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 of Community-Acquired Pneumonia in Adults

Outpatient Treatment for Healthy Adults Without Comorbidities

Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy for previously healthy outpatients with community-acquired pneumonia. 1

• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin. 1
• 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%. 1, 2
• 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

Outpatient Treatment for Adults With Comorbidities or Immunosuppression

For patients with underlying health conditions (COPD, diabetes, chronic heart/liver/renal disease, malignancy) or compromised immune systems, combination therapy is required. 1

• Preferred regimen: Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5, for a total duration of 5-7 days. 1
• Alternative regimen: Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1, 2
• If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1

Hospitalized Non-ICU Patients

For hospitalized patients without ICU-level severity, use either β-lactam plus macrolide combination therapy or respiratory fluoroquinolone monotherapy—both regimens have equivalent efficacy. 1

• Preferred combination: Ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg IV or oral daily. 1, 3
• Alternative monotherapy: Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily. 1, 4
• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative. 1
• Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30%. 1

Severe CAP Requiring ICU Admission

All ICU patients require mandatory combination therapy with a β-lactam PLUS either azithromycin or a respiratory fluoroquinolone—monotherapy is inadequate for severe disease. 1

• 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. 1
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 1
• Systemic corticosteroid administration within 24 hours of development of severe CAP may reduce 28-day mortality. 3

Special Populations Requiring Broader 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, or prior respiratory isolation of P. aeruginosa. 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 5-7 mg/kg IV daily or tobramycin 5-7 mg/kg IV daily). 1

MRSA Risk Factors

Add MRSA coverage when specific risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1

• 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

• Typical duration for uncomplicated CAP is 5-7 days. 1, 3
• Extend duration to 14-21 days for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1, 2
• For severe microbiologically undefined pneumonia, treat for 10 days. 2
• Treatment duration should generally not exceed 8 days in a responding patient, as longer courses increase antimicrobial resistance risk without improving outcomes. 1

Transition from IV to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, afebrile for 24-48 hours, able to take oral medications, and has normal GI function—typically 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, OR amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin. 1

Diagnostic Testing for Hospitalized Patients

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

• Test all patients for COVID-19 and influenza when these viruses are common in the community, as their diagnosis may affect treatment and infection prevention strategies. 3
• Urinary antigen testing for Legionella pneumophila serogroup 1 should be considered in severe CAP or ICU patients. 1

Follow-Up and Monitoring

Arrange 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

• The chest radiograph need not be repeated prior to hospital discharge in patients with satisfactory clinical recovery. 2
• For outpatients, clinical review at 48 hours or sooner if clinically indicated. 2

Critical Pitfalls to Avoid

• Never delay the first antibiotic dose beyond 8 hours from diagnosis—this increases 30-day mortality by 20-30% in hospitalized patients. 1
• Never use macrolide monotherapy in hospitalized patients—this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae. 1
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—macrolide-resistant S. pneumoniae may also be resistant to doxycycline. 1
• Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns. 1
• Do not automatically escalate to broad-spectrum antibiotics (antipseudomonal or anti-MRSA coverage) based solely on immunosuppression without documented risk factors. 1
• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas aeruginosa or MRSA are present. 1

Prevention

• Administer pneumococcal polysaccharide vaccine for persons ≥65 years and those with selected high-risk concurrent diseases. 1
• Provide annual influenza vaccination for all patients, especially those with medical illnesses and healthcare workers. 1
• Counsel smoking cessation as a goal for all patients hospitalized with CAP who smoke. 1