Product Name: TRI-RID

Type: Oral Liquid Solution - Antibiotic with Mucolytic Agent

COMPOSITION

Each 100 ml contains:

• Enrofloxacin (as HCl) ...... 10 g (10% w/v, 100 mg/ml)
• Colistin Sulfate ...... 5 MIU (Million International Units)
• Bromhexine ...... 0.50 g (0.5% w/v, 5 mg/ml)

DESCRIPTION

TRI-RID is a unique triple-action oral solution that combines the synergistic antibacterial activity of enrofloxacin and colistin with the potent mucolytic action of bromhexine. This formulation is specifically designed for the comprehensive management of respiratory and gastrointestinal infections in poultry, addressing both the bacterial etiology of disease and the associated clinical signs of respiratory distress [citation:2].

Enrofloxacin is a synthetic broad-spectrum antibiotic belonging to the fluoroquinolone class, known for its rapid bactericidal action against a wide range of gram-negative and gram-positive bacteria as well as mycoplasmas [citation:2]. Colistin sulfate (polymyxin E) is a polypeptide antibiotic that increases bacterial cell membrane permeability, leading to cell death. The combination of enrofloxacin and colistin provides enhanced synergistic activity against major digestive and respiratory pathogens [citation:2][citation:3].

MECHANISM OF ACTION

Enrofloxacin:

• Inhibits bacterial DNA gyrase (topoisomerase II), preventing DNA supercoiling and replication
• Disrupts DNA transcription and repair processes
• Exhibits concentration-dependent bactericidal activity
• Partially metabolized in the body to ciprofloxacin, an active metabolite

Colistin Sulfate:

• Acts as a cationic surface-active agent, binding to lipopolysaccharides in the outer membrane of gram-negative bacteria
• Displaces divalent cations (Ca²⁺, Mg²⁺), destabilizing the cell membrane
• Increases membrane permeability, leading to leakage of cellular contents and cell death
• Poorly absorbed from the gastrointestinal tract, exerting its primary effect in the gut lumen

Bromhexine:

• Acts as a potent mucolytic agent, increasing the production of serous bronchial secretions
• Reduces the viscosity of mucus by depolymerizing mucopolysaccharides
• Enhances ciliary activity in the respiratory tract, facilitating clearance of infectious material
• Promotes expectoration and improves respiratory function in diseased birds [citation:2]

SYNERGISTIC COMBINATION

• Enrofloxacin and colistin together provide a "1+1>2" synergistic effect, enhancing bactericidal activity against both gram-negative and gram-positive bacteria [citation:2]
• Colistin disrupts the outer membrane, facilitating enrofloxacin entry into bacterial cells
• Bromhexine complements the antibacterial action by clearing respiratory secretions, allowing better penetration of antibiotics to infected tissues
• This triple-action formulation addresses both infection and its clinical manifestations

ANTIMICROBIAL SPECTRUM

TRI-RID is effective against a broad range of microorganisms [citation:2]:

Gram-Negative Bacteria:

• Escherichia coli - colibacillosis, airsacculitis, pericarditis, septicemia
• Salmonella spp. - fowl typhoid, pullorum disease, paratyphoid infections
• Pasteurella multocida - fowl cholera
• Haemophilus paragallinarum (Avibacterium paragallinarum) - infectious coryza
• Campylobacter spp.
• Klebsiella spp., Proteus spp., Bordetella avium

Gram-Positive Bacteria:

• Staphylococcus spp.
• Streptococcus spp.

Mycoplasma:

• Mycoplasma gallisepticum - chronic respiratory disease (CRD)
• Mycoplasma synoviae - infectious synovitis, respiratory disease [citation:2]

INDICATIONS

TRI-RID is indicated for the treatment of respiratory and gastrointestinal infections in poultry caused by enrofloxacin and colistin-sensitive bacteria [citation:2][citation:3].

Disease Conditions:

• Chronic Respiratory Disease (CRD) - mycoplasmosis caused by Mycoplasma gallisepticum
• Colibacillosis - E. coli infections, including airsacculitis, pericarditis, perihepatitis, and septicemia [citation:2]
• Salmonellosis - fowl typhoid, pullorum disease, paratyphoid infections
• Fowl Cholera - Pasteurella multocida infection
• Infectious Coryza - Haemophilus paragallinarum infection
• Necrotic Enteritis - Clostridium perfringens infection
• Mixed bacterial infections involving both respiratory and gastrointestinal tracts
• Secondary bacterial infections associated with viral diseases (Newcastle disease, Infectious Bronchitis) [citation:2]

PHARMACOKINETIC PROPERTIES

• Enrofloxacin: Rapidly and well absorbed after oral administration, reaching peak concentrations in 1-3 hours. Widely distributed throughout the body, with tissue levels in lungs, liver, kidneys, and bones 2-3 times higher than serum levels. Partially metabolized to ciprofloxacin. Excreted primarily in urine and bile.
• Colistin: Poorly absorbed from the gastrointestinal tract, exerting its primary bactericidal effect in the gut lumen. Excreted almost completely in feces.
• Bromhexine: Rapidly absorbed and distributed to respiratory tissues, where it exerts its mucolytic action. Enhances the penetration of antibiotics into bronchial secretions.

DOSAGE & ADMINISTRATION

TRI-RID is administered via drinking water. For optimal results, fresh solution should be prepared daily.

Recommended Dosage:

• Poultry (Broilers, Layers, Breeders, Turkeys): 0.5 - 1 ml per liter of drinking water
• Treatment Duration: 3-5 consecutive days. For severe or chronic respiratory infections, up to 7 days may be required
• Alternative Dosage (based on enrofloxacin): 10 mg enrofloxacin per kg body weight per day (equivalent to 0.1 ml per kg) [citation:2]

Administration Guidelines:

• Calculate total daily water consumption based on flock size, age, and environmental temperature
• Prepare fresh medicated water daily; discard any unused solution after 24 hours
• Ensure medicated water is the only source of drinking water during treatment
• For best results, administer over 4-8 hours; may withhold water for 1-2 hours before treatment to encourage rapid consumption
• Do not use water containing heavy mineral salts, as this may reduce absorption
• Do not use with bacteriostatic antibiotics (tetracyclines, macrolides, chloramphenicol) due to potential antagonism

EFFICACY DATA

Synergistic Antibacterial Activity:

• Research confirms that the combination of enrofloxacin and colistin provides superior bactericidal activity compared to either agent alone, achieving a synergistic effect against major poultry pathogens [citation:2]
• The combination is widely used by poultry farmers for treatment of E. coli and Salmonella infections, with surveys showing it is one of the most frequently prescribed antibiotic combinations [citation:2]

Role of Bromhexine:

• Bromhexine has been shown to enhance the penetration of antibiotics into bronchial secretions, improving therapeutic outcomes in respiratory infections [citation:2]
• The mucolytic action helps clear airway obstructions, facilitating breathing and recovery in affected birds
• Products containing bromhexine in combination with antibiotics are commonly used for respiratory disease management in poultry [citation:2][citation:3]

RESISTANCE CONSIDERATIONS

Growing Concern:

• Antimicrobial resistance is an increasing concern in poultry production. Studies show that enrofloxacin and colistin use can select for resistance not only to themselves but also to other antibiotic classes
• Research demonstrates that enrofloxacin administration increases antimicrobial resistance to enrofloxacin itself, as well as to beta-lactams, tetracycline, and colistin
• The combination of enrofloxacin and colistin is recommended over single-agent therapy to overcome resistance and achieve synergistic effects [citation:2]

Responsible Use Recommendations:

• Veterinary consultation and susceptibility testing are recommended where available
• Use combination therapy to reduce the risk of resistance development
• Adhere strictly to recommended dosages and treatment durations; avoid subtherapeutic dosing which promotes resistance
• Avoid use in healthy animals for prophylaxis
• Respect official withdrawal times to protect consumers from harmful antimicrobial residues

DRUG INTERACTIONS

• Antagonistic: Do not use concurrently with bacteriostatic antibiotics (tetracyclines, macrolides, chloramphenicol, lincosamides) due to potential antagonism
• Interactions: Avoid concurrent use with theophylline, polyether ionophores, nonsteroidal anti-inflammatory drugs, and magnesium/calcium supplements which may reduce absorption
• Nephrotoxicity: Avoid combination with other nephrotoxic drugs (aminoglycosides, cephalosporins)
• Synergistic: Colistin enhances the efficacy of enrofloxacin by disrupting bacterial cell membranes; bromhexine may enhance antibiotic penetration into respiratory tissues

CONTRAINDICATIONS & PRECAUTIONS

• Egg production: Do not use in laying hens producing eggs for human consumption. Do not administer to layer replacement birds within 14 days of coming into lay
• Young birds: Use with caution in very young chicks; fluoroquinolones may cause articular cartilage lesions in growing animals
• Liver and kidney dysfunction: Use with caution or avoid in animals with impaired hepatic or renal function
• Hypersensitivity: Do not use in animals with known hypersensitivity to fluoroquinolones, polymyxin antibiotics, or bromhexine
• Keep out of reach of children
• Store in a cool, dry place below 30°C, protected from direct sunlight
• Shake well before use
• Use within 28 days after first opening

ADVERSE REACTIONS

• In hypersensitive animals: convulsions, tremor, vomiting, anorexia, hemolytic anemia may occur
• Articular cartilage lesions in young animals with prolonged or high-dose use
• Digestive disturbances such as intestinal dysbiosis, mild diarrhea
• Bromhexine is generally well tolerated; rare gastrointestinal upset may occur
• In case of overdose: excitation followed by apathy, rapid breathing (polypnea), and rapid heartbeat
• If adverse reactions occur, discontinue use and consult a veterinarian

WITHDRAWAL PERIOD

• Meat (Poultry): 7 days
• Eggs: Not for use in laying hens producing eggs for human consumption
• Note: Withdrawal periods may vary by country; always follow local regulatory requirements

STORAGE

• Store in a cool, dry place below 30°C
• Protect from direct sunlight and freezing
• Keep container tightly closed when not in use
• Do not freeze

Target Species: Poultry (Broilers, Layers, Breeders, Turkeys, Ducks, Geese, Quail)

Pack Sizes: 1 Liter HDPE bottle

PRODUCT SUMMARY
TRI-RID Liquid Antibiotic Enrofloxacin as HCl 10g, Colistin Sulphate 5 MIU, Bromhexine 0.50g per 100ml Poultry 1 Liter

FOR VETERINARY USE ONLY