What are the best antibiotics for community-acquired pneumonia (CAP) and influenza (flu)?

Antibiotic Treatment for Community-Acquired Pneumonia and Influenza

Antibiotics are NOT indicated for uncomplicated influenza, but ARE essential for community-acquired pneumonia (CAP), with treatment selection based on severity and patient comorbidities. 1, 2

Critical Distinction: Influenza vs. CAP

Influenza (Flu) Treatment

• Uncomplicated influenza does NOT require antibiotics 1
• Antiviral therapy (oseltamivir or zanamivir) should be administered as soon as possible for moderate to severe influenza-like illness during widespread local circulation, particularly for clinically worsening disease 1
• Treatment should not be delayed for test confirmation, as negative influenza tests do not exclude disease 1
• Antibiotics are only indicated when influenza is complicated by secondary bacterial pneumonia 1

Influenza-Related Pneumonia

When influenza progresses to pneumonia with new focal chest signs or infiltrates on imaging:

• Preferred outpatient regimen: Doxycycline 200 mg loading dose, then 100 mg daily OR co-amoxiclav 625 mg three times daily for 7 days 1
• Alternative: Macrolide (erythromycin 500 mg four times daily OR clarithromycin 500 mg twice daily) for those intolerant of preferred choices 1
• Coverage must include Staphylococcus aureus in addition to typical CAP pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) 1

Community-Acquired Pneumonia Treatment

Outpatient CAP - Healthy Adults Without Comorbidities

First-line: Amoxicillin 1 gram three times daily for 5-7 days 2, 3

• Provides optimal coverage for S. pneumoniae (the most common pathogen, accounting for 48% of identified cases) 2
• Strong recommendation with moderate-quality evidence 2, 3

Alternative: Doxycycline 100 mg twice daily for 5-7 days 2, 3

• Conditional recommendation with low-quality evidence 2
• Provides broader coverage including atypical organisms 3

Macrolides (azithromycin 500 mg day 1, then 250 mg daily; OR clarithromycin 500 mg twice daily) ONLY if local pneumococcal macrolide resistance is <25% 2, 3

• Conditional recommendation with moderate-quality evidence 2
• Avoid macrolide monotherapy in areas with ≥25% resistance due to risk of breakthrough bacteremia 2, 3

Outpatient CAP - Adults With Comorbidities

Preferred: Combination therapy with β-lactam PLUS macrolide 2, 3

• Amoxicillin-clavulanate 875 mg/125 mg twice daily (or 2000 mg/125 mg twice daily) PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days 2, 3
• Alternative β-lactams: cefpodoxime, cefuroxime, or cefprozil 1, 2
• Strong recommendation with moderate-quality evidence 2, 3

Alternative: Respiratory fluoroquinolone monotherapy 2, 3

• Levofloxacin 750 mg daily for 5 days 2, 4
• Moxifloxacin 400 mg daily for 5-7 days 2
• Strong recommendation with moderate-quality evidence 2
• Reserve fluoroquinolones for patients with contraindications to β-lactams or macrolides due to resistance concerns and adverse effects (tendinopathy, peripheral neuropathy, CNS effects) 3

Inpatient CAP - Non-ICU Hospitalized Patients

Preferred: β-lactam PLUS macrolide 2, 5

• Ceftriaxone 1-2 grams IV daily PLUS azithromycin 500 mg IV/oral daily 2, 5
• Alternatives: cefotaxime 1-2 grams IV every 8 hours OR ampicillin-sulbactam 3 grams IV every 6 hours 2
• Strong recommendation with high-quality evidence 2

Alternative: Respiratory fluoroquinolone monotherapy 2

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 2
• Strong recommendation with high-quality evidence 2

For penicillin-allergic patients: Use respiratory fluoroquinolone 2

Inpatient CAP - ICU Patients (Severe Pneumonia)

Mandatory combination therapy: β-lactam PLUS either azithromycin OR respiratory fluoroquinolone 2, 5

• Ceftriaxone 2 grams IV daily (or cefotaxime 1-2 grams IV every 8 hours) PLUS azithromycin 500 mg IV daily 2, 5
• OR β-lactam PLUS levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 2, 5
• Strong recommendation with level I-II evidence 5

For penicillin-allergic ICU patients: Respiratory fluoroquinolone PLUS aztreonam 2 grams IV every 8 hours 2

Special Considerations for Drug-Resistant Pathogens

Add coverage for Pseudomonas aeruginosa if: 2

• Structural lung disease (bronchiectasis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of P. aeruginosa

Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 2

Add coverage for MRSA if: 2

• Post-influenza pneumonia
• Cavitary infiltrates on imaging
• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics

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 2

Pediatric CAP Treatment

Outpatient - Children <5 Years Old

Presumed bacterial pneumonia: Amoxicillin 90 mg/kg/day in 2 doses 1

• Alternative: Amoxicillin-clavulanate (amoxicillin component 90 mg/kg/day in 2 doses) 1

Presumed atypical pneumonia: Azithromycin 10 mg/kg day 1, then 5 mg/kg/day days 2-5 1

• Alternatives: clarithromycin 15 mg/kg/day in 2 doses OR erythromycin 40 mg/kg/day in 4 doses 1

Outpatient - Children ≥5 Years Old

Presumed bacterial pneumonia: Amoxicillin 90 mg/kg/day in 2 doses (maximum 4 g/day) 1

• For children without clear distinction between bacterial and atypical CAP, add a macrolide to β-lactam 1

Inpatient - Fully Immunized Children

Ampicillin OR penicillin G in regions with minimal high-level penicillin resistance 1

• Alternatives: ceftriaxone 50-100 mg/kg/day every 12-24 hours OR cefotaxime 150 mg/kg/day every 8 hours 1
• Add vancomycin OR clindamycin for suspected CA-MRSA 1

Inpatient - Not Fully Immunized or High Penicillin Resistance

Ceftriaxone OR cefotaxime 1

• Add vancomycin or clindamycin for suspected CA-MRSA 1

Duration of Therapy

Standard duration: 5-7 days for uncomplicated CAP once clinical stability achieved 2, 3

• Minimum 5 days with patient afebrile for 48-72 hours and no more than one sign of clinical instability 2

Extended duration (14-21 days) required for: 2, 3

• Legionella pneumophila
• Staphylococcus aureus
• Gram-negative enteric bacilli

Transition to Oral Therapy

Switch from IV to oral when: 2

• Hemodynamically stable
• Clinically improving
• Able to ingest medications
• Normal gastrointestinal function
• Typically by day 2-3 of hospitalization 2

Critical Pitfalls to Avoid

• Never use antibiotics for uncomplicated influenza without evidence of bacterial superinfection 1
• Never delay antibiotic administration beyond 8 hours in hospitalized CAP patients—this increases 30-day mortality by 20-30% 2
• Never use macrolide monotherapy in hospitalized patients or those with comorbidities 2, 3
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance ≥25% 2, 3
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients 2
• Avoid extending therapy beyond 7 days in responding patients without specific indications 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