Product Name: XCELSIO

Type: Feed Additive Powder - Bacteriophage Preparation

COMPOSITION

Contains a carefully selected cocktail of strictly virulent bacteriophages specifically targeting:

• Salmonella spp.
• Escherichia coli (including avian pathogenic E. coli, APEC)
• Staphylococcus aureus
• Clostridium perfringens
• Bacillus subtilis

Note: Quantitative concentration (PFU/g) available upon request; contact manufacturer for specific certificate of analysis.

DESCRIPTION

Bacteriophage

XCELSIO is an innovative, broad-spectrum bacteriophage-based feed additive designed to provide targeted control of major pathogenic bacteria in livestock and poultry production systems. Bacteriophages are naturally occurring viruses that specifically infect and kill bacteria, offering a precise and effective alternative to conventional antimicrobials .

Unlike antibiotics that broadly impact both harmful and beneficial bacteria, bacteriophages have a very narrow host range, targeting only specific bacterial species or strains while leaving the beneficial microbiota of the animal completely unharmed . This selectivity makes XCELSIO an ideal component of antibiotic-free production programs and integrated disease management strategies .

The product contains a cocktail of strictly virulent (lytic) bacteriophages, meaning they actively kill their target bacteria through a natural life cycle that results in bacterial cell lysis (destruction) . This multi-phage cocktail approach ensures broad coverage against different strains of the target pathogens and helps prevent the development of phage-resistant bacteria .

MECHANISM OF ACTION

XCELSIO works through the natural lytic cycle of bacteriophages:

1. Recognition and Attachment:

• Bacteriophages recognize and bind to specific receptors on the surface of their target bacteria
• This specificity ensures that only pathogenic bacteria are targeted, leaving beneficial microbes untouched

2. Infection and Replication:

• The phage injects its genetic material into the bacterial cell
• The phage hijacks the bacterium's cellular machinery to produce multiple copies of new phages

3. Bacterial Lysis:

• Newly assembled phages produce enzymes (lysins) that break down the bacterial cell wall
• The bacterial cell bursts (lyses), releasing the new phages to seek out and infect remaining target bacteria
• This self-amplifying characteristic means that phages continue to multiply as long as target bacteria are present

4. Biofilm Disruption:

• Bacteriophages can penetrate and disrupt bacterial biofilms, which are protective matrices that make bacteria more resistant to conventional disinfectants and antibiotics
• Studies show phages can reduce biofilm formation by over 90% and remove existing mature biofilms

TARGET PATHOGENS AND INDICATIONS

XCELSIO is specifically formulated to target five major pathogenic bacteria affecting livestock and poultry production:

1. Salmonella spp.:

• Causes salmonellosis, a major foodborne disease affecting both animals and humans
• In poultry, Salmonella infections lead to reduced performance, mortality, and food safety concerns
• In cattle, Salmonella Dublin causes severe illness and persistent herd infections
• Bacteriophage treatment significantly reduces Salmonella colonization in the cecum and spleen
• Phages can reduce Salmonella on chicken meat by more than 92% (1.15 log10 CFU/mL reduction)

2. Escherichia coli (including APEC):

• Avian pathogenic E. coli (APEC) causes colibacillosis, a leading cause of mortality and morbidity in poultry worldwide
• In livestock, E. coli infections can cause diarrhea, septicemia, and reduced performance
• Bacteriophages effectively target E. coli without affecting beneficial gut flora

3. Staphylococcus aureus:

• Causes mastitis in dairy cattle, skin infections, and systemic disease
• In poultry, can cause arthritis, bumblefoot, and septicemia
• Important zoonotic pathogen with public health implications

4. Clostridium perfringens:

• Causes necrotic enteritis in poultry, a significant disease costing the industry over $6 billion annually
• In livestock, causes enterotoxemia, gas gangrene, and sudden death
• Bacteriophage supplementation significantly improves feed intake, body weight gain, and feed conversion ratio in birds challenged with C. perfringens
• Phage treatment reduces intestinal lesion scores and mortality in necrotic enteritis models

5. Bacillus subtilis:

• While often used as a probiotic, certain strains can cause opportunistic infections in immunocompromised animals
• The inclusion of B. subtilis-targeting phages allows for population management when needed
• Combined B. subtilis and bacteriophage supplementation in geese significantly enhanced body weight and feed efficiency

XCELSIO is indicated for:

• Prevention and control of bacterial infections in poultry (broilers, layers, breeders, turkeys, ducks, geese) and livestock (cattle, swine, sheep, goats)
• Reduction of foodborne pathogens to improve food safety and reduce carcass contamination at processing
• Support for antibiotic-free production systems as a natural alternative to antimicrobial growth promoters
• Management of necrotic enteritis in poultry, reducing mortality and improving performance
• Reduction of Salmonella and E. coli shedding to improve flock health and reduce environmental contamination
• Biofilm control in the gastrointestinal tract and production environment

KEY ADVANTAGES OF BACTERIOPHAGE TECHNOLOGY

• Targeted specificity: Kills only pathogenic bacteria without disrupting beneficial gut microbiota
• No antibiotic resistance: Different mechanism of action means no cross-resistance with antibiotics; phages can kill multidrug-resistant bacteria
• Self-amplifying: Phages multiply at the site of infection as long as target bacteria are present, providing sustained activity
• Biofilm penetration: Effectively penetrates and disrupts bacterial biofilms that protect pathogens from conventional treatments
• No withdrawal period: Safe for animals, humans, and the environment; leaves no residues in meat, milk, or eggs
• Compatible with probiotics: Can be used alongside beneficial bacteria like Bacillus subtilis for synergistic effects
• Environmentally sustainable: Reduces environmental contamination with antibiotics and resistant bacteria

DOSAGE & ADMINISTRATION

XCELSIO is administered by mixing thoroughly into the complete feed. For optimal results, continuous feeding is recommended, particularly during periods of high disease challenge.

Recommended Inclusion Rates:

• Poultry (Broilers, Layers, Breeders, Turkeys, Ducks, Geese): 0.5 - 2 kg per ton of feed
• Swine (Piglets, Growers, Sows): 0.5 - 1.5 kg per ton of feed
• Cattle (Calves, Dairy, Beef): 10 - 50 g per animal per day, or 0.5 - 1 kg per ton of concentrate feed
• Sheep & Goats: 5 - 10 g per animal per day, or 0.5 - 1 kg per ton of feed

Dosing Considerations Based on Challenge Level:

• Preventive (low challenge): Lower end of dosage range, continuous use
• Meta-phylactic (moderate challenge): Mid-range dosage, continuous use during risk periods
• Therapeutic (high challenge/outbreak): Upper end of dosage range, may be combined with water-soluble formulation (XCELSIO wsp) for rapid response

Administration Guidelines:

• Ensure uniform mixing in feed using a gradual dilution process (premix with small amount of feed before incorporating into final mix)
• For optimal results, use continuously throughout the production cycle, particularly during high-stress periods (weaning, transport, peak production)
• Stable during feed processing including pelleting at temperatures below 70°C
• Compatible with most feed ingredients, mineral premises, vitamins, and other feed additives including probiotics and organic acids
• Research shows phages remain viable when combined with common preservatives like acetate, lactate, benzoate, and propionate

EFFICACY DATA

Against Clostridium perfringens (Necrotic Enteritis):

• Bacteriophage supplementation significantly improved feed intake, body weight gain, and feed conversion ratio in broilers challenged with C. perfringens (P < 0.05)
• Intestinal lesion scores and mortality were effectively reduced with phage treatment
• Jejunal histomorphology and hematological indices showed notable restoration in phage-treated birds

Against Salmonella:

• Low-dose phage treatment (10⁵ PFU/mL) reduced splenic Salmonella colonization in chickens and improved albumin-to-globulin ratios
• Phage treatment enriched beneficial taxa like Lactobacillus crispatus and Blautia coccoides
• On chicken meat, phage treatment reduced Salmonella Enteritidis by 1.15 log10 CFU/mL (>92% reduction) after 12 hours at 4°C
• Phages inhibited more than 70-91% of Salmonella biofilm formation and removed up to 96% of mature biofilms

Against E. coli:

• Bacteriophage products have demonstrated effectiveness in controlling colibacillosis in poultry, showing lower mortality rates compared to untreated groups

Combined with Bacillus subtilis:

• Combined supplementation of B. subtilis and bacteriophages in geese significantly enhanced body weight and feed efficiency
• The combination treatment reduced serum and aquatic endotoxin levels while suppressing pathogenic bacteria (E. coli and Salmonella) in water systems
• Intestinal morphology improved with increased villus height and optimized villus-to-crypt ratios

CONTRAINDICATIONS & PRECAUTIONS

• No known contraindications when used as directed at recommended inclusion rates
• Not for direct administration to animals; must be thoroughly mixed with feed
• Ensure adequate mixing to prevent segregation during transport and handling
• Do not exceed recommended dosage without veterinary consultation
• Keep out of reach of children
• Store in a cool, dry place away from direct sunlight and moisture
• Protect from temperatures exceeding 40°C (104°F) for extended periods
• Use within 24 months of manufacturing date when stored properly
• Wear appropriate dust mask during handling to avoid inhalation of fine particles
• Generally Recognized as Safe (GRAS) for use in animal feed; safe for animals, humans, and the environment

WITHDRAWAL PERIOD

• Zero days for meat, milk, and eggs
• Bacteriophages are naturally occurring and leave no residues in animal products

STORAGE

• Store in original unopened packaging in a cool, dry place
• Keep at temperature below 25°C (77°F) for optimal stability
• Protect from humidity, moisture, and direct sunlight
• Close tightly after each use to prevent moisture absorption
• Do not store near chemicals, pesticides, or fertilizers
• Avoid exposure to high temperatures or freeze-thaw cycles

Target Species: Poultry (broilers, layers, breeders, turkeys, ducks, geese), Swine (piglets, growers, sows), Cattle (dairy, beef, calves), Sheep, Goats

Pack Sizes: 1 Kg, 20 Kg

PRODUCT SUMMARY
XCELSIO Feed Additive Powder Bacteriophage Bacteriophages targeting Salmonella spp., E. coli, Staphylococcus aureus, Clostridium perfringens, Bacillus subtilis Poultry 1 Kg,20Kg

FOR VETERINARY USE ONLY