What is the recommended antibiotic regimen and supportive care for community‑acquired pneumonia in an otherwise healthy adult outpatient, in outpatients with comorbidities, and for hospitalized patients (non‑ICU and ICU)?

Community-Acquired Pneumonia Management in Adults

Outpatient Treatment – Healthy Adults Without Comorbidities

Amoxicillin 1 g orally three times daily for 5–7 days is the first-line antibiotic for previously healthy outpatients with CAP, providing superior pneumococcal coverage against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains 1, 2, 3.

• Doxycycline 100 mg orally twice daily for 5–7 days serves as an acceptable alternative when amoxicillin is contraindicated, offering coverage of both typical and atypical pathogens 1, 2, 3.
• Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for 4 days; or clarithromycin 500 mg twice daily) should only be used in regions where documented pneumococcal macrolide resistance is <25%—in most U.S. areas resistance is 20–30%, making macrolides unsafe as first-line agents 1, 2, 3.
• Avoid oral cephalosporins (cefuroxime, cefpodoxime) as first-line therapy; they demonstrate inferior in-vitro activity compared with high-dose amoxicillin, lack atypical coverage, and offer no proven clinical superiority 1, 2.

Outpatient Treatment – Adults With Comorbidities

For patients with comorbidities (COPD, diabetes, chronic heart/liver/renal disease, alcoholism, malignancy, immunosuppression, or recent antibiotic use within 90 days), combination therapy is mandatory 1, 2, 3.

• 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, for a total of 5–7 days 1, 2, 3.
• Alternative β-lactams: Cefpodoxime or cefuroxime can substitute for amoxicillin-clavulanate when combined with a macrolide, though they have inferior pneumococcal activity 1, 2.
• Fluoroquinolone monotherapy alternative: Levofloxacin 750 mg orally once daily or moxifloxacin 400 mg orally once daily for 5–7 days is equally effective but should be reserved for patients with β-lactam allergy or macrolide intolerance due to FDA warnings about tendon rupture, peripheral neuropathy, and aortic dissection 1, 2, 3.
• If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk 1, 2.

Hospitalized Patients (Non-ICU)

Two equally effective regimens exist with strong recommendations and high-quality evidence 1, 3:

1. β-lactam plus macrolide combination: Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily 1, 3.

   • 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, 2.

2. Respiratory fluoroquinolone monotherapy: Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 1, 3.

   • Reserve fluoroquinolones for penicillin-allergic patients or when combination therapy is contraindicated 1, 2.

• Administer the first antibiotic dose immediately in the emergency department—delays beyond 8 hours increase 30-day mortality by 20–30% 1, 3.
• Obtain blood cultures and sputum Gram stain/culture before starting antibiotics in all hospitalized patients to enable pathogen-directed therapy 1, 3.

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—β-lactam monotherapy is linked to significantly higher mortality 1, 3.

• Preferred ICU regimen: 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) 1, 3.
• Alternative β-lactams: Cefotaxime 1–2 g IV every 8 hours or ampicillin-sulbactam 3 g IV every 6 hours 1.
• For penicillin-allergic ICU patients: Aztreonam 2 g IV every 8 hours plus levofloxacin 750 mg IV daily 1.

Special Pathogen Coverage (Risk Factor–Based)

Antipseudomonal Coverage

Add antipseudomonal therapy only when specific risk factors are present 1, 3:

• Structural lung disease (bronchiectasis, cystic fibrosis)
• Recent hospitalization with IV antibiotics within 90 days
• Prior respiratory isolation of Pseudomonas aeruginosa

Regimen: Antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours or cefepime 2 g IV every 8 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) 1, 3.

MRSA Coverage

Add MRSA therapy only when risk factors are present 1, 3:

• Prior MRSA infection or colonization
• Recent hospitalization with IV antibiotics within 90 days
• Post-influenza pneumonia
• Cavitary infiltrates on imaging

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 regimen 1, 3.

Duration of Therapy and Transition to Oral Antibiotics

• Minimum duration: 5 days, continuing until the patient is afebrile for 48–72 hours with no more than one sign of clinical instability 1, 3.
• Typical duration for uncomplicated CAP: 5–7 days 1, 3.
• Extended duration (14–21 days): Required only for Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 1, 2, 3.

Switch from IV to oral therapy when all clinical stability criteria are met 1, 3:

• Hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm)
• Clinically improving (afebrile 48–72 hours, respiratory rate ≤24 breaths/min)
• Oxygen saturation ≥90% on room air
• Able to take oral medications with normal GI function
• Typically achievable by hospital day 2–3

Oral step-down options: Amoxicillin 1 g three times daily plus azithromycin 500 mg daily, or continue azithromycin alone after 2–3 days of IV β-lactam coverage 1.

Supportive Care

• Oxygen therapy: Maintain PaO₂ >8 kPa (60 mmHg) and SpO₂ >92%; high-flow oxygen is safe in uncomplicated pneumonia 4.
• Monitoring: Assess temperature, respiratory rate, pulse, blood pressure, mental status, and oxygen saturation at least twice daily in hospitalized patients 4, 1.
• Fluid management: Evaluate for volume depletion and consider IV fluids as needed 4.

Follow-Up and Prevention

• Outpatient review at 48 hours (or sooner if symptoms worsen) to assess treatment response, oral intake, and need for escalation 4, 1, 2.
• Routine follow-up at 6 weeks for all patients; obtain chest radiograph only if symptoms persist, physical signs remain, or high risk for underlying malignancy (smokers >50 years) 4, 1.
• Pneumococcal vaccination: Offer to all adults ≥65 years and those with high-risk conditions 1, 3.
• Annual influenza vaccination: Recommend for all patients, especially those with chronic medical illnesses 1, 3.
• Smoking cessation counseling: Provide to all current smokers 1, 3.

Critical Pitfalls to Avoid

• Never delay antibiotic administration—initiate therapy immediately upon diagnosis, as delays beyond 8 hours increase 30-day mortality by 20–30% 1, 3.
• Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and leads to treatment failure 1, 3.
• Never use macrolide monotherapy in outpatients with comorbidities or in regions where pneumococcal macrolide resistance exceeds 25%—breakthrough bacteremia is significantly more common with resistant strains 1, 2, 3.
• Do not add broad-spectrum antipseudomonal or MRSA agents routinely—restrict their use to patients with documented risk factors to prevent unnecessary resistance, adverse effects, and cost 1, 3.
• Do not extend therapy beyond 7–8 days in responding patients without specific indications—longer courses increase antimicrobial resistance risk without improving outcomes 1, 2.
• Obtain blood and sputum cultures before starting antibiotics in all hospitalized patients to allow pathogen-directed therapy and safe de-escalation 1, 3.