What is the recommended treatment for a typical adult with community‑acquired pneumonia (CAP) and no known drug allergies?

Treatment of Community-Acquired Pneumonia in Adults

For a typical adult with community-acquired pneumonia (CAP) and no drug allergies, prescribe amoxicillin 1 g orally three times daily for 5–7 days if the patient is previously healthy without comorbidities and can be managed as an outpatient; for hospitalized patients not requiring ICU care, administer ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg daily. 1

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Outpatient Management (Previously Healthy Adults)

First-Line Therapy

• Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line agent because it retains activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, and provides superior pneumococcal coverage compared with oral cephalosporins. 1, 2

Alternative Regimens

• Doxycycline 100 mg orally twice daily for 5–7 days serves as an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical bacterial pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1, 3
• Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should be reserved only for regions where local pneumococcal macrolide resistance is documented to be <25%; in most U.S. areas resistance is 20–30%, making macrolide monotherapy unsafe as first-line therapy. 1, 2

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Outpatient Management (Patients with Comorbidities or Recent Antibiotic Use)

When Combination Therapy Is Required

• Adults with COPD, diabetes, chronic heart/lung/liver/renal disease, malignancy, or antibiotic use within the past 90 days require combination therapy or respiratory fluoroquinolone monotherapy. 1, 3

Combination Regimen

• Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin (500 mg day 1, then 250 mg daily for 5–7 days) provides comprehensive coverage of typical and atypical pathogens, achieving approximately 91.5% favorable clinical outcomes. 1
• Alternative β-lactams (cefpodoxime or cefuroxime) must be combined with a macrolide or doxycycline to achieve similar spectrum. 1

Fluoroquinolone Monotherapy

• Levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily for 5–7 days may be used when β-lactams or macrolides are contraindicated, but should be reserved for patients with comorbidities or treatment failure due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1, 4, 5

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Hospitalized Patients (Non-ICU)

Standard Empiric Regimen

• Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily is the guideline-recommended regimen, providing coverage for typical pathogens (S. pneumoniae, H. influenzae, M. catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1, 3
• Alternative β-lactams include cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours, always combined with a macrolide. 1

Alternative for Penicillin Allergy

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is the preferred alternative for penicillin-allergic patients. 1, 4
• For severe fluoroquinolone contraindications, aztreonam 2 g IV every 8 hours plus azithromycin 500 mg IV daily provides coverage for both typical and atypical pathogens. 4

Critical Timing

• Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30% in hospitalized patients. 1, 3

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Severe CAP Requiring ICU Admission

Mandatory Combination Therapy

• Ceftriaxone 2 g IV once daily plus azithromycin 500 mg IV daily (or a respiratory fluoroquinolone: levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is required for all ICU patients; β-lactam monotherapy is associated with higher mortality in critically ill patients with bacteremic pneumococcal pneumonia. 1, 3

For Penicillin-Allergic ICU Patients

• Aztreonam 2 g IV every 8 hours plus levofloxacin 750 mg IV daily (or moxifloxacin 400 mg IV daily) provides adequate coverage when β-lactams are contraindicated. 4

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Special Pathogen Coverage (Risk-Based)

Pseudomonas aeruginosa

• Add antipseudomonal coverage only when specific risk factors are present: structural lung disease (bronchiectasis, cystic fibrosis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of P. aeruginosa. 1, 3
• Regimen: piperacillin-tazobactam 4.5 g IV every 6 hours plus ciprofloxacin 400 mg IV every 8 hours (or levofloxacin 750 mg IV daily) plus an aminoglycoside (gentamicin or tobramycin 5–7 mg/kg IV daily) for dual antipseudomonal coverage. 1, 3

Methicillin-Resistant Staphylococcus aureus (MRSA)

• Add MRSA coverage only when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1, 3
• Regimen: vancomycin 15 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL) or linezolid 600 mg IV every 12 hours, added to the base CAP regimen. 1, 3

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Duration of Therapy and Transition to Oral Antibiotics

Minimum Duration

• Treat for at least 5 days and continue until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability (temperature ≤37.8°C, heart rate ≤100 bpm, respiratory rate ≤24 breaths/min, systolic BP ≥90 mmHg, SpO₂ ≥90% on room air, able to maintain oral intake, normal mental status). 1, 3

Typical Course

• For uncomplicated CAP, a total course of 5–7 days is typical. 1, 3

Extended Duration

• Extend therapy to 14–21 days only when Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli are isolated. 1, 3

IV to Oral Switch

• Switch from IV to oral antibiotics when the patient is hemodynamically stable (SBP ≥90 mmHg, HR ≤100 bpm), clinically improving, afebrile 48–72 hours, respiratory rate ≤24 breaths/min, SpO₂ ≥90% on room air, and able to take oral medication—typically by hospital day 2–3. 1, 6
• Oral step-down options include amoxicillin 1 g three times daily plus azithromycin 500 mg daily (or continuation of azithromycin alone after 2–3 days of IV therapy). 1

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Critical Pitfalls to Avoid

Macrolide Misuse

• Never use macrolide monotherapy in hospitalized patients because it fails to cover typical pathogens such as S. pneumoniae and leads to treatment failure. 1, 3
• Avoid macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25%; this increases risk of breakthrough bacteremia and treatment failure. 1, 2

Fluoroquinolone Overuse

• Restrict fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and rising resistance; reserve for patients with comorbidities, β-lactam allergy, or treatment failure. 1, 4, 5

Diagnostic Sampling

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in all hospitalized patients to enable pathogen-directed therapy and safe de-escalation. 1, 3

Unnecessary Broad-Spectrum Coverage

• Do not add antipseudomonal or MRSA agents routinely; restrict their use to patients with documented risk factors to avoid unnecessary resistance, adverse effects, and cost. 1, 3

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Follow-Up and Monitoring

Outpatient Review

• Clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1
• Signs of treatment failure warranting hospital referral include: no clinical improvement by day 2–3, development of respiratory distress (respiratory rate >30/min, oxygen saturation <92%), inability to tolerate oral antibiotics, or new complications such as pleural effusion. 1

Escalation Strategy

• If amoxicillin monotherapy fails, add or substitute a macrolide (azithromycin or clarithromycin) to provide atypical pathogen coverage. 1
• If combination therapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1

Long-Term Follow-Up

• Routine follow-up at 6 weeks for all patients; chest radiograph only for those with persistent symptoms, abnormal physical findings, or high risk for underlying malignancy (e.g., smokers >50 years). 1

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Prevention

Vaccination

• Offer pneumococcal polysaccharide vaccine to all adults ≥65 years and those with high-risk conditions. 1, 3
• Recommend annual influenza vaccination for all patients, especially those with chronic medical illnesses. 1, 3

Smoking Cessation

• Provide smoking-cessation counseling to all current smokers. 1, 3