Is ampicillin (Ampicillin) effective against gram-negative infections?

Ampicillin's Effectiveness Against Gram-Negative Infections

Ampicillin alone has limited effectiveness against many gram-negative infections due to widespread beta-lactamase production, making it suitable only for specific susceptible gram-negative organisms. 1

Spectrum of Activity Against Gram-Negative Bacteria

Ampicillin demonstrates activity against select gram-negative organisms:

• Susceptible gram-negative organisms:

  • Haemophilus influenzae
  • Neisseria gonorrhoeae and N. meningitidis
  • Proteus mirabilis
  • Many strains of Salmonella (including S. typhosa)
  • Shigella
  • Some strains of Escherichia coli 1

• Gram-negative organisms typically resistant to ampicillin:

  • Penicillinase-producing strains of E. coli
  • Pseudomonas aeruginosa
  • Proteus vulgaris
  • Klebsiella pneumoniae
  • Enterobacter aerogenes 1

Clinical Applications for Gram-Negative Infections

Effective Uses

• HACEK group infections: Ampicillin plus gentamicin is recommended as an alternative to ceftriaxone for infective endocarditis caused by HACEK organisms (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella) 2

• Specific pediatric infections: Ampicillin is recommended for:

  • Febrile infants 8-60 days old with urinary tract infections (combined with gentamicin or ceftazidime) 2
  • Bacterial meningitis in infants (combined with ceftazidime) 2

Limitations

• Beta-lactamase production: Ampicillin is inactivated by penicillinase (beta-lactamase), making it ineffective against many gram-negative bacteria that produce these enzymes 1

• Enterobacteriaceae infections: Third-generation cephalosporins or carbapenems are preferred over ampicillin for most Enterobacteriaceae infections 2

• Acinetobacter infections: While ampicillin alone is not effective, ampicillin-sulbactam may be used for Acinetobacter baumannii infections with MIC ≤4 mg/L 2

Combination Therapy for Enhanced Gram-Negative Coverage

Ampicillin with Beta-Lactamase Inhibitors

• Ampicillin-sulbactam: Significantly expands gram-negative coverage to include:
  • Some beta-lactamase-producing E. coli
  • Acinetobacter baumannii (sulbactam has intrinsic activity) 2, 3

Ampicillin with Aminoglycosides

• Synergistic effect: Combining ampicillin with gentamicin provides synergistic activity against:
  • HACEK organisms 2
  • Enterococcal species 2
  • Some resistant gram-negative bacteria 4

Current Recommendations for Gram-Negative Infections

1. For susceptible isolates only: Use ampicillin only when susceptibility is confirmed by culture and sensitivity testing 1

2. For mixed infections: Ampicillin should be combined with agents that provide broader gram-negative coverage when treating polymicrobial infections 5

3. For resistant gram-negative infections: Consider alternative agents:

   • Carbapenems for 3rd-generation cephalosporin-resistant Enterobacteriaceae 2
   • Ceftriaxone or other third-generation cephalosporins for most gram-negative infections 2

Practical Considerations

• Susceptibility testing: Always obtain cultures and susceptibility testing before using ampicillin for gram-negative infections 1

• Resistance patterns: Local antibiograms should guide empiric therapy decisions, as resistance patterns vary geographically 2

• Treatment duration: For uncomplicated gram-negative bacteremia, 7 days of appropriate antibiotic therapy may be sufficient once clinical stability is achieved 6

In summary, ampicillin has activity against specific gram-negative bacteria but should not be used empirically for most gram-negative infections without confirmed susceptibility due to widespread resistance. Combination therapy with beta-lactamase inhibitors or aminoglycosides significantly expands its gram-negative spectrum.