Is amoxicillin (amoxicillin) effective for treating Haemophilus influenzae type b (Hib) infections?

Amoxicillin for Haemophilus influenzae Infections

Amoxicillin alone should not be used for Haemophilus influenzae infections unless susceptibility is confirmed, as up to 25-50% of non-typeable strains may produce β-lactamase, rendering amoxicillin ineffective. 1

Effectiveness and Resistance Patterns

• Amoxicillin is only effective against H. influenzae strains that do not produce β-lactamase and are not β-lactamase-negative ampicillin-resistant (BLNAR) 1
• Current data from various studies show that only 58-82% of H. influenzae isolates are susceptible to regular and high-dose amoxicillin 1
• β-lactamase production is the primary mechanism of resistance among H. influenzae and is a well-known predictor of treatment failure in respiratory tract infections 1
• In Europe, the mean prevalence of β-lactamase-producing strains was 7.6%, with regional variations ranging from 0.7% to 17.6% 1
• A 2008 surveillance study showed an increased prevalence of amoxicillin-resistant strains of H. influenzae, with overall amoxicillin resistance observed in 25.0% of strains 2

Recommended Treatment Approach

First-line Treatment Options

• For confirmed or suspected β-lactamase-producing H. influenzae:

  • Amoxicillin-clavulanate is the recommended first-line treatment 3
  • The FDA specifically indicates amoxicillin-clavulanate for "lower respiratory tract infections caused by β-lactamase-producing isolates of Haemophilus influenzae" 3

• For H. influenzae with unknown susceptibility:

  • A second or third-generation cephalosporin or fluoroquinolone is recommended for empiric treatment of suspected β-lactamase producing H. influenzae 1
  • In Taiwan, high rates of susceptibility were found for cefuroxime, cefixime, cefpodoxime, cefotaxime, and amoxicillin-clavulanate 1

Pediatric Considerations

• For children with H. influenzae infections:
  • High-dose amoxicillin-clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate) is recommended when coverage for β-lactamase-positive H. influenzae is desired 1
  • For inpatient treatment of pediatric community-acquired pneumonia caused by H. influenzae, ampicillin or penicillin G can be used in fully immunized children if local penicillin resistance is minimal 1
  • For children not fully immunized or in areas with significant penicillin resistance, ceftriaxone or cefotaxime is recommended 1

Clinical Efficacy and Pharmacology

• Amoxicillin-clavulanate has shown excellent response in treating β-lactamase-producing strains of H. influenzae, with 18 of 19 β-lactamase-producing strains eradicated during therapy in one study 4
• The addition of clavulanic acid to amoxicillin effectively overcomes β-lactamase resistance 3, 2
• Third-generation cephalosporins (cefixime and cefpodoxime) and amoxicillin plus clavulanic acid continue to be very active against both β-lactamase-positive and BLNAR strains of H. influenzae 2

Common Pitfalls and Caveats

• Using amoxicillin alone empirically without knowing susceptibility patterns can lead to treatment failure due to β-lactamase production 1
• Non-β-lactamase producing and ampicillin-resistant (BLNAR) H. influenzae strains are increasing in some regions, particularly Japan and Europe, though they remain rare in some areas like Taiwan (0-8.3%) 1
• Gastrointestinal side effects (especially nausea) are common with amoxicillin-clavulanate 4
• Levofloxacin resistance in H. influenzae has increased significantly in some regions (e.g., from 2.0% in 2004 to 24.3% in 2010 in Taiwan) 1
• When susceptibility test results show susceptibility to amoxicillin (indicating no β-lactamase production), amoxicillin-clavulanate should not be used to avoid unnecessary exposure to clavulanate 3

In conclusion, while amoxicillin has historically been used for H. influenzae infections, increasing β-lactamase production makes it unreliable as empiric monotherapy. Treatment should be guided by local resistance patterns and, when available, individual susceptibility testing.