Product Name: LC-ZONE

Type: Oral Water-Soluble Powder - Antibiotic Combination

COMPOSITION

Each gram contains:

• Lincomycin Hydrochloride USP ...... 100 mg
• Colistin Sulfate BP ...... 800,000 IU

DESCRIPTION

LC-ZONE is a broad-spectrum antibiotic combination powder containing lincomycin (a lincosamide antibiotic) and colistin (a polymyxin antibiotic). This synergistic combination provides enhanced antibacterial activity against both gram-positive and gram-negative pathogens, making it a valuable tool for the treatment of mixed bacterial infections in poultry

Lincomycin is a lincosamide antibiotic produced by Streptomyces lincolnensis that inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, interfering with peptidyl transferase activity. Colistin sulfate (polymyxin E) is a polypeptide antibiotic that acts as a surface-active agent, disrupting bacterial cell membrane integrity by interacting with phospholipids. The combination exhibits synergy against a wide range of pathogens, including Escherichia coli, Clostridium perfringens, Salmonella species, and Mycoplasma species

MECHANISM OF ACTION

Lincomycin:

• Inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit
• Interferes with the peptidyl transferase reaction, preventing peptide bond formation
• Active against gram-positive bacteria, anaerobic bacteria, and Mycoplasma species

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:

• Studies have demonstrated that the combination of lincomycin and colistin exhibits synergy against approximately 90% of tested isolates, with additive effects against the remaining isolates
• In vitro studies confirm synergy against Escherichia coli, with the MIC for colistin reduced by a factor of 2 in combination with lincomycin
• The combination is particularly effective against simultaneous infections caused by Mycoplasma gallisepticum and avian pathogenic E. coli (APEC)

ANTIMICROBIAL SPECTRUM

LC-ZONE is effective against a broad range of microorganisms:

Gram-Positive Bacteria:

• Clostridium perfringens - causative agent of necrotic enteritis
• Staphylococcus spp. - staphylococcosis
• Streptococcus spp. - streptococcal infections
• Other anaerobic gram-positive bacteria

Gram-Negative Bacteria:

• Escherichia coli - colibacillosis, coli-septicemia, airsacculitis
• Salmonella spp. - salmonellosis, fowl typhoid, pullorum disease
• Pasteurella multocida - fowl cholera
• Haemophilus paragallinarum - infectious coryza
• Klebsiella spp., Proteus spp., Pseudomonas aeruginosa

Mycoplasma:

• Mycoplasma gallisepticum - chronic respiratory disease (CRD)
• Mycoplasma synoviae - infectious synovitis, respiratory disease

INDICATIONS

LC-ZONE is indicated for the treatment and control of infections caused by lincomycin and colistin-sensitive bacteria in poultry

Disease Conditions:

• Necrotic Enteritis - caused by Clostridium perfringens, characterized by intestinal necrosis, diarrhea, and mortality
• Colibacillosis - E. coli infections including airsacculitis, pericarditis, perihepatitis, and septicemia
• Salmonellosis - fowl typhoid (Salmonella gallinarum), pullorum disease (Salmonella pullorum), and paratyphoid infections
• Chronic Respiratory Disease (CRD) - mycoplasmosis caused by Mycoplasma gallisepticum
• Fowl Cholera - Pasteurella multocida infection
• Infectious Coryza - Avibacterium paragallinarum infection
• Mixed bacterial infections involving both gram-positive and gram-negative pathogens
• Secondary bacterial infections associated with viral diseases

PHARMACOKINETIC PROPERTIES

• Lincomycin: Rapidly absorbed after oral administration; widely distributed throughout the body; achieves therapeutic concentrations in respiratory and intestinal tissues; partially metabolized in the liver; excreted primarily in urine and bile
• Colistin: Poorly absorbed from the gastrointestinal tract (minimal systemic bioavailability); exerts its primary bactericidal effect in the intestinal lumen; excreted almost completely in feces
• Advantage: The combination provides both systemic (lincomycin) and locally acting (colistin) antibacterial coverage, making it effective for mixed respiratory and gastrointestinal infections

DOSAGE & ADMINISTRATION

LC-ZONE is administered via drinking water. For optimal results, fresh medicated water should be prepared daily.

Recommended Dosage:

• Poultry (Broilers, Layers, Breeders): 1 g per liter of drinking water
• Alternative Dosage (body weight): 0.1 g per kg body weight (100 mg lincomycin + 800,000 IU colistin per kg body weight)
• Treatment Duration: 3-5 consecutive days. For chronic or severe infections, up to 7 days may be required

Administration Guidelines:

• Calculate total daily water consumption based on flock size, age, and environmental temperature
• Dissolve the required amount of LC-ZONE in a small volume of water, then add to the main drinking water tank
• For use in automatic water proportioners, prepare stock solution according to manufacturer specifications
• Prepare fresh medicated water daily; discard any unused solution after 24 hours
• Ensure medicated water is the sole 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 with bacteriostatic antibiotics (tetracyclines, macrolides, chloramphenicol) due to potential antagonism

EFFICACY AND SYNERGY DATA

Synergistic Activity:

• In vitro studies demonstrate that the combination of lincomycin and colistin exhibits synergy against approximately 90% of tested isolates, including Mycoplasma gallisepticum and avian pathogenic E. coli (APEC)
• The synergy allows for effective bacterial control at lower concentrations than either agent alone, reducing the risk of resistance development
• In vivo studies in chickens with simultaneous MG and APEC infection showed that treated groups had no APEC detected and only minimal MG detection (1 out of 6 birds) after treatment
• Histopathological findings in treated groups were similar to normal controls, confirming the therapeutic efficacy of the combination

Withdrawal Period Study:

• A peer-reviewed study published in the Pakistan Veterinary Journal (2020) evaluated tissue residues of lincomycin-colistin combination in broiler chickens
• Antibiotic residues were highest in the liver and kidney but were lower than the maximum residue limit (MRL) on day 1 and rapidly decreased from day 3
• The withdrawal time (WT) was calculated as 2.95 days based on kidney residue levels, rounded off to 3 days
• The study recommended a withdrawal period of 3 days as a precautionary principle for public health

RESISTANCE CONSIDERATIONS

Mechanisms of Resistance:

• Lincomycin resistance: Methylation of the 23S rRNA binding site; efflux pumps; enzymatic inactivation
• Colistin resistance: Plasmid-mediated mcr genes; modifications to lipopolysaccharides; biofilm formation
• Cross-resistance with macrolides may occur for lincomycin due to similar binding sites

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
• Do not use for disease prevention or growth promotion
• Prolonged or repeated use should be avoided; improve management, cleaning, and disinfection practices instead

DRUG INTERACTIONS

• Antagonistic: Do not use concurrently with bacteriostatic antibiotics (tetracyclines, macrolides, chloramphenicol) due to potential antagonism
• Interactions: Avoid concurrent use with other aminoglycosides or nephrotoxic drugs
• Synergistic: The combination of lincomycin and colistin itself is synergistic; no other significant synergistic interactions documented

CONTRAINDICATIONS & PRECAUTIONS

• Egg production: Not for use in laying hens producing eggs for human consumption
• Young birds: Use with caution in very young chicks; lincomycin may affect intestinal flora development
• 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 lincosamides or polymyxin antibiotics
• Sensitive species: Do not allow rabbits, hamsters, guinea pigs, horses, or ruminants access to water containing this product. Ingestion by these species may result in severe gastrointestinal effects
• Keep out of reach of children
• Store in a cool, dry place below 30°C, protected from direct sunlight
• Protect from moisture
• Use within 28 days after first opening

ADVERSE REACTIONS

• At recommended doses, the combination is generally well tolerated in poultry
• Occasionally, mild diarrhea may occur due to intestinal flora changes
• If adverse reactions occur, discontinue use and consult a veterinarian

WITHDRAWAL PERIOD

• Meat (Poultry): 3 days (based on scientific residue depletion studies establishing a withdrawal time of 2.95 days, rounded to 3 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 moisture
• Keep container tightly closed when not in use
• Do not freeze

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

Pack Sizes: 1 Kg HDPE container

PRODUCT SUMMARY
LC-ZONE Powder Antibiotic Lincomycin HCL USP 100mg, Colistin Sulphate BP 800,000 IU per gram Poultry 1 Kg

FOR VETERINARY USE ONLY