What is the recommended treatment for Streptococcus pneumoniae (S. pneumoniae) community-acquired pneumonia (CAP)?

Treatment for Streptococcus pneumoniae Community-Acquired Pneumonia

For S. pneumoniae CAP, use amoxicillin 1 g three times daily for healthy outpatients, or ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily for hospitalized patients, with treatment duration of 5-7 days once clinically stable. 1

Outpatient Treatment (Healthy Adults Without Comorbidities)

Amoxicillin 1 g three times daily is the preferred first-line therapy for healthy adults without comorbidities, based on its effectiveness against S. pneumoniae and moderate quality evidence. 1

• Doxycycline 100 mg twice daily serves as an acceptable alternative if amoxicillin cannot be used. 1
• Macrolides (azithromycin 500 mg on day 1, then 250 mg daily; or clarithromycin 500 mg twice daily) should only be used in areas where pneumococcal macrolide resistance is <25%. 1, 2
• In areas with high macrolide resistance (>25%), avoid macrolide monotherapy to prevent treatment failure. 1

Outpatient Treatment (Adults With Comorbidities)

For patients with comorbidities (chronic heart, lung, liver, or renal disease; diabetes; alcoholism; malignancy; asplenia), use combination therapy:

• β-lactam (amoxicillin-clavulanate, cefpodoxime, or cefuroxime) plus macrolide (azithromycin or clarithromycin) or doxycycline. 1, 2
• Alternatively, respiratory fluoroquinolone monotherapy (levofloxacin 750 mg daily, moxifloxacin 400 mg daily, or gemifloxacin) is equally effective. 1, 2

Inpatient Treatment (Non-ICU)

Ceftriaxone 1-2 g IV daily plus azithromycin 500 mg daily is the preferred regimen with strong recommendation and high-quality evidence. 1, 2, 3

Alternative regimens include:

• Respiratory fluoroquinolone monotherapy (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily) with equally strong evidence. 1, 2
• β-lactam plus doxycycline (conditional recommendation, lower quality evidence). 1

Critical: Administer the first antibiotic dose while still in the emergency department for hospitalized patients, as delayed administration increases mortality. 2, 1

Inpatient Treatment (ICU)

Mandatory combination therapy with β-lactam (ceftriaxone 2 g IV daily, cefotaxime 1-2 g IV every 8 hours, or ampicillin-sulbactam 3 g IV every 6 hours) plus either azithromycin 500 mg daily or respiratory fluoroquinolone (levofloxacin 750 mg IV daily or moxifloxacin 400 mg IV daily). 2, 1

• This dual coverage targets both typical and atypical pathogens with strong recommendation. 2

Special Considerations for Drug-Resistant S. pneumoniae

For multi-drug resistant S. pneumoniae (MDRSP - resistant to ≥2 of: penicillin MIC ≥2 mcg/mL, 2nd generation cephalosporins, macrolides, tetracyclines, trimethoprim-sulfamethoxazole):

• Levofloxacin has demonstrated 95% clinical and bacteriologic success rates against MDRSP, including macrolide-resistant strains. 4, 5
• Ceftriaxone and cefotaxime remain effective for penicillin-resistant pneumococci with MIC ≤2 mcg/mL. 1, 6
• Avoid using penicillin MIC breakpoints for oral therapy; S. pneumoniae should be considered susceptible if penicillin MIC ≤1 mcg/mL for pneumonia. 6

Duration of Therapy

Treat for a minimum of 5 days and until afebrile for 48-72 hours with no more than 1 sign of clinical instability (temperature >37.8°C, heart rate >100/min, respiratory rate >24/min, systolic BP <90 mmHg, oxygen saturation <90%, inability to maintain oral intake, abnormal mental status). 2, 1

• Standard duration is 5-7 days for uncomplicated S. pneumoniae CAP. 1, 3
• Longer courses (14-21 days) are only needed for complications like empyema, meningitis, or endocarditis. 2

Transition to Oral Therapy

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

• Inpatient observation while receiving oral therapy is unnecessary; discharge when clinically stable. 2

Critical Pitfalls to Avoid

• Never use macrolide monotherapy in areas with >25% pneumococcal macrolide resistance or for hospitalized patients. 1
• Avoid cefuroxime, cefepime, piperacillin-tazobactam, or carbapenems as first-line empiric therapy for S. pneumoniae CAP unless specific risk factors for Pseudomonas or MRSA exist. 1
• Do not delay antibiotic administration beyond 8 hours in hospitalized patients, as this increases 30-day mortality by 20-30%. 2
• Obtain blood and sputum cultures before initiating antibiotics in all hospitalized patients to allow pathogen-directed therapy. 2, 1
• Reserve fluoroquinolones appropriately to limit emergence of resistance; they are preferred for patients with β-lactam allergies or treatment failures. 2, 6

Penicillin-Allergic Patients

• Outpatients: Use respiratory fluoroquinolone (levofloxacin, moxifloxacin) or doxycycline. 1
• Inpatients: Use respiratory fluoroquinolone monotherapy. 2, 1
• ICU patients: Use respiratory fluoroquinolone plus aztreonam. 2, 1