What is the recommended antibiotic treatment for a patient with Community-Acquired Pneumonia (CAP)?

Community-Acquired Pneumonia: Antibiotic Treatment Recommendations

For hospitalized non-ICU patients with community-acquired pneumonia, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily as first-line therapy, treating for a minimum of 5 days and until afebrile for 48-72 hours with no more than one sign of clinical instability. 1, 2

Outpatient Treatment

Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line agent, providing excellent coverage against Streptococcus pneumoniae and other common respiratory pathogens 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though with lower quality supporting evidence 1, 3
• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented <25%, as resistance rates now commonly exceed this threshold 1, 4

Adults With Comorbidities

• Use combination therapy: amoxicillin-clavulanate 875/125 mg twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1, 4
• Alternative: respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily OR moxifloxacin 400 mg daily) for 5-7 days 1, 4
• Comorbidities requiring combination therapy include COPD, diabetes, chronic heart/liver/renal disease, malignancy, or recent antibiotic use within 90 days 1

Inpatient Non-ICU Treatment

Two equally effective regimens exist with strong evidence:

Preferred Regimen

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (strong recommendation, high-quality evidence) 1, 2
• 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

Alternative Regimen

• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 4
• This option demonstrates fewer clinical failures in systematic reviews but should be reserved for penicillin-allergic patients or specific clinical scenarios 1

Transition to Oral Therapy

• Switch from IV to oral when hemodynamically stable, clinically improving, afebrile for 48-72 hours, able to take oral medications, and has normal GI function—typically by day 2-3 1, 5
• Oral step-down: amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily 1

ICU Treatment for Severe CAP

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 1, 6

Standard ICU Regimen

• Ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours) PLUS azithromycin 500 mg IV daily 1, 6
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) 1, 6

Hemodynamic Instability

• Administer the first antibiotic dose immediately in the emergency department—delays beyond 4-8 hours increase 30-day mortality by 20-30% 1, 6
• Continue IV therapy for at least 2 days before considering oral transition 6
• Consider systemic corticosteroids (hydrocortisone or methylprednisolone) within 24 hours for persistent septic shock, as this may reduce 28-day mortality 6, 2

Special Populations Requiring Broader Coverage

Pseudomonas Aeruginosa Risk Factors

Add antipseudomonal coverage if the patient has:

• Structural lung disease (bronchiectasis, COPD with frequent exacerbations) 1, 4
• Recent hospitalization with IV antibiotics within 90 days 1, 4
• Prior respiratory isolation of P. aeruginosa 1, 4

Antipseudomonal regimen:

• Piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours OR meropenem 1 g IV every 8 hours 1, 6
• PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 1, 6
• PLUS aminoglycoside (gentamicin 5-7 mg/kg IV daily) for dual antipseudomonal coverage 1

MRSA Risk Factors

Add MRSA coverage if the patient has:

• Post-influenza pneumonia 1, 4
• Cavitary infiltrates on imaging 1, 4
• Prior MRSA infection or colonization 1, 4
• Recent hospitalization with IV antibiotics within 90 days 1, 4

MRSA regimen:

• Vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 1, 6
• Add to standard β-lactam/macrolide or fluoroquinolone base regimen 1, 6

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, 5

Standard Duration

• Uncomplicated CAP: 5-7 days total (including IV days) 1, 5
• Recent evidence supports 3-day treatment for patients achieving clinical stability by day 3, particularly in younger patients with fewer comorbidities 5

Extended Duration (14-21 days)

• Legionella pneumophila 1, 4
• Staphylococcus aureus 1, 4
• Gram-negative enteric bacilli 1, 4
• Documented bacteremia 6
• Extrapulmonary complications 6

Critical Pitfalls to Avoid

Timing Errors

• Never delay antibiotic administration beyond 4-8 hours from diagnosis, as this dramatically increases mortality 1, 6
• Administer the first dose in the emergency department before hospital admission 1, 6

Coverage Errors

• Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1, 4
• Never use macrolides in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure 1, 4
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, QT prolongation) and resistance concerns 1, 7

Inappropriate Escalation

• Do not automatically escalate to broad-spectrum antibiotics (antipseudomonal agents, anti-MRSA coverage) without documented risk factors, as this increases resistance without improving outcomes 1, 6
• Standard β-lactams (ceftriaxone, cefotaxime) should not be replaced with cefepime or piperacillin-tazobactam unless specific Pseudomonas risk factors are present 1

Duration Errors

• Do not extend therapy beyond 7 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1, 5
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed de-escalation 1

Penicillin-Allergic Patients

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily) is the preferred alternative for non-ICU patients 1, 4
• For ICU patients: aztreonam 2 g IV every 8 hours PLUS levofloxacin 750 mg IV daily 1
• Doxycycline 100 mg twice daily can substitute for macrolides in combination regimens 1, 3

Monitoring and Follow-Up

• Clinical review at 48 hours or sooner if no improvement—obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens 1
• If no improvement by day 2-3 on amoxicillin monotherapy, add or substitute a macrolide 1
• If no improvement on combination therapy, switch to respiratory fluoroquinolone OR consider adding rifampicin for severe cases 1
• Schedule clinical review at 6 weeks for all hospitalized patients, with chest radiograph reserved for persistent symptoms, physical signs, or high malignancy risk (smokers, age >50 years) 1