What is the treatment algorithm for community-acquired pneumonia (CAP)?

Treatment Algorithm for Community-Acquired Pneumonia

Initial Assessment and Site-of-Care Decision

The first critical step is determining whether the patient requires outpatient treatment, hospital admission, or ICU care using validated severity assessment tools. 1, 2

Severity Stratification Tools

• Use the Pneumonia Severity Index (PSI) to calculate mortality risk and guide admission decisions: patients in risk classes I-III can typically be treated as outpatients, while classes IV-V require hospitalization 1, 2, 3
• Alternatively, apply CURB-65 criteria (Confusion, Urea >7 mmol/L, Respiratory rate ≥30, Blood pressure <90/60, age ≥65): scores of 0-1 suggest outpatient treatment, 2 suggests hospital admission, and ≥3 indicates severe pneumonia requiring ICU consideration 2
• For patients admitted through the emergency department, administer the first antibiotic dose while still in the ED to minimize time to treatment and reduce mortality 1, 2

ICU Admission Criteria (Severe CAP)

Patients meeting any of the 2007 IDSA/ATS severe CAP criteria should be admitted to the ICU: 1

• Major criteria (1 required): invasive mechanical ventilation needed, or septic shock requiring vasopressors 1
• Minor criteria (≥3 required): respiratory rate ≥30/min, PaO₂/FiO₂ ratio ≤250, multilobar infiltrates, confusion/disorientation, uremia (BUN ≥20 mg/dL), leukopenia (WBC <4,000), thrombocytopenia (platelets <100,000), hypothermia (core temperature <36°C), or hypotension requiring aggressive fluid resuscitation 1

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Outpatient Treatment Algorithm

Previously Healthy Adults Without Comorbidities

For healthy outpatients without comorbidities or risk factors for drug-resistant pathogens, first-line therapy is amoxicillin 1 g three times daily. 1, 2

• Alternative options include:
  • Doxycycline 100 mg twice daily 1
  • Macrolide monotherapy (azithromycin 500 mg day 1, then 250 mg daily for 4 days; or clarithromycin 500 mg twice daily) ONLY in areas where pneumococcal macrolide resistance is <25% 1, 2

Pitfall to avoid: Macrolide monotherapy should not be used in areas with high pneumococcal resistance (≥25%), as treatment failures have been documented despite high tissue penetration 1

Outpatients With Comorbidities

For adults with chronic heart, lung, liver, or renal disease; diabetes mellitus; alcoholism; malignancy; or asplenia, use combination therapy or respiratory fluoroquinolone monotherapy. 1, 2

Combination Therapy (Preferred):

• β-lactam: amoxicillin/clavulanate 875 mg/125 mg twice daily, OR cefpodoxime 200 mg twice daily, OR cefuroxime 500 mg twice daily 1
• PLUS macrolide: azithromycin 500 mg day 1 then 250 mg daily, OR clarithromycin 500 mg twice daily 1
• OR doxycycline 100 mg twice daily (if macrolide-intolerant) 1

Monotherapy Alternative:

• Respiratory fluoroquinolone: levofloxacin 750 mg daily, OR moxifloxacin 400 mg daily, OR gemifloxacin 320 mg daily 1, 2

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Non-Severe Inpatient Treatment (General Medical Ward)

For hospitalized patients not requiring ICU care, the preferred regimen is a β-lactam PLUS a macrolide. 1, 2, 4

Standard Regimen for Patients With Cardiopulmonary Disease or Risk Factors for Drug-Resistant S. pneumoniae (DRSP):

• β-lactam options: ceftriaxone 1-2 g IV daily, OR cefotaxime 1-2 g IV every 8 hours, OR ampicillin/sulbactam 1.5-3 g IV every 6 hours, OR ceftaroline 1
• PLUS macrolide: azithromycin 500 mg IV/PO daily, OR clarithromycin 500 mg PO twice daily 1

The β-lactam can be switched to oral therapy after 1-2 days if the patient shows appropriate clinical response. 1

Alternative Regimen:

• Respiratory fluoroquinolone monotherapy: levofloxacin 750 mg IV/PO daily, OR moxifloxacin 400 mg IV/PO daily 1

Important caveat: While fluoroquinolone monotherapy is an option, the role in severe CAP is uncertain, and combination therapy with a β-lactam plus macrolide may be preferred for more severely ill ward patients 1

For Patients Without Cardiopulmonary Disease or DRSP Risk Factors:

• Azithromycin monotherapy 500 mg IV daily for 2-5 days, then 500 mg PO daily (total 7-10 days) is effective, including for pneumococcal bacteremia 1
• However, few admitted patients fall into this low-risk category 1

Special Considerations for Aspiration Risk or Nursing Home Residents:

• Add anaerobic coverage: use ampicillin/sulbactam, OR amoxicillin/clavulanate, OR add clindamycin/metronidazole to the regimen 1
• If lung abscess is documented, clindamycin or metronidazole must be incorporated 1

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Severe CAP Requiring ICU Care

For severe CAP, therapy must cover S. pneumoniae (including DRSP), Legionella, other atypicals, and H. influenzae, with stratification based on Pseudomonas aeruginosa risk. 1

Without Pseudomonas Risk Factors:

Use a non-antipseudomonal β-lactam PLUS either azithromycin OR a respiratory fluoroquinolone. 1, 2

• β-lactam options: ceftriaxone 1-2 g IV daily, OR cefotaxime 1-2 g IV every 8 hours, OR ampicillin/sulbactam 3 g IV every 6 hours 1
• PLUS azithromycin 500 mg IV daily (preferred over erythromycin due to administration difficulties and tolerance) 1
• OR respiratory fluoroquinolone: levofloxacin 750 mg IV daily, OR moxifloxacin 400 mg IV daily 1

Critical point: Erythromycin is not recommended for severe CAP due to administration difficulties and poor tolerance 1

With Pseudomonas Risk Factors:

Risk factors for P. aeruginosa include: severe structural lung disease (bronchiectasis), recent hospitalization with parenteral antibiotics within 90 days, or severe CAP from nursing homes known to harbor this organism 1

Use an antipseudomonal β-lactam PLUS either ciprofloxacin OR (azithromycin PLUS aminoglycoside). 1, 2

• Antipseudomonal β-lactam: piperacillin/tazobactam 4.5 g IV every 6 hours, OR cefepime 2 g IV every 8 hours, OR imipenem 500 mg IV every 6 hours, OR meropenem 1 g IV every 8 hours 1
• PLUS ciprofloxacin 400 mg IV every 8 hours 1
• OR azithromycin 500 mg IV daily PLUS aminoglycoside (gentamicin or tobramycin) 1

Important: Antipseudomonal β-lactams should NOT be used as primary therapy when P. aeruginosa is not suspected, as they provide unnecessarily broad coverage. 1

MRSA Coverage:

• Add vancomycin 15 mg/kg IV every 12 hours OR linezolid 600 mg IV every 12 hours if community-acquired MRSA is suspected (post-influenza pneumonia, compatible Gram stain, or nursing home with known MRSA) 1, 2

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Duration of Therapy and Transition to Oral Therapy

Patients should be treated for a minimum of 5 days and be afebrile for 48-72 hours with no more than 1 sign of clinical instability before discontinuing therapy. 1, 2

Clinical Stability Criteria (All Must Be Met):

• Temperature ≤37.8°C 1
• Heart rate ≤100 beats/min 1
• Respiratory rate ≤24 breaths/min 1
• Systolic blood pressure ≥90 mm Hg 1
• Oxygen saturation ≥90% or PaO₂ ≥60 mm Hg on room air 1
• Ability to maintain oral intake 1
• Normal mental status 1

Switch to Oral Therapy:

Patients should be switched from IV to oral therapy when they are hemodynamically stable, improving clinically, able to ingest medications, and have a normally functioning GI tract. 1, 2

• Most non-severe inpatients reach clinical stability in 2-3 days and should be switched to oral therapy and discharged shortly thereafter 3
• Inpatient observation while receiving oral therapy is not necessary 1

Longer duration may be needed if: initial therapy was not active against the identified pathogen, or if complicated by extrapulmonary infection (meningitis, endocarditis) 1

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Pathogen-Specific Modifications

Drug-Resistant S. pneumoniae (DRSP):

For penicillin MIC ≥2 mg/L, use: high-dose amoxicillin (1 g every 8 hours), OR amoxicillin/clavulanate (875 mg twice daily), OR ceftriaxone, OR cefotaxime, OR respiratory fluoroquinolone 1

For penicillin MIC ≥4 mg/L, use: respiratory fluoroquinolone, OR vancomycin, OR clindamycin 1

Important: Macrolides remain effective for organisms with penicillin MIC ≤2.0 mg/L despite in vitro resistance, due to high tissue penetration, but should be used in combination with a β-lactam when DRSP risk factors are present 1

Legionella:

Preferred treatment: respiratory fluoroquinolone (levofloxacin 750 mg daily preferred), OR macrolide (azithromycin preferred) 2

Mycoplasma or Chlamydophila:

Treatment options: macrolide, OR doxycycline, OR respiratory fluoroquinolone 2

Influenza/Pandemic Considerations:

Test all patients for COVID-19 and influenza when these viruses are common in the community, as diagnosis affects treatment (antiviral therapy) and infection prevention strategies. 4

For suspected H5N1 infection: treat with oseltamivir PLUS antibacterial agents targeting S. pneumoniae and S. aureus (the most common causes of secondary bacterial pneumonia) 1

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Adjunctive Therapies for Severe CAP

Corticosteroids:

Systemic corticosteroid administration within 24 hours of severe CAP development may reduce 28-day mortality. 4, 5

Vasopressor Support:

Patients with persistent septic shock despite adequate fluid resuscitation should be considered for drotrecogin alfa activated within 24 hours of admission. 1

Hypotensive, fluid-resuscitated patients should be screened for occult adrenal insufficiency. 1

Respiratory Support:

Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation unless they require immediate intubation due to severe hypoxemia (PaO₂/FiO₂ ratio <150) and bilateral alveolar infiltrates 1, 5

Low-tidal-volume ventilation (6 mL/kg ideal body weight) should be used for patients with diffuse bilateral pneumonia or ARDS. 1

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Management of Treatment Failure

Up to 15% of patients with CAP may not respond appropriately to initial antibiotic therapy. 1, 3

Systematic Approach to Non-Responders:

• Conduct careful review of: clinical history, examination, prescription chart, and all available investigations 2
• Consider: drug-resistant or unusual pathogens, nonpneumonia diagnoses (pulmonary embolism, malignancy, inflammatory conditions), or pneumonia complications (empyema, lung abscess) 1, 2
• Extensive diagnostic evaluation is most useful in the nonresponding patient 6

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Common Pitfalls and Caveats

• Delayed antibiotic administration increases mortality: ensure first dose within 8 hours of hospital arrival, ideally in the ED 1, 2
• Inadequate pathogen coverage is associated with worse outcomes: always consider local resistance patterns and patient risk factors 2
• Do not use first-generation cephalosporins, cefaclor, loracarbef, or trimethoprim/sulfamethoxazole if DRSP is suspected due to lack of efficacy 1
• Vancomycin should have a limited role in empiric therapy: reserve for high-level resistance failures or suspected meningitis 1
• Pneumococcal resistance to quinolones can occur, particularly with ciprofloxacin and levofloxacin: preliminary reports of levofloxacin failures exist 1

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Follow-Up and Prevention

• Clinical review should be arranged at 6 weeks with either the general practitioner or hospital clinic 2
• Chest radiograph at follow-up for patients with persistent symptoms, physical signs, or higher risk of underlying malignancy 2
• Pneumococcal and influenza vaccination should be administered to appropriate at-risk populations prior to discharge 2, 3
• Tobacco cessation counseling should be provided if eligible 3