What is the recommended empiric antibiotic therapy for a patient with community-acquired pneumonia (CAP), considering factors such as severity, age, and underlying health conditions like chronic obstructive pulmonary disease (COPD) or heart disease?

Community-Acquired Pneumonia Management

Outpatient Treatment

For previously healthy adults without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, with doxycycline 100 mg twice daily as an acceptable alternative. 1

• Macrolides (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 to be <25%. 1, 2
• For patients with comorbidities (COPD, diabetes, chronic heart/liver/renal disease, malignancy), use combination therapy: amoxicillin-clavulanate 875/125 mg twice daily plus azithromycin (500 mg day 1, then 250 mg daily for days 2-5) or respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2
• If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1

Inpatient Non-ICU Treatment

For hospitalized patients not requiring ICU admission, use either ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily, or respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily)—both regimens have strong evidence and equal efficacy. 1, 2

• Administer the first antibiotic dose immediately in the emergency department, as delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1
• For penicillin-allergic patients, use respiratory fluoroquinolone monotherapy. 1, 2
• Switch from IV to oral therapy when the patient is hemodynamically stable, clinically improving, afebrile for 48-72 hours, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 1

ICU Treatment for Severe CAP

All ICU patients require mandatory combination therapy with a β-lactam plus either azithromycin or a respiratory fluoroquinolone—monotherapy is inadequate for severe disease. 1, 2

• Preferred 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 levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. 1, 2
• For penicillin-allergic ICU patients, use aztreonam 2 g IV every 8 hours plus a respiratory fluoroquinolone. 1, 2

Special Pathogen Coverage

Add antipseudomonal coverage only when specific risk factors are present: structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of Pseudomonas aeruginosa. 1, 3

• Antipseudomonal regimen: piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 hours or 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). 1, 2

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

• MRSA 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—typical duration for uncomplicated CAP is 5-7 days. 1, 2

• Extend duration to 14-21 days only for specific pathogens: 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, as longer courses increase antimicrobial resistance risk without improving outcomes. 1

Diagnostic Testing

Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy. 1

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

Treatment Failure Management

If no clinical improvement by day 2-3, obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens. 1, 4

• Consider chest CT to reveal unsuspected pleural effusions, lung abscess, or central airway obstruction. 4
• For non-severe pneumonia initially treated with amoxicillin monotherapy, add or substitute a macrolide. 1
• For non-severe pneumonia on combination therapy, switch to a respiratory fluoroquinolone. 1
• For severe pneumonia not responding to combination therapy, consider adding rifampicin. 1

Follow-Up

Schedule clinical review at 6 weeks for all patients, with chest radiograph reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years). 1, 5

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 macrolide resistance exceeds 25%—this leads to treatment failure. 1, 2
• Never delay antibiotic administration beyond 8 hours in hospitalized patients, though recent evidence suggests a strict 4-hour threshold may not be necessary for all patients—prioritize based on age, comorbidities, and pneumonia severity. 1, 6
• Never add antipseudomonal or MRSA coverage without documented risk factors—this promotes resistance without improving outcomes. 1