What is the appropriate initial treatment for an adult patient with pneumonia?

Treatment for Community-Acquired Pneumonia in Adults

For healthy outpatients without comorbidities, amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line treatment, with doxycycline 100 mg twice daily as an acceptable alternative. 1, 2

Outpatient Treatment Algorithm

Previously Healthy Adults (No Comorbidities)

• First-line: Amoxicillin 1 g orally three times daily for 5-7 days (strong recommendation, moderate quality evidence) 1, 2
• Alternative: Doxycycline 100 mg orally twice daily for 5-7 days (conditional recommendation, low quality evidence) 1, 2
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily): Only use in areas where pneumococcal macrolide resistance is documented <25% (conditional recommendation, moderate quality evidence) 1, 2, 3

Critical pitfall: Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as this leads to treatment failure and breakthrough bacteremia with resistant strains. 1, 2

Adults with Comorbidities

Comorbidities include: chronic heart/lung/liver/renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, or recent antibiotic use within 90 days. 1, 2

Option 1 - Combination therapy (preferred):

• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5-7 days (strong recommendation, moderate quality evidence) 1, 2, 4
• Alternative β-lactams: Cefpodoxime 200 mg twice daily OR cefuroxime 500 mg twice daily, combined with macrolide or doxycycline 1, 2

Option 2 - Fluoroquinolone monotherapy:

• Levofloxacin 750 mg orally daily OR moxifloxacin 400 mg orally daily for 5-7 days (strong recommendation, moderate quality evidence) 1, 2
• Reserve fluoroquinolones for β-lactam allergy or macrolide intolerance due to FDA black box warnings about disabling adverse effects including tendon rupture, peripheral neuropathy, QT prolongation, and aortic dissection 2, 4

Hospitalized Non-ICU Patients

Two equally effective regimens exist with strong recommendations and high-quality evidence: 1, 2

Regimen 1: β-lactam plus macrolide (preferred)

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

Regimen 2: Respiratory fluoroquinolone monotherapy

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 2
• Use for penicillin-allergic patients 1, 2

Critical timing: Administer the first antibiotic dose in the emergency department immediately upon diagnosis—delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1, 2

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate and associated with higher mortality. 1, 2

Standard ICU regimen:

• Ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours) PLUS azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1, 2

Special pathogen coverage:

For Pseudomonas aeruginosa risk factors (structural lung disease, recent hospitalization with IV antibiotics within 90 days, prior P. aeruginosa isolation):

• Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) PLUS azithromycin 1, 2

For MRSA risk factors (prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, cavitary infiltrates):

• 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 base regimen 1, 2

Duration of Therapy

• Minimum 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 1, 2, 6
• Typical duration for uncomplicated CAP: 5-7 days 1, 2, 6
• Extended duration (14-21 days) required for: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2

Clinical stability criteria: Temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic BP ≥90 mmHg, oxygen saturation ≥90% on room air, ability to maintain oral intake, normal mental status. 2

Transition to Oral Therapy

Switch from IV to oral antibiotics when: 1, 2

• Hemodynamically stable
• Clinically improving
• Able to take oral medications
• Normal gastrointestinal function
• Typically achievable by day 2-3 of hospitalization 1, 2

Oral step-down options:

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 2
• Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg orally daily 2, 4
• Levofloxacin 750 mg orally daily OR moxifloxacin 400 mg orally daily 2

Diagnostic Testing for Hospitalized Patients

Obtain before initiating antibiotics: 1, 2

• Blood cultures (2 sets from separate sites)
• Sputum Gram stain and culture
• Urinary antigen testing for Legionella pneumophila serogroup 1 (in severe CAP or ICU patients)

Management of Treatment Failure

If no clinical improvement by day 2-3: 1, 2

• Obtain repeat chest radiograph, CRP, white cell count
• Consider chest CT to evaluate for complications (pleural effusion, lung abscess, central airway obstruction)
• Obtain additional microbiological specimens

Antibiotic adjustments for treatment failure:

• Non-severe pneumonia on amoxicillin monotherapy: Add or substitute macrolide 1, 2
• Non-severe pneumonia on combination therapy: Switch to respiratory fluoroquinolone 1, 2
• Severe pneumonia not responding to combination therapy: Consider adding rifampicin 1, 2

Follow-Up

• Outpatients: Clinical review at 48 hours or sooner if clinically indicated 1, 2
• All patients: Scheduled clinical review at 6 weeks with chest radiograph reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1, 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy for hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1, 2
• Never delay antibiotic administration beyond 8 hours in hospitalized patients—increases mortality 1, 2
• Never use oral cephalosporins (cefuroxime, cefpodoxime) as first-line oral agents—inferior in vitro activity compared to high-dose amoxicillin 2
• Never add antipseudomonal or MRSA coverage without documented risk factors—avoid indiscriminate broad-spectrum use 1, 2
• Never extend therapy beyond 7-8 days in responding patients without specific indications—increases antimicrobial resistance risk 2, 6