What is the recommended antibiotic treatment for Streptococcus pneumoniae infections?

Recommended Antibiotic Treatment for Streptococcus pneumoniae Infections

High-dose amoxicillin is the first-line treatment for Streptococcus pneumoniae infections in most cases, with specific alternatives based on resistance patterns, severity, and patient factors. 1

First-line Treatment Options

For Uncomplicated Infections (Outpatient)

• Previously healthy patients with no risk factors for drug-resistant S. pneumoniae (DRSP):
  • A macrolide (azithromycin, clarithromycin, or erythromycin) 1
  • Doxycycline as an alternative option 1

For Patients with Comorbidities or Risk Factors for Resistance

• High-dose amoxicillin (1 g three times daily) is preferred for adults 1
• Amoxicillin-clavulanate (2 g twice daily) for patients at high risk of infection with amoxicillin-resistant organisms 1
• Risk factors requiring broader coverage include:
  • Geographic regions with high endemic rates (>10%) of penicillin non-susceptible S. pneumoniae 1
  • Severe infection (temperature ≥39°C or risk of suppurative complications) 1
  • Age >65 years 1
  • Recent hospitalization 1
  • Antibiotic use within the past month 1
  • Immunocompromised status 1

For Hospitalized Patients (Non-ICU)

• Recommended regimens:
  • A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg) 1, 2
  • OR a β-lactam plus a macrolide 1
    • Preferred β-lactams: cefotaxime, ceftriaxone, or ampicillin 1

For Severe Infections (ICU Patients)

• Combination therapy:
  • A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either:
    • Azithromycin 1
    • OR a respiratory fluoroquinolone 1

For Penicillin-Allergic Patients

• Non-severe allergy:

  • Respiratory fluoroquinolones (levofloxacin, moxifloxacin) 1, 2
  • Doxycycline (for mild-moderate infections) 1

• Severe allergy (Type I):

  • For hospitalized patients: respiratory fluoroquinolone plus aztreonam 1
  • For outpatients: respiratory fluoroquinolone monotherapy 1
  • Combination therapy with clindamycin plus a third-generation oral cephalosporin (cefixime or cefpodoxime) for non-type I hypersensitivity 1

Special Considerations

Multi-Drug Resistant S. pneumoniae (MDRSP)

• MDRSP defined as resistance to ≥2 of: penicillin, 2nd generation cephalosporins, macrolides, tetracyclines, and trimethoprim-sulfamethoxazole 2
• Treatment options:
  • Levofloxacin has demonstrated 95% clinical and bacteriologic success in MDRSP infections 2
  • High-dose amoxicillin-clavulanate remains effective against many resistant strains 1, 3

Duration of Therapy

• 5-7 days for uncomplicated pneumococcal infections 1
• 10 days for pneumococcal pneumonia 1
• Shorter courses (5 days) are appropriate for less severe illness 1

Important Clinical Pearls

• Despite in vitro resistance, β-lactams remain clinically effective for pneumococcal pneumonia when the MIC ≤2 μg/mL due to favorable pharmacokinetic/pharmacodynamic parameters 4, 3
• Macrolide resistance in S. pneumoniae is high in some regions (>40% in the US), which may lead to treatment failures if used as monotherapy 1, 5
• Fluoroquinolones should be reserved for patients with risk factors for resistance or treatment failure with first-line agents to prevent development of resistance 1, 6
• For bacteremic pneumococcal pneumonia, combination therapy with a β-lactam plus either a macrolide or fluoroquinolone is associated with better outcomes 6
• The high prevalence of macrolide-resistant S. pneumoniae (>40% in the US) and resistance to trimethoprim-sulfamethoxazole among both S. pneumoniae (50%) and H. influenzae (27%) makes these agents unsuitable for empiric monotherapy 1