Penicillin G
**Penicillin G** (benzylpenicillin) is a narrow-spectrum, natural beta-lactam antibiotic derived from *Penicillium chrysogenum*. It is highly effective against most **Gram-positive aerobes** (e.g., *Streptococcus* spp., non-penicillinase-producing *Staphylococcus*), some Gram-negative bacteria (e.g., *Pasteurella*), and many **anaerobes** (e.g., *Clostridium* spp.). > **Clinical Pearl:** The salt form of Penicillin G dictates its route of administration and pharmacokinetic profile: * **Aqueous salts (Sodium or Potassium):** Formulated for IV or IM use. They provide rapid, high peak serum concentrations but have a very short half-life, requiring frequent dosing (e.g., q4-6h). * **Repository salts (Procaine and Benzathine):** Formulated as suspensions for **IM or SC use ONLY** (never IV). Procaine provides a depot effect lasting 12-24 hours, while Benzathine provides very low, prolonged concentrations lasting several days. Penicillin G is susceptible to degradation by beta-lactamase (penicillinase) enzymes produced by many *Staphylococci* and Gram-negative enteric bacteria.
Mechanism: Penicillin G is a **time-dependent bactericidal** antibiotic. * It covalently binds to **Penicillin-Binding Proteins (PBPs)** located on the inner membrane of the bacterial cell wall. * This binding โ **inhibits the transpeptidation enzyme** responsible for cross-linking peptidoglycan strands. * Failure of cell wall synthesis โ activation of autolytic enzymes within the cell wall โ **osmotic lysis** and bacterial death. Because it targets cell wall synthesis, it is most effective against actively dividing bacteria.
Dosing by species
- Soft tissue, systemic infections ยท 40,000 Units/kg ยท PO ยท q6-8h ยท for as long as necessary ยท Penicillin G potassium
- Soft tissue infections ยท 20,000 Units/kg ยท IM, SC ยท q12h ยท for as long as necessary ยท Penicillin G procaine
- Orthopedic infections ยท 20,000-40,000 Units/kg ยท IM ยท q8h ยท for as long as necessary ยท Penicillin G procaine
- Resistant organisms (Actinomyces) ยท 50,000-100,000 Units/kg ยท IM, SC ยท q12h ยท for as long as necessary ยท Penicillin G procaine
- Susceptible infections ยท 50,000 Units/kg ยท IM ยท q5 days ยท Penicillin G benzathine
- Susceptible infections ยท 20,000-40,000 Units/kg ยท IM ยท once a day to twice daily ยท Procaine Pen G
- Susceptible infections ยท 20,000 Units/kg ยท SC, IM or IV ยท q4h ยท Sodium or potassium Pen G
- Susceptible infections ยท 40,000 Units/kg ยท PO ยท three times daily ยท Sodium or potassium Pen G
- Susceptible infections ยท 25,000 Units/kg ยท IM or SC ยท once per day ยท Penicillin G procaine. For moderately susceptible bacteria give twice daily.
- Clostridial abomasitis and enteritis in calves ยท 10,000-20,000 Units/kg ยท PO ยท q12-24h ยท for 1-4 days ยท Procaine Penicillin G. Oral preferred to provide activity in intestinal lumen.
Routes of administration
Contraindications
- Known hypersensitivity to penicillins or cephalosporins
- Intravenous administration of Procaine or Benzathine suspension formulations
- Oral administration in horses and hindgut fermenters (rabbits, guinea pigs) due to risk of fatal dysbiosis (unless specifically indicated, e.g., calves with clostridial enteritis)
Adverse effects
- Hypersensitivity reactions (anaphylaxis, urticaria, rash)
- Gastrointestinal upset (anorexia, vomiting, diarrhea) with oral use
- Procaine toxicity (CNS excitement, seizures) in small birds and horses if inadvertently given IV
- Pain or tissue reaction at IM injection sites
Drug interactions
- Bacteriostatic Antibiotics (e.g., Tetracyclines, Macrolides) ยท May antagonize the bactericidal activity of penicillins, which require actively dividing cells to be effective.
- Aminoglycosides (e.g., Amikacin, Gentamicin) ยท In vivo synergy against certain bacteria; however, physically incompatible if mixed in the same syringe or IV line (inactivation of the aminoglycoside).
- Probenecid ยท Competitively inhibits renal tubular secretion of penicillins, significantly prolonging their half-life and increasing serum concentrations.
Monitoring
- Clinical efficacy (resolution of infection signs)
- Signs of toxicity or hypersensitivity (anaphylaxis, rash)
- Electrolytes (if using high doses of Na or K salts IV)
Overdose
Because penicillins usually have minimal toxicity associated with their use, monitoring for efficacy is usually all that is required unless toxic signs develop. > **Clinical Pearl:** Massive overdoses, particularly of aqueous salts given rapidly IV, can lead to neuromuscular hypersensitivity, seizures, or electrolyte imbalances (hyperkalemia with potassium salt, hypernatremia with sodium salt). Treatment is supportive.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.