Antibiotics

Antibiotics and its use in dentistry.
There are various classes of antibiotics mentioned along with antibiotic resistance.

1. ANTIBIOTICS DR. DIPLINA BARMAN 1

2. DEFINITION OF ANTIBIOTICS HISTORY CLASSIFICATION OF ANTIBIOTICS MECHANISM OF ACTION PRINICIPLE OF ANTIBIOTIC THERAPY CHOICE OF AN ANTIMICROBIAL AGENTS COMBINED USE OF ANTIMICROBIAL AGENTS ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS PROPHYLACTIC ANTIBIOTICS ANTIBIOTIC RESISTANCE PUBLIC HEALTH SIGNIFICANCE OF ANTIBIOTICS SUMMARY CONCLUSION REFERENCES CONTENTS 2

3. What is Antibiotic? Substances produced by microorganisms, Selectively suppress the growth , kill other microorganisms at very low concentrations. ‘ Chemotherapeutic agent’ - synthetic compounds, Antimicrobial agent (AMA) - synthetic + naturally obtained drugs that attenuate microorganisms. 3

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5. HISTORY 5

6. 1877 - Pasteur demonstrated Phenomenon of antibiosis . 1929 – Fleming - Penicillium mould - destroy Staphylococcus on the culture plate. He named penicillin but could not purify it. 1941 - Chain and Florey found out the clinical use of penicillin. 1944 -Waksman and his colleagues discovered Streptomycin . 6

7. CLASSIFICATION OF ANTIBIOTICS Chemical structure Mechanism of action Type of organism against which they are active Spectrum of activity Type of action Source 7

8. 1.Sulfonamides and related drugs: Sulfadiazine, Sulfones — Dapsone (DDS), Paraaminosalicylic acid (PAS). 2. Diaminopyrimidines : Trimethoprim , Pyrimethamine . 3. Quinolones : Nalidixic acid, Norfloxacin , Ciprofloxacin, etc. 4.β-lactam antibiotics: Penicillins, Cephalosporins , Monobactams . 5. Tetracyclines : Oxytetracycline , Doxycycline , etc. 6. Nitrobenzene derivative: Chloramphenicol . 7. Aminoglycosides : Streptomycin, Gentamicin , Neomycin, etc. 8. Macrolide antibiotics : Erythromycin, Clarithromycin , Azithromycin , etc . 8 Chemical structure

9. 9. Lincosamide antibiotics: Lincomycin , Clindamycin . 10. Polypeptide antibiotics: Polymyxin -B, Bacitracin . 11. Glycopeptides: Vancomycin 12. Oxazolidinone : Linezolid . 13. Nitrofuran derivatives: Nitrofurantoin . 14. Nitroimidazoles : Metronidazole, Tinidazole . 15. Nicotinic acid derivatives: Isoniazid , Pyrazinamide . 16. Polyene antibiotics: Nystatin , Amphotericin -B. 17. Azole derivatives: Miconazole , Clotrimazole , Ketoconazole , Fluconazole 18. Others: Rifampin , Viomycin , Ethambutol , Thiacetazone , Griseofulvin . 9

10. 1. Inhibit cell wall synthesis: Penicillins, Cephalosporins , Vancomycin , Bacitracin . 2. Cause leakage from cell membranes: Polypeptides— Polymyxins , Bacitracin , Polyenes—Amphotericin B, Nystatin . 3. Inhibit protein synthesis: Tetracyclines , Chloramphenicol , Erythromycin, Clindamycin . 4. Cause misreading of m-RNA code and affect permeability: Aminoglycosides — Streptomycin, Gentamicin , etc. 10 B. Mechanism of action

11. 5. Inhibit DNA gyrase : Fluoroquinolones — Ciprofloxacin. 6. Interfere with DNA function: Rifampicin , Metronidazole. 7. Interfere with DNA synthesis: Acyclovir, Zidovudine . 8.Interfere with intermediary metabolism: Sulfonamides, Sulfones , Trimethoprim , Pyrimethamine , Ethambutol . 11

12. 1. Antibacterial: Penicillins, Aminoglycosides , Erythromycin, etc. 2. Antifungal: Griseofulvin , Amphotericin B, Ketoconazole , etc. 3. Antiviral: Acyclovir, Amantadine , Zidovudine , etc. 4. Antiprotozoal : Chloroquine , Pyrimethamine , Metronidazole, etc 5. Antihelmintic : Mebendazole , Niclosamide , Diethyl carbamazine , etc . 12 C. Type of organisms against which primarily active :

13. D. Spectrum of activity Narrow spectrum Penicillin G Streptomycin Erythromycin   Broad spectrum Tetracyclines Chloramphenicol   13

14. SULFONAMIDES First antimicrobial agents (AMAs) Effective against pyogenic bacterial infections. Primarily bacteriostatic - gram positive , gram negative bacteria. Used in combination with trimethoprim (as cotrimoxazole ) or pyrimethamine (for malaria). Doses and Uses Sulfadiazine : 0.5 g QID to 2 g TDS - meningitis Sulfadoxine : used in combination with pyrimethamine for malaria. Adverse effects Nausea, vomiting and epigastric pain. Crystalluria is dose related but infrequent now. Hypersensitivity : 2–5% patients.   14

15. COTRIMOXAZOLE Sulfamethoxazole + trimethoprim - 20 : 1. Individually- bacteriostatic Combination- Bacteriocidal . Uses: tonsillitis, pharyngitis , sinusitis, otitis media. Orodental infections, Patients allergic to β- lactam antibiotics. Dose : 80 mg trimethoprim + 400 mg sulfamethoxazole tab BD for 2 days then 1 BD. Eg . Septran . Mechanism of action 15

16. FLUOROQUINOLONES Active against : gram positive cocci , anaerobes. Mechanism of action : Inhibit the enzyme bacterial DNA gyrase which nicks double-stranded DNA, introduces negative supercoils and then reseals the nicked ends. 16

17. CIPROFLOXACIN Most potent first generation FQ. Rapid bactericidal activity. β- lactam and aminoglycoside resistant bacteria. Contraindicated during pregnancy . Eg . CIPLOX 250, 500, 750 mg tab 17 Uses: Urinary tract infection, typhoid fever. Ciprofloxacin + metronidazole = refractory mixed infections like periodontitis .

18. Norfloxacin Less potent than ciprofloxacin. Primarily used for urinary and genital tract infections. NORFLOX 200, 400, 800 mg tab. Ofloxacin Intermediate between ciprofloxacin and norfloxacin . Suited for orodental infections as it is active against certain anaerobes. ZANOCIN 100, 200, 400 mg tab. 18

19. METRONIDAZOLE Broad spectrum antiprotozoal drug. Selectively toxic to anaerobic microorganisms. Pharmacokinetics completely absorbed from the small intestines. metabolized in liver primarily by oxidation excreted in urine Adverse effects Most common : anorexia, nausea, bitter or metallic taste. Less frequent side effects are—headache, glossitis , dryness of mouth, Contraindicated in the first trimester of pregnancy. FLAGYL, METROGYL, METRON, 200, 400 mg tab. 19 NITROIMIDAZOLES Bacteriostatic

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21. USES Dose : 200–400 mg TDS. ANUG (in combination with either penicillin V, amoxicillin, erythromycin or tetracycline). Periodontitis, pericoronitis , acute apical infections and some endodontic infections also respond well to metronidazole given for 5–7 days. Amoebic infection. 21

22. Ornidazole Activity similar to metronidazole , but it is slowly metabolized for amoebiasis , anaerobic infections. ORNIDA 500 mg tab, 125 mg/5 ml suspension.   22

23. Beta- Lactam Antibiotics Antibiotics having a β- lactam ring. penicillins and cephalosporins . most commonly used antibiotics in dentistry. Mechanism of action—inhibition of synthesis of the bacterial peptidoglycan cell wall. Bacterial cell wall synthesis 23

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25. PENICILLINS First antibiotic - 1941. Originally obtained from the fungus Penicillium notatum , but presently from P. chrysogenum . Consists of fused thiazolidine and β- lactam rings to which side chains are attached through an amide linkage. 25

26. c. Extended spectrum penicillins : i ) Aminopenicillins : Ampicillin , Amoxicillin. ii) Carboxypenicillins : Carbenicillin . iii) Ureidopenicillins : Piperacillin . 26

27. PENICILLIN-G (BENZYL PENICILLIN ) Narrow spectrum Activity is limited primarily to gram-positive bacteria and few others. Streptococci , pneumococci gram-positive bacilli and spirochetes are highly sensitive. Many bacteria are inherently insensitive to PnG . Acquired resistance through production of penicillinase . 27

28. Adverse effects: Pain at i.m. injection site, nausea on oral ingestion. In large doses, toxicity to the brain may be manifested as mental confusion, muscular twitchings. Hypersensitivity. Uses: Dental infections like those caused as a sequelae of carious lesions and are caused by both aerobic and anaerobic bacteria. Periodontal abcess , periapical abscess , pericoronitis , acute suppurative pulpitis , ANUG , cellulitis etc. Pharyngitis , tonsillitis, otitis media etc. 28

29. SEMISYNTHETIC PENICILLINS P roduced by chemically combining specific side chains (in place of benzyl side chain of PnG ) or by incorporating specific precursors in the mould cultures. Eg . P rocaine penicillin and B enzathine penicillin are salts of PnG and not semisynthetic penicillins. The aim of producing semisynthetic penicillins has been to overcome the shortcomings of PnG , which are: 1. Poor oral efficacy. 2. Susceptibility to penicillinase . 3. Narrow spectrum of activity. 4. Hypersensitivity reactions 29

30. Phenoxymethyl penicillin (Penicillin V) Acid stable. Better oral absorption. Plasma t½ is 30–60 min. Antibacterial spectrum is similar to penicillin G but it is about 1/5 as active against Neisseria , other gram-negative bacteria and anaerobes. Dose: 250–500 mg, children 125–250 mg; given 6 hourly. 30

31. PENICILLINASE-RESISTANT PENICILLINS Have side chains that protect the β- lactam ring from attack by staphylococcal penicillinase . Methicillin   It is highly penicillinase resistant but not acid resistant—must be injected. Cloxacillin   Highly penicillinase as well as acid resistant. More active than methicillin against penicillinase producing Staphylococcus. 31

32. S emisynthetic penicillins active against gram-negative bacilli. Ampicillin Active against all organisms sensitive to PnG . More active than PnG for Strep. viridans and enterococci (therefore better suited for dental infections). Dose: 0.5–2 g oral/ i.m ./ i.v . depending on severity of infection, every 6 hours; children 25–50 mg/kg/day. 32 EXTENDED SPECTRUM PENICILLINS

33. USES: 1. Urinary tract infections 2. Respiratory tract infections 3. Meningitis 4. Subacute bacterial endocarditis : preferred over PnG .   Adverse effects: Diarrhoea is frequent after oral administration of ampicillin   Interactions: Hydrocortisone inactivates ampicillin if mixed in the i.v . solution.   33

34. C lose congener of ampicillin . Oral absorption is better. Incidence of diarrhoea is lower. One of the most frequently used antibiotics for treatment of dental infections 250–500 mg TDS given for 5 days. Prophylaxis of local wound infection , distant infection ( endocarditis ) following dental surgery in susceptible patients. Dose: 0.25–1 g TDS oral/ i.m . 34 AMOXICILLIN

35. F amily of enzymes produced by many gram-positive and gram-negative bacteria that inactivate β- lactam antibiotics by opening the β- lactam ring. Eg .: clavulanic acid, sulbactam and tazobactam . Obtained from Streptomyces clavuligerus . Permeates the outer layers of the cell wall of gram negative bacteria and inhibits the periplasmically located β- lactamase . 35 BETA-LACTAMASE INHIBITORS Clavulanic acid

36. Addition of clavulanic acid re-establishes the activity of amoxicillin against β- lactamase producing resistant Staph. Aureus . Skin and soft tissue infections, dental infections. Eg . AUGMENTIN, Amoxicillin 250 mg + clavulanic acid 125 mg tab; 1–2 tab TDS, severe infections 4 tabs 6 hourly. 36 USES:

37. CEPHALOSPORINS Group of semisynthetic antibiotics. Obtained from a fungus Cephalosporium . Mechanism of action : Bactericidal action. Chemically related to penicillins; the nucleus consists of a β - lactam ring fused to a dihydrothiazine ring. 37

38. Classification of Cephalosporins First generation Second generation Third generation Fourth 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 of third generation but highly resistent to beta lactamases Parenteral - Cephalothin Cefazolin Cephaloridine Oral- Cephalexin Cephadine Cefadroxil Parenteral - Cefuroxim Cefoxitin Oral- Cefaclor Cefuroxim axetal Parenteral - Cefotaxim Ceftizoxime Ceftraxone Cefoperazone Oral- Cefexime Parenteral - Cefepime Cefiperome 38

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40. FIRST GENERATION CEPHALOSPORINS 1960 , high activity against gram-positive but weaker against gram-negative bacteria. Cefazolin PnG sensitive organisms, i.e. streptococci , meningococci , C. diphtheriae , H.influenzae etc. Preferred parenteral first generation cephalosporin, especially for surgical prophylaxis. Dose: 0.25 g 8 hourly (mild cases), 1 g 6 hourly (severe cases) i.m . or i.v .   40

41. Cephalexin Orally effective. Used in dentistry as an alternative to amoxicillin. Dose: 0.25–1 g 6–8 hourly (children 25–100 mg/kg/day). Cefadroxil C lose congener of cephalexin . G ood tissue penetration including that in alveolar bone (tooth socket) E xerts more sustained action at the site of infection. Dose : 0.5–1 g BD. DROXYL 0.5, 1 g tab, 41

42. Third generation Cephalosporins Activity against gram-negative Enterobacteriaceae ; some inhibit Pseudomonas as well. Cefotaxime : 3 rd generation anaerobic & some gram positive bacteria meningitis (gram negative bacilli), life threatning /hospital aquired infections. septicaemias and infections in immunocompromised patients. 42

43. Tetracycline Broad spectrum antibiotic. Primarily bacteriostatic . Inhibit protein synthesis by binding to 30S ribosomes in susceptible organism. Tetracyclines have chelating property. 43 ADMINISTRATION   Orally taken ½ hr before or 2 hr after food Not recommended by i.m . route. PRECAUTIONS: 1. S hould not be used during pregnancy, lactation and in children. 2. Should be avoided in patients on diuretics. 3. S hould be used cautiously in renal or hepatic insufficiency. 4 . Should not mix injectable tetracyclines with penicillin. Broad spectrum antibiotics

44. Epigastric pain, nausea, vomiting and diarrhoea . Acute hepatic necrosis in pregnant women. Risk of kidney damage . B rown discolouration , ill-formed teeth, more susceptible to caries. Tetracyclines given between 3 months and 6 years of age affect the crown of permanent anterior dentition. Given during late pregnancy or childhood, tetracyclines can cause temporary suppression of bone growth. 44 ADVERSE EFFECTS:

45.   General medical uses: The drug of first choice in: (a) Atypical pneumonia due to Mycoplasma pneumoniae (b) Cholera (c) Brucellosis. (d) Relapsing fever due to Borrelia recurrentis . (g) Rickettsial infections: typhus , Q fever, etc. Uses in Orodental conditions : Periodontal inflammation Chronic periodontitis Juvenile periodontitis 45

46. Broad-spectrum antibiotic. Gram-positive and negative bacteria, rickettsiae , chlamydia , mycoplasma etc. Inhibits bacterial protein synthesis. Attaches to the 50S ribosome and hinder the access of aminoacyl-tRNA to the acceptor site for amino acid incorporation. Primarily bacteriostatic , high concentrations - cidal effect. Rapidly and completely absorbed after oral ingestion. Oral administration —as capsules; 250–500 mg 6 hourly 46 CHLORAMPHENICOL

47. Adverse effects Bone marrow depression 2. Hypersensitivity reactions Rashes, fever etc 3. Irritative effects Nausea, vomiting, diarrhoea , pain on injection. 4. Superinfections 5. Gray baby syndrome : at high doses (~100 mg/kg) USES No indication in dentistry despite its broad-spectrum antimicrobial action. Enteric fever Meningitis As second choice drug (a) to tetracyclines for brucellosis, cholera, rickettsial and chlamydial infections. (b) to erythromycin for whooping cough 47

48. MACROLIDE ANTIBIOTICS Antibiotics having a macrocyclic lactone ring with attached sugars. . ERYTHROMYCIN Isolated from Streptomyces erythreus . Widely employed, mainly as an alternative to penicillin. Narrow spectrum. Active against gram-positive and a few gram-negative organisms. Mechanism of Action Erythromycin is bacteriostatic at low concentration but cidal at high concentrations. Erythromycin acts by inhibiting bacterial protein synthesis. It combines with 50S ribosome subunit and interferes with ‘translocation’. 48

49. Uses : Second choice drug to penicillins for: Periodontal/ periapical abscesses Necrotizing ulcerative gingivitis Postextraction infections Cellulitis , etc. In patients allergic to penicillins, or those with penicillin resistant infections. 49

50. AZITHROMYCIN Has an expanded spectrum. Improved pharmacokinetics. Better tolerability and drug interaction profiles. More active than other macrolides against H. influenzae , and certain anaerobes like Peptostreptococcus , few Clostridia. Better activity against oral spirochetes and gram negative anaerobes. Can be used in orodental infections in place of erythromycin. Dose: 500 mg once daily 1 hour before or 2 hours after food. 50 NEWER MACROLIDES

51. CLINDAMYCIN Dental infections - anaerobic bacteria. Patients resistant to penicilin . Dentoalveolar abscesses , bone infections caused by Staphylococci or Bacteroides . Alternative antibiotic for prophylaxis of endocarditis due to postextraction bacteraemia in patients with damaged heart valves or other risk factors. Dose: 150–300 mg QID oral; 200–600 mg i.v . 8 hourly. 51

52. AMINOGLYCOSIDES Broad spectrum of action Rapid bactericidal effect Inhibitors of Protein Synthesis Systemic aminoglycosides Streptomycin Amikacin Gentamicin Kanamycin Tobramycin Topical aminoglycosides Neomycin Framycetin USES Gram-positives, except Streptococus and Enterococcus . Combine with aminoglycoside ( Gentamicin or Streptomycin) & penicillin, ampicillin or vancomycin produces a synergistic bactericidal effect. In serious infection, with beta- lactams or fluoroquinolones . Gram-negative nosocomial infections 52

53. TOXICITIES Ototoxicity -Cochlear damage - Vestibulaar damage Nephrotoxicity Neuromuscular blockade 53

54. Polyenes : Amphotericin B (AMB), Nystatin , AMPHOTERICIN B (AMB) Combine with ergosterol present in fungal cell membrane, and create micropores through which ions, amino acids and other water-soluble substances move out. Candida albicans , Histoplasma capsulatum ,, aspergillus etc. Not absorbed orally, excretion occurs slowly both in urine and bile. Uses: can be used topically for oral, vaginal and cutaneous candidiasis 54 ANTIFUNGAL DRUGS

55. NYSTATIN Used only locally. In dentistry, topically applied nystatin is the 2nd choice drug to clotrimazole for oral thrush, denture stomatitis , antibiotic associated stomatitis , corticosteroid associated oral candidiasis and mucocutaneous candidiasis of lips, etc 1 mg tablet is placed in the mouth to dissolve slowly 4 times a day, or it can be crushed and suspended in glycerine for application on the lesions. Bitter foul taste and nausea are the side effects. 55

56. To determine the severity of infection. To evaluate state of patient’s host defense mechanisms. To determine whether patient should be treated by general dentist or specialist. To treat infection surgically. To support the patient medically. Choose and prescribe appropriate antibiotic. Proper antibiotic administration. Monitoring the patient. 56 PRINCIPLES OF ANTIBIOTIC THERAPY

57. CHOICE OF AN ANTIMICROBIAL AGENT 2.Organism related considerations 57

58. Age : Larger doses of chloramphenicol - grey baby syndrome. Sulfonamides displace bilirubin from protein binding sites—can cause kernicterus in the neonate. The t½ of aminoglycosides is prolonged in the elderly and they are more prone to develop VIII nerve toxicity. Tetracyclines accumulate in the developing teeth and bone — discolour and weaken them— are contraindicated below the age of 6 years. 58

59. Renal and hepatic function 59

60. Local factors : Presence of pus and secretions Presence of necrotic material or foreign body Haematomas foster bacterial growth Lowering of pH at site of infection Drug allergy : Erythromycin or Clindamycin are the alternative drugs for dental infection in patients allergic to penicillin 60

61. Impaired host defence : Pyogenic infections occur readily in neutropenic patients; while if cell-mediated immunity is impaired (e.g. AIDS), infections by low-grade pathogens and intracellular organisms abound. In an individual with normal host defence , a bacteriostatic AMA may achieve cure; while intensive therapy with cidal drugs is imperative in those with impaired host defence . 61

62. Pregnancy 62

63. Genetic factors: Sulfonamides, chloramphenicol and fluoroquinolones are likely to produce haemolysis in G-6PD deficient patient. Organism-related considerations Antibiotic susceptibility test Disc diffusion test 63

64. Minimum inhibitory concentration (MIC) The lowest concentration of an antibiotic which prevents visible growth of a bacterium determined. Done in microwell culture plates using serial dilutions of the antibiotic. For treatment purposes, the dosage of antibiotic given should yield a peak body fluid concentration 3-5 times higher than the MIC or MIC x 4 = dosage to obtain peak achievable concentration. 64

65. Broth dilution methods showing MIC and MBC Minimum bactericidal concentration (MBC) MBC is the concentration of the antibiotic which kills 99.9% of the bacteria. 65

66. DRUG FACTORS Spectrum of activity: For definitive therapy → a narrow spectrum drug is preferred. For empirical therapy → often a broad-spectrum drug is preferred. Type of activity: A bactericidal antibiotic may be preferred over bacteriostatic . Acute infections generally resolve faster with bactericidal than with bacteriostatic drugs 66

67. Relative toxicity: Obviously, a less toxic antibiotic is preferred, e.g. a β- lactam over an aminoglycoside or erythromycin over clindamycin . Pharmacokinetic profile: A drug, which penetrates better and attains higher concentration, is likely to be more effective. 67

68. COMBINED USE OF ANTIMICROBIALS More than one AMAs are frequently used concurrently. The objectives of using antimicrobial combinations are: To achieve synergism: Eg .: combination of a β- lactamase inhibitor clavulanic acid or sulbactam with amoxicillin or ampicillin for β- lactamase producing H. influenzae . Penicillin/ ampicillin + streptomycin/ gentamicin for enterococcal SABE. Penicillin + sulfonamide for actinomycosis 68

69. 2. To reduce severity or incidence of adverse effects. 3. To prevent emergence of resistance. 4. To broaden the spectrum of antimicrobial action. Treatment of mixed infection Initial treatment of severe infections 69

70. Disadvantages of antimicrobial combinations They foster a casual rather than rational outlook in the diagnosis of infections and choice of AMA. 2. Increased incidence and variety of adverse effects. Toxicity of one agent may be enhanced by another, e.g. vancomycin tobramycin and gentamicin + cephalothin produce exaggerated kidney failure. 3. Increased chances of superinfections . 4. Higher cost of therapy. 70

71. PROPHYLACTIC USE OF ANTIMICROBIALS Refers to the use of AMAs for preventing the setting in of an infection or suppressing contacted infection before it becomes clinically manifest. Antimicrobial prophylaxis in dentistry This is warranted for two distinct purposes viz. (a) prevention of local wound infection (b) prevention of distant infection (e.g. bacterial endocarditis ) in predisposed patients following dental procedures. 71

72. Prophylaxis of dental wound infection Clear risk of wound infection. Simple extractions and minor periodontal procedures does not require. Incidence of postoperative infection is higher when oral surgery had lasted 2 hours or more eg . prosthesis insertion into the bone or soft tissue, such as dental implants and extensive reconstructive surgeries. All orodental procedures which disturb/ damage mucosa including extractions, scaling, etc. need to be covered by prophylaxis in diabetics, corticosteroid recipients and other immunocompromised subjects 72

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74. PROPHYLAXIS OF DISTANT INFECTION Gentamicin 120 mg (2 mg/kg) i.m ./ i.v . may be given just before the dental procedure in addition to amoxicillin (or its substitute) and another dose of amoxicillin 500 mg (12.5 mg/kg) be repeated 6 hours after the procedure. If patient is allergic to penicillin : vancomycin 1 g (20 mg/kg) i.v . over 2 hours + gentamicin 120 mg (2 mg/kg) i.m ./ i.v . just before the procedure. 74

75. FAILURE OF ANTIMICROBIAL THERAP Y 1. Improper selection of drug, dose, route or duration of treatment. 2. Treatment begun too late. 3. Failure to take necessary adjuvant measures, e.g . drainage of abscesses . 4.Poor host defence —as in leukaemias , neutropenia and other causes; especially if bacteriostatic AMA is used. 5. Infecting organism present behind barriers, such as vegetation on heart valves (in SABE), inside the eyeball, blood-brain barrier. 75

76. Penicillins . Cephalosporins . Erythromycins. Clindamycin and Lincomycin . Metronidazole . Aminoglycosides . Fluoro quinolones – ciprofloxacin. Sulfonamides and trimethoprim 76 ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS:

77. AHA RECOMMENDATIONS PROPHYLAXIS RECOMMENDED: 1.Extractions 2.Periodontal surgery 3.Implants placement 4.Endodontic surgery 5.Subgingival antibiotic fiber strips 6.Intraligamentary LA injections. NOT RECOMMENDED: 1.Restorative dentistry 2.LA injections 3.Intracanal endodontic treatment 4.post-op suture removal 5.Oral radiographs 77

78. Odontogenic infection, oral and maxillofacial implications Initial stage- Aerobic bacteria invade. Severe infection- Aerobic and anaerobic bacteria invade. Advanced stage- anaerobic infection. Pericoronitis : Acute pericoronitis , if severe, may require antibiotic therapy. Treatment - debridement, drainage of the site, penicillin 500 mg qid , amoxacillin 500mg qid , clindamycin 300mg qid Dento Alveolar Abscess: Penicillin is the drug of choice 78

79. Soft tissue wounds : open for six hours or more, (considered infected,) if primary closure is elected, a delayed primary closure is preffered . delayed technique cannot be utilized,-antibiotic support is helpful. early primary closure -amoxicillin with clavulanic acid Chronic inflammatory periodontal diseases : TOPICAL MEASURES - Tetracyclins , metronidazole 250mg tid , , penicillins500mg qid , cephalosporins . ANUG Topical measures with systemic antibiotic penicillin, metronidazle 400mg qid , 79

80. For hospitalalized / when inta -venous therapy is indicated- Aqueous penicillin, 2 million Units IV Q6h, metronidazole 500mg q6h for 4 - 6 weeks OR Ampicillin / sulbactum 1.5 to 3.0 gm IV q6h for 2 days then amoxacillin / clavulanate ( augmentin )875, 125.mg PO bd for 4 to 6 weeks. For out patient treatment penicillin V 2gm + metronidazole 500mg q8h for 2 to 4 weeks after last sequestrum removal and patient with out symptons . OR cefoxitin 1 gm q8h IV OR IM cephalexin 500mg q6h PO for 2 to 4 weeks OR clindamycin 600, 900mg q6h IV then clindamycin 300, 450 mg PO. Antibiotic regimen for osteomyelitis 80

81. Regimen for fracture therapeutic doses for 10 to 14 days. should begin as early as possible after diagnosis. Pre-operatively penicillin 2 million units or cefazolin 0.5 gm-1.5 gm 12 hr [25- 50 mg/kg]. Post-operatively Penicillin 500mg 6 hr [30-40 mg /kg] Cephalexin 500mg 6 hr [25- 50 mg/kg] In suspected intra-cranial contamination - Pre-operatively- naficillin 2-6 gm 6hr+ gentamycin 3-5mg/kg 8 hr Post- operatrively - cephalexin 500mg 6 hr[25-50 mg/kg] 81

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84. 84 ANTIBIOTIC RESISTANCE Resistance arises through one of three mechanisms: natural resistance in certain types of bacteria, genetic mutation, one species acquiring resistance from another.

85. 85 PUBLC HEALTH IMPORTANCE OF THE ANTIBIOTICS Limited supportive care provided by health professionals. Difficulty in treating various infections Antibiotic Resistance – Economic burden to the healthcare system. Increased prevalence of resistant and multi-resistant bacterial strains An overview of antimicrobial resistance and its public health significance, Brazilian journal of Microbiology 45, 1, 1-5(2014)

86. 86 S U M M A R Y DEFINITION OF ANTIBIOTICS HISTORY CLASSIFICATION OF ANTIBIOTICS COMBINED USE OF ANTIMICROBIAL AGENTS ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS PROPHYLACTIC ANTIBIOTICS ANTIBIOTIC RESISTANCE PUBLIC HEALTH SIGNIFICANCE OF ANTIBIOTICS

87. Antibiotics are used to treat infections and are also responsible for making them more difficult to treat because of their misuses and development of resistance. The only way to keep antibiotics useful is to use them appropriately and judiciously . CONCLUSIONS 87

88. THE PHARMACOLOGIC BASIS OF THERAPEUTICS GOODMAN & GILMAN 11 TH ED ESSENTIALS OF MEDICAL PHARMACOLOGY K.D.TRIPATHI 5 TH ED TEXTBOOK OF PHARMACOLOGY - TOPAZIAN TEXTBOOK OF MUCROBIOLOGY- C. P. BAVEJA 3 RD ED. BURKET’S ORAL MEDICINE, 12 TH ED SYMPOSIUM ON ANTIMICROBIAL THERAPY, GENERAL PRINCIPLES OF ANTIMICROBIAL THERAPY AN OVERVIEW OF ANTIMICROBIAL RESISTANCE AND ITS PUBLIC HEALTH SIGNIFICANCE, BRAZILIAN JOURNAL OF MICROBIOLOGY 45, 1, 1-5(2014) REFERENCES 88

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