What is the recommended treatment for an adult patient with suspected community-acquired pneumonia, particularly those with underlying health conditions or compromised immune systems?

Treatment for Community-Acquired Pneumonia in Adults

For adults with suspected community-acquired pneumonia, particularly those with underlying health conditions or compromised immune systems, hospitalized patients should receive combination therapy with a β-lactam (ceftriaxone 1-2 g IV daily) plus azithromycin (500 mg daily), while outpatients with comorbidities require either combination therapy with amoxicillin-clavulanate plus a macrolide or respiratory fluoroquinolone monotherapy. 1

Outpatient Management

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, providing optimal coverage against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis 1, 2
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients intolerant of amoxicillin 1, 2
• Macrolides (azithromycin or clarithromycin) should only be used when local pneumococcal macrolide resistance is documented to be <25%, as higher resistance rates lead to treatment failure 1, 3

Adults With Comorbidities or Immunosuppression

• Combination therapy is mandatory for patients with COPD, diabetes, chronic heart/liver/renal disease, malignancy, or recent antibiotic use within 3 months 1
• Preferred regimen: 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) 1, 4
• For immunocompromised patients, including those on tyrosine kinase inhibitors or other immunosuppressive therapies, use the same combination therapy approach as for patients with comorbidities 1

Hospitalized Non-ICU Patients

Standard Empirical Therapy

• Two equally effective regimens exist: β-lactam plus macrolide combination OR respiratory fluoroquinolone monotherapy 1, 5
• Preferred combination: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily, providing coverage for both typical bacterial pathogens (S. pneumoniae, H. influenzae) and atypical organisms (Mycoplasma, Chlamydophila, Legionella) 1, 5
• 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
• Fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily 1, 4

Critical Timing Considerations

• Administer the first antibiotic dose immediately in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1
• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy 1, 2

Penicillin-Allergic Patients

• Use respiratory fluoroquinolone as the preferred alternative (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• Alternative: Aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 1

Severe CAP Requiring ICU Admission

Mandatory Combination Therapy

• All ICU patients require combination therapy—monotherapy is inadequate for severe disease 1, 5
• 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 either azithromycin 500 mg IV daily OR respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• Systemic corticosteroid administration within 24 hours of severe CAP development may reduce 28-day mortality 5, 2

Special Pathogen Coverage

For Pseudomonas aeruginosa (only when risk factors present):

• Risk factors: Structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, prior respiratory isolation of P. aeruginosa, or mechanical ventilation >8 days 1
• 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 PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) 1

For MRSA (only when risk factors present):

• Risk factors: Prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 1
• 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, 5, 2
• Typical duration for uncomplicated CAP is 5-7 days 1, 2
• Extended duration (14-21 days) required for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1

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 gastrointestinal function—typically by day 2-3 of hospitalization 1
• Clinical stability criteria: Temperature ≤37.8°C, heart rate ≤100 beats/min, respiratory rate ≤24 breaths/min, systolic blood pressure ≥90 mmHg, oxygen saturation ≥90% on room air 1
• Oral step-down options: Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg daily, or amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin 1

Diagnostic Testing

• Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis affects treatment (antiviral therapy) and infection prevention strategies 5, 2
• Obtain blood cultures and sputum cultures before initiating antibiotics in all hospitalized patients 1, 2
• Consider urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—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, 3
• Do not automatically add antipseudomonal or MRSA coverage without documented risk factors—this promotes resistance without improving outcomes 1
• Avoid extending therapy beyond 7-8 days in responding patients without specific indications, as longer courses increase antimicrobial resistance risk 1
• Do not use oral cephalosporins (cefuroxime, cefpodoxime) as first-line oral agents—they have inferior in vitro activity compared to high-dose amoxicillin 1

Follow-Up

• Clinical review at 6 weeks for all hospitalized patients 6, 1
• Chest radiograph at 6 weeks reserved for patients with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 6, 1
• Chest radiograph not required before hospital discharge in patients with satisfactory clinical recovery 6