What is the recommended treatment for Haemophilus influenzae (H. influenzae) infections?

Treatment for Haemophilus influenzae Infections

For Haemophilus influenzae infections, high-dose amoxicillin-clavulanate is the recommended first-line treatment to ensure coverage of β-lactamase-producing strains, with ceftriaxone being the preferred option for severe infections or meningitis. 1

First-line Treatment Options

Non-severe Infections (Outpatient)

• High-dose amoxicillin-clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in 2 divided doses for children; 4g/day of amoxicillin with 250 mg/day of clavulanate for adults) is recommended as first-line therapy due to increasing prevalence of β-lactamase-producing H. influenzae 1
• The 14:1 ratio of amoxicillin to clavulanate is preferred to minimize gastrointestinal side effects while maintaining efficacy 1
• For patients with penicillin allergy, alternatives include:
  • Cefdinir (14 mg/kg/day in 1-2 doses) 1
  • Cefuroxime axetil (750 mg twice daily for adults) 1, 2
  • Macrolides (clarithromycin 250-500 mg twice daily or azithromycin 500 mg on day 1, then 250 mg daily for 4 days) in areas with low resistance rates 1

Severe Infections (Inpatient)

• For hospitalized patients with severe H. influenzae infections, parenteral therapy is recommended: 1
  • Ceftriaxone (1-2 g IV daily for adults; 50-100 mg/kg/day for children) is highly effective against H. influenzae, including β-lactamase-producing strains 3, 4
  • Cefotaxime (1 g IV every 8 hours) is an effective alternative 1
  • Intravenous amoxicillin-clavulanate (2 g every 6 hours) for patients with mixed infections or suspected aspiration 1

Treatment by Specific Infection Type

H. influenzae Meningitis

• Ceftriaxone is the drug of choice (100 mg/kg on day one, followed by 80-100 mg/kg once daily) 4, 5
• Treatment should continue for 7-10 days 5, 6
• CSF concentrations of ceftriaxone remain 10-100 times higher than the MIC of H. influenzae even 24 hours after dosing, making once-daily dosing effective 4, 5

Lower Respiratory Tract Infections

• For community-acquired pneumonia or bronchitis where H. influenzae is suspected:
  • Outpatient: High-dose amoxicillin-clavulanate or a respiratory fluoroquinolone 1
  • Hospitalized patients: Ceftriaxone, cefotaxime, or IV amoxicillin-clavulanate, often combined with a macrolide to cover atypical pathogens 1
• Duration of therapy should be at least 7 days for non-severe infections and 10-14 days for severe infections 1

Otitis Media with H. influenzae

• High-dose amoxicillin-clavulanate is recommended due to increasing β-lactamase production 1
• Treatment duration is typically 7-10 days 1

Special Considerations

β-lactamase Production

• Current data show that 58-82% of H. influenzae isolates are susceptible to amoxicillin, meaning 18-42% produce β-lactamase 1
• In areas with high rates of β-lactamase-producing H. influenzae, always use β-lactamase-stable antibiotics (amoxicillin-clavulanate, cephalosporins, or fluoroquinolones) 1

Treatment Failure

• If no improvement after 48-72 hours of initial therapy:
  • Switch to ceftriaxone if on oral therapy 1
  • Consider adding a macrolide if atypical pathogens are suspected 1
  • Obtain cultures to guide targeted therapy 1

Monitoring Response

• Assess clinical response within 48-72 hours for severe infections and 5-7 days for non-severe infections 1
• For meningitis, CSF should be sterile within 24-48 hours of initiating appropriate therapy 4, 5

Common Pitfalls to Avoid

• Using standard-dose amoxicillin alone for empiric therapy when β-lactamase-producing H. influenzae cannot be ruled out 1
• Inadequate dosing of cephalosporins for CNS infections - higher doses are required to achieve adequate CSF concentrations 7, 5
• Stopping antibiotics too early when clinical improvement is seen - complete the full course to prevent relapse 1, 8
• Failing to consider H. influenzae in vaccinated individuals - non-typeable strains not covered by the Hib vaccine can still cause disease 1