If a culture is susceptible to ampicillin (Ampicillin), can you give ceftriaxone (Ceftriaxone)?

Ceftriaxone Can Be Used When Culture Shows Susceptibility to Ampicillin

Yes, ceftriaxone can be used when a culture shows susceptibility to ampicillin, particularly for HACEK organisms and certain streptococcal infections, but this substitution is not universally applicable for all organisms.

Rationale for Substitution Based on Organism Type

HACEK Organisms

• For HACEK group organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella), ceftriaxone is actually the preferred treatment even when ampicillin susceptibility is demonstrated 1
• Previously, HACEK organisms were uniformly susceptible to ampicillin, but β-lactamase–producing strains are increasingly common
• The American Heart Association recommends that unless adequate growth for in vitro susceptibility testing is available, HACEK organisms should be considered ampicillin resistant 1
• Ceftriaxone is recommended as first-line therapy for HACEK infective endocarditis at a dose of 2g/24h IV for 4 weeks in native valve endocarditis and 6 weeks in prosthetic valve endocarditis 1

Streptococcal Infections

• For viridans group streptococci (VGS) with penicillin MIC ≥0.5 μg/mL, ceftriaxone combined with gentamicin may be a reasonable alternative treatment option if the organism is susceptible to ceftriaxone 1
• For penicillin-susceptible streptococci, a 4-week regimen of ceftriaxone given once daily is a recommended approach for infective endocarditis 1

Limitations and Exceptions

Enterococcal Infections

• For Enterococcus faecalis, ampicillin-ceftriaxone combination therapy has become an accepted treatment for serious infections like endocarditis 2
• However, for Enterococcus faecium, time-kill studies show that the ampicillin-ceftriaxone combination does not provide uniform synergy, even when the organism is ampicillin-susceptible 3
• Therefore, substituting ceftriaxone for ampicillin in enterococcal infections is not recommended unless as part of a combination therapy

Other Considerations

• The spectrum of activity of ceftriaxone is generally greater than first and second-generation cephalosporins against Gram-negative bacteria, but less than earlier generations against many Gram-positive bacteria 4
• For Group B Streptococcus infections in infants, ampicillin with an aminoglycoside is recommended for infants up to seven days of age, while ceftriaxone is only recommended for infants 29 to 90 days of age 1

Clinical Decision Algorithm

1. Identify the organism from culture

2. If HACEK organism:

   • Use ceftriaxone 2g/day IV regardless of ampicillin susceptibility
   • Duration: 4 weeks for native valve IE, 6 weeks for prosthetic valve IE

3. If Streptococcus (viridans group, S. pneumoniae):

   • If penicillin-susceptible: Either ampicillin or ceftriaxone is appropriate
   • If penicillin MIC ≥0.5 μg/mL: Consider ceftriaxone plus gentamicin

4. If Enterococcus:

   • Do not substitute ceftriaxone for ampicillin as monotherapy
   • Consider ampicillin-ceftriaxone combination for E. faecalis
   • For E. faecium, even if ampicillin-susceptible, the combination has less reliable synergy

5. For other organisms:

   • Check specific susceptibility patterns
   • Consider local antibiotic stewardship guidelines
   • Consult infectious disease specialist if uncertainty exists

Important Caveats

• Always consider the site of infection, as penetration of antibiotics varies by tissue
• For central nervous system infections, ceftriaxone has excellent CSF penetration
• When treating serious infections like endocarditis, consult with infectious disease specialists
• Consider antibiotic stewardship principles - use narrower spectrum agents when possible

Remember that while in vitro susceptibility to ampicillin may suggest susceptibility to ceftriaxone for some organisms, this relationship is not universal and depends on the specific bacterial species and resistance mechanisms.