Penicillin G (benzylpenicillin) is one of the most important injectable antibiotics in rabbit medicine. It is the drug of choice for rabbit syphilis (treponematosis, caused by Treponema cuniculi) and is also used to treat pasteurellosis, abscesses, and other susceptible bacterial infections. The critical safety point that cannot be overstated is that penicillin G must ONLY be administered by injection in rabbits — oral penicillins of any type are potentially fatal to rabbits because they destroy the essential bacterial flora in the cecum, leading to fatal enterotoxemia. This is a prescription medication that must be administered under veterinary supervision.
The Critical Rule: INJECTABLE ONLY
Oral penicillins kill rabbits. This includes amoxicillin tablets, amoxicillin/clavulanate (Clavamox), ampicillin capsules, and any other oral penicillin formulation. The reason is fundamental to rabbit physiology:
- Rabbits are hindgut fermenters that depend on a complex ecosystem of beneficial bacteria in the cecum
- Oral penicillins pass through the stomach and small intestine and reach the cecum in active form
- In the cecum, penicillins kill susceptible beneficial bacteria (primarily gram-positive organisms)
- This allows overgrowth of Clostridium spiroforme and other toxin-producing clostridia
- These clostridia produce iota toxin and other enterotoxins
- The result is acute, fatal enterotoxemia — often within 24 to 72 hours
Injectable penicillin G, by contrast, is absorbed from the injection site into the bloodstream and distributed to tissues without passing through the GI tract. It is then excreted primarily by the kidneys rather than in active form through the bile into the gut, making it safe at appropriate doses.
What Is Penicillin G Used For?
- Rabbit syphilis (treponematosis) — caused by Treponema cuniculi; the standard treatment and drug of choice
- Pasteurellosis — Pasteurella multocida infections (when susceptible), including upper respiratory disease, pneumonia, abscesses, and otitis
- Abscesses — subcutaneous and deep abscesses caused by susceptible organisms (adjunct to surgical debridement)
- Skin and soft tissue infections — bite wounds, cellulitis, and post-surgical infections
- Dental infections — tooth root abscesses and mandibular/maxillary osteomyelitis
How Does Penicillin G Work?
Penicillin G is a beta-lactam antibiotic that kills bacteria by inhibiting cell wall synthesis. It binds to penicillin-binding proteins (PBPs), preventing the cross-linking of peptidoglycan in the bacterial cell wall. Without a structurally intact cell wall, bacteria undergo osmotic lysis and die.
Penicillin G is bactericidal and is most effective against gram-positive bacteria, including Treponema cuniculi, many streptococci, and some staphylococci. It has limited activity against most gram-negative organisms, though it does retain activity against some Pasteurella multocida strains.
Dosage
Dosing must be determined by your rabbit veterinarian. Injectable penicillin G should be administered by a veterinarian or by an owner trained in injection technique.
| Formulation | Typical Dose | Route | Frequency |
|---|---|---|---|
| Penicillin G Procaine/Benzathine (Combi-Pen) | 42,000—84,000 IU/kg | SC (subcutaneous) | Every 48 hours |
| Penicillin G Procaine | 40,000—60,000 IU/kg | SC or IM | Every 24 hours |
| Penicillin G Sodium/Potassium (aqueous) | 20,000—60,000 IU/kg | SC, IM, or IV | Every 6—8 hours |
For rabbit syphilis: The standard protocol is penicillin G procaine/benzathine (Combi-Pen or Dual-Pen) at 42,000 to 84,000 IU/kg subcutaneously every 48 hours for a minimum of 3 injections (some protocols call for 14 days total or until lesions resolve plus additional injections). All in-contact rabbits should be treated simultaneously.
For pasteurellosis and abscesses: Long-term injectable penicillin therapy combined with surgical debridement is often necessary. Treatment courses of 4 to 8 weeks are common for deep infections.
Injection technique:
- Subcutaneous injection is given in the scruff of the neck or over the shoulders
- Rotate injection sites to reduce tissue irritation
- Warm the medication to room temperature before injection to reduce pain
- Use an appropriate needle gauge (25—27 gauge for most rabbits)
- Procaine penicillin formulations are thick and may require a slightly larger needle
Side Effects
When given by injection, side effects are generally mild:
- Pain or swelling at injection sites
- Mild decreased appetite for 12 to 24 hours after injection
- Soft stool (usually mild and transient)
Serious side effects:
- Anaphylaxis — rare but possible allergic reaction; signs include acute respiratory distress, collapse, and swelling
- Injection site abscess — if injection technique is not sterile
- GI disturbance — even injectable penicillin can occasionally affect cecal flora at very high doses; monitor droppings
- Procaine toxicity — procaine penicillin formulations contain procaine, a local anesthetic; excessive doses or inadvertent IV injection can cause CNS excitement followed by depression
Rabbit Syphilis (Treponematosis)
Rabbit syphilis deserves special mention as it is the primary indication for penicillin G:
- Caused by Treponema cuniculi (closely related to human Treponema pallidum but NOT zoonotic — rabbit syphilis cannot infect humans)
- Transmitted through direct contact, often venereal but also through nursing and close social contact
- Signs include crusty, ulcerated lesions around the nose, lips, eyelids, and genital/perineal area
- Lesions can be confused with myxomatosis, dermatophytosis, or other skin conditions
- Diagnosis is through dark-field microscopy, PCR, or serologic testing
- Penicillin G is curative with appropriate treatment duration
- All in-contact rabbits should be treated, even if asymptomatic
Drug Interactions
- Bacteriostatic antibiotics (chloramphenicol, tetracyclines) — may reduce the bactericidal activity of penicillin
- Aminoglycosides — synergistic effect (can be beneficial in serious infections, but do not mix in the same syringe)
- Probenecid — reduces renal excretion of penicillin, increasing blood levels
Monitoring
- Monitor droppings daily — any decrease in fecal pellet size or number, diarrhea, or cecal dysbiosis requires immediate veterinary attention
- Assess injection sites for swelling, heat, or abscess formation
- Monitor appetite and activity level
- For syphilis, monitor lesion resolution; complete healing may take 2 to 4 weeks after completing treatment
- Culture and sensitivity testing is valuable for pasteurellosis cases, as some Pasteurella strains are resistant to penicillin
Storage
Store penicillin G formulations in the refrigerator (2—8 degrees C / 36—46 degrees F) unless label specifies otherwise. Protect from freezing and light. Check expiration dates regularly. Multidose vials should be discarded 28 days after first puncture or at expiration, whichever comes first.
Frequently Asked Questions
My dog was prescribed amoxicillin — can I give some to my rabbit? Absolutely NOT. Oral amoxicillin is potentially fatal to rabbits. Never give any oral antibiotic to your rabbit without explicit veterinary instruction. Many antibiotics that are routine in dogs and cats are deadly to rabbits.
Can I learn to give injections at home? Many rabbit owners successfully learn to give subcutaneous injections at home after training from their veterinarian. This can reduce stress for both rabbit and owner during long treatment courses.
Is rabbit syphilis contagious to humans? No. Treponema cuniculi is specific to rabbits and cannot infect humans or other animal species.
Always consult your rabbit-savvy veterinarian before starting, stopping, or changing any medication. Rabbit pharmacology is unique and medications safe for other species may be fatal. This information is for educational purposes and does not replace professional veterinary advice.