Why are penicillins (antibiotics) used to treat Pasteurella (Gram-negative bacteria) infections?

Treatment of Pasteurella with Penicillins Despite Being Gram-Negative

Penicillins are the treatment of choice for Pasteurella multocida infections despite its Gram-negative status because of exceptional susceptibility patterns and clinical efficacy demonstrated in practice guidelines. 1

Why Penicillins Work Against This Gram-Negative Organism

While most Gram-negative bacteria are resistant to penicillins due to their outer membrane structure and beta-lactamase production, Pasteurella multocida represents an important exception:

1. Natural Susceptibility: P. multocida demonstrates exceptional susceptibility to penicillin, with very low MICs (≤0.06 μg/mL) 2

2. Rare Beta-Lactamase Production: Unlike many Gram-negative organisms, P. multocida rarely produces beta-lactamases that would inactivate penicillins 2

3. FDA-Approved Indication: The FDA specifically lists Pasteurella infections including bacteremia and meningitis as approved indications for penicillin G 3

Clinical Evidence Supporting Penicillin Use

The Infectious Diseases Society of America (IDSA) practice guidelines for skin and soft tissue infections explicitly recommend:

• For animal bites where Pasteurella is common: "Patients not allergic to penicillin should receive treatment with oral amoxicillin-clavulanate or with intravenous ampicillin-sulbactam or ertapenem (B-II), because agents such as dicloxacillin, cephalexin, erythromycin, and clindamycin have poor activity against Pasteurella multocida." 1

• This recommendation carries a B-II evidence rating, indicating moderate evidence from well-designed clinical trials without randomization, cohort studies, or case-controlled analytic studies 1

Alternative Treatment Options

For patients with penicillin allergies, the guidelines recommend:

• Mild Penicillin Allergy: Cefoxitin or carbapenem antibiotics may be used parenterally 1

• Severe Penicillin Allergy: Oral or intravenous doxycycline, trimethoprim-sulfamethoxazole, or a fluoroquinolone plus clindamycin 1

In vitro studies have shown that ciprofloxacin and trimethoprim-sulfamethoxazole also demonstrate excellent activity against Pasteurella isolates and could be considered as alternatives 4, 2

Clinical Considerations

• Rapid Treatment: Inflammation at the site of infection typically develops within the first day after injury (commonly animal bites), making prompt treatment essential 5

• Potential for Spread: While usually confined to skin and soft tissue, P. multocida infections can spread to other organs and cause severe systemic infections if not properly treated 5

• Duration of Therapy: For soft tissue infections, treatment typically continues for 7-10 days, though this may be extended for more serious infections 1

Common Pitfalls to Avoid

1. Assuming All Gram-Negatives Are Penicillin-Resistant: While this is generally true, P. multocida is a notable exception that clinicians must recognize

2. Using Narrow-Spectrum Anti-Staphylococcal Agents: Medications like dicloxacillin or cephalexin have poor activity against P. multocida despite being effective against many other skin infection pathogens 1

3. Inadequate Duration: Single-dose treatments have shown variable cure rates in animal studies, suggesting the need for complete treatment courses 6

4. Forgetting the Polymicrobial Nature: Animal bite wounds often contain multiple organisms, so coverage may need to include anaerobes and other potential pathogens 1

In conclusion, despite being a Gram-negative organism, Pasteurella multocida remains highly susceptible to penicillins, making them the first-line treatment option based on both clinical evidence and antimicrobial susceptibility patterns.