What is the recommended treatment for Community-Acquired Pneumonia (CAP)?

Treatment of Community-Acquired Pneumonia

For outpatient CAP without comorbidities, use amoxicillin 1 g orally three times daily for 5-7 days as first-line therapy; for hospitalized non-ICU patients, use ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily; and for ICU patients, mandatory combination therapy with ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily is required. 1

Outpatient Treatment Algorithm

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 including drug-resistant strains 1, 2
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative for patients who cannot tolerate amoxicillin 1
• Avoid macrolide monotherapy (azithromycin, clarithromycin) unless local pneumococcal macrolide resistance is documented <25%—in most U.S. regions, resistance exceeds this threshold 1, 3

Adults With Comorbidities (COPD, diabetes, heart/liver/renal disease, malignancy, or recent antibiotic use)

• Combination therapy: amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for days 2-5 1
• Alternative β-lactams include cefpodoxime or cefuroxime, always combined with a macrolide or doxycycline 1
• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily OR moxifloxacin 400 mg daily) is equally effective but should be reserved for penicillin allergy or macrolide intolerance due to FDA warnings about serious adverse events 1, 4

Hospitalized Non-ICU Patients

Standard Regimens (Two Equally Effective Options)

• β-lactam plus macrolide: ceftriaxone 1-2 g IV daily PLUS azithromycin 500 mg daily (strong recommendation, high-quality evidence) 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 azithromycin 1
• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily (strong recommendation, high-quality evidence) 1, 4

Critical Timing Consideration

• Administer the first antibiotic dose in the emergency department immediately upon diagnosis—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 5, 1, 2

Penicillin-Allergic Patients

• Use respiratory fluoroquinolone as the preferred alternative 1
• For true severe penicillin allergy with fluoroquinolone contraindication: aztreonam 2 g IV every 8 hours PLUS azithromycin 500 mg IV daily 1

Severe CAP Requiring ICU Admission

Mandatory Combination Therapy

• Ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours) PLUS azithromycin 500 mg IV daily 1, 2
• Alternative: β-lactam PLUS respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) 1
• Monotherapy is inadequate for ICU patients and associated with higher mortality 1

Special Pathogen Coverage—Add Only When Risk Factors Present

For Pseudomonas aeruginosa (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 (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 the base regimen 1, 2

Duration of Therapy

Standard Duration

• Minimum 5 days AND until afebrile for 48-72 hours with no more than one sign of clinical instability 5, 1, 2, 6
• 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, ability to maintain oral intake, normal mental status 1
• Typical duration for uncomplicated CAP is 5-7 days—do not extend beyond 7-8 days in responding patients without specific indications 1, 6, 7

Extended Duration (14-21 Days) Required For

• Legionella pneumophila 1, 2
• Staphylococcus aureus 1, 2
• Gram-negative enteric bacilli 1, 2
• Extrapulmonary complications (meningitis, endocarditis) 5

Transition from IV to Oral Therapy

Criteria for Switch

• Hemodynamically stable 5, 1, 2
• Clinically improving 5, 1, 2
• Able to ingest medications 5, 1, 2
• Normal gastrointestinal function 5, 1, 2
• Typically achievable by day 2-3 of hospitalization 1

Oral Step-Down Options

• Amoxicillin 1 g orally three times daily PLUS azithromycin 500 mg orally daily 1
• Amoxicillin-clavulanate 875/125 mg orally twice daily PLUS azithromycin 500 mg orally daily 1
• Levofloxacin 750 mg orally once daily 1, 4
• Doxycycline 100 mg orally twice daily (if already receiving IV doxycycline) 1

Diagnostic Testing for Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in ALL hospitalized patients 1, 8
• Urinary antigen testing for Legionella pneumophila serogroup 1 in severe CAP or ICU patients 1
• Once etiology is identified, switch to pathogen-directed therapy 5, 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in hospitalized patients—provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—leads to treatment failure 1, 3
• Never delay antibiotic administration in hospitalized patients—each hour of delay increases mortality 1
• Never add antipseudomonal or MRSA coverage without documented risk factors—indiscriminate broad-spectrum use increases resistance 1
• Never use oral cephalosporins (cefuroxime, cefpodoxime) as first-line oral agents—inferior in vitro activity compared to high-dose amoxicillin 1
• Never extend therapy beyond 7-8 days in responding patients without specific indications—increases antimicrobial resistance risk without improving outcomes 1, 6, 7

Follow-Up

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 2
• Scheduled clinical review at 6 weeks for all hospitalized patients 5, 2
• Chest radiograph at 6 weeks only for patients with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 5, 2