What are the initial treatment recommendations for Community-Acquired Pneumonia (CAP)?

Community-Acquired Pneumonia Treatment

Outpatient Treatment (Non-Hospitalized Patients)

For previously healthy adults without comorbidities, amoxicillin 1 g orally three times daily is the preferred first-line therapy, with doxycycline 100 mg twice daily as an acceptable alternative. 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 in areas where pneumococcal macrolide resistance is documented to be <25%, as resistance rates of 30-40% are common and often co-exist with β-lactam resistance 1, 2
• For the first dose of doxycycline, give 200 mg to achieve adequate serum levels more rapidly 1

For outpatients with comorbidities (chronic heart/lung/liver/renal disease, diabetes, alcoholism, malignancy, asplenia) or recent antibiotic use within 90 days, use combination therapy with a β-lactam plus macrolide OR respiratory fluoroquinolone monotherapy. 1, 2

• Combination regimen: β-lactam (amoxicillin-clavulanate 2 g twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline 1, 2
• Fluoroquinolone monotherapy: levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 1, 2, 3
• Critical pitfall: Reserve fluoroquinolones for patients with β-lactam allergies or specific indications due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, CNS effects) and resistance concerns 1, 2

Inpatient Treatment (Non-ICU Hospitalized Patients)

For hospitalized patients not requiring ICU admission, use either β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy—both regimens have equivalent efficacy with strong evidence. 1, 2

• Preferred combination: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (IV initially, then oral when stable) 1, 2, 4
• Alternative combination: Ampicillin-sulbactam 3 g IV every 6 hours OR cefotaxime 1-2 g IV every 8 hours PLUS azithromycin 1, 2
• Fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2, 3
• For penicillin-allergic patients, use respiratory fluoroquinolone monotherapy 1, 2
• Alternative for β-lactam allergic patients: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 2

Administer the first antibiotic dose while still in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1, 2

• Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients 1, 2
• Switch from IV to oral therapy 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 1, 2

ICU Treatment (Severe CAP)

For severe CAP requiring ICU admission, mandatory combination therapy consists of a β-lactam PLUS either azithromycin OR a respiratory fluoroquinolone. 1, 2

• β-lactam options: Ceftriaxone 2 g IV daily, cefotaxime 1-2 g IV every 8 hours, OR ampicillin-sulbactam 3 g IV every 6 hours 1, 2
• PLUS azithromycin 500 mg IV daily OR levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2

For patients with risk factors for Pseudomonas aeruginosa (structural lung disease like bronchiectasis, recent hospitalization with IV antibiotics within 90 days, prior respiratory isolation of P. aeruginosa), use antipseudomonal coverage: 1, 2

• 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) 1, 2
• PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 1, 2
• OR antipseudomonal β-lactam PLUS aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 1, 2

For suspected community-acquired MRSA (prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates on imaging), 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, 4

• Clinical stability criteria: 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, normal mental status 1, 2
• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2
• For severe microbiologically undefined pneumonia, treat for 10 days 1

Special Considerations and Critical Pitfalls

Never use macrolide monotherapy in hospitalized patients—this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and leads to treatment failure. 1, 2

• Avoid extending therapy beyond 7 days in responding patients without specific indications, as this increases antimicrobial resistance risk 1, 2
• Do NOT use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 2
• If the patient received antibiotics recently, select an alternative regimen from a different antibiotic class to minimize resistance risk 1, 2
• For patients failing to improve by day 2-3, obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens; consider adding or substituting a macrolide, switching to a respiratory fluoroquinolone, or adding rifampicin 1, 2

Testing Recommendations

Test all patients with CAP for COVID-19 and influenza when these viruses are common in the community, as their diagnosis affects treatment (antiviral therapy) and infection prevention strategies. 4

• Chest radiograph is strongly recommended to confirm the diagnosis in all suspected CAP patients 1
• Chest radiograph need not be repeated prior to hospital discharge in patients with satisfactory clinical recovery 1
• Schedule clinical review at 6 weeks for all hospitalized patients, with chest radiograph reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1, 2