Product Name: ENC-ZONE 200

Type: Oral Liquid Solution - Antibiotic Combination

COMPOSITION

Each 1000 ml contains:

• Enrofloxacin (BP Vet) ...... 200 g (20% w/v, 200 mg/ml)
• Colistin Sulfate BP ...... 500 MIU (Million International Units)

DESCRIPTION

ENC-ZONE 200 is a highly concentrated, broad-spectrum antibiotic oral solution combining enrofloxacin (20%) and colistin sulfate for the treatment of bacterial infections in poultry. This ultra-concentrated formulation delivers twice the enrofloxacin concentration of standard products, allowing for reduced dosage volumes while maintaining therapeutic efficacy. The synergistic combination provides enhanced antibacterial activity against both gram-positive and gram-negative pathogens, making it a valuable tool in poultry health management

Enrofloxacin is a synthetic broad-spectrum antibiotic belonging to the fluoroquinolone group. It inhibits bacterial DNA gyrase (topoisomerase II), an enzyme critical for DNA replication, transcription, and repair, leading to rapid bacterial cell death

Colistin sulfate (polymyxin E) is a polypeptide antibiotic that acts as a surface-active agent, disrupting bacterial cell membrane integrity by interacting with phospholipids, leading to increased permeability and cell lysis

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

Synergistic Combination:

• Research confirms that the combination of enrofloxacin and colistin provides superior bactericidal activity compared to either agent alone, achieving a "1+1>2" synergistic effect
• Colistin disrupts the outer membrane, facilitating enrofloxacin entry into bacterial cells
• In experimental colibacillosis in broilers, the combination decreased mortality, increased feed consumption and body weight, and improved feed conversion ratio compared to single-agent therapy
• The combination is recommended over single-agent therapy to overcome resistance and achieve synergistic effects

INDICATIONS

ENC-ZONE 200 is indicated for the treatment and control of diseases caused by bacteria sensitive to enrofloxacin and colistin sulfate in poultry

Target Pathogens:

• Escherichia coli - including avian pathogenic E. coli (APEC) causing colibacillosis
• Salmonella spp. - including Salmonella Gallinarum (fowl typhoid) and Salmonella Pullorum (pullorum disease)
• Pasteurella multocida - causing fowl cholera
• Haemophilus paragallinarum - causing infectious coryza
• Mycoplasma spp. - Mycoplasma gallisepticum, Mycoplasma synoviae, Mycoplasma meleagridis
• Clostridium perfringens - causing necrotic enteritis
• Staphylococcus spp. and Streptococcus spp.
• Klebsiella spp., Proteus spp., Pseudomonas aeruginosa, Bordetella spp., Campylobacter spp.

Disease Conditions:

• Colibacillosis - airsacculitis, pericarditis, perihepatitis, septicemia
• Salmonellosis - fowl typhoid, pullorum disease, paratyphoid infections
• Chronic Respiratory Disease (CRD) - complicated by bacterial infections
• Necrotic Enteritis - Clostridium perfringens infection
• Fowl Cholera - Pasteurella multocida infection
• Infectious Coryza - Haemophilus paragallinarum infection
• Mycoplasmosis - M. gallisepticum and M. synoviae infections
• Secondary bacterial infections associated with viral diseases

PHARMACOKINETIC PROPERTIES

• Enrofloxacin absorption: Well and rapidly absorbed from the gastrointestinal tract, reaching peak concentrations in 1-3 hours. Widely distributed throughout the body, with concentrations in lungs, liver, kidneys, and bones 2-3 times higher than in blood
• Enrofloxacin elimination: Partially metabolized to ciprofloxacin. Excreted primarily in urine and bile
• Colistin absorption: Poorly absorbed from the gastrointestinal tract, with minimal systemic absorption. Exerts its primary bactericidal effect in the gastrointestinal tract
• Colistin elimination: Excreted almost completely in feces

DOSAGE & ADMINISTRATION

ENC-ZONE 200 is administered via drinking water. Due to its high concentration, careful calculation of dosage is recommended to avoid under- or over-dosing.

Recommended Dosage:

• Standard Treatment: 0.25 ml per liter of drinking water (equivalent to 1 ml per 4 liters) for 3-5 days
• Alternative Calculation: 0.05 ml per kg body weight per day (equivalent to 10 mg enrofloxacin per kg)
• Severe Infections (Salmonellosis, Chronic Diseases): 0.5 ml per liter of drinking water (1 ml per 2 liters) for 5-7 days
• Dosage Comparison: At 20% concentration, ENC-ZONE 200 requires only half the volume of 10% enrofloxacin products to deliver the same therapeutic dose

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 efficacy
• Do not use with bacteriostatic antibiotics (tetracyclines, macrolides, chloramphenicol) due to potential antagonism

EFFICACY DATA

Clinical Efficacy in Colibacillosis:

• A study conducted in Pakistan on experimentally induced colibacillosis in broilers found that combined use of enrofloxacin plus colistin significantly decreased mortality, increased cumulative feed consumption, increased mean body weight, and improved feed conversion ratio compared to single use of either antibiotic alone
• The combination is widely used by poultry farmers for treatment of E. coli infections, with surveys showing it is one of the most frequently prescribed antibiotic combinations

Impact on Breeding Roosters:

• Research indicates that enrofloxacin (10 mg/kg) and colistin (2.5 mg/kg) can induce a significant decrease in sperm volume, count, viability, and motility parameters in breeding roosters, with the highest impact observed on the third day of treatment. Some parameters improve after cessation of treatment
• Breeder operations should consider timing of antibiotic treatment relative to artificial insemination schedules

In Vitro Synergy:

• In vitro studies demonstrate that enrofloxacin and colistin work synergistically, with no antagonism observed
• The combination helps prevent the emergence of mutants with reduced susceptibility to fluoroquinolone antibiotics

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
• Colistin administration increases resistance to colistin itself, as well as to enrofloxacin and beta-lactams

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
• Consider alternative strategies such as phage therapy or probiotics (e.g., metaprobiotics like Probiocid-Ultra) which have been shown to decrease antimicrobial resistance genes and eliminate antimicrobial-resistant enterobacteria

DRUG INTERACTIONS

• Antagonistic: Do not use concurrently with bacteriostatic antibiotics (tetracyclines, macrolides, chloramphenicol, lincosamides) due to potential antagonistic effects
• Interactions: Avoid concurrent use with theophylline, polyether ionophores, nonsteroidal anti-inflammatory drugs, and magnesium/calcium supplements
• Nephrotoxicity: Avoid combination with other nephrotoxic drugs (aminoglycosides, cephalosporins)
• Synergistic: Colistin enhances the efficacy of enrofloxacin by disrupting bacterial cell membranes

CONTRAINDICATIONS & PRECAUTIONS

• Egg production: Do not use in laying hens producing eggs for human consumption. Not recommended for use in replacement chickens less than 2 weeks before the start of egg laying due to enrofloxacin accumulation in eggs
• Liver and kidney dysfunction: Do not use in animals with impaired hepatic or renal function
• Hypersensitivity: Do not use in animals with known hypersensitivity to fluoroquinolones or polymyxin antibiotics
• Young birds: Use with caution in very young chicks; consult veterinary guidance
• Breeding stock: Use with caution in breeding roosters as studies have shown temporary negative effects on sperm parameters
• Keep out of reach of children
• Store in a cool, dry place away from direct sunlight
• Shake well before use
• Use within 28 days after first opening

ADVERSE REACTIONS

• In animals with hypersensitivity: convulsions, tremor, vomiting, anorexia, hemolytic anemia may occur
• In case of overdose: excitation followed by apathy, rapid breathing (polypnea), and rapid heartbeat may occur
• If adverse reactions occur, discontinue use and consult a veterinarian

WITHDRAWAL PERIOD

• Meat (Poultry): 3-11 days depending on regulatory jurisdiction. Typical withdrawal: 8-11 days. Consult local regulations
• 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, Pigeons, Quail)

Pack Sizes: 1 Liter HDPE bottle

PRODUCT SUMMARY
ENC-ZONE 200 Liquid Antibiotic Enrofloxacin (BP Vet) 200g, Colistin Sulphate BP 500MIU per 1000ml Poultry 1 Liter

FOR VETERINARY USE ONLY