Treatment of Community-Acquired Pneumonia in Adults
For outpatient healthy adults, start amoxicillin 1 g orally three times daily for 5–7 days; for hospitalized non-ICU patients, use ceftriaxone 1–2 g IV daily plus azithromycin 500 mg daily; and for ICU patients, escalate to ceftriaxone 2 g IV daily plus azithromycin 500 mg IV daily or a respiratory fluoroquinolone. 1
Outpatient Management
Previously Healthy Adults (No Comorbidities)
Amoxicillin 1 g orally three times daily for 5–7 days is the preferred first-line agent because it retains activity against approximately 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, and provides superior pneumococcal coverage compared with oral cephalosporins. 1
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
Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is documented to be <25%; in most U.S. regions, resistance is 20–30%, making macrolides unsafe as first-line agents. 1
Adults with Comorbidities or Recent Antibiotic Use
Combination therapy with a β-lactam (amoxicillin-clavulanate 875/125 mg twice daily, cefpodoxime, or cefuroxime) plus a macrolide (azithromycin or clarithromycin) or doxycycline 100 mg twice daily is required for patients with COPD, diabetes, chronic heart/liver/renal disease, malignancy, or antibiotic use within the past 3 months. 1
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily) is an alternative when β-lactams or macrolides are contraindicated, though fluoroquinolones should be reserved for this population due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection). 1
Monitoring and Escalation Criteria
Arrange a clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1
Indicators 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
If amoxicillin monotherapy fails, add or substitute a macrolide to provide atypical pathogen coverage (Mycoplasma, Chlamydophila, Legionella). 1
If combination therapy fails, switch to a respiratory fluoroquinolone (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1
Inpatient Management (Non-ICU)
Standard Empiric Regimen
Ceftriaxone 1–2 g IV once daily plus azithromycin 500 mg IV or orally daily is the preferred regimen for hospitalized patients not requiring ICU admission, providing coverage for typical bacterial pathogens (S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms (Mycoplasma, Chlamydophila, Legionella). 1
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
Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) is equally effective and reserved for penicillin-allergic patients or when combination therapy is contraindicated. 1
Timing and Diagnostic Testing
Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30%. 1
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
Transition to Oral Therapy
Switch from IV to oral antibiotics when the patient is hemodynamically stable (systolic BP ≥90 mmHg, heart rate ≤100 bpm), clinically improving, afebrile for 48–72 hours, respiratory rate ≤24 breaths/min, oxygen saturation ≥90% on room air, and able to take oral medications—typically by hospital day 2–3. 1
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
ICU Management (Severe CAP)
Mandatory Combination Therapy
- Combination therapy with 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 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 linked to higher mortality in critically ill patients with bacteremic pneumococcal pneumonia. 1
ICU Admission Criteria
- ICU admission is indicated when any one major criterion is present (septic shock requiring vasopressors or respiratory failure requiring mechanical ventilation) or when ≥3 minor criteria are met (confusion, respiratory rate ≥30/min, systolic BP <90 mmHg, multilobar infiltrates, PaO₂/FiO₂ <250). 1
Special Pathogen Coverage (Risk Factor–Based)
Antipseudomonal Coverage
Add antipseudomonal therapy 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 Pseudomonas aeruginosa. 1
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) to achieve dual antipseudomonal coverage. 1
MRSA Coverage
Add MRSA therapy only when risk factors are present: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging. 1
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
Duration of Therapy
Treat for a minimum of 5 days and continue 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
Extended duration of 14–21 days is required for infections caused by Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli. 1
Special Populations
Penicillin-Allergic Patients
For outpatients with comorbidities and penicillin allergy, use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 2
For hospitalized non-ICU patients with penicillin allergy, use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 2
For ICU patients with penicillin allergy, use aztreonam 2 g IV every 8 hours plus azithromycin 500 mg IV daily or a respiratory fluoroquinolone. 2
Pregnant Patients
- For pregnant patients with anaphylactic penicillin allergy, use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) for hospitalized non-ICU cases, recognizing that fluoroquinolones are generally avoided in pregnancy but may be necessary when β-lactams are contraindicated. 2
Elderly Patients and Nursing Home Residents
For elderly patients with comorbidities, use combination therapy (amoxicillin-clavulanate 875/125 mg twice daily plus azithromycin) or respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 1
For nursing home patients with penicillin allergy, use respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily or moxifloxacin 400 mg daily). 2
Critical Pitfalls to Avoid
Never use macrolide monotherapy in hospitalized patients; it provides inadequate coverage for typical bacterial pathogens like S. pneumoniae and is associated with treatment failure. 1
Never use macrolide monotherapy in outpatients when local pneumococcal macrolide resistance exceeds 25%; this increases the risk of breakthrough bacteremia and treatment failure. 1
Never delay antibiotic administration beyond 8 hours in hospitalized patients; this increases 30-day mortality by 20–30%. 1
Never add broad-spectrum antipseudomonal or MRSA agents automatically; restrict their use to patients with documented risk factors to prevent resistance, adverse effects, and unnecessary cost. 1
Never use fluoroquinolones as first-line agents in uncomplicated outpatient CAP; reserve them for patients with comorbidities or documented treatment failure due to FDA warnings about serious adverse events and rising resistance. 1
Never use oral cephalosporins (cefuroxime, cefpodoxime) as first-line therapy; they show inferior in-vitro activity compared with high-dose amoxicillin and lack coverage of atypical pathogens. 1
Follow-Up and Prevention
Schedule a routine follow-up visit at 6 weeks; obtain a chest radiograph only if symptoms persist, physical signs remain abnormal, or the patient has high risk for underlying malignancy (e.g., smokers >50 years). 1
Offer pneumococcal polysaccharide vaccine to all adults ≥65 years and those with high-risk conditions (chronic heart, lung, liver disease, diabetes, immunosuppression). 1
Recommend annual influenza vaccination for all patients, especially those with chronic medical illnesses. 1
Provide smoking-cessation counseling to all current smokers. 1