What are the recommended antibiotics for a typical adult patient with community-acquired pneumonia?

Antibiotic Treatment for Community-Acquired Pneumonia

For typical adult patients with community-acquired pneumonia (CAP), treatment depends on severity and comorbidities: healthy outpatients should receive amoxicillin 1 g three times daily for 5-7 days, while hospitalized patients require combination therapy with a β-lactam plus macrolide or respiratory fluoroquinolone monotherapy. 1

Outpatient Treatment for Healthy Adults Without Comorbidities

Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, providing excellent coverage against Streptococcus pneumoniae (the most common pathogen) including many drug-resistant strains. 1, 2

• Doxycycline 100 mg orally twice daily for 5-7 days serves as an acceptable alternative, particularly for patients who cannot tolerate amoxicillin, though this carries lower quality evidence. 1, 3

• 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%, as resistance significantly increases treatment failure risk. 1, 2

Critical Pitfall for Outpatients

Never use macrolide monotherapy in areas where pneumococcal resistance exceeds 25%, as breakthrough bacteremia occurs more frequently with resistant strains. 1, 2

Outpatient Treatment for Adults With Comorbidities

Patients with comorbidities (COPD, diabetes, heart/liver/renal disease, malignancy, recent antibiotic use within 90 days) require combination therapy or fluoroquinolone monotherapy. 1, 2

Preferred Combination Regimen

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days total 1, 2
• Alternative β-lactams include cefpodoxime or cefuroxime, always combined with a macrolide or doxycycline 1, 2

Alternative Monotherapy

• Respiratory fluoroquinolone: levofloxacin 750 mg daily for 5 days OR moxifloxacin 400 mg daily for 5-7 days 1, 4
• Reserve fluoroquinolones for penicillin-allergic patients or when combination therapy is contraindicated, due to concerns about resistance and serious adverse events 1, 2

Critical Decision Point

If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong evidence: 1

Preferred Combination Therapy

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily 1, 5
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always with macrolide 1

Alternative Monotherapy

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 4
• Systematic reviews demonstrate fewer clinical failures with fluoroquinolone monotherapy compared to β-lactam/macrolide combinations 1

Transition to Oral Therapy

Switch from IV to oral antibiotics 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, 5

Severe CAP Requiring ICU Admission

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

• Ceftriaxone 2 g IV daily PLUS azithromycin 500 mg IV daily 1
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 4
• A 2025 network meta-analysis demonstrated that β-lactam plus macrolide significantly reduced overall mortality compared to β-lactam monotherapy 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. 1, 6

• Typical duration for uncomplicated CAP is 5-7 days 1, 6
• Short-course regimens (≤7 days) have equivalent clinical cure rates with fewer adverse events compared to longer courses 1, 6
• Extended duration (14-21 days) is required ONLY for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2

Clinical Stability Criteria Before Discontinuation

• Temperature ≤37.8°C
• Heart rate ≤100 beats/minute
• Respiratory rate ≤24 breaths/minute
• Systolic blood pressure ≥90 mmHg
• Oxygen saturation ≥90% on room air
• Ability to maintain oral intake
• Normal mental status 1

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

Add antipseudomonal coverage ONLY when risk factors are present: structural lung disease, recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 1

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside 1

MRSA Risk Factors

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

• Vancomycin 15 mg/kg IV every 8-12 hours OR linezolid 600 mg IV every 12 hours 1

Critical Timing Considerations

Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department. Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients. 1, 5

Diagnostic Testing for Hospitalized Patients

Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in ALL hospitalized patients to allow for pathogen-directed therapy and de-escalation. 1, 5

Common Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1, 2
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns 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, 6
• Never delay antibiotic administration—each hour of delay in the first 6 hours increases mortality by 7.6% 1