What is the recommended treatment for a patient presenting with pneumonia?

Treatment of Pneumonia

For hospitalized patients with community-acquired pneumonia without risk factors for resistant bacteria, treat with ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily for a minimum of 5 days and until afebrile for 48-72 hours. 1, 2

Outpatient Treatment

Previously 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, 3
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients intolerant of amoxicillin 1
• Macrolides (azithromycin or clarithromycin) 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 a β-lactam plus macrolide is required: amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin 500 mg on day 1, then 250 mg daily for days 2-5 1
• Alternative: respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily), though fluoroquinolones should be reserved for specific situations due to resistance concerns and serious adverse events 1

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong evidence 1, 2:

Preferred Regimen: β-lactam Plus Macrolide

• Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily provides coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 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 a macrolide 1
• Oral combination therapy with amoxicillin plus a macrolide (erythromycin or clarithromycin) is preferred for patients requiring hospitalization for clinical reasons 4, 3

Alternative Regimen: Respiratory Fluoroquinolone Monotherapy

• Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 1
• Systematic reviews demonstrate fewer clinical failures and treatment discontinuations compared to β-lactam/macrolide combinations 1
• This is the preferred alternative for penicillin-allergic patients 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease 1, 2:

• Ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily OR
• Ceftriaxone 2 g IV daily plus respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1
• Systemic corticosteroid administration within 24 hours of development of severe CAP may reduce 28-day mortality 2

Special Populations Requiring Broader Coverage

Pseudomonas Aeruginosa Risk Factors

Add antipseudomonal coverage if the patient has 1:

• Structural lung disease (bronchiectasis, COPD with frequent exacerbations)
• 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, plus aminoglycoside (gentamicin 5-7 mg/kg IV daily) and azithromycin 1

MRSA Risk Factors

Add MRSA coverage if the patient has 1:

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

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 to the base regimen 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, 3, 2
• Typical duration for uncomplicated CAP is 5-7 days 1, 2
• Extended duration (14-21 days) is required for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

Transition from IV to Oral Therapy

Switch from IV to oral antibiotics when the patient meets ALL of the following criteria 1, 3:

• Hemodynamically stable (systolic BP >90 mmHg, heart rate <100)
• Clinically improving (respiratory rate <24, oxygen saturation >90% on room air)
• Afebrile for 48-72 hours
• Able to take oral medications
• Normal gastrointestinal function

Typical timing: day 2-3 of hospitalization 1

Oral step-down options 1:

• Amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily
• Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin 500 mg orally daily

Critical Timing Considerations

Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department 1, 2:

• Delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 1

Diagnostic Testing

For all hospitalized patients, obtain BEFORE initiating antibiotics 1:

• Blood cultures (two sets from separate sites)
• Sputum Gram stain and culture (if patient can produce adequate sample)
• COVID-19 and influenza testing when these viruses are common in the community 2
• Urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1

Follow-Up

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 1
• Chest radiograph need not be repeated prior to hospital discharge in patients with satisfactory clinical recovery 4, 3
• 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) 4, 1, 3

Common Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients, as it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25% 1
• 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, 5
• Do not use cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas or MRSA are present 1
• Avoid extending therapy beyond 7 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk without improving outcomes 1

Azithromycin-Specific Warnings

Discontinue azithromycin immediately if signs of the following occur 5:

• Hepatotoxicity (abnormal liver function, hepatitis, cholestatic jaundice)
• Serious allergic reactions (angioedema, anaphylaxis, Stevens-Johnson syndrome)
• QT prolongation (particularly in elderly patients, those with known QT prolongation, bradyarrhythmias, or on QT-prolonging drugs)
• Clostridium difficile-associated diarrhea