respiratory fluoroquinolone is the preferred alternative 3, 1
• Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily provides coverage for both typical and atypical pathogens 1

Administer the first antibiotic dose immediately in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1

Inpatient Treatment (ICU/Severe CAP)

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 3, 1

Standard 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 3, 1
• Alternative: β-lactam PLUS levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 3, 1

For Pseudomonas Risk Factors (structural lung disease, recent hospitalization with IV antibiotics, prior P. aeruginosa isolation):

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 3, 1
• PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 500 mg IV daily for dual antipseudomonal coverage 3, 1

For MRSA Risk Factors (prior MRSA infection, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates):

• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 3, 1

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. 3, 1, 2

• Typical duration for uncomplicated CAP: 5-7 days 3, 1, 2
• Extended duration (14-21 days) required for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 3, 1
• Treatment duration should generally not exceed 8 days in responding patients without specific indications 3, 1

Transition from IV 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 GI function—typically by day 2-3 of hospitalization. 3, 1

Oral Step-Down Options:

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1
• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg orally daily 1
• Levofloxacin 750 mg orally daily 1, 5
• Moxifloxacin 400 mg orally daily 1

Special Populations

Nursing Home Patients:

• Receiving treatment in nursing home: respiratory fluoroquinolone alone OR amoxicillin-clavulanate plus macrolide 3
• If hospitalized: same regimens as medical ward and ICU patients 3

Suspected Aspiration with Infection:

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily OR clindamycin 600 mg IV every 8 hours 3

Influenza with Bacterial Superinfection:

• β-lactam (ceftriaxone or cefotaxime) OR respiratory fluoroquinolone 3

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never use macrolide monotherapy in areas where pneumococcal resistance exceeds 25%—this leads to treatment failure 1
• Never delay antibiotic administration beyond 8 hours in hospitalized patients—this increases 30-day mortality by 20-30% 1
• Never use the same antibiotic class if the patient received antibiotics within the past 90 days—this substantially increases resistance risk 1, 4
• Never automatically escalate to broad-spectrum antibiotics based solely on comorbidities—only add antipseudomonal or MRSA coverage when specific risk factors are documented 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP—reserve for patients with comorbidities or macrolide contraindications due to resistance concerns and serious adverse events 1

Diagnostic Testing for Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients 1
• Consider urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1
• If no clinical improvement by day 2-3, obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens 3, 1