What is the first line treatment for drug-resistant Streptococcus pneumoniae (strep pneumonia)?

First-Line Treatment for Drug-Resistant Streptococcus pneumoniae

For drug-resistant Streptococcus pneumoniae (DRSP), the first-line treatment is either a respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg daily) or combination therapy with a high-dose β-lactam plus a macrolide. 1

Treatment Algorithm Based on Patient Setting

Outpatient Treatment for DRSP

1. For patients with comorbidities or recent antibiotic use (risk factors for DRSP):

   • Option 1: A respiratory fluoroquinolone (moxifloxacin, gemifloxacin, or levofloxacin 750 mg daily)
   • Option 2: Combination therapy with a β-lactam effective against S. pneumoniae plus a macrolide (or doxycycline as an alternative)
     • Preferred β-lactam: High-dose amoxicillin (1 g three times daily) or amoxicillin-clavulanate (2 g twice daily)
     • Alternative when parenteral therapy is feasible: Ceftriaxone

2. Important caveat: Avoid using agents in the same class as what the patient has recently received 1

Inpatient (Non-ICU) Treatment for DRSP

1. Option 1: A respiratory fluoroquinolone (strong recommendation; level I evidence)
2. Option 2: A β-lactam plus a macrolide (strong recommendation; level I evidence)
   • Preferred β-lactams: Cefotaxime, ceftriaxone, or ampicillin
   • For selected patients: Ertapenem
   • Alternative to macrolide: Doxycycline (level III evidence)
   • For penicillin-allergic patients: A respiratory fluoroquinolone 1

Inpatient (ICU) Treatment for DRSP

• A β-lactam (cefotaxime, ceftriaxone, or ampicillin-sulbactam) plus either azithromycin or a fluoroquinolone
• For penicillin-allergic patients: A respiratory fluoroquinolone and aztreonam 1

Specific Antibiotic Considerations for DRSP

β-lactams

• High-dose amoxicillin (1 g three times daily) targets >93% of S. pneumoniae strains and is the preferred oral β-lactam 1
• Ceftriaxone is an alternative when parenteral therapy is needed
• Oral cephalosporins (cefpodoxime, cefuroxime) are less active than high-dose amoxicillin or ceftriaxone 1

Fluoroquinolones

• Respiratory fluoroquinolones (moxifloxacin, gemifloxacin, levofloxacin 750 mg) have excellent activity against DRSP
• Levofloxacin is FDA-approved specifically for DRSP 2
• Should be used judiciously to prevent development of resistance 1

Special Considerations

• For highly resistant S. pneumoniae (penicillin MIC ≥4 mg/L), options include:
  • A respiratory fluoroquinolone
  • Vancomycin
  • Clindamycin (if susceptible) 1

Clinical Pearls and Pitfalls

Pitfalls to Avoid

• Do not use macrolide monotherapy for patients with a significant risk of DRSP infection, as clinical failure can occur with resistant isolates 1
• Avoid first-generation cephalosporins, cefaclor, loracarbef, and trimethoprim/sulfamethoxazole for suspected DRSP due to potential lack of efficacy 1
• Do not continue using antibiotics from the same class that the patient has recently received 1

Important Considerations

• Penicillin resistance in S. pneumoniae does not necessarily correlate with increased mortality in non-meningeal infections until MIC values exceed 4 mg/L 1
• The combination of a β-lactam plus a macrolide has shown a significant reduction in mortality compared to cephalosporin alone in retrospective studies 1
• Duration of treatment should generally not exceed 8 days in a responding patient 1

By following this treatment algorithm and considering the specific characteristics of the patient and local resistance patterns, clinicians can effectively manage drug-resistant S. pneumoniae infections while minimizing the risk of treatment failure and further development of antimicrobial resistance.