What is the treatment for invasive pneumococcal disease?

Treatment of Invasive Pneumococcal Disease

For invasive pneumococcal disease, initiate empiric therapy with a third-generation cephalosporin (ceftriaxone or cefotaxime) in most cases, particularly in regions with penicillin resistance or for life-threatening infections including meningitis, septicemia, and complicated pneumonia. 1, 2

Initial Antibiotic Selection

For Non-Meningeal Invasive Disease

• Ampicillin or penicillin G can be used for fully immunized patients when local epidemiologic data confirm lack of substantial high-level penicillin resistance (MIC ≤2 µg/mL for non-meningeal infections) 1

• Third-generation cephalosporins (ceftriaxone 50-100 mg/kg/day or cefotaxime 150 mg/kg/day) are preferred for:

  • Patients who are not fully immunized 1
  • Regions with documented high-level penicillin resistance 1, 2
  • Life-threatening infections including empyema 1
  • Bacteremia and septicemia 3

• Combination therapy with a beta-lactam plus a macrolide is recommended for hospitalized patients with severe invasive disease, as this combination has been associated with improved outcomes in bacteremic pneumococcal pneumonia 1, 4

For Pneumococcal Meningitis

• Third-generation IV cephalosporins (ceftriaxone or cefotaxime) are mandatory in most European countries and recommended globally due to concerns about penicillin resistance 1, 5

• Vancomycin should be added to the initial empiric regimen for suspected pneumococcal meningitis until susceptibility results are available, as it is the only antibiotic to which all S. pneumoniae strains remain susceptible 5

• Dexamethasone (0.15 mg/kg every 6 hours for 4 days) should be administered with or within 24 hours of the first antibiotic dose for confirmed pneumococcal meningitis, as it reduces mortality and neurological sequelae 1

• Administer ceftriaxone over 60 minutes in neonates to reduce the risk of bilirubin encephalopathy 3

Dosing Recommendations

Pediatric Patients

• Ceftriaxone: 50-100 mg/kg/day for serious infections; 100 mg/kg/day (not to exceed 4 grams daily) for meningitis 3

• Cefotaxime: 150 mg/kg/day divided every 8 hours 1

• Amoxicillin (for susceptible strains): 80-100 mg/kg/day in 2-3 divided doses 1

Adults

• Ceftriaxone: 1-2 grams once or twice daily (up to 4 grams/day for severe infections) 3

• Ampicillin: 150-200 mg/kg/day divided every 6 hours 1

• Penicillin G: 200,000-250,000 U/kg/day divided every 4-6 hours 1

Duration of Therapy

• Bacteremia/septicemia: Continue for at least 2 days after signs and symptoms resolve; usual duration 4-14 days 3

• Pneumonia: 7-10 days for uncomplicated cases 1, 2

• Meningitis: 7-14 days, with initial dose of 100 mg/kg followed by daily dosing 3

• Bone and joint infections: May require longer therapy depending on clinical response 3

Adjusting Therapy Based on Susceptibility

When Culture Results Available

• If penicillin-susceptible (MIC ≤0.06 µg/mL): Switch to penicillin G or amoxicillin monotherapy for non-meningeal infections 1

• If penicillin-resistant but cephalosporin-susceptible (ceftriaxone/cefotaxime MIC ≤2 µg/mL): Continue third-generation cephalosporin 1

• If highly resistant: Consider respiratory fluoroquinolones (levofloxacin, moxifloxacin) or vancomycin based on susceptibility testing 1

Special Considerations

Vancomycin Use

• Restrict vancomycin to confirmed highly resistant strains or meningitis cases to minimize emergence of vancomycin-resistant organisms 5

• Vancomycin has not been shown to be more effective than third-generation cephalosporins for pneumococcal pneumonia at current North American resistance levels 1

Staphylococcus aureus Co-infection

• Add vancomycin or clindamycin (based on local susceptibility) if clinical, laboratory, or imaging characteristics suggest S. aureus co-infection, which can complicate invasive pneumococcal disease 1

Critical Illness Management

• For fluid-resistant shock, consider early inotropic support and ventilatory assistance 1

• For inotrope-resistant shock, intravenous vasopressin and corticosteroid dose titration are appropriate rescue strategies 1

Common Pitfalls to Avoid

• Do not use diluents containing calcium (Ringer's solution, Hartmann's solution) with ceftriaxone, as precipitation can occur; this is particularly critical in neonates 3

• Do not delay antibiotic administration for diagnostic procedures in critically ill patients; blood cultures should be obtained but treatment should not be postponed 1

• Do not assume penicillin resistance equals treatment failure in pneumonia—serum and pulmonary levels of beta-lactams typically exceed MICs even for resistant strains 6

• Do not use oral cefixime for invasive pneumococcal disease, as it has poor activity against S. pneumoniae 7

Monitoring and Follow-up

• Assess clinical response after 48-72 hours; fever should resolve within 24-48 hours for pneumococcal infections 1

• Repeat imaging should not be ordered earlier than 7 days after treatment initiation unless clinical deterioration occurs 1

• Persistent fever or clinical worsening after 48 hours warrants reassessment, repeat cultures, and consideration of alternative diagnoses or resistant organisms 1