Penstrep-400 is one of the most widely used combination injectable antibiotics in farm animal practice. Its dual mechanism — penicillin G targeting Gram-positive bacteria at the cell wall while dihydrostreptomycin simultaneously attacks Gram-negative bacteria at the ribosome — provides broader coverage than either drug alone, making it a practical first-line choice when the causative organism has not been identified. This guide covers everything: how it works, correct dosing for every species, the critical sow abortion risk, the small herbivore penicillin toxicity warning, and how to interpret the unusual kidney withdrawal period.
What Is Penstrep-400?
Penstrep-400 is a sterile white suspension manufactured by Interchemie for intramuscular injection in cattle, calves, sheep, goats, and pigs. Each ml contains:
- Procaine penicillin G: 200,000 IU
- Dihydrostreptomycin sulphate: 200mg
The product comes in 100ml multi-dose vials. It is a suspension — vigorous shaking before each use is essential. If the bottle is not adequately mixed, the dihydrostreptomycin settles and the dose drawn will not contain the correct proportions of both antibiotics.
How Penstrep-400 Works: Two Bactericidal Mechanisms
Understanding the mechanisms of the two components explains both why the combination is effective and why certain drug combinations are contraindicated.
Procaine Penicillin G: Cell Wall Synthesis Inhibitor
Penicillin G (benzylpenicillin) kills bacteria by inhibiting transpeptidase enzymes — specifically penicillin-binding proteins (PBPs) — that cross-link the peptidoglycan strands forming the bacterial cell wall. Bacteria have high internal osmotic pressure. When cell wall synthesis is disrupted, the wall weakens and the bacterium literally bursts from osmotic pressure.
This mechanism has an important implication: penicillin is only effective against actively dividing bacteria. The drug targets the synthesis of new cell wall material, which only happens during bacterial cell division. If bacterial growth is halted (by a bacteriostatic antibiotic), penicillin loses its effectiveness. This is why concurrent use of tetracyclines, macrolides, chloramphenicol, and lincosamides is contraindicated — they stop bacterial growth, directly antagonising penicillin.
Procaine penicillin G is the depot form of penicillin — procaine is the salt that slows absorption from the injection site, extending therapeutic blood levels after a single IM injection rather than requiring IV administration.
Penicillin G is effective primarily against Gram-positive bacteria (Streptococcus, Clostridium, Corynebacterium, Listeria, Erysipelothrix) and has limited Gram-negative activity due to the outer membrane barrier in Gram-negative organisms. It has no activity against penicillinase-producing (beta-lactamase-positive) staphylococci.
Dihydrostreptomycin: 30S Ribosomal Inhibitor
Dihydrostreptomycin is an aminoglycoside antibiotic that kills bacteria by binding irreversibly to the 30S ribosomal subunit. This binding causes two problems for the bacterium: first, it prevents the 30S subunit from attaching correctly to mRNA; second, it causes misreading of the genetic code during translation, producing non-functional or toxic proteins. The result is bacterial cell death — aminoglycosides are bactericidal.
Dihydrostreptomycin covers primarily Gram-negative aerobic bacteria (E. coli, Pasteurella, Salmonella, Campylobacter, Klebsiella, Haemophilus) — exactly the spectrum that penicillin G misses. Together, the two drugs achieve comprehensive coverage.
An important synergy: penicillin G’s disruption of the bacterial cell wall increases membrane permeability, enhancing the uptake of dihydrostreptomycin into bacterial cells. The combination achieves greater killing than mathematical addition of individual activities would predict in some organisms.
What Conditions Does Penstrep-400 Treat?
The primary indications in cattle, calves, sheep, goats, and pigs are:
- Arthritis (joint-ill in calves and lambs; joint infections in adult animals)
- Mastitis (acute bacterial udder infections)
- Respiratory tract infections (pneumonia, bronchopneumonia including pasteurellosis, enzootic pneumonia)
- Gastrointestinal infections (neonatal scours/colibacillosis, enteritis)
- Urinary tract infections
- Erysipelas in pigs (Erysipelothrix rhusiopathiae — penicillin G is the drug of choice)
- Listeriosis (circling disease) in ruminants
- Clostridial infections (foot rot, blackleg)
- Secondary bacterial infections complicating viral disease (e.g., BVD, IBR)
Dosage by Species: Complete Guide
Administer by deep intramuscular injection once daily for 3 consecutive days. Shake the bottle vigorously before each use.
| Species | Dose | Duration | Max Volume per Injection Site |
|---|---|---|---|
| Cattle (adult) | 1ml per 20kg body weight | 3 days | 20ml |
| Calves | 1ml per 10kg body weight | 3 days | 5ml |
| Sheep | 1ml per 10kg body weight | 3 days | 5ml |
| Goats | 1ml per 10kg body weight | 3 days | 5ml |
| Pigs (swine) | 1ml per 10kg body weight | 3 days | 10ml |
Worked Examples for Common Livestock Weights
| Animal | Weight | Daily Dose | Injection Site Split Required? |
|---|---|---|---|
| Calf (neonatal scours) | 40 kg | 4ml | No — under 5ml site limit |
| Calf (growing) | 80 kg | 8ml | Yes — split into 2 × 4ml |
| Dairy cow | 500 kg | 25ml | Yes — split into 2 sites (12.5ml each) |
| Beef steer | 350 kg | 17.5ml | Yes — split into 2 sites |
| Lamb | 25 kg | 2.5ml | No |
| Adult sheep | 70 kg | 7ml | Yes — split into 2 sites |
| Sow | 200 kg | 20ml | Yes — 2 sites × 10ml |
| Growing pig | 60 kg | 6ml | No — under 10ml site limit |
How Many Doses from the 100ml Bottle?
| Animal | Weight | Daily Volume | Full 3-Day Courses from 100ml |
|---|---|---|---|
| Calf | 50kg | 5ml | ~6 courses |
| Lamb/sheep | 60kg | 6ml | ~5 courses |
| Pig | 100kg | 10ml | ~3 courses |
| Cow | 500kg | 25ml | 1 full course + 25ml remaining |
Withdrawal Periods — And Why Kidney Takes So Long
| Tissue | Withdrawal |
|---|---|
| Meat and offal (except kidney) | 21 days |
| Kidney | 45 days |
| Milk (dairy cattle) | 3 days (72 hours) |
The kidney withdrawal is more than twice the meat withdrawal. This is because dihydrostreptomycin, like all aminoglycosides, selectively accumulates in renal proximal tubular cells where it binds to intracellular structures. While plasma and muscle concentrations fall within 3 weeks, the renal tubular cells retain dihydrostreptomycin at detectable concentrations for considerably longer. Animals treated with Penstrep-400 must not enter the food chain as kidney products for 45 days from the last treatment.
Critical Safety Warnings
⚠️ Sow Abortion Risk
Therapeutic doses of procaine penicillin G can cause abortion in pregnant sows. Procaine — the carrier molecule that extends penicillin absorption — has uterotonic properties in pigs, stimulating uterine contractions. This effect is not seen consistently in cattle and sheep. Do not use Penstrep-400 in pregnant sows unless the clinical benefit to the sow clearly outweighs the risk under specific veterinary assessment. If treatment is essential in late pregnancy, consider whether alternative antibiotics without uterotonic risk are appropriate.
⚠️ NEVER Use in Rabbits, Guinea Pigs, Hamsters or Small Herbivores
This is a life-critical warning. Penicillin-class antibiotics cause fatal enterotoxaemia in rabbits, guinea pigs, hamsters, gerbils, chinchillas, and related species. Penicillins disrupt the balanced gut flora of these animals, triggering catastrophic overgrowth of Clostridium difficile and related toxin-producing organisms. The resulting toxin-mediated enterotoxaemia is rapidly fatal — often within 24–48 hours. A single therapeutic injection can kill a rabbit or guinea pig. Penstrep-400 is indicated only for cattle, calves, sheep, goats, and pigs.
⚠️ Aminoglycoside Ototoxicity and Nephrotoxicity
Dihydrostreptomycin carries the same ototoxicity (permanent hearing damage and vestibular dysfunction) and nephrotoxicity risks as other aminoglycosides. The kidneys are both the primary excretion route and the organ most at risk from accumulation. Risk factors that increase toxicity include:
- Pre-existing renal impairment
- Dehydration (reduces drug clearance)
- Overdosage
- Treatment duration beyond 3 days
- Concurrent use of other nephrotoxic drugs
Always use the correct dose based on accurate bodyweight and do not extend treatment beyond the recommended 3-day course without veterinary reassessment.
Drug Interactions — Why Certain Combinations Are Forbidden
Concurrent use of the following is contraindicated with Penstrep-400:
- Tetracyclines (oxytetracycline, doxycycline): bacteriostatic; halt bacterial cell growth, blocking penicillin’s mechanism
- Macrolides (tylosin, tulathromycin, tilmicosin, erythromycin): bacteriostatic at clinical doses; antagonise penicillin G
- Chloramphenicol / florfenicol: bacteriostatic; antagonise penicillin G
- Lincosamides (lincomycin): bacteriostatic; antagonise penicillin G
The underlying principle: penicillin G kills bacteria only during active cell division. Bacteriostatic drugs suspend bacterial growth. When a bacteriostatic drug is given simultaneously with penicillin G, the bacteria stop dividing — and penicillin has no target to act on. This is not merely a minor interaction; in some studies, the combination is no more effective than the bacteriostatic drug alone and may be less effective than penicillin alone.
Where to Buy Penstrep-400
You can order Penstrep-400 (Procaine Penicillin G + Dihydrostreptomycin) 100ml from PetShopBoss.com with free worldwide shipping.
Related: Shotapen LA 100ml (Long-Acting Benzylpenicillin + Dihydrostreptomycin) | Oxytetracycline 10% Injectable 100ml | Baytril 5% Enrofloxacin Injectable 100ml

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