What is the recommended approach to treating bacterial pneumonia in adults with varying ages and underlying health conditions?

Approach to Bacterial Pneumonia

Initial Assessment and Risk Stratification

The treatment approach for bacterial pneumonia depends primarily on severity of illness and site of care, with healthy outpatients receiving amoxicillin monotherapy, patients with comorbidities requiring combination β-lactam/macrolide therapy or respiratory fluoroquinolone, and all ICU patients mandating combination therapy with a β-lactam plus either azithromycin or respiratory fluoroquinolone. 1

Severity Assessment and Site-of-Care Decision

• Use the Pneumonia Severity Index (PSI) score to guide initial site-of-care decisions, with classes I-III typically managed outpatient and classes IV-V considered for hospitalization 1
• ICU admission criteria include severe hypoxemia (PaO₂/FiO₂ <250), septic shock requiring vasopressors, or multilobar infiltrates with respiratory failure 2, 1
• Elderly or debilitated patients should have a lower threshold for hospitalization regardless of PSI score 1

Outpatient Treatment

Previously Healthy Adults Without Comorbidities

• Amoxicillin 1 g orally three times daily for 5-7 days is the preferred first-line therapy, providing superior coverage against Streptococcus pneumoniae including drug-resistant strains 1
• Doxycycline 100 mg orally twice daily serves as an acceptable alternative, though with lower quality supporting evidence 2, 1
• Macrolides (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 <25% 2, 1

Adults With Comorbidities or Recent Antibiotic Use

Comorbidities include chronic heart/lung/liver/renal disease, diabetes mellitus, alcoholism, malignancies, asplenia, immunosuppression, or antibiotic use within the previous 3 months 2, 1

• Combination therapy: β-lactam plus macrolide or doxycycline 2, 1

  • High-dose amoxicillin-clavulanate 2 g twice daily (preferred β-lactam) plus azithromycin 500 mg day 1, then 250 mg daily for days 2-5 2, 1
  • Alternative β-lactams: cefpodoxime, cefuroxime 500 mg twice daily 2
  • Doxycycline 100 mg twice daily can substitute for macrolide 2

• Alternative monotherapy: Respiratory fluoroquinolone 2, 1

  • Levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin 320 mg daily 2, 1
  • However, avoid indiscriminate fluoroquinolone use in uncomplicated cases due to FDA warnings about serious adverse events and resistance concerns 1

Inpatient Non-ICU Treatment

Two equally effective regimens exist with strong recommendations and high-quality evidence: β-lactam plus macrolide combination or respiratory fluoroquinolone monotherapy. 2, 1

Preferred Regimens

• β-lactam plus macrolide combination 2, 1

  • Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily (IV or oral) 2, 1
  • Alternative β-lactams: cefotaxime 1-2 g IV every 8 hours, ampicillin-sulbactam 3 g IV every 6 hours 2, 1
  • Doxycycline 100 mg twice daily can substitute for macrolide 2

• Respiratory fluoroquinolone monotherapy 2, 1, 3

  • Levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 2, 1, 3
  • Systematic reviews demonstrate fewer clinical failures compared to β-lactam/macrolide combinations 1

• For penicillin-allergic patients, respiratory fluoroquinolone is the preferred alternative 2, 1

Critical Timing Considerations

• Administer the first antibiotic dose immediately upon diagnosis, ideally while still in the emergency department—delayed administration beyond 8 hours increases 30-day mortality by 20-30% 1

Severe CAP Requiring ICU Admission

Combination therapy is mandatory for all ICU patients—monotherapy is inadequate for severe disease. 2, 1

Standard ICU Regimen

• β-lactam plus either azithromycin OR respiratory fluoroquinolone 2, 1
  • Ceftriaxone 2 g IV daily (or cefotaxime 1-2 g IV every 8 hours, or ampicillin-sulbactam 3 g IV every 6 hours) 2, 1
  • PLUS azithromycin 500 mg IV daily 2, 1
  • OR levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily 2, 1

Special Populations Requiring Broader Coverage

Add antipseudomonal coverage when specific risk factors are present:

• Risk factors: structural lung disease (bronchiectasis), recent hospitalization with IV antibiotics within 90 days, or prior respiratory isolation of Pseudomonas aeruginosa 2, 1
• Regimen: antipseudomonal β-lactam (piperacillin-tazobactam 4.5 g IV every 6 hours, cefepime 2 g IV every 8 hours, imipenem, or meropenem) 2, 1
• PLUS ciprofloxacin 400 mg IV every 8 hours OR levofloxacin 750 mg IV daily 2, 1
• PLUS aminoglycoside (gentamicin or tobramycin 5-7 mg/kg IV daily) for dual antipseudomonal coverage 1

Add MRSA coverage when specific risk factors are present:

• Risk factors: prior MRSA infection/colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates on imaging 2, 1
• Add vancomycin 15 mg/kg IV every 8-12 hours (target trough 15-20 mg/mL) OR linezolid 600 mg IV every 12 hours 2, 1

Diagnostic Testing

Outpatient Setting

• Diagnostic testing is generally not required for outpatients with uncomplicated CAP 2
• Consider testing if treatment failure occurs or atypical presentation 2

Hospitalized Patients

• Obtain blood cultures and sputum Gram stain/culture before initiating antibiotics in ALL hospitalized patients 2, 1
• For severe CAP or ICU patients, also perform urinary antigen tests for Legionella pneumophila serogroup 1 and Streptococcus pneumoniae 2
• For intubated patients, obtain endotracheal aspirate sample 2

Duration of Therapy

Treat for a minimum of 5 days and until the patient is afebrile for 48-72 hours with no more than one sign of clinical instability. 2, 1

• Typical duration for uncomplicated CAP: 5-7 days 2, 1
• Treatment duration should generally not exceed 8 days in a responding patient, as longer courses increase antimicrobial resistance risk without improving outcomes 1
• Extended duration (14-21 days) required for specific pathogens: Legionella pneumophila, Staphylococcus aureus, or Gram-negative enteric bacilli 2, 1, 4
• For severe microbiologically undefined pneumonia: 10 days 1, 4

Transition from IV to Oral Therapy

Switch from IV to oral antibiotics when the patient is hemodynamically stable, clinically improving, able to take oral medications, and has normal GI function—typically by day 2-3 of hospitalization. 2, 1

Oral Step-Down Options

• Amoxicillin 1 g orally three times daily plus azithromycin 500 mg orally daily 1
• Amoxicillin-clavulanate 875/125 mg orally twice daily plus azithromycin 500 mg orally daily 1
• Levofloxacin 750 mg orally daily or moxifloxacin 400 mg orally daily (if started on fluoroquinolone) 1, 3

Management of Treatment Failure

If no clinical improvement by day 2-3: 1, 4

• Obtain repeat chest radiograph, CRP, white cell count, and additional microbiological specimens 1, 4
• For non-severe pneumonia initially on amoxicillin monotherapy: add or substitute a macrolide 1, 4
• For non-severe pneumonia on combination therapy: switch to respiratory fluoroquinolone 1, 4
• For severe pneumonia not responding to combination therapy: consider adding rifampicin 1
• Reassess for complications (empyema, abscess), alternative diagnoses, or resistant organisms 1

Special Considerations for Elderly Patients

• For elderly patients requiring hospitalization, combination therapy with amoxicillin and a macrolide (erythromycin or clarithromycin) is preferred 4
• When oral treatment is contraindicated, use IV ampicillin or benzylpenicillin plus erythromycin or clarithromycin 4
• Monotherapy with amoxicillin may be considered for elderly patients admitted for non-clinical reasons (e.g., social factors) who would otherwise be treated in the community 4
• For severe pneumonia in elderly patients, use IV combination of broad-spectrum β-lactamase stable antibiotic (co-amoxiclav, cefuroxime, or ceftriaxone) plus macrolide 4
• Higher doses of amoxicillin than traditionally used are recommended for elderly patients 4

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas where pneumococcal macrolide resistance exceeds 25%—this leads to treatment failure 2, 1
• Never use macrolide monotherapy for hospitalized patients, as this provides inadequate coverage for typical bacterial pathogens like S. pneumoniae 1
• Avoid using cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy unless specific risk factors for Pseudomonas aeruginosa or MRSA are present 1
• Do not automatically escalate to broad-spectrum antibiotics based solely on immunosuppression without documented risk factors 1
• If patient received antibiotics within the past 90 days, select an agent from a different antibiotic class to reduce resistance risk 2, 1
• Avoid extending therapy beyond 7 days in responding patients without specific indications 1

Follow-Up

• Clinical review at 48 hours or sooner if clinically indicated for outpatients 1, 4
• Schedule clinical review at 6 weeks for all hospitalized patients 1, 4
• Chest radiograph at 6 weeks reserved for those with persistent symptoms, physical signs, or high risk for underlying malignancy (smokers, age >50 years) 1, 4
• Chest radiograph not required before hospital discharge in patients with satisfactory clinical recovery 1, 4

Prevention

• Pneumococcal polysaccharide vaccine for persons ≥65 years and those with selected high-risk concurrent diseases 1
• Annual influenza vaccination for all patients, especially those with medical illnesses and healthcare workers 1, 4
• Smoking cessation as a goal for all patients hospitalized with CAP who smoke 1