Community-Acquired Pneumonia Treatment Guidelines

Outpatient Treatment for Healthy Adults Without Comorbidities

For previously healthy adults with community-acquired pneumonia, start amoxicillin 1 g orally three times daily for 5–7 days as first-line therapy. 1, 2 This regimen provides activity against 90–95% of Streptococcus pneumoniae isolates, including many penicillin-resistant strains, making it superior to oral cephalosporins for pneumococcal coverage. 1, 2

Alternative regimens:

Doxycycline 100 mg orally twice daily for 5–7 days is an acceptable alternative when amoxicillin cannot be used, offering coverage of both typical and atypical pathogens. 1, 2, 3
Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily days 2–5; or clarithromycin 500 mg twice daily) should only be used in regions where documented pneumococcal macrolide resistance is <25%. 4, 1, 2 In most U.S. regions, macrolide resistance among S. pneumoniae ranges from 20–30%, making macrolide monotherapy unsafe as first-line. 1, 2

Critical pitfall: Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%, as breakthrough pneumococcal bacteremia occurs significantly more frequently with resistant strains. 1, 2

Outpatient Treatment for Adults With Comorbidities or Recent β-Lactam Exposure

For adults with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia; immunosuppression) or antibiotic use within the past 3 months, use combination therapy or fluoroquinolone monotherapy. 4, 1, 3

Preferred combination regimen:

Amoxicillin-clavulanate 875 mg/125 mg orally twice daily PLUS azithromycin 500 mg day 1, then 250 mg daily for 5–7 days total. 1, 2 This combination achieves approximately 91.5% favorable clinical outcomes by covering typical bacterial pathogens with the β-lactam and atypical organisms (Mycoplasma, Chlamydophila, Legionella) with the macrolide. 1, 2
Alternative β-lactams include cefpodoxime or cefuroxime, always combined with a macrolide or doxycycline. 1, 2, 3

Fluoroquinolone monotherapy alternative:

Levofloxacin 750 mg orally once daily OR moxifloxacin 400 mg orally once daily for 5–7 days. 4, 1, 3 Fluoroquinolones are active against >98% of S. pneumoniae strains, including penicillin-resistant isolates. 2, 5 However, reserve fluoroquinolones for patients with β-lactam allergy or when combination therapy is contraindicated, due to FDA warnings about serious adverse events (tendon rupture, peripheral neuropathy, aortic dissection) and rising resistance. 1, 2, 3

Key decision point: If the patient used antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk. 1, 2, 3

Inpatient Treatment (Non-ICU Ward)

For hospitalized patients not requiring ICU admission, use either β-lactam plus macrolide combination therapy or respiratory fluoroquinolone monotherapy—both regimens have strong evidence and equivalent efficacy. 4, 1, 3

Preferred combination regimen:

Ceftriaxone 1–2 g IV once daily PLUS azithromycin 500 mg IV or orally daily. 4, 1, 2 This combination provides comprehensive coverage for typical pathogens (S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis) and atypical organisms. 4, 1
Alternative β-lactams: cefotaxime 1–2 g IV every 8 hours OR ampicillin-sulbactam 3 g IV every 6 hours, always combined with azithromycin. 4, 1, 3

Fluoroquinolone monotherapy alternative:

Levofloxacin 750 mg IV daily OR moxifloxacin 400 mg IV daily. 4, 1, 3 Systematic reviews demonstrate fewer clinical failures and treatment discontinuations with fluoroquinolone monotherapy compared to β-lactam/macrolide combinations. 1

For penicillin-allergic patients: Use respiratory fluoroquinolone as the preferred alternative. 4, 1

Timing is critical: Administer the first antibiotic dose in the emergency department immediately upon diagnosis; delays beyond 8 hours increase 30-day mortality by 20–30%. 1, 2, 6

Diagnostic sampling: Obtain blood cultures and sputum Gram stain/culture before starting antibiotics in all hospitalized patients to enable pathogen-directed therapy. 4, 1, 6

ICU Treatment for Severe CAP

For patients requiring ICU admission, combination therapy is mandatory—β-lactam monotherapy is associated with higher mortality in critically ill patients. 4, 1, 3

Preferred ICU regimen:

Ceftriaxone 2 g IV once 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). 4, 1, 3

Evidence: A 2025 network meta-analysis of 8,142 patients demonstrated that β-lactam plus macrolide was the most effective regimen, significantly reducing overall mortality compared to β-lactam monotherapy and β-lactam plus fluoroquinolone. 1

For penicillin-allergic ICU patients: Use aztreonam 2 g IV every 8 hours PLUS a respiratory fluoroquinolone. 4, 1

Special Pathogen Coverage

Pseudomonas aeruginosa Coverage (Only When Risk Factors Present)

Add antipseudomonal therapy only if the patient has:

Structural lung disease (bronchiectasis, cystic fibrosis)
Recent hospitalization with IV antibiotics within 90 days
Prior respiratory isolation of P. aeruginosa
Chronic broad-spectrum antibiotic exposure (≥7 days in the past month) 4, 1

Antipseudomonal regimen:

Piperacillin-tazobactam 4.5 g IV every 6 hours OR cefepime 2 g IV every 8 hours OR imipenem OR meropenem
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 4, 1

Critical pitfall: Do not use piperacillin-tazobactam or cefepime empirically for standard CAP without documented Pseudomonas risk factors—this promotes antimicrobial resistance without clinical benefit. 1

MRSA Coverage (Only When Risk Factors Present)

Add MRSA therapy only if the patient has:

Prior MRSA infection or colonization
Recent hospitalization with IV antibiotics within 90 days
Post-influenza pneumonia
Cavitary infiltrates on imaging 4, 1

MRSA 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. 4, 1

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. 4, 1, 2, 3

Typical duration for uncomplicated CAP: 5–7 days. 4, 1, 2, 3

Extended duration (14–21 days) required only for:

Legionella pneumophila
Staphylococcus aureus
Gram-negative enteric bacilli 4, 1, 2, 3

Clinical stability criteria for oral transition or discharge:

Temperature ≤37.8°C
Heart rate ≤100 bpm
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, 2

Switch from IV to oral therapy when all stability criteria are met, typically by hospital day 2–3. 4, 1, 2

Oral step-down options:

Amoxicillin 1 g three times daily PLUS azithromycin 500 mg daily (or azithromycin alone after 2–3 days of IV therapy) 1
Amoxicillin-clavulanate 875 mg/125 mg twice daily PLUS azithromycin 1, 2

Common Pitfalls and Critical Errors to Avoid

Never use macrolide monotherapy in hospitalized patients—it provides inadequate coverage for typical pathogens like S. pneumoniae and is associated with treatment failure. 1, 2
Never delay antibiotic administration—delays beyond 8 hours increase 30-day mortality by 20–30% in hospitalized patients. 1, 2, 6
Do not add broad-spectrum antipseudomonal or MRSA agents routinely—restrict their use to patients with documented risk factors to avoid unnecessary resistance, adverse effects, and cost. 4, 1
Do not extend therapy beyond 7–8 days in responding patients without specific indications (Legionella, S. aureus, gram-negative bacilli)—longer courses increase antimicrobial resistance risk without improving outcomes. 1, 2
Avoid indiscriminate fluoroquinolone use in uncomplicated outpatient CAP due to FDA warnings about serious adverse events and resistance concerns. 1, 2, 3
Do not use β-lactam monotherapy in ICU patients—combination therapy is mandatory and reduces mortality. 4, 1
Obtain blood and sputum cultures before starting antibiotics in all hospitalized patients to allow pathogen-directed therapy and safe de-escalation. 4, 1, 6

Follow-Up and Monitoring

Outpatient follow-up: Clinical review at 48 hours (or sooner if symptoms worsen) to assess symptom resolution, oral intake, and treatment response. 1, 2

Signs of treatment failure warranting hospital referral:

No clinical improvement by day 2–3
Development of respiratory distress (respiratory rate >30/min, oxygen saturation <92%)
Inability to tolerate oral antibiotics
New complications such as pleural effusion 1, 2

Escalation strategy for outpatient failure:

If amoxicillin monotherapy fails, add or substitute a macrolide to cover atypical pathogens. 1, 2
If combination therapy fails, switch to a respiratory fluoroquinolone. 1, 2

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, 2

Prevention

Vaccination:

Pneumococcal polysaccharide vaccine for all adults ≥65 years and those with high-risk conditions 1, 2
Annual influenza vaccination for all patients 1, 2

Smoking cessation: Make smoking cessation a goal for all patients hospitalized with CAP who smoke. 1, 6

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