What is the initial approach to managing a patient with Community-Acquired Pneumonia (CAP), considering disease severity, patient comorbidities, and appropriate antibiotic therapy?

Community-Acquired Pneumonia (CAP) Discussion Outline for Internal Medicine

I. Initial Assessment and Severity Stratification

The first critical step is determining disease severity to guide site of care and antibiotic selection, using validated criteria rather than clinical gestalt alone. 1

A. Severity Assessment Tools

• Use the CRB-65 score (Confusion, Respiratory rate ≥30/min, Blood pressure systolic <90 or diastolic ≤60 mmHg, age ≥65 years) for outpatient risk stratification as it requires no laboratory testing and is well-validated in primary care settings 2

• For hospitalized patients, apply modified ATS criteria to identify severe CAP requiring ICU admission: presence of either 2 of 3 minor criteria (systolic BP ≤90 mmHg, multilobar disease, PaO2/FiO2 ratio ≤250) OR 1 of 2 major criteria (need for mechanical ventilation or septic shock) 1

• Additional high-risk features include confusion, BUN ≥19.6 mg/dL, respiratory rate ≥30/min, and bilateral or multilobar infiltrates 1

B. Risk Factor Assessment

• Identify risk factors for drug-resistant S. pneumoniae (DRSP): age ≥65 years, β-lactam therapy within 3 months, alcoholism, multiple medical comorbidities, immunosuppressive illness or therapy, exposure to child in daycare center 1

• Identify risk factors for enteric gram-negatives: nursing home residence, underlying cardiopulmonary disease, multiple medical comorbidities, recent antibiotic therapy 1

• Identify risk factors for Pseudomonas aeruginosa: bronchiectasis, broad-spectrum antibiotic therapy for ≥7 days within past month, malnutrition, chronic corticosteroid therapy >10 mg/day 1

• Identify risk factors for MRSA: prior MRSA infection, recent hospitalization, CAP following influenza, or recent antibiotic use 3

II. Diagnostic Approach

A. Clinical Diagnosis

• Diagnose CAP when a patient presents with ≥2 signs (temperature >38°C or ≤36°C; leukocyte count <4000/μL or >10,000/μL) OR symptoms (new or increased cough or dyspnea) plus consistent radiographic findings (air space density) without alternative explanation 4

• Physical examination should specifically assess respiratory rate, blood pressure, mental status, and signs of respiratory distress or hypoxemia 1

B. Microbiological Testing

• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized CAP patients 3

• 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

• Recognize that only 38% of hospitalized CAP patients have a pathogen identified; of those, up to 40% have viruses and approximately 15% have S. pneumoniae 4

• Do not use procalcitonin measurement routinely for diagnosis 2

C. Imaging

• Chest radiography, lung ultrasonography, or computed tomography can establish diagnosis 2

• Recognize that chest radiograph may not be sensitive to early pneumonia 1

III. Empiric Antibiotic Therapy by Clinical Setting

A. Outpatient Treatment - Previously Healthy, No Recent Antibiotics

For previously healthy outpatients without comorbidities or recent antibiotic use, first-line therapy is amoxicillin 1 g every 8 hours, doxycycline 100 mg twice daily (with 200 mg first dose), or a macrolide (azithromycin 500 mg Day 1, then 250 mg Days 2-5). 5, 6

• Macrolide monotherapy should only be used in areas where pneumococcal resistance to macrolides is <25% 2

• Macrolides are particularly appropriate when atypical pathogens (Mycoplasma, Chlamydophila, Legionella) are suspected 5

B. Outpatient Treatment - With Comorbidities or Recent Antibiotics

For outpatients with comorbidities (COPD, diabetes, heart failure, chronic kidney disease) or recent antibiotic use within 3 months, use either a respiratory fluoroquinolone (levofloxacin or moxifloxacin) OR a β-lactam (amoxicillin-clavulanate or ceftriaxone) plus a macrolide. 5, 2

• Patients with recent exposure to one antibiotic class should receive treatment from a different class due to resistance risk 5

• Reserve fluoroquinolones for patients with β-lactam allergies or specific indications to prevent resistance development 5

C. Hospitalized Non-ICU Patients

For hospitalized non-ICU patients without risk factors for resistant pathogens, use a β-lactam (ceftriaxone 1-2 g every 24 hours) PLUS a macrolide (azithromycin or clarithromycin) for minimum 3 days. 1, 5, 4

• Alternative regimen: respiratory fluoroquinolone monotherapy (levofloxacin or moxifloxacin) 5

• The first antibiotic dose should be administered while still in the emergency department as early administration is associated with improved outcomes 5

D. Severe CAP/ICU Patients Without Pseudomonas Risk

For ICU patients without Pseudomonas risk factors, use a β-lactam (ceftriaxone, cefotaxime, or ampicillin-sulbactam) PLUS either azithromycin OR a respiratory fluoroquinolone (levofloxacin or moxifloxacin). 5

• This regimen provides coverage for S. pneumoniae, Legionella, H. influenzae, and enteric gram-negatives 1, 7

E. Severe CAP/ICU Patients With Pseudomonas Risk

For patients with Pseudomonas risk factors (bronchiectasis, recent broad-spectrum antibiotics ≥7 days, malnutrition, chronic steroids), use an antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS either ciprofloxacin/levofloxacin OR an aminoglycoside (gentamicin, tobramycin, or amikacin) plus azithromycin. 5, 3

F. MRSA Coverage

Add vancomycin or linezolid only when locally validated risk factors for MRSA are present: prior MRSA infection, recent hospitalization, CAP following influenza, or recent antibiotic use 3

• Do not add MRSA coverage empirically based solely on healthcare-associated pneumonia (HCAP) criteria 3

IV. Duration and De-escalation of Therapy

A. Treatment Duration

Treat patients for a minimum of 5 days, ensuring they are afebrile for 48-72 hours and have no more than 1 CAP-associated sign of clinical instability before discontinuing therapy. 1

• Clinical stability criteria include: temperature ≤37.8°C, heart rate ≤100/min, respiratory rate ≤24/min, systolic BP ≥90 mmHg, oxygen saturation ≥90% on room air, ability to maintain oral intake, normal mental status 1

• Longer duration (14-21 days) may be needed for Legionella, staphylococcal, or gram-negative enteric bacilli infections, or if complicated by extrapulmonary infection 1, 5

B. Pathogen-Directed Therapy

Once etiology is identified by reliable microbiological methods, direct antimicrobial therapy at that specific pathogen. 1

• De-escalate therapy within 48-72 hours based on culture results and clinical response 3

C. Transition to Oral Therapy

Switch from intravenous to oral antibiotics when patients are clinically stable, afebrile for 24 hours, and able to tolerate oral intake. 5

• Inpatient observation while receiving oral therapy is not necessary if patients have no other active medical problems and a safe environment for continued care 1

V. Adjunctive Therapies for Severe CAP

A. Corticosteroids

Consider systemic corticosteroid administration within 24 hours of development of severe CAP as it may reduce 28-day mortality 4

• Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency 1

B. Vasopressor Support

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

C. 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

• Use low-tidal-volume ventilation (6 mL/kg ideal body weight) for patients undergoing mechanical ventilation who have diffuse bilateral pneumonia or ARDS 1

VI. Treatment Failure and Non-Response

A. Definition and Timing

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

• Evaluate for treatment failure if no clinical improvement within 48-72 hours 1

B. Systematic Approach to Non-Response

Use a systematic classification of possible causes of failure based on time of onset and type of failure: 1

• Early failure (<72 hours): inadequate antimicrobial coverage, resistant pathogens, incorrect diagnosis (pulmonary embolism, heart failure, malignancy), complications (empyema, lung abscess)

• Late failure (>72 hours): nosocomial superinfection, drug fever, Clostridioides difficile infection, progression of underlying disease

• Conduct careful review of clinical history, examination, prescription chart, and all available investigation results 5

• Consider additional investigations including repeat chest radiograph, CRP, white cell count, and further microbiological testing 5

VII. Prevention Strategies

A. Vaccination

Administer the 20-valent pneumococcal conjugate vaccine (PCV20) alone OR the 15-valent pneumococcal conjugate vaccine (PCV15) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) one year later to all adults ≥65 years or those 19-64 years with underlying conditions. 2

• The 13-valent pneumococcal conjugate vaccine (PCV13) is no longer recommended for routine administration 2

• Assess vaccination status at hospital admission for all patients, especially those with medical illnesses 1

• Vaccination may be performed either at hospital discharge or during outpatient treatment 1

B. Influenza Vaccination

Offer influenza vaccine to persons at hospital discharge or during outpatient treatment during fall and winter. 1

• Health care workers in inpatient and outpatient settings and long-term care facilities should receive annual influenza immunization 1

• The intranasally administered live attenuated vaccine is an alternative for persons 5-49 years without chronic underlying diseases, immunodeficiency, asthma, or chronic medical conditions 1

C. Smoking Cessation

Smoking cessation should be a goal for persons hospitalized with CAP who smoke. 1

• Smokers who will not quit should also be vaccinated for both pneumococcus and influenza 1

VIII. Common Pitfalls and Caveats

A. Antibiotic Selection Errors

• Avoid overreliance on fluoroquinolones as this leads to resistance; reserve for patients with β-lactam allergies or specific indications 5

• Do not use macrolide monotherapy in areas with pneumococcal macrolide resistance ≥25% or in patients with risk factors for DRSP 5

• Avoid inadequate coverage for atypical pathogens (Mycoplasma, Chlamydophila, Legionella) which are present in mixed infections 1, 5

B. Severity Assessment Errors

• Do not rely solely on prediction rules (PSI, CURB-65) to replace clinical judgment; consider patient preferences, ability to maintain oral intake, substance abuse history, cognitive impairment, and ability to perform activities of daily living 1

• Do not view age alone (without comorbid illness) as a predictor of enteric gram-negative infection 1

C. Diagnostic Errors

• Do not use sputum Gram stain alone to define likely etiologic pathogen and guide initial therapy as this practice has no firm basis in published studies 1

• Do not use clinical syndromes to predict microbial etiology as this approach is unreliable 1

D. MDRO Coverage Errors

• Abandon the HCAP classification entirely and only cover empirically for MRSA or P. aeruginosa when locally validated risk factors for either specific pathogen are present 3

• Do not provide empiric MDRO coverage based on HCAP criteria alone; consider strongest validated risk factors including previous hospitalization within 90 days, antibiotic use within 90 days, malignancy, cardiovascular disease, and structural lung disease 3

E. Treatment Duration Errors

• Do not continue therapy beyond clinical stability (minimum 5 days, afebrile 48-72 hours, ≤1 sign of instability) unless specific pathogens or complications warrant longer treatment 1

• Failure to adjust therapy based on culture results leads to unnecessary prolonged therapy; direct antimicrobial therapy at specific pathogen once identified 5

F. Timing Errors

• Delaying antibiotic administration is associated with increased mortality, particularly in severe pneumonia; administer first dose in emergency department 5