What is the recommended treatment for a patient diagnosed with community-acquired pneumonia (CAP), considering factors such as severity of illness, underlying health conditions, and vaccination status?

Community-Acquired Pneumonia Treatment

Treatment for community-acquired pneumonia must be stratified by severity and patient risk factors, with empiric antibiotic selection targeting both typical and atypical pathogens while considering local resistance patterns and underlying comorbidities.

Severity Assessment and Site-of-Care Decision

• Assess severity immediately using CURB-65 score (Confusion, Urea >7 mmol/L, Respiratory rate ≥30, Blood pressure <90/60, Age ≥65), with scores ≥2 mandating hospitalization due to higher mortality risk 1, 2.
• Patients with multilobar infiltrates, respiratory rate >24, or inability to maintain oral intake require hospital admission regardless of CURB-65 score 1, 2.
• ICU admission is mandatory if patients meet ≥3 minor criteria: respiratory rate ≥30, PaO₂/FiO₂ <250, multilobar infiltrates, confusion, BUN ≥20 mg/dL, leukopenia, thrombocytopenia, hypothermia, or hypotension requiring aggressive fluid resuscitation 1, 2.

Outpatient Treatment (Non-Severe CAP)

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, providing superior coverage against Streptococcus pneumoniae including drug-resistant strains 2, 3.
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though with lower quality evidence 2, 4.
• Macrolides (azithromycin 500 mg day 1, then 250 mg daily for days 2-5; or clarithromycin 500 mg twice daily) should ONLY be used in areas where pneumococcal macrolide resistance is documented <25% 2, 5, 4.

Adults With Comorbidities or Recent Antibiotic Use

• Combination therapy is mandatory: β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) PLUS macrolide (azithromycin or clarithromycin) OR doxycycline 2, 4.
• Alternative: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily), though this should be reserved for penicillin-allergic patients due to resistance concerns and FDA warnings about serious adverse events 2, 3, 4.
• Comorbidities requiring combination therapy include: COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within the past 3 months 2, 4.

Inpatient Treatment (Non-ICU Hospitalized Patients)

• Two equally effective regimens exist with strong evidence: β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy 2, 6, 4.

Preferred Regimen: β-Lactam Plus Macrolide

• Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily provides comprehensive coverage for typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 2, 6, 4.
• Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin 2, 4.
• Recent evidence from a 2025 multicenter matched cohort study (n=8,492) demonstrated azithromycin was associated with significantly lower in-hospital mortality (OR 0.71,95% CI 0.56-0.9) and 90-day mortality (HR 0.83,95% CI 0.73-0.95) compared to doxycycline when combined with β-lactams 7.

Alternative Regimen: Respiratory Fluoroquinolone Monotherapy

• Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily as monotherapy is equally effective as combination therapy 2, 3, 4.
• This regimen is preferred for penicillin-allergic patients 2, 4.

Severe CAP Requiring ICU Admission

• Combination therapy is MANDATORY for all ICU patients—monotherapy is inadequate and associated with higher mortality 2, 6, 4.
• Preferred 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, 6, 4.
• A 2025 network meta-analysis of 8,142 patients demonstrated β-lactam plus macrolide was the most effective regimen, significantly reducing overall mortality compared to β-lactam monotherapy and β-lactam plus fluoroquinolone 2.

Special Pathogen Coverage

Pseudomonas aeruginosa Risk Factors

• Add antipseudomonal coverage ONLY when specific risk factors are present: structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, prior respiratory isolation of P. aeruginosa, or chronic broad-spectrum antibiotic use 1, 2, 4.
• Regimen: 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 1, 2, 4.
• For ICU patients with Pseudomonas risk factors: add aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) for dual antipseudomonal coverage 1, 2.

MRSA Risk Factors

• Add MRSA coverage ONLY when specific risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 2, 4.
• Regimen: Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/L) OR linezolid 600 mg IV every 12 hours to the base regimen 2, 4.

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, 2, 6, 4.
• Typical duration for uncomplicated CAP is 5-7 days 1, 2, 6, 4.
• Extended duration (14-21 days) is required for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2, 4.
• For severe microbiologically undefined pneumonia, 10 days of treatment is recommended 1, 2.

Transition from IV 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, 2, 6, 4.
• Oral step-down options: amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily, OR amoxicillin-clavulanate 875/125 mg twice daily PLUS azithromycin, OR respiratory fluoroquinolone monotherapy 2, 4.

Critical Timing Considerations

• Administer the first antibiotic dose in the emergency department IMMEDIATELY upon diagnosis—delayed administration beyond 8 hours increases 30-day mortality by 20-30% in hospitalized patients 2, 6, 4.
• Obtain blood cultures and sputum Gram stain/culture BEFORE initiating antibiotics in ALL hospitalized patients to allow pathogen-directed therapy and de-escalation 2, 4.

Management of Treatment Failure

• If no clinical improvement by day 2-3: obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens 1.
• Consider chest CT to evaluate for complications (pleural effusion, lung abscess, central airway obstruction) 1, 2.
• For non-severe pneumonia initially treated with amoxicillin monotherapy: add or substitute a macrolide 1.
• For non-severe pneumonia on combination therapy: switch to respiratory fluoroquinolone 1.
• For severe pneumonia not responding to combination therapy: consider adding rifampicin 1.

Vaccination and Prevention

• Assess vaccination status at hospital admission and administer pneumococcal vaccine to all patients ≥65 years and those with high-risk conditions (chronic lung, heart, renal, liver disease, diabetes, immunosuppression) 1, 2.
• Administer 20-valent pneumococcal conjugate vaccine alone OR 15-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine one year later 2.
• Offer annual influenza vaccine to all patients, especially during fall and winter 1, 2, 4.
• Make smoking cessation a goal for all patients hospitalized with CAP who smoke 2, 4.

Critical Pitfalls to Avoid

• NEVER use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 2, 4.
• NEVER use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—this leads to treatment failure 2, 3, 4.
• NEVER delay antibiotic administration beyond 8 hours—this significantly increases mortality 2, 6, 4.
• NEVER add antipseudomonal or MRSA coverage empirically without documented risk factors—this promotes resistance and increases adverse events 2, 4.
• NEVER extend therapy beyond 7-8 days in responding patients without specific indications—longer courses increase antimicrobial resistance risk without improving outcomes 2, 4.
• NEVER use oral cephalosporins (cefuroxime, cefpodoxime) as first-line oral agents—these have inferior in vitro activity compared to high-dose amoxicillin 2.

Follow-Up

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 1, 2, 4.
• Scheduled 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) 1, 2, 4.
• Chest radiograph is NOT required before hospital discharge in patients with satisfactory clinical recovery 1, 2.