Antimicrobial agents

antimicrobial agents and antimicrobials used in dentistry . public health significance

1. CONTENTS Introduction classification of antimicrobial agents Selection of antimicrobial agents Antibiotics Classification of antibiotics Antimicrobial resistance Factors involved in the usage of antibiotics rationally Ideal antibiotics antibiotics combination

2. Contents Disadvantage and misuse of antibiotics Antimetabolites Antifungal drugs Antiviral drugs Antiprotozoal drugs Public health significance Conclusion References

3. Introduction An  antimicrobial   is an agent that kills or inhibits the growth of microorganisms without harming the cells of the host. The antimicrobial agent may be a chemical compounds and physical agents. These agents interfere with the growth and reproduction of causative organisms like bacteria, fungi, parasites , virus .

4. Classification of antimicrobial agents Drugs by susceptible organisms Antibacterial Antiviral Antifungal Antiprotozoal Anthelmintic

5. Selection Of Antimicrobial Agents

6. The effect of site of infection on therapy

7. Status of the patient 1.Immune system 2.Renal dysfunction 3.Hepatic dysfunction 4.Poor Perfusion 5.Pregnancy 6.Lactation 7.age Safety of the agent Cost of therapy

8. Chemotherapeutic spectra

9. Antibiotics A substance produced by which selectively suppress the growth of or kill other microorganisms at low concentrations and has the capacity to inhibit the growth of bacteria. It has a high chemotherapeutical index to reduce the active process in bacteria . in a diluted solution.

10. Classification of antibiotics 1 . Based on chemical structures 2. Based on the sources 3. Based on mechanism of action 4. Based on spectrum of action / activity 5. Based on modes of action

11. 1. Based on chemical structures 1 . Groups of sulfonamides  Sulfamethoxazole, sulfadiazine 2. Groups of Penicillin  Penicillin G (Benzyl penicillin), Penicillin V, Ampicillin , amoxicillin, nafcillin 3. Groups of cephalosporin's  cefalotin , cefazolin, cefamandole , cefuroxime,cefotaxime , ceftriaxone . 4. Groups of aminoglycosides  streptomycin, neomycin , kanamycin, gentamycin, tobramycin 5. Groups of chloramphenicol  chloramphenicol, tiamphenicol

12. 6. Groups of tetracyclines  chlortetracycline, oxytetracycline , doxycycline, minocycline 7. Groups of macrolides  erythromycin, roxithromycin , spiramycin , azithromycin 8. Groups of polyenes  amphotericin B, nystatin 9. Groups of Lincomycins  lincomycin , clindamycin 10. Groups of polymixins  Polymyxin B, Polymyxin E

13. II. Based on the sources a. Antibiotic from microbes A.B. from fungi - Penicillin from P. notatum A.B . from bacteria • A.B. from eubacteria - polymyxin from bacillus polymyxa • A.B. from micromonosporaceae - gentamyicin from micromonospora purpurea b. Antibiotics from algae - Usnat Acid c. Antibiotics from higher plants - Garlisina from Allium sativum d. Antibiotics from animals - Eritrina from hemoglobin of cow

14. III. Based on mechanism of action A. Inhibition of cell wall synthesis leads to the death of the bacteria lysis (bactericidal effect)  penicillin , cycloserine , vancomycin, bacitracin B . Disruption of cell membrane function  polymyxin (polymyxin B, polymyxin E), polyenes, nystatin C. Inhibition of protein synthesis:  This antibiotics inhibit one of the reactions in the process of transcription 1. Inhibition of translation process of microbes

15. • Inhibit ribosome on the 30 S subunit - streptomycin , tetracyclines , netilmycin , kanamycin • Inhibit ribosome on the 50 S subunit - chloramphenicol , clindamycin, lincomycin Inhibits the transcription process of microbes - Rifampin , actinomycin D. Inhibits specific metabolic reaction Inhibits the enzymatic reactions -sulfonamides , INH, PAS, trimethoprim

16. IV. Based on spectrum of action Broad spectrum: Effective to Gram +, Gram - bacteria , mycoplasmas , chlamydiae , rickettsiae , sometimes protozoa -chloramphenicol , tetracyclines Narrow spectrum: Effective to Gram + ve / Gram - ve bacteria only - penicillins , cephalosporins , erythromycins , polymyxins

17. Antimicrobial resistance – WHO (2017) Antimicrobial resistance occurs when microorganisms such as bacteria, viruses, fungi and parasites change in ways that render the medications used to cure the infections they cause ineffective . When the microorganisms become resistant to most antimicrobials they are often referred to as “superbugs”. This is a major concern because a resistant infection may kill, can spread to others, and imposes huge costs to individuals and society.

18. Lack of government commitment to address these issues, poor surveillance and a diminishing arsenal of tools to diagnose, treat and prevent also hinder the control of antimicrobial drug resistance .

19. Some approaches to solve resistance problems 1. Reduce the usage of prophylactic antibiotics 2. Use narrow spectrum antibiotics 3. Always follow directions for use of antibiotics 4. Prescribe antibiotics based on clinical situation and not on patient’s will or pharmaceutical advertisements . Rational drug: drugs given after accurate diagnosis . It will be effective with minimal side effects .

20. 1. Accurate diagnosis 2. Accurate choices of antibiotics 3. Deliver accurate dose 4. Accurate dosing interval 5. Accurate examinations of pathophysiologic conditions of the patient Factors involved in the usage of AB rationally, effectively and safely.

21. Ideal antibiotics : Effective even in the presence of body fluids exudate , protein or enzymes. Ability to reach the infected tissue, enough drug concentration during the span of a dosing interval in blood / infected area. Do not cause resistance Have a minimal toxic effects for the patient Safe for pregnancy and pediatric patients cost effective

22. Sensitivity tests / resistance tests Qualitative : Stokes method Ericcson method Kirby-Bauer method Comparison method Quantitative : MIC

23. Antibiotic Combinations : The result may be addictive , potentiative or antagonistic Addictive response : one in which the antimicrobial effect of the combination is equal to the sum of the effects of the two drugs alone. Potentiative interaction: one in which the effect of the combination is GREATER than the sum of the effects of the individual agents. Antagonistic response : in certain cases the combination of two antibiotics may be less effective than one of the agents by itself .

24. Disadvantages of antibiotic combinations Increased risk of toxic and allergic reactions Possible antagonism of antimicrobial agents Increased risk of superinfection Selection of drug resistant bacteria Increased cost

25. Penicillin Mechanism of action: the drugs weaken the cell wall, causing the bacterium to take up excessive amounts of water and then rupture Penicillinases (beta- lactamases) enzymes that cleave the beta-lactam ring and thereby render penicillin and other beta-lactam antibiotics Classification : Narrow-spectrum (penicillinase sensitive) Narrow-spectrum that are penicillinase resistant (antistaphylococcal) Broad spectrum penicillin's (aminopenicillins) Extended spectrum penicillin's (antipseudomonal)

26. PENICILLIN G ANTIMICROBIAL SPECTRUM : active against most gram + ve bacteria, gram – ve cocci (Neisseria, meningitis) and spirochetes . With few exceptions gram – ve bacteria are resistance . Therapeutic uses: Pneumonia and meningitis caused by streptococcus pneumonia Pharyngitis caused by streptococcus pyogens Infectious endocarditis( streptococcus viridans ) Gangrene , tetanus Syphilis (treponema pallidum) Side effects and toxicities : Pain at the site of infection , neurotoxicity with too high plasma levels. Inadvertent intra-arterial injection can produce severe reactions ( gangrene,necrosis ) and must be avoided .

27. PENICILLIN ALLERGY Penicillin are the most common cause of drug allergy (1-10% of the patients will experience an allergic response) there is no direct relationship between size of dose and intensity of allergic response. Cross sensitivity :5-10% of patients allergic to penicillin's are also allergic to cephalosporin's Types of allergic reactions: Immediate (occurring 2-30 min after administration) Accelerated (occur within 1-72 hours) Late reactions (days or even weeks) Anaphylaxis (laryngeal edema, bronchoconstriction, severe hypotension) in 0.2% of patients ,treatment – epinephrine + respiratory support .

28. Skin tests for penicillin allergy Penicillin skin testing , Solensky , Franklin Adkinson Jr, Feb 2014

29. Management of patients with history of penicillin allergy Ask patients for previous history of allergy to penicillin If the patient refers to a positive history of allergy AVOID PENICILLIN entirely If the allergy is mild a CEPHALOSPORINE is appropriate as alternative. If the allergy is severe avoid CEPHALOSPHORINS For many i nfections VANCOMYCIN AND ERYTHROMYCIN are effective and safe .

30. Penicillinase-resistant Penicillin’s Antistaphylococcol Resistance to beta lactamases . Acid labile : Methicillin, nafcillin , cloxacillin , dicloxacillin Acid resistant: flucloxacillin . Broad spectrum penicillin’s Aminopenicillins Ampicillin :( SPECTRUM: bordetella pertussis , E coli , salmonella , shigella ) Adverse effects – rashes (4-10% with ampicillin) diarrhoea

31. EXTENDED SPECTRUM PENICILLINS Used to treat infections with Pseudomonas Aeruginosa (ie Ticarcillin) Penicillins combined with beta lactamase inhibitor ie Amoxicillin + clavulanic acid = Augmentin a.Carboxypenicillins : Carbenicillin , ticarcillin , b. Aminopenicillin : Amipicillin , amoxicilllin . c. Ureidopenicillin : Mezlocillin , piperacillin.

32. CEPHALOSPORINS Broad spectrum antibiotics with low toxicity mechanism of action : disruption of cell wall synthesis and consequent lysis of cell .

33. CEPHALOSPORINS First generation- More active Second generation- Third generation Forth generation More active against gram positive organism more selective against gram positive and gram negative organisms Highly active against gram negative organisms similar antibacterial activity as that 0f third generation but highly resistant to beta lactamases Parenteral- Cephalothin Cefazolin Cephaloridine Oral- Cephalexin Cephadine Cefadroxil Parenteral Cefuroxime Cefoxitin Oral Cefaclor Cefuroxime acetyl Parenteral- Cefotaxim Ceftizoxime Ceftriaxone Cefoperazone Oral cefexim Parenteral- Cefepime Cefiperome

34. Adverse effects Allergic reactions : rash that develops after days of treatment severe immediate reactions are rare. Bleeding : five cephalosporins cause bleeding tendencies ( cefamandole , cefmentazole , cefoperazone , cefotetan and moxalactam ) 2 mechanism involved : -reduction in prothrombin levels and - impairment of platelet aggregation . (only with moxalactam ) Thrombophlebitis : it may develop during IV infusion (>change in infusion site) Pain at site of IV infusion

35. IMIPENEM Relatively new beta-lactam antibiotic with very broad spectrum. Antimicrobial spectrum : highly active against gram + ve and gram- ve cocci . It is also the most effective beta-lactam antibiotic against anaerobic bacteria . Pharmacokinetics it is not absorbed from the GI tract . IV or IM administration . Adverse effects (generally well tolerated) GI effects (nausea, vomiting , diarrhoea) Hypersensitivity reactions (rashes ,pruritus ) Superinfections with bacteria or fungi develop in about 4%of patients . Rarely seizures have occurred

36. Bacteriostatic Inhibitors Of Protein Synthesis Aminoglycosides MLSK (Macrolides, Lincosamides , Streptogramins , Ketolides ) Tetracyclines Glycylcyclines Phenicols Ansamycins

37. Aminoglycosides Action : severe infections MOA :Disruption of bacterial Protein Synthesis Antimicrobial spectrum : aerobic gram- ve bacilli( E.Coli , klebsiella , pneumonia, proteus mirabilis, pseudomonas aeruginosa) the drugs are inactive against most gram+ve bacteria the drugs are ineffective against anaerobes. Potential for serious AE ototoxicity, nephrotoxicity Not given orally due to their poor absorption Low dose: bacteriostatic High dose: bactericidal Gentamicin , tobramycin, amikacin

38. Macrolides MOA : bind to the 23S rRNA in the 50S subunit ribosome inhibiting protein synthesis Dose : 250-500 mg/day x 5-10 days anti bacterial spectrum – similar to penicillin (against gram+ve bacteria and against some gram- ve ) against penicillin resistant staphylococci. partially destroyed by gastric juice, (enteric coated tablets) Various preparation- enteric coated tablets Estolate form (most resistant by gastric acid) Drugs belonging to this group- erythromycin, olindomycin, Spiramycin

39. New macrolides- roxithromycin , clarithromycin Similar spectrum of erythromycin More resistant to acid hydrolysis. Better tissue level are achieved Therapeutic uses: Legionella pneumophila pneumonia (legionnaires disease) Whooping cough ( bordetella pertussis) Corynebacterium diptheriae (diphtheria) Chlamydial infections Mucoplasma pneumonia Alternative to penicillin G in penicillin allergy

40. Adverse effects GI effects (nausea , vomiting , diarrhoea) liver injury (cholestatic hepatitis . Happens with erythromycin estolate in adults with pre existing history of liver disease ) Drug interactions : CAUTION WHEN combined with astemizole and terfenadine (antihistamines) , theophylline , warfarin(anticoagulant), carbamazepine (anticonvulsant) Erythromycin antagonises the effect of chloramphenicol and clindamycin .

41. Lincosamides Clindamycin ( Cleocin ) MOA : binds to the 50S ribosomal subunit and inhibits protein synthesis Antimicrobial spectrum : anaerobic bacteria (gram- ve and gram + ve ) Widely distributed in tissue fluids and tissues, including bone. Avoid in the routine odontogenic infection An excellent alternative drug in penicillin-resistant anaerobic infections Used in Osteomyelitis of the jaws Dose: 100-450mg 6 h x 7-10 days Adverse events : - GI upset, pseudomembranous colitis (symptoms include profuse watery diarrhoea ,abdominal pain fever and leucocytosis) - hypersensitivity reactions (rashes) Drug interactions: neuromuscular blocking agents

42. Tetracycline Broad spectrum antibiotic . MOA: Suppression of bacterial growth by inhibiting protein synthesis Low absorption through GIT. Rapid renal excretion Therapeutic uses Treatment of infectious diseases ( rickettsial diseases – rocky mountain spotty fever , typhus fever , Q fever ) Infections caused by chlamydia trachomatis , brucellosis , cholera , pneumonia caused by mucoplasma pneumonia , lyme disease .

43. Gastric infections with helicobacter pylori Treatment of acne (orally and topically for severe acne vulgaris ) Peptic ulcer disease (combination of tetracycline's, metronidazole and bismuth salicylate against helicobacter pylori ) Absorption : the drugs should not be administered together with -calcium supplements -milk products and iron supplements -magnesium containing laxatives -antacids

44. Adverse Effects Of Tetracyclines Gastrointestinal irritation(nausea , vomiting , diarrhoea ) Effects on bones and teeth (teeth discolouration in children under 5 years old the drugs can also supress long –bone growth ) Superinfection (C. difficile pseudomembranous colitis ,fungus infections usually with candida albicans Hepatotoxicity(fatty infiltration of the liver) Renal toxicity (the drugs may exacerbate renal dysfunction in patients with pre-existing kidney dysfunction ) Photosensitivity

45. Doxycycline ( Vibramycin ) MOA : inhibit protein synthesis by preventing aminoacyl transfer RNA from entering the acceptor sites on the ribosome Dose: 100mg bid x 7-14 days High potency. Complete absorption from intestine. High plasma binding. Contraindications: - Food - pregnancy Drug interactions: anti-epileptics

46. Antibiotics commonly used in odontogenic infections

47. 4 . Anti - Metabolites • Sulfonamides • Trimethoprim

48. Sulfonamides MOA : suppression of bacterial growth by inhibiting synthesis of folic acid Antimicrobial spectrum : Enterococcus –poorly expressed , S . pneumonia , Ps . aeruginosa THERAPEUTIC USES : urinary tract infections . Adverse effects : Hypersensitivity reactions (rashes , drug fever , photosensitivity ) Hematologic effects (haemolytic anaemia in patients with G-6PD deficiency) Kernicterus The drugs should not be given to infants under the age of 2months, pregnant and breast feeding mothers

49. Trimethoprim MOI: Inhibitor of dihydrofolate reductase ( suppresses bacterial synthesis of DNA ,RNA and proteins Therapeutic uses : It is approved only for the initial treatment of acute uncomplicated urinary tract infections due to susceptible organisms ( E.coli,proteus mirabilis etc ) Adverse effects : Generally the drug is well tolerated Most common adverse effect include itching and rash GI reactions occur occasionally Caution when administering the drug to patients with suspected folate deficiency – increase danger of bone marrow suppression

50. Fluoroquinolones Ciprofloxacin (Cipro ), Garenoxacin MOA: Inhibition of DNA gyrase Antimicrobial spectrum: Gram-negative and Gram-positive ( Anaerobes,, S.pneumoniae and Pseudomonas ) Dose : 250-500 mg qid x 7-10 days Contraindications : <18 yrs old, pregnancy Adverse events : spontaneous tendon rupture Drug interactions : probenecid, warfarin Ciprofloxacin , Levofloxacin, Norfloxacin, Ofloxacin Spectrum -Staphylococci, Streptococci and Pneumococci ( sporfloxacin ). More widespread tissue distribution

51. Antifungal Agents Major antifungal drugs comes from three families Polyenes (Amphotericin B) Imidazole's (ketoconazole , miconazole) Antimetabolites (flucytosine)

52. Classification of antifungal drugs Topical Systemic Amphotericin B Amphotericin B Carbol-Fuchsin Dapsone Clotrimazole Fluconazole Econazole Flucytosine Ketoconazole Griseofulvin Nystatin Itraconazole Silver Sulfadiazine Ketoconazole Oxiconazole Miconazole Miconazole KI (Potassium Iodide)

53. Amphotericin B Obtained from Streptomyces nodosus It is a member of the polyene family of antibiotics Administered by IV infusion with 5%dextrose (0.1mg/ml) or (0.3mg/ml) Can be applied topically as a 3%cream ,ointments or lotion is useful in treatment of superficial candida infections . Adverse effects: Local irritation gastrointestinal disturbances Hypotension Renal toxicity Delirium along with fever, nausea ,abdominal pain , anorexia

54. AZOLE DERIVATIVES Clotrimazole (Mycelex), ketoconazole ( Nizoral ), fluconazole ( Diflucan ) MOA: inhibit cell wall synthesis Dose: 1 00mg 6.5 h; 200mg 8.5h; 300mg 9.6h Therapeutic uses: -blastomycosis -histoplasmosis -effective against chronic mucocutaneous candidiasis -successful treatment of oral candidiasis by systemic ketoconazole ADVERSE EFFECTS : -anorexia -epigastric pain –GI upset -hepatotoxicity -adrenocortical suppression with high doses Drug interactions: major p-450 enzyme inhibitor

55. TREATMENT OF ORAL CANDIDIASIS Clotrimazole troches 10 mg ,dissolve 1 troche in mouth 5 times a day for 14 days Nystatin oral suspension 500,000 units: Swish 5 mL in mouth then swallow (optional), 4 times a day for 14 days Nystatin pastilles 100,000 units: dissolve 1 in mouth 4 times a day for 14 days clotrimazole 1% cream Topical agents (mild to moderate oral candidiasis)

56. Systemic agents Fluconazole 100 mg: Dispense 15 tablets, take 2 tablets on day 1, followed by 1 tablet a day for the remainder of the 14-day treatment period Itraconazole oral suspension 10 mg/10 mL: Dispense 140 mL, swish and swallow 10 mL per day for 7 to 14 days. Voriconazole 200 mg: Dispense 14 tablets, take 1 tablet twice daily for 2 weeks or at least 7 days following resolution of symptoms

57. Antiviral Drugs Viruses have no cell wall and made up of nucleic acid components Viruses are obligate intracellular parasite They do not have a metabolic machinery of their own –uses host enzymes Certain viruses multiply in the cytoplasm but others do in nucleus Most multiplication take place before diagnosis is made

58. Antiviral Medications Antiviral drugs Used to treat infections caused by viruses other than HIV Antiretroviral drugs Used to treat infections caused by HIV, the virus that causes AIDS Herpes-Simplex Viruses - HSV-1 (oral herpes) -HSV-2 (genital herpes ) Varicella Zoster Virus Chickenpox Shingles 

59. Antiviral drugs : nonretroviral Mechanism of action  Inhibit viral replication Used to treat non-HIV viral infections  Influenza viruses  HSV (herpes simplex virus), VZV ( varicella zoster virus)  CMV (cytomegalovirus)  Hepatitis A, B, C (HAV, HBV, NCV ) Adverse Effects  Vary with each drug  Healthy cells are often killed also, resulting in serious toxicities

60. Antiviral spectrum ,MOA and clinical uses of antiviral drugs Agent Antiviral spectrum Mechanism of action Clinical uses Amantidine,rimantidine Influenza A virus Blockade of uncoating process Prophylaxis of influenza A infection . Idoxuridine HSV Inhibition of DNA synthesis Treatment of herpetic keratitis Vidarabine , trifluridine HSV Inhibition of DNA synthesis Treatment of herpetic keratitis and keratoconjuctivitis Penciclovir HSV Inhibition of DNA synthesis Treatment of recurrent herpetic labialis Acyclovir HSV and VZV Inhibition of DNA synthesis Treatment of primary and recurrent herpetic infections , mucocutaneous herpetic infections in immunocompromised patients ,VZV infections ,herpetic encephalitis

61. Agent Antiviral spectrum Mechanism of action Clinical uses Foscarnet HSV, VZV, CMV Inhibition of DNA synthesis Treatment of CMV retinitis and acyclovir resistant HSV and VZV infections Ribavirin RSV inhibition of DNA synthesis , purine metabolism Treatment of RSV pneumonia and bronchitis Reverse transcriptase inhibitors HIV Inhibition OF DNA synthesis Treatment of HIV infection and AIDS Protease inhibitor HIV Blockade of HIV protease Treatment of HIV infection and AIDS

62. Antiprotozoal drugs

63. Metronidazole Uses : -anaerobes in intra abdominal abscess -bone and joint infections ,septicaemia -peptic ulcer disease -endometritis In Periapical abscess , periodontal abscess , acute pericoronitis of impacted or partially erupted teeth : often used in conjugation with Amoxicillin . Primary agent used in ANUG 500mg TID for 5-7days ADVERSE EFFECTS : nausea ,diarrhoea ,metallic taste infrequent adverse effects : hypersensitivity reactions, headache ,vomiting , CNS toxicity in long term systemic use

64. Triple Antibiotic Paste metronidazole , ciprofloxacin, and minocycline combination would be needed -diverse flora in root canal metronidazole -at a high concentration, it cannot kill all the bacteria, indicating the necessity for combination of other drugs Metronidazole ( nitroimidazole ) -a broad spectrum against protozoa & anaerobic bacteria . Minocycline (semisynthetic tetracycline) with a similar spectrum of activity. Ciprofloxacin, a synthetic fluoroquinolone, has a bactericidal mode of action Increase in root thickness and length, resembling normal maturation of the root . the infected area requires a normal blood supply which is no longer in necrotic pulps. Therefore , local application of antibiotics most effective mode for delivering the drug . • 30% reduction in bacteria -2 weeks. successful treatment- sterilization of canals and healing of periapical pathology, immature root development, necrotic pulps, and apical periodontitis • drawbacks of this technique- Development of resistant bacterial strains and tooth discoloration J Phrm Bioallied Science Aug 2012,4(suppl2) S230-233

65. New era of antimicrobial therapeutics  There has been an urgent need for new avenues of therapeutic treatment, and a new era of prophylytic (preventative) treatment has begun. Here the most plausible approaches are : - antimicrobial peptides -bacteriophage therapy -bacterial vaccines -cationic peptides -cyclic D,L-a-peptides -Bacterial interference

66. Newer antimicrobial agents in use Newer Antibiotics in Use Cefepime - 4th Generation cefalosporin Aztreonam Linezolid Tigecycline Teicoplanin Levofloxacin/ Moxifloxacin Imipenem / Meropenem Daptomycin Tigecycline Dalfopristin-quinupristin

67. Newer antifungals in use Voriconazole , ravuconazole , and posaconazole     Echinocandins and pneumocandins are a new class of antifungals Acylhydrazones New antivirals in use Doravirine Ribavirin Phosphonoformate

68. Public Health Significance Only little is known about the occurrence, fate, effects and risks associated with the release of antibiotics and other drugs into the environment. There is still a lack of fundamental data on the occurrence, fate and effects of antimicrobials in the environment needed for proper risk assessment and risk management both for humans and the environment. Although antibiotics are used by patients outside hospitals, in livestock attention should also be paid to their use in hospitals.

69. Emergence of resistance to multiple antimicrobial agents in pathogenic bacteria has become a significant public health threat as there are fewer, or even sometimes no, effective antimicrobial agents available for infections caused by these bacteria. Gram‐positive and Gram‐negative bacteria are both affected by the emergence and rise of antimicrobial resistance . Increasing resistance to antimicrobial agents that are important in the treatment of human diseases, such as fluoroquinolones and third-generation cephalosporins for the treatment of Salmonella and Campylobacter infections, has significant public health implications

70. Awareness about antimicrobial resistance Medical colleges &health education

71. CONCLUSION The therapeutic benefit of antimicrobial agents should be balanced with their unintended adverse consequences . Inappropriate antibiotic use is associated with antibiotic resistance and Clostridium defficile infections , Antimicrobial drugs prescribing should be prudent, thoughtful and rational.

72. References Goodman & Gilman . The pharmacologic basis of therapeutics :2011:12 th edition:1365-1382 K.D.Tripathi Essentials of Medical Pharmacology:2013:7th edition:702-930 Franklin S.Weine . Endodontic Therapy:2003:6th edition:450-560 Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard JR. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clinical infectious diseases. 2011 Feb 15;52(4):e56-93. ntology 2000. 2002 Jan;28(1):106-76. Cohen ML. Epidemiology of drug resistance: implications for a post—antimicrobial era. Science. 1992 Aug 21;257(5073):1050-5.

73. References Lorian V, editor. Antibiotics in laboratory medicine. Lippincott Williams & Wilkins; 2005 . Taneja N, Rao P, Arora J, Dogra A. Occurrence of ESBL & Amp-C [beta]-lactamases & susceptibility to newer antimicrobial agents in complicated UTI. Indian Journal of Medical Research. 2008;127(1):85 . Anderson AD, Nelson JM, Rossiter S, Angulo FJ. Public health consequences of use of antimicrobial agents in food animals in the United States. Microbial Drug Resistance. 2003 Dec 1;9(4):373-9