Medication as an aid for Prevention and Control of Poultry Pathogens
Prevention and Control of Poultry Pathogens Depends Upon: 1-Veterinary biosecurity and hatchery hygiene 2- Destruction of large numbers of pathogens * Using disinfectants. * Feed decontamination through: Physical destruction of microorganisms ( irradiation, pelting). Chemical mechanisms (Dietary acid additives). 3-Strengthen resistance of the host.
Strengthen resistance of the host Improved nutrition. Vaccination. Medication.
Medication in poultry is massive rather than individual one.
Purpose of poultry medication:- Control (treatment) of serious microbial disease. Prevention of a disease where it is known that the preventive medication steps should reduce the incidence of the problem (e.g. the use of anticoccidial agents).
Types of Preventive or Prophylactic Medication in Poultry
Continous prophylactic medication: As a regular basis or for certain period of time. Short-term prophylactic medication (Strategic medication): Used at certain time or age group to prevent the diseases that most likely occur at that time of age. Improvement of the performance medication: Antibiotics are usually in the feed to improve weight gains, feed conversion and egg production. Anti-stress medication: Vitamins plus other nutriceuticals (amino acids, or minerals) helps to overcome stress. They are given before, during or after stress (such as; physiological depression, transportation, vaccination, overcrowding etc.).
Routes of drugs administration in poultry Route Drinking water Drench Feed Aerosol I/M injection S/C injection Advantages Minimal labor, minimal stress moderate sick can drink. More flexible than in feed Every bird exact dose Treat very sick birds No labor required. No stress on birds. Delivers drug to site of respiratory infection Exact dose / bird. Treats very sick birds. Rapid onset of action. Exact dose / bird. Treat very sick birds. Less carcass damage (in neck easier than I/M). Disadvantages Very sick stop drinking. Flock dosage uneven. Some drugs are poor palatable. Labor intensive Handling. Stress on bird. Moderate sick stop eating. Uneven drug mixing. Dose Calculation? Much drug wasted. Special equipment Expose people to drug Labor intensive handling. Stress (bird). May damage carcass. Long withhold period. Labor intensive handling. Stress (bird). Long withhold period. Absorption slower than I/M.
Poultry Antibacterials
The role of antibiotics in therapy of enteropathogens can not be ignored. Usage of antibiotic feed additives (growth promoters) has proven useful in stabilizing the intestinal microflora and improving the general performances of poultry and preventing some specific intestinal pathologies
Tedious and Costly Process (need special factories and environment, as well as a special well trained and educated labors). Problems face production (e.g. yeast mutation, temperature changes, fermentors ).
Classification of Antibiotics
1- According to Effect on bacteria: Bacteriostatic: Inhibits growth and multiplication e.g. sulphonamides, tetracycline., chloramphenicol. Bactericidal: Kill the bacteria e.g. streptomycin, ampicillin.
2- According to mechanism of actions
3- According to Spectrum: Antibiotics affect on Gm+ bacteria e.g. Penicillin. Antibiotics affect on Gm- bacteria e.g. Streptomycin. Broad spectrum antibiotics e.g. Tetracyclines.
4- According to concentration in different organs: High conc. in respiratory tract e.g. Spiramcyin, Ampicillin, Tylosin. High conc. in kidneys (excretory organs) e.g. Sulphadimidin, Sulphamethazin. High conc. in liver and gall bladder e.g. Chloramphebicol, Ampicillin.
5-According to Degree of absorption from GIT Weak e.g. Neomycin, Streptomycin. Moderate e.g. Sulphonamides. High e.g. Erythromycin.
6- According to Chemical composition: Quinolons group: Naldixic acid. Flumequine, Enro., Nor., Dano & Cipro floxacine. Furan derivatives group: Furaltadone, Nitrofurazone, Furazolidone. Aminoglucosides group: Streptomycin, Neomycin, Gentamycin, Kanamycin, Apramycin & Spectinomycin. Tetracycline's group: Oxytetracycline, Chlortetracycline & Doxycycline.
Sulphonamides group: Rapid absorption rapid excretion :S.diazine, S.merazine, S.dimidine. Rapid absorption slow excretion: S.dimethoxine. Slow absorption: Sulpha quinoxaline. Penicillin group: Penicillin, Ampicillin; Amoxicillin.
Macrolides group: Erythromycin, Tylosin, Spiramycin, Tiamutin, Kitasamycin & Josamycin. Chloramphenicol group: Cloramphenicol. Polypeptides group: Colistin & Polymyxine. Aminocycolitical group: Lincomycin & Clindamycin.
The most effective Avoid resistance- least adverse effects Route of administration (Aerosol paranteral) Effective concentration at the site of action Withdrawal time
Strengthen Resistance of Birds However! Usage of Antibiotics in Sub therapeutic levels (Growth promoters) or misuse Therapeutic levels 1- Development of resistant population of bacteria (So subsequent use for therapy is difficult, Ghadban;1999). 2- Negative effect on lactic acid bacteria (Bougon et al.,1987). Affect on indigenous gut flora (intestinal upsets) and persist even after their cessation (Watkins and Kratzer; 1984).
Disadvantages of antibiotics cont. * Residues (withdrawal time). * Creation of resistant Salmonellae and. Coli-forms for human beings (DuPont and Steele;1987). * Presence of links between drug resistant poultry microbes and antibiotic resistance in humans (Ghadban;1999).
In 2006 all growth promotors already banned in EU. Many other countries will have to follow this measures to export to EU.
(Ghadban; 1999). Strengthen Resistance of Birds Consequently; Many governments around the world are banning or severely limiting the use of antibiotics at non-therapeutic levels. Now many supermarkets are already selling antibiotic-free meat
Strengthen Resistance of Birds Raising poultry without antibiotics may result in Poor performance Enteritis 1- Economic problem (Engster et al.; 2002). 2- Animal welfare problem (Norton; 2000).? Alternative methods of controlling infectious diseases are looked for
American Medical Association urged that nontherapeutic use in animals of antimicrobials should be terminated (Schuff; 2001).
Strengthen Resistance of Birds WHO is urging the meat producing countries around the world to use Environmentally Friendly alternative methods of controlling infectious diseases
Examples of Environmentally Friendly Alternatives
1- Dietary acid additives (Chemical Feed Decontamination)
Weak undissociated (non-ionised) organic acids penetrate bacteria cell wall Releasing Bacterial cell DNA Disrupt DNA synthesis Bacterial internal ph decrease Specific mechanism will act to bring ph to normal level consumes energy and stop growth Finally killed in the hostile environment of the crop by the combined effects of the acids, higher water activity and body temperature
Protect organic acids in a matrix crossing upper digestive system without denaturation. In intestine, matrix will be emulsified and hydrolysed by liver and pancreatic secretions and intact acids liberated in nondissociated form.
Benefits: No withdrawal period - Bird performance does not suffer - Public health benefits - Preventing vertical transmission of GIT Pathogens - Limit horizontal spread of salmonellae.
2- Probiotics
As early as 1928, Voltera reported that native microflora competitively exclude (CE) bacterial contamination from the intestinal tract of poultry.
Accordingly; Competitive exclusion (CE) is a term describes the protective effect of natural or native bacterial micro flora of GIT which limits colonization of some bacterial pathogens.
Competitive exclusion (CE) Nigel Horrox (1997) mentioned that the bird s microflora is potentially depleted for a period of time at hatching and following any medication with an anti-microbial product.
Competitive exclusion (CE) Electron Microscopy of Caecum Day-old-chick prior to acquiring the normal healthy adult intestinal flora. Protective adult bacteria of many different strains colonise the caecum.
Competitive exclusion (CE) First CE products were simply fecal contents. Researchers have developed defined mixtures of bacteria for use as CE products. These products are called: Probiotics or direct-fed microbial or CE cultures
Competitive exclusion (CE) Probiotic * Pure culture of one or more living M.O. given in feed and proliferate in the host-bird s GIT. * Implies antagonistic activity and competition for attachment sites by ensuring that the bird Maintains beneficial microbial population in GIT
Competitive exclusion (CE) Improving feed intake and digestion Intestinal bacterial flora takes part in the metabolism of nutrients and synthesis of vitamins (Nahanshon et al.; 1992 and 1996). Microbial antagonisms 1- Production of bacteriocins, organic acids and hydrogen peroxide (Fuller; 1989). 2- Neutralizes enterotoxins produced by pathogenic bacteria (Schwab et al.; 1980) Maintaining beneficial microbial population in GIT Immune stimulation 1- T cell function Enhancement and increase anti-salmonella IgM antibodies (Dunhan et al.; 1993). 2- Stimulation of lga production (Nahanshon et al.; 1994). 3- Increase macrophages effectiveness (Goldin and Gorbach (1984). Altering metabolism *Increase digestive enzyme activity (amylase, protease and lipase) (Ghadban; 1999). * Decrease bacterial enzyme activity (Reduction in b-glucuronidase ) (Coloe et al.; 1984 and 1987 and Jin et al.; 1997). * Reduce ammonia in the excreta and litter of broilers (Chiang and Hsiem; 1995).
Competitive exclusion (CE) Usage of probiotics is recommended: 1- In newly hatched chicks for rapid establishment of micro flora (to safeguard the host against enteric bacterial pathogens) (Mead; 2000). 2- In altered intestinal flora due to stress, usage of antibiotics or coccidiostats (to restore a protective micro flora) (Joan Jeffrey; 1998).
Competitive exclusion (CE) Fuller (1989) concluded that the auspicious effect of probiotics over the host is due to: 1- Stooping implementation of pathogenic bacteria over intestinal mucus membranes. 2- Better adhesion of lactic acid bacteria to intestinal epithelium. Lowering PH
Competitive exclusion (CE) Sensitivity of some GIT bacteria to low ph 1 2 3 4 5 6 7 8 9 10 3.5 4.5 Moulds Yeasts Lactic acid bacteria C. perfringens Staphylococci Salmonellae E. coli Streptococci
Competitive exclusion (CE) This microbe versus microbe army is the body's first line of defense that prevents a range of illnesses. Certainly this might be valuable in decreasing the use of antibiotics (whose usage may result in bacterial resistance and formation of residues in organs and tissues of treated birds).
Anticoccidial drugs Widely used. A drug may be efficacious against one or several of Eimeria species. Preventing disease + control subclinical coccidiosis in broilers.
As most of the damage is done when signs of coccidiosis are widespread in a flock, The concept of preventive medication emerged. Accordingly; Almost all broiler flocks receive preventive medication (prophylactically), and treatment is used as a last resort. Outbreaks of disease are usually treated with water-soluble drugs such as sulphonamides, amprolium or toltrazuril.
Programs for Use of Anticoccidial Drugs as preventive medication in Broilers. 1- Continuous Use of a Single Drug. Used from day 1 to slaughter (or with a withdrawal period of 3 7 days). 2- Shuttle or Dual Programs. One product in the starter and another in the grower feed. 3- Switching or Rotation of Products (Time interval for an entire operation).
The ionophores (Ionophorous antibiotics) Fermentation products. membranes for alkaline metal cations. Highly toxic at elevated doses. Toxic interactions between some ionophors and certain antibiotics ( e.g. tiamulin).
The polyether ionophores upset the osmotic balance of the protozoan cell by altering the permeability of cell membranes for alkaline metal cations.
Types of ionophors Monovalent ionophores: Maduramicin, Semduramicin (toxic for layers), Monensin (toxic for turkeys and incompatible with tiamulin), Narasin (incompatible with tiamulin), Salinomycin (toxic for turkeys, layers, horses and ruminants). Divalent ionophores: Lasalocid. stimulates water consumption and excretion, resulting in a wet litter.
The Chemical Coccidiostats Very effective ; however, must be managed well because coccidia can develop resistance to some products very quickly.
Sulfonamides compete for the incorporation of PABA and metabolism of folic acid. Amprolium competes for absorption of thiamine by the parasite. The quinoline coccidiostats and clopidol inhibit energy metabolism in the cytochrome system of the coccidia.
Resistance to anticoccidial drugs in the field is widespread that usually arises by: 1- Selection of pre-existing mutants. 2- Genetic recombination in the coccidia which result in the transfer of resistant genes among parasite population. N.B.: Anticoccidial drug combination has advantage that might reduce the problem of drug resistance because the chance of selecting mutants resistant to a combination of drugs is less than if those drugs are used alone.
As most of the damage c is done when u signs of coccidiosis rare widespread in a flock, The concept of r preventive e medication emerged. n Accordingly; a t F e Almost all broiler flocks e receive preventive medication, d and treatment is used as a last resort. A d d
Programs for Use of Anticoccidial Drugs as preventive medication in Broilers. 1-Continuous Use of a Single Drug. Used from day 1 to slaughter, or with a withdrawal period of 3 7 days. 2-Shuttle or Dual Programs. One product in the starter and another in the grower feed (intended to improve coccidiosis control). The use of shuttle programs is thought to reduce buildup of drug resistance. 3-Rotation of Products. Buildup of coccidia isolates that have reduced sensitivity after products have been used for a long time, leads to boost in productivity for a few months after a change of anticoccidial drugs.
N.B.: 1-The primary defense against drug resistance is the use of less intensive programs, shuttle programs, with frequent rotation of drugs. 2-Rotation programs, used alone, will not prevent the development of resistance because the periods of use of drugs between changes is often adequate for resistance development.
Amprolium (Thiamine analogues): Not very effective against intestinal coccidiosis - Competes for absorption of thiamine by the parasite. Toltrazuril ( Baycox, Toltrazul 25-75 ppm) Given in water. Cross resistance with diclazuril). Nitrobenzamides: Contraindicated in layers.
Clopidol (Pyridones)(Coyden) - Clopidol (100 ppm) and Methylbenzoquate (8.35 ppm) (Lerbek) : (Coyden 25 (rm) 0.5 kg/tone.,lerbek 20% (rm) 0.5 kg/tone.) Inhibit energy metabolism in cytochrome system of coccidia - Weak efficacy against E. Tenella. Decoquinate (Hydroxyquinolones) (Doccox 30 ppm) (Deccox 6% (rm) 30-40 g/tone.) Inhibit energy metabolism in cytochrome system of coccidia
Halofuginone (Febrifugine) (Stenorol- Hoechst Rossel) 3ppm : (e.g. rabbits, guinea fowl). Stenerol (Hoechst) (Toxic for quail, Rapid development of resistance - Toxic for quail, rabbits and guinea fowls - Weak efficacy against E. tenella.
Broad Spectrum Chemical Coccidiostats Nicarbazine (Carbanilide) (Nicarb 25%-Nicarazin) MSD AG Vet : Severely depresses weight gain when fed to birds over 20 days - Toxic effects when fed at environmental temperatures above 29 C Toxic for layers. Diclazuril (Clinacox-Janssen) 1 ppm : (e.g. Clinacox (Jansen-Belgium), Ezmo (Amoun), Zox (Adeco) 200 gm. / Ton ). Cross resistance with toltrazuril. Robenidine (Guanidines) (Cycostat-Robenz) 33 ppm Canamid: (7-Robindine e.g. Cycostat (Roche) Rapidly develop resistance. Medicinal tast in meat if withdrawal period not observed
Organic coccidiostates Organic coccidiostate (e.g. steroidal sapogenins) can control both intestinal and caecal coccidiosis in chickens.
Mycotoxin Decontamination 1) Control of Fungal Growth: (Mold inhibitors) Antifungal feed additives (Propionic acid, methyl propane, sod. propionate, potassium sorbate, crystal violet, sod. bisulphate and benzoic acid). 2- Detoxification of contaminated Feed 1-Physical Detoxification. 2- Chemical Detoxification. 3- Biological Detoxification.
A- Physical Detoxification 1- Organic solvent extraction: 95% ethanol, Acetone, Isopropanol (Impractical and Cost prohibitive). 2- Heat inactivation: Little change since some mycotoxins are heat resistant. 3- Irradiation: Short & long wave UV light Induce significant reduction (Impractical, limited scale). 4- Adsorbents: Bind physically with chemical substances preventing their absorption from GIT. (Activated charcoal, bentonite, Hydrated Sod. Ca aluminosilicate or HSCAS, Mannan-oligosaccharides & beta glucan). 5- Anticaking agents: Sequester and reduce toxin bioavailability in vivo.
B) Chemical Detoxification: 1- Ammoniation. Needs 2-3 weeks and dehydration of the grains (reduce aflatoxin levels by greater than 99%). 2-Hydrogen peroxide (H2O2).(Reduce 97% of aflatoxin). 3- Organic acids. E.g. isobutyric, propionic, citric and acetic acids. 4- Non ionic surfactants. Triton X 100, Tergitol. 5- Chemo-sorbents. Zeolite and bentonites compounds. (Alter the effect of T-2 toxins and zearalenone).
C-Biological Detoxification (Biotransformation) Enzymatic detoxification by using Yeasts and bacteria: Viable yeast and yeast cell wall as well as L-form lactobacilli fermentation extract.. Biotransformation neutralizes the toxic effect of mycotoxins. Trichothecenes, including T-2 toxin, HT-2 toxin can be degraded to harmless metabolites by the action of fermentation extracts
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-Control of viral diseases is by effective vaccines. -Antiviral drugs is not common in veterinary medicine. Amantadine Act on early step of viral replication after attachement of virus to cell receptors, the effect seems to lead to inhibiton or delay of the uncoating process that precedes primary transcription. -15 mg/kg.b.wt. I/V for equine influenza. -Trial for minimizing mortality caused by ND was conducted. Ribavirin - It acts by inhibition of viral associated enzymes. - Doesn t have a wide margin of safety in animals. - Reduce virus titres in infected animals with orthopox virus.
1- Avermectins Ivermectin, Abamectin, Moxidectin They paralyze the worms by potentiation the inhibitory effect of GABA. (Dose 200 μg/kg.b.wt.) - Ivermectin bolus provided a season-long protection against lung worms in calves. -S/C 200 μg/kg.b.wt. for lung worms in cattle. -Moxidectin pour-on (0.5 mg/kg.b.wt.) for D. viviparus. 2- Levamisole : Immuno-stimulant 3- Benzimidazoles : Fenbendazole, Albendazole,.
I Polyne macrolide antibiotics Polyne antifungal antibiotics isolated from strains of actinomyces e.g. amphotericin β and nystatin Amphotericin B The polyenes bind to sterol components in the phospholipid-sterol membrane of fungal cells to form complex that induce physical changes in the membrane. -Fungistatic but at high concentration it is fungicidal. -It s immunopotentiator (both humoral and cellular). -Effective against yeast (pulmonary candidasis caused by candida albicans)
-0.1 mg/kg.b.wt. for 34 days. Safe and effective. -Pulmonary histoplasmosis in horse treatment I/V for 5 weeks. II Imidazoles Possess antibacterial, antifungal, antiprotozoal and anthelmintic activity e.g. Ketoconazole, Clotrimazole, econazole, miconazole. Thiabendazole : anthelmintic and antifungal. Alter the cell membrane permeability by blocking the synthesis of ergosterol, the primary sterol of fungi - Miconazole has a wide antifungal activity against yeast & fungi in vet. Practice.
-Ketoconazole is the most active of the antifungal imidazoles. -Thiabendazole is effective against Aspergillus. -Itraconazole for fungal rhinitis Hepatotoxicity is a possible sequel to itraconazole therapy.
1- Beta lactams Penicillins and Cephalosporins Mode of action: Bind to and inhibit enzymes needed for the synthesis of the peptido-glycan wall. i.e. Inhibit bacterial cell wall They are lethal to dividing bacteria as defective walls cannot protect the organism
A- Penicillins Produced by fungus Penicillium chrysogenum 1- Narrow-spectrum β-lactamase sensitive penicillins active mainly on Grampositive e.g. benzyl penicillin, phenoxymethyl-penicillin 2- Narrow-spectrum β-lactamase resistant penicillins e.g. Cloxacillin & oxacillin 3- Broad-spectrum β-lactamase sensitive penicillins e.g. Ampicillin, Amoxicillin 4- Broad-spectrum β-lactamase sensitive penicillins with extended spectra : broad spectrum + effect on pseudomonas aeurginosa, certain proteus spp. And Klebsiella 5- β-lactamase protected broad-spectrum penicillin (potentiaited penicillins) e.g. Clavulanate potentiated amoxicillin, Sulbactam-potentiated ampicillin. Penicillins primarily effective against Gram-positive bacteria. Broad-spectrum, semisynthetic penicillins are effective against some gram-negative pathogens.
B- Cephalosporins Obtained from Cephalosporium acremonium, but now the semisynthetic cephelosprins are produced. Bactericidal. 1 st generation: (e.g. cephalothin, cephaloridine, cephaprin, cefazolin, cefelixin, cephradine and cefadroxil). Act on gram +ve 2 nd generation: (e.g. cefamandole, cefoxitin, cefuroxime, cefonicid). Act on gram +ve and gram ve. 3 rd generation: (e.g. cefonicid, Ceftiofure). Works best against Gram ve 4 th generation: (e.g. cefquinome). Active against Gram +ve and -ve N.B.: Both 3rd and 4th generations are highly resistant to destruction by beta-lactamases.
2- Aminoglycosides Source: Actinomycetes (like Streptomyces) Mode of action: Bind to the 30S subunit of the bacteria ribosome and inhibit the rate of protein synthesis. Classes: 1- Narrow spectrum aminoglycosides (grame -ve ) : Streptomycin, Dihydrostreptomycin. 2- broad- spectrum aminoglycosides: Neomycin, Gentamicin, Framycetin, Promomycin. Kanamycin,Amikacin, Tobramycin. 3- Miscellaneous : Apramycin, Spectinomycin N.B.: Products containing penicllin and streptomycin are often used in combination
3- Tetracyclines Source: Soil actinomycetes or their semi-synthetic derivatives. Mode of action: Bacteriostatic inhibit protein synthesis Broad-spectrum, effective against aerobic and anaerobic Gram-positive and negative bacteria, mycoplasma, rickettsiae and some protozoa. Classes: Naturally: Oxytetracycline, Chlorotetracycline, Methylchlorotetracycline Semi-synthetically: Tetracycline, Methacycline, Minocycline, Doxycycline Short-acting: Tetracycline, Chlorotetracycline, Oxytetracycline. Intermediate acting: Demethylchlo, Rotetracycline, Methacycline Long acting: Doxycycline, Minocycline
4- Macrolides Source: Soil actinomycetes or their semi-synthetic derivatives. Erythromycin, clarithromycin, oleandomycin, spiramycin, josamycin, tylosin and tilmicosin. Mode of action: Bacteristatic. Inhibit bacterial protein synthesis by binding to the 50S ribosome. active against most gram-positive and Mycoplasma,
5- Lincosamides Source: Soil actinomycetes (Lincomycin). A semi-synthetic derivative, called clindamycin is now widely used. Mode of action: Bind to the bacterial 50S ribosome to inhibit protein synthesis. active against gram-positive aerobes and anaerobes and mycopalsma species.
6- Chloramphenicol Source: Mode of action: Broad-spectrum antibiotics. Since August,1994, Chloramphenicol Union. was banned in the European Bind to the bacterial 50S ribosome to inhibit protein synthesis. active against gram-positive and gram-negative bacteria and several anaerobes. Highly effective and well-tolerated broad-spectrum antibiotic. Two related drugs have been developed: Thiamphenicol and Florfenicol
7- Ketolides 9- Miscellaneous antibiotics a. polymyxins: Polymyxin B and Polymyxin E, Colistin b- Bacitracins c-aminocyclitols (Spectinomycin, Apramycin) d- Tiamulin Semi-synthetic agents derived from erythromycin to overcome resistance in streptococcus pneumoniae. Active against Gram-positive bacteria responsible for respiratory tract infections. Inhibit bacterial protein synthesis Telithromycin 8- Oxazolidinone Excellent antimicrobial activity against wide variety of Gram-positive pathogens. Exhibit good penetration into pulmonary tissues. Linezolid is the first agent of the class, used for lower resp. tract infections.
Source: Derivatives of p-aminobenzene sulfonic acid. Structurally similar to p-aminobenzoic acid (PABA(. Classified into : Short acting, long acting, enteric., topically acting or : Highly soluble, poorly soluble, potentiated. Mode of action: Competition with PABA so inhibit formation of folic acid. They are broad-spectrum agents. Synthetic antibacterial drugs A- Sulfonamides Potentiated sulfonamides Combinations of sulfonamide with trimethoprim or ormetoprim. Synergistic action. Antibacterial spectrum: Sulfonamide - diaminopyrimidine combinations are active against gram-negative and gram-positive organisms. The antibacterial spectrum does not include Pseudomonas or Mycobacterium spp.
Mode of action: Bacteriocidal. Inhibit bacterial DNA gyrase (an enzyme that controls DNA supercoiling as the replicating strands separate). Antimicrobial spectrum : Active against a wide range of gram-negative and gram-positive aerobes. These newer quinolones also have significant activety against Mycoplasma, Chlamydia spp. and Mycobacterium tuberculosis B- Quinolones and Fluoroquinolones Source: Quinolone carboxylic acid derivatives are synthetic antimicrobial agents. Quinolons : (Nalidixic A., Oxolonic acid, Flumequie). Recently, a number of broad spectrum antimicrobial agents have been produced by modification of various 4-quinolone ring structures Fluoroquinolones : (enrofloxacin, ciprofloxacin, norfloxacin, danofloxacin, pefloxacin, ofloxacin, difloxacin, clinafloxacin)