What is the best current treatment for community-acquired pneumonia?

Treatment of Community-Acquired Pneumonia

For outpatient CAP without comorbidities, use amoxicillin 1 g orally three times daily; for hospitalized non-ICU patients, use IV ceftriaxone 1-2 g daily plus azithromycin 500 mg daily; and for ICU patients, use IV β-lactam (ceftriaxone 2 g daily, cefotaxime 1-2 g every 8 hours, or ampicillin-sulbactam 3 g every 6 hours) plus either azithromycin 500 mg daily or a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1

Outpatient Treatment Algorithm

Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily is the preferred first-line agent, providing effective coverage against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis with moderate quality evidence supporting its use. 1

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin, though this carries lower quality evidence. 1, 2

• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should ONLY be used when local pneumococcal macrolide resistance is documented to be <25%, as resistance leads to treatment failure. 1, 3

Adults With Comorbidities or Recent Antibiotic Use

• Combination therapy with β-lactam plus macrolide is recommended: amoxicillin-clavulanate 2 g twice daily (or cefpodoxime or cefuroxime) plus azithromycin or clarithromycin or doxycycline. 1

• Alternative monotherapy with respiratory fluoroquinolone: levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily, though fluoroquinolone use should be minimized due to FDA warnings about serious adverse events and resistance concerns. 1

Inpatient Non-ICU Treatment

Standard Regimen

• β-lactam plus macrolide combination: ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily provides coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) with strong recommendation and high-quality evidence. 1

• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily demonstrates equivalent efficacy with fewer clinical failures compared to β-lactam/macrolide combinations. 1

• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative, avoiding cross-reactivity concerns with cephalosporins. 1

When Oral Treatment is Contraindicated

• Use IV ampicillin or benzylpenicillin together with IV erythromycin or clarithromycin for patients unable to take oral medications. 4

ICU Treatment for Severe CAP

Mandatory Combination Therapy

• All ICU patients require combination therapy with β-lactam plus either azithromycin or respiratory fluoroquinolone to reduce mortality in severe disease. 1

• 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

• Macrolide option: azithromycin 500 mg IV daily. 1

• Fluoroquinolone options: levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily. 1

• Patients with severe pneumonia should receive parenteral antibiotics immediately after diagnosis to prevent mortality. 4

Special Populations Requiring Broader Coverage

Pseudomonas Risk Factors

• Add antipseudomonal coverage for patients with: structural lung disease (bronchiectasis, COPD), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 1

• Antipseudomonal regimen: antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus ciprofloxacin or levofloxacin, or plus aminoglycoside (gentamicin 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily) plus azithromycin. 1

MRSA Risk Factors

• Add MRSA coverage for patients with: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1

• 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 added to the base regimen. 1, 5

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, with typical duration for uncomplicated CAP being 5-7 days. 1

• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli when these pathogens are suspected or confirmed. 4, 1

• For severe microbiologically undefined pneumonia, 10 days of treatment is recommended. 4

Transition to Oral Therapy

• Switch from IV to oral antibiotics 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

• Patients treated initially with parenteral antibiotics should be transferred to oral regimen as soon as clinical improvement occurs and temperature has been normal for 24 hours. 4

• Oral step-down regimen: amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily (or clarithromycin 500 mg orally twice daily as alternative macrolide). 1

Critical Pitfalls to Avoid

• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and increased mortality. 1, 3

• NEVER delay antibiotic administration beyond 8 hours in hospitalized patients, as this increases 30-day mortality by 20-30%. 1

• NEVER use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 1

• NEVER use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present, as these agents have inferior outcomes. 1

• NEVER extend therapy beyond 7 days in responding patients without specific indications (such as Legionella, S. aureus, or Gram-negative bacilli), as this increases antimicrobial resistance risk. 1

Monitoring and Follow-Up

• Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy and de-escalation. 1

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

• For non-severe pneumonia initially treated with amoxicillin monotherapy that fails to improve, add or substitute a macrolide. 4

• For non-severe pneumonia on combination therapy that fails to improve, switch to a respiratory fluoroquinolone. 4

• For severe pneumonia not responding to combination therapy, consider adding rifampicin. 4

• Clinical review should be arranged for all patients at around 6 weeks, with chest radiograph reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years). 4, 1