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Penicillin G, also called benzylpenicillin, is a prescription antibiotic used in horses under veterinary direction for select bacterial infections. It has long been used in equine practice, but its value depends on choosing the right formulation, route, and treatment plan for the individual horse.
Penicillin G can be highly useful, but it must be chosen carefully. It does not work against viruses, fungi, mycoplasma, parasites, or many gram-negative bacteria. It also does not work against bacteria that produce certain enzymes that inactivate penicillin. Culture and susceptibility testing are important whenever possible. [1][2]
Safe use requires attention to possible side effects, injection-related reactions, antibiotic resistance, and competition rules, especially when procaine penicillin G is used. Veterinary oversight helps confirm whether Penicillin G is appropriate and ensures treatment supports the horse’s health without creating unnecessary risk.
Continue reading to learn how Penicillin G works in horses, when veterinarians may prescribe it, how different formulations are administered, and what owners should know about safety, drug interactions, and regulatory considerations.
Penicillin G for Horses
Penicillin G, also known as benzylpenicillin, is a naturally derived beta-lactam antibiotic and the original form from which many other penicillin drugs were developed. It kills susceptible bacteria by interfering with the formation of their protective cell wall, causing actively growing bacteria to rupture and die. [1]
Penicillin G is available in several injectable formulations because the drug is combined with different salts or compounds that affect how quickly it is absorbed and how long it remains active.
Aqueous sodium or potassium salts enter the bloodstream rapidly and produce higher blood concentrations over a shorter period. Procaine and benzathine formulations are absorbed more gradually from the injection site, extending the duration of exposure. [1][3]
Procaine penicillin G is commonly used when a longer-acting injectable formulation is needed. Benzathine-containing products are absorbed even more slowly and may remain detectable for longer, but they often produce blood concentrations that are too low for many infections. Their use is therefore generally limited to bacteria that are highly sensitive to penicillin G. [1][3]
Available Forms
Penicillin G is approved for equine veterinary use as an injectable formulation. It is available in several salt or depot forms. [1] A depot form is formulated to remain at the injection site and release the drug gradually, extending the duration of effect compared to faster-acting aqueous forms.
- Penicillin G sodium: an aqueous form used for injection after reconstitution
- Penicillin G potassium: an aqueous form used for injection after reconstitution
- Penicillin G procaine: a depot injectable form that releases penicillin G more slowly after intramuscular injection
- Penicillin G benzathine: a longer-acting depot form that produces lower, prolonged concentrations
- Penicillin G procaine / benzathine combinations: mixed depot products available in some jurisdictions
Brand and other names for Penicillin G include: [1]
- Benzylpenicillin
- Crystalline penicillin G
- Aqueous penicillin G
- Procaine penicillin G
- Benzathine penicillin G
- Pfizerpen®
- Bicillin L-A®
- Bicillin C-R®
- Permapen®
- Depocillin®
- Duplocillin®
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Drug Class: Beta-Lactam Antibiotics (“Natural Penicillins”)
Penicillin antibiotics are beta-lactam antimicrobials. The term beta-lactam refers to a chemical ring structure that is essential for the drug’s activity against bacteria. [1]
Natural penicillins include Penicillin G and Penicillin V. Penicillin G is generally preferred for injectable use, while Penicillin V is more acid-stable for oral use in some species. In adult horses, however, oral penicillin absorption is limited and oral natural penicillins are not typically used for systemic treatment of infections. [1][2]
Other beta-lactam antibiotics used in veterinary medicine include: [1]
- Ampicillin
- Amoxicillin
- Ceftiofur
- Cephalexin
- Ticarcillin
- Piperacillin
Mechanism of Action
Penicillin G is bactericidal, meaning it kills susceptible bacteria rather than only slowing their growth. It works best against actively multiplying bacteria. [1]
Unlike animal cells, bacteria have a protective cell wall. Penicillin G binds to bacterial enzymes called penicillin-binding proteins, which help build and create structural support for the cell wall. When these enzymes are blocked, the affected bacteria cannot maintain a stable cell wall and may rupture as they grow and divide. [1]
Penicillin G is not effective against organisms that lack the target cell-wall structure, such as viruses, fungi, Mycoplasma, and Rickettsia parasites. It can also fail against bacteria that produce beta-lactamase enzymes, which break down the beta-lactam ring and inactivate the drug. [1]
After injection, Penicillin G distributes through many body tissues but has limited penetration into cerebrospinal fluid, joints, and milk unless inflammation is present. It is removed mainly by the kidneys, with a short elimination half-life for aqueous formulations in animals with normal renal function. [1][2]
Uses in Horses
Penicillin G is used in horses for bacterial infections when the organism is expected or proven to respond and when the drug can reach the infection site. Product approval and label claims vary by country and formulation. [1]
Some veterinary-labelled procaine Penicillin G products are approved for use in horses, while other routes, products, combinations, or specific clinical protocols may be off-label.
Antibiotic Spectrum
Penicillin G is mainly useful against certain gram-positive bacteria, some anaerobes, spirochetes, and some gram-negative cocci. It is not a broad-spectrum solution for every infection. [1]
Penicillin G may be effective against the following species: [1]
- Beta-hemolytic Streptococcus species
- Streptococcus equi
- Streptococcus zooepidemicus
- Many gram-positive anaerobes
- Some Clostridium species, excluding C. difficile
- Actinomyces species
- Some spirochetes
Penicillin G is usually not effective against: [1]
- Penicillinase-producing bacteria
- Many gram-negative aerobic or anaerobic bacilli
- Rickettsia parasites
- Mycobacteria
- Fungi
- Mycoplasma
- Viruses
On-Label Uses
On-label uses depend on the specific penicillin G product, formulation, route, and jurisdiction, so treatment decisions should always follow the product label and veterinary direction.
Examples of on-label uses for equine penicillin G include: [1][2][3]
- Streptococcal infections, including strangles
- Wounds and soft tissue infections where susceptible bacteria are confirmed
- Bacterial pneumonia
- Metritis (uterine infections)
Off-Label Uses
Off-label use, also called “extra-label” use, refers to prescribing a medication for a use that differs from the product label, such as a different indication, route, duration, or patient group. Off-label use is permitted under veterinary prescribing regulations based on the practitioner’s expertise and supporting research.
Penicillin G may be prescribed off-label in horses for: [1]
- Guttural pouch carrier treatment for strangles
- Severe systemic infections in combination with other therapies
Administration Routes
Penicillin G may be administered intravenously, intramuscularly, or by specialized local injection routes depending on the formulation and condition being treated. Injectable treatment should be directed by a veterinarian or trained veterinary staff. [1] The primary administration route in horses is intramuscular. [1]
Aqueous sodium or potassium penicillin G rapidly reaches peak blood concentrations but is cleared quickly. Procaine penicillin G is absorbed more slowly from the injection site and produces more prolonged blood concentrations.
Benzathine penicillin G produces prolonged but lower concentrations and may not be adequate in many cases unless the target bacteria is highly vulnerable. [1][3][4]
Oral Penicillin G is not appropriate for systemic therapy in horses. In one equine study, oral penicillin G had very low systemic availability and produced high concentrations in cecal fluid, which may increase risk of antimicrobial-associated colitis. [2]
Dosage
Dosing of penicillin G varies significantly depending on the horse’s age, condition, the formulation being considered, and the species of bacteria causing the infection.
Penicillin G formulations in North America are only approved for intramuscular use in horses. [1] Dosage is typically 6000 – 21 000 IU/kg of body weight intramuscularly twice daily until clinical signs resolve. The precise dose depends on the type of penicillin G salt found in the formulation. Injection sites should be rotated to reduce pain and swelling at the administration site. [1]
For strangles, treatment decisions depend on the stage and severity of disease. Antibiotics may be considered early when fever and lethargy are present, or when lymph node enlargement is accompanied by fever, appetite loss, or breathing difficulty. Horses with lymph node enlargement but otherwise normal attitude and appetite may not be treated with antibiotics. [1]
Specialized protocols, such as guttural pouch carrier treatment for S. equi, may combine systemic and topical penicillin G after endoscopic removal of visible inflammatory material. These procedures require veterinary diagnosis, equipment, and monitoring. [1]
Storage
Store penicillin G according to the manufacturer’s label for the specific formulation.
Penicillin G sodium and potassium powders for injection are generally stored at room temperature before reconstitution and protected from moisture.
After reconstitution, storage time depends on the product label and refrigeration. Procaine penicillin G and benzathine penicillin G injectable suspensions are commonly stored at 2 – 8°C (35 – 46°F) and protected from freezing. [1]
Safety Warnings & Precautions
Penicillin G should be used as part of a complete veterinary treatment plan. Antibiotics do not replace diagnosis, drainage, surgery, wound care, quarantine, supportive care, or biosecurity measures when those are needed.
Culture and susceptibility testing help confirm whether Penicillin G is likely to work against the bacteria involved. This is especially important for deep infections, recurrent infections, hospital-associated infections, and cases that do not respond as expected.
Monitoring
Horses receiving systemic antibiotics should be monitored for treatment response and side effects. A horse that worsens during treatment may have resistant bacteria, an infection site that needs drainage or surgery, a non-bacterial disease, poor drug penetration into the affected tissue, or a serious complication.
Monitoring during Penicillin G treatment may include: [1]
- Temperature, attitude, appetite, pain, and hydration
- Size, heat, pain, and drainage from infected wounds or abscesses
- Respiratory signs, lymph node swelling, or other disease-specific findings
- Manure consistency and signs of diarrhea or colitis
- Injection-site swelling, pain, or discharge
- Culture and susceptibility results when available
- Kidney values, electrolytes, or other bloodwork in sick or high-risk horses
Contact your veterinarian if the horse’s signs worsen, fail to improve, or return after treatment begins. Also seek veterinary guidance immediately for diarrhea, severe lethargy, colic signs, breathing difficulty, collapse, or suspected allergic reaction.
Antibiotic Resistance
Antibiotic resistance occurs when bacteria adapt in ways that make antibiotics less effective. This means an antibiotic that once controlled a bacterial infection may no longer work as expected. Resistant bacteria can survive treatment, multiply, and spread to other horses, animals, environments, and, in some cases, people.
This matters because resistant infections are harder to treat. They may require additional testing, longer treatment, different antibiotics, hospitalization, or more intensive veterinary care. In serious cases, resistance can limit the number of safe and effective treatment options available.
Antibiotic resistance can develop when antibiotics are used unnecessarily, given at the wrong dose, stopped too early, or used without confirming that the bacteria involved are likely to respond. This is why veterinarians use culture and susceptibility testing when appropriate and choose antibiotics based on the infection, the horse’s condition, and local resistance patterns.
Horse owners play an important role in preventing resistance. Never give leftover antibiotics, share medications between horses, change the dose, skip doses, or stop treatment early unless your veterinarian directs you to do so.
Completing the prescribed treatment plan and following veterinary instructions helps protect your horse, other horses, and the long-term effectiveness of important antibiotics.
Contraindications
Contraindications refer to circumstances where a drug should be avoided or used with caution.
Penicillin G should not be used in horses with known hypersensitivity to penicillins unless the veterinarian determines there is no safer alternative and emergency precautions are in place. Horses with a known allergy to other beta-lactam antibiotics, such as cephalosporins, should also be treated cautiously. [1]
Oral formulations of penicillin G are generally not used in horses due to poor absorption from the gastrointestinal tract and the potential impact on the hindgut microbiome. [1][2]
Use caution in horses with: [1]
- Kidney disease
- Electrolyte abnormalities
- Congestive heart failure
- Severe systemic illness
Penicillins cross the placenta and are excreted in milk at low concentrations. Use in pregnant or lactating mares should be based on veterinary risk-benefit assessment. [1]
Side Effects
Penicillins generally have a wide safety margin when used appropriately, but adverse reactions can occur. Hypersensitivity reactions are among the most important risks because they are not dose-dependent and may occur even when the medication is used correctly. [1]
Potential side effects and adverse reactions include: [1][4]
- Allergic or hypersensitivity reactions, including hives, swelling, fever, rash, or anaphylaxis
- Injection-site pain, swelling, inflammation, or abscess formation
- Diarrhea, colitis, or disruption of normal gut flora
- Reduced appetite or signs of gastrointestinal upset
- Behavioral or neurologic reactions after procaine penicillin G, including excitement, trembling, ataxia (incoordination), collapse, or seizure-like signs
- Blood cell changes such as eosinophilia, neutropenia, leukopenia, thrombocytopenia, or anemia
- Central nervous system effects with very high parenteral doses or prolonged use, especially when renal function is impaired
Adverse reactions to procaine penicillin G in horses have been reported and may involve procaine toxicosis, hypersensitivity, or accidental intravascular administration of a depot product. Because these reactions can be sudden and dramatic, injectable penicillin should be administered only as directed by a veterinarian. [4]
Acute Toxicity (Overdose)
Acute oral penicillin overdose is unlikely to cause severe systemic toxicity, but gastrointestinal upset and disruption of hindgut flora may occur. In horses, oral penicillin G is not recommended for systemic therapy because of poor blood absorption and high hindgut exposure. [1][2]
Overdose or inappropriate parenteral use may increase the risk of neurologic signs, electrolyte problems from sodium or potassium salts, injection-site complications, or allergic reactions. Very high doses of parenteral penicillins have caused central nervous system effects in people, especially with renal disease. [1]
If overdose, accidental access, severe diarrhea, collapse, seizure-like activity, or a sudden allergic reaction is suspected, move the horse to a quiet, safe area if possible and contact your veterinarian immediately. Do not give additional doses unless a veterinarian instructs you to do so.
Drug Interactions
Potential drug interactions with penicillin G include: [1]
- Aminoglycoside antibiotics: Penicillins can have synergistic antibacterial effects with aminoglycosides against some bacteria, but they should not be mixed directly in the same syringe, fluid bag, or sample because beta-lactams can inactivate aminoglycosides in vitro.
- Bacteriostatic antibiotics: Drugs such as chloramphenicol, erythromycin, and tetracyclines may interfere with penicillin activity in some acute infections because penicillins work best against actively growing bacteria.
- Probenecid: Can reduce renal tubular secretion of many penicillins, increasing serum concentrations and half-life.
- Methotrexate: Penicillins may reduce renal elimination of methotrexate, increasing toxicity risk.
- Other injectable drugs and fluids: Compatibility varies by product, concentration, pH, temperature, and diluent; never mix medications unless directed by a licensed veterinarian.
Penicillins may also affect some laboratory tests. They can cause false-positive urine glucose results in some cases, and beta-lactams may lower measured aminoglycoside concentrations if blood samples are stored before analysis. [1]
Regulatory Status & Legal Considerations
Penicillin G is a prescription antibiotic in many jurisdictions. Veterinary-labelled penicillin G products and approved uses vary by country, species, formulation, and route. Some procaine penicillin G products are labelled for use in horses, but not all formulations or clinical protocols are necessarily on-label. [1]
Antibiotic stewardship is an important legal and ethical responsibility. Penicillin G should not be used without veterinary assessment or simply because an infection is suspected. Inappropriate antibiotic use can contribute to resistance, treatment failure, and adverse effects.
Status in Competition
Under FEI rules, most ordinary antimicrobials are not prohibited simply because they are antibiotics. However, procaine is listed as a controlled medication because it is a local anesthetic, and procaine penicillin G products contain procaine. [5][6]
This means aqueous penicillin G sodium or potassium and procaine-containing penicillin G products should not be treated the same for competition planning. Procaine-containing products may create a positive test risk because of the procaine component, even when the medication was used therapeutically as an antibiotic. [4][5]
The FEI Detection Times list includes detection-time guidance for commonly used controlled medications, but detection times are not the same as withdrawal times. A withdrawal time must be determined by the treating veterinarian with an additional safety margin based on the horse, product, route, treatment schedule, timing, health status, and competition rules. [6][7]
Always check the current FEI Prohibited Substances List, the FEI detection-time list, and the rules for your specific federation before treating a competition horse. A horse requiring antibiotics may also be unfit to compete even if the antimicrobial itself is not listed as prohibited.
Frequently Asked Questions
Here are some frequently asked questions about Penicillin G use in horses:
Penicillin G is used in horses for selected bacterial infections when the bacteria are expected or confirmed to be susceptible. Veterinarians may consider it for some streptococcal infections, clostridial infections, wound or soft tissue infections, foal infections, and other cases where the drug can reach the infection site effectively. It is not appropriate for every infection and does not work against viruses, fungi, mycoplasma, parasites, or many gram-negative bacteria.
Penicillin G works in horses by interfering with bacterial cell-wall construction. Susceptible bacteria need a stable cell wall to survive, especially while they are growing and dividing. When Penicillin G blocks the enzymes involved in building that wall, the bacteria may rupture and die.
Penicillin G requires veterinary oversight in horses because the correct product, route, dose, duration, and monitoring plan depend on the infection and the individual horse. A veterinarian must determine whether the infection is likely to respond, whether culture and susceptibility testing are needed, and whether other treatment such as drainage, wound care, supportive care, quarantine, or surgery is also necessary. Giving Penicillin G without a veterinary diagnosis can delay proper treatment, increase side effect risk, and contribute to antimicrobial resistance.
Incorrect Penicillin G use can contribute to antibiotic resistance when bacteria survive exposure and adapt in ways that make treatment less effective. Resistance risk increases when antibiotics are used unnecessarily, given at the wrong dose, stopped too early, shared between horses, or used without confirming that the bacteria are likely to respond. Resistant infections can be harder to treat and may require additional testing, different antibiotics, hospitalization, or more intensive veterinary care.
Penicillin G is usually administered to horses by injection, with the route depending on the formulation and clinical situation. Available forms include aqueous sodium or potassium products, procaine penicillin G, benzathine penicillin G, and some depot combination products. Injectable treatment should be given only as directed by a veterinarian or trained veterinary staff because formulation errors, injection complications, and adverse reactions can be serious.
Oral Penicillin G is not appropriate for systemic treatment in horses. It has poor systemic availability after oral administration, meaning it may not reach useful blood concentrations for treating internal infections. Oral exposure can also produce high concentrations in the cecum, which may disrupt hindgut bacteria and increase the risk of antibiotic-associated diarrhea or colitis.
Penicillin G treats certain susceptible bacteria in horses, especially some gram-positive bacteria, some anaerobes, some spirochetes, and certain gram-negative cocci. It is often discussed for susceptible Streptococcus species and some Clostridium species, excluding organisms that are naturally resistant or produce enzymes that inactivate penicillin. It is not a broad-spectrum antibiotic and will not treat viruses, fungi, mycoplasma, rickettsial organisms, or many gram-negative bacteria.
Side effects of Penicillin G in horses can include allergic reactions, injection-site pain or swelling, diarrhea, colitis, reduced appetite, blood cell changes, and rare liver enzyme changes or neurologic effects. Hypersensitivity reactions are especially important because they can occur even when the medication is used correctly. Contact a veterinarian promptly if a horse develops hives, facial swelling, breathing difficulty, collapse, diarrhea, fever, or sudden changes after treatment.
Penicilins have a wide safety margin and are well-tolerated by most horses, but side effects can occur. Procaine penicillin G can cause sudden behavioral or neurologic reactions in some horses. Reported signs may include excitement, trembling, incoordination, collapse, or seizure-like activity, and these reactions may relate to procaine toxicosis, hypersensitivity, or accidental injection into a blood vessel. Because these events can be sudden and dramatic, procaine penicillin G should be handled and administered only under veterinary direction.
If your horse gets worse while taking Penicillin G, contact your veterinarian promptly. Do not change the dose or stop treatment on your own. Worsening signs may mean the bacteria are resistant, the infection needs drainage or surgery, the drug is not reaching the affected tissue, or the condition is not caused by bacteria. Seek urgent veterinary help for diarrhea, colic signs, severe lethargy, breathing difficulty, collapse, suspected allergic reaction, or sudden neurologic signs.
The full course of Penicillin G should be completed exactly as prescribed unless your veterinarian gives different instructions. Stopping antibiotics early can allow bacteria to survive, which may lead to relapse and increase the risk of antimicrobial resistance. If side effects occur or you are concerned about the treatment plan, call your veterinarian before making changes.
Long-term Penicillin G use in horses should only occur when a veterinarian determines it is necessary and appropriate. Prolonged or repeated antibiotic use can increase the risk of adverse effects, gut flora disruption, injection-site complications, antimicrobial resistance, and competition or residue concerns. Horses on extended treatment may need closer monitoring, follow-up exams, or laboratory testing depending on their condition.
Alternatives to Penicillin G depend on the bacteria involved, infection site, severity, culture results, resistance patterns, patient risk factors, and legal requirements. The best choice must be made by a veterinarian because using the wrong antibiotic can be ineffective and may increase resistance risk. Notify your veterinarian if your horse has a known hypersensitivity or history of adverse reactions to penicillins when consulting on a treatment plan.
Penicillin G use in competition horses depends on the formulation, governing body, timing, and current medication rules. Plain antimicrobial use is not automatically prohibited under FEI rules, but procaine in procaine penicillin G is a Controlled Medication because it is a local anesthetic. Competition horses treated with procaine-containing products need careful withdrawal planning with the treating veterinarian and current FEI or federation rules.
Summary
Penicillin G is a prescription antibiotic used in horses for selected bacterial infections when the organism is expected or proven to respond. Safe use depends on choosing the right formulation, route, dose, and treatment plan under veterinary supervision.
- Penicillin G kills susceptible bacteria by interfering with cell-wall construction
- It is mainly used against certain gram-positive bacteria, anaerobes, spirochetes, and gram-negative cocci
- It does not treat viruses, fungi, mycoplasma, parasites, or many gram-negative bacteria
- Injectable formulations differ in absorption, duration, and appropriate route of use
- Side effects can include allergic reactions, injection-site problems, diarrhea, colitis, and neurologic reactions
- Antibiotics should only be administered under veterinary direction according to the prescription label
- Plumb. D. C. Plumb's Veterinary Drug Handbook: Desk. John Wiley & Sons. 2018.
- Horspool. L. J. I. and McKellar. Q. A. Disposition of Penicillin g Sodium Following Intravenous and Oral Administration to Equidae. British Veterinary Journal. 1995.
- Love. D. N. et al. Serum Concentrations of Penicillin in the Horse after Administration of a Variety of Penicillin Preparations. Equine Veterinary Journal. 1983.
- Uboh. C. E. et al. Pharmacokinetics of Penicillin G Procaine versus Penicillin G Potassium and Procaine Hydrochloride in Horses. American Journal of Veterinary Research. 2000.
- Clean Sport for Horses - FEI Prohibited Substances List. FEI. 2025.
- 2026 Equine Prohibited Substances List. FEI. 2025.
- FEI List of Detection Times 2024. FEI. 2024.
