Antibiotics in Oral and Maxillofacial Surgery

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Antibiotics in Oral and Maxillofacial Surgery

  1. 1. ANTIBIOTIC S IN ORAL & MAXILLOFACIAL SURGERY PRESENTED BY: DR HANEEF MODERATED BY : DR SHIREEN FATIMA
  2. 2. CONTENTS  HISTORY & INTRODUCTION  CLASSIFICATION  PRINCIPLES OF ANTIBIOTIC THERAPY  ANTIBIOTIC SIDE EFFEECTS  ANTIBIOTIC RESISTANCE  ANTIBIOTIC FAILURES  MISUSE OF ANTIBIOTICS  ANTIBIOTIC PROPHYLAXIS  INDIVIDUAL DRUGS - Chemistry - Mechanisms of action - Spectrum - Sensitive organisms - Resistance - Adverse effects - Uses  SPECIAL CONDITIONS- Pregnancy - Chronic renal failure - Hepatic failure - Diabetes mellitus - Head and neck infections in immunocompromised state  NEWER ANTIBIOTICS  ANTICANCER DRUGS  SHOULD ANTIBIOTICS BE USED?  CONCLUSION  REFERENCES
  3. 3. INTRODUCTION ANTIBIOTIC TERMINOLOGY DEFINITION: SUBSTANCES DERIVED FROM MICROORGANISMS WHICH SUPPRESS THE GROWTH / KILL THE MICROORGANISMS AT A VERY LOW CONCENTRATION OR A CHEMICAL SUBSTANCE PRODUCED BY MICROORGANISMS HAVING THE PROPERTY OF INHIBITING THE GROWTH OF OR DESTROYING OTHER MICROORGANISMS IN HIGH DILUTION CHEMOTHERAPY :TREATMENT OF SYSTEMIC INFECTIONS WITH SPECIFIC DRUGS THAT SELECTIVELY SUPPRESS THE INFECTING MICROORGANISM WITHOUT SIGNIFICANTLY AFFECTING THE HOST.
  4. 4. TERMINOLOGY  Antimicrobial - This term refers to both antibiotics and synthetic agents active against microbes.  Microcidal - (Bacteriocidal. Vincidal, Fungicidal) The organism is lysed or killed by direct damage on susceptible cell targets.  Microstatic - (Bacteriostatic, Virostatic, Fungistatic)  The organism is reversibly inhibited at specific metabolic processes.  action and host defense mechanisms. Multiplication of the organism is inhibited.  Narrow Spectrum Antimicrobial - An antimicrobial that acts on a limited number of microbial species, e.g. Nitroimidiazole derivatives etc  Broad Spectrum Antimicrobial - An antimicrobial that acts on a wide range of species, e.g., erythromycin for Gram positive. Gram negative, Legionella, Mycoplasma, etc.
  5. 5. HISTORY  (A) The period of emperical use South American Indians used the bark of the cinchona tree to extract quinine to control malaria and mercury was known to cure syphilis in the late 1400's,‘mouldy curd’ by Chinese on boils, mercury by Paracelsus (16th century) for syphilis, Cinchona bark (17th century) for fevers.  (B) Ehrlich’s phase of dyes & organometallic compounds (1890- 1935): methylene blue, tryptan red, etc. He coined the term ‘Chemotherapy’ 5
  6. 6. HISTORY  (C) The Modern Era of chemotherapy was ushered in by Domagk in 1935 by demonstrating the therapeutic effect of prontosil , a sulfonamide dye in pyogenic infection. Other pioneers in the field of antibiotics were Louis Pasteur, Alexander Fleming, Chain Florey , Waksman. All received Nobel prizes for their discoveries. 6
  7. 7. CLASSIFICATION BASED ON TYPE OF ORGANISM THEY ACT UPON: 1. Antibacterial – penicillin amino glycosides erythromycin 2. Antifungal - griseofulvin amphotericin ketoconazole 3. Antiviral- acyclovir amantidine zidovudine 4. Antiprotozoal- metronidazole chloroquine
  8. 8. BASED ON MECHANISM OF ACTION: 1. Inhibit cell wall synthesis: penicillins cephalosporins cyclosporins 2. Leakage from cell membrane: polypeptides-polymixin, bacitracin polyenes- amphotericin B ,nystatin 3. Inhibits protein synthesis: tetracyclines, chloramphenicol, erythromycin, clindamycin. 4. Causes misreading of m.RNA: aminoglycosides 5. Inhibits DNA gyrase: fluoroquinolones 6. Interfere with DNA function : rifampin, metronidazole. 7. Interfere with DNA synthesis: acyclovir, idoxuridine.
  9. 9. CHEMICAL STRUCTURE Sulfonamides and related drugs : ○ Sulfones – Dapsone (DDS) ○ Para amino salicylic acid (PAS) Diaminopyrimidines ○ Trimethoprim, pyrithamine Quinolones ○ Nalidixic acid, Norfloxacin, Ciprofloxacin etc  - lactam antibiotics ○ Penicillins, cephalosporins, monobactams, carbapenems Tetracyclines ○ Oxytetracycline, Doxycycline etc Nitrobenenzene Derivative ○ Chloramphenicol Aminoglycosides ○ Streptomycin Gentamycin, Neomycin etc
  10. 10. - Macrolide antibiotics ○ Erythromycin, Roxithromycin, Azithromycin etc  Polypeptide antibiotics ○ Polymyxin – B, colistin, Bacitracin, Tyrothricin etc  Glycopeptides ○ Vancomycin, Teicoplamin  Oxazolidinase ○ Linezolid  Nitrofuran derivatives ○ Nitrofurantoin, Furazolidine  Nitroimidazoles ○ Metronidazole, Tinidazole  Polyene antibiotics ○ Nystatin, Amphotericin – B, Hamycin  Azole derivatives ○ Miconazole, clotrimazole, ketoconazole, fluconazole
  11. 11. SPECTRUM OF ACTIVITY  Narrow spectrum Penicillin G, streptomycin and erythromycin.  Broad spectrum Tetracyclines, chloramphenicol.  Extended spectrum Semi synthetic Penicillins, new cephalosporins, aminoglycoside.
  12. 12. TYPE OF ORGANISMS AGAINST WHICH PRIMARILY ACTIVE :  Antibacterial Penicillins, Aminoglycosides, erythromycin etc  Antifungal Griseofulvin, amphotericin B, ketoconazole etc  Antiviral Idoxuridine, Acyclovir, Amantadine, Zidovudine etc  Antiprotozoal Chloroquine, pyrimethamine, metronidazole etc  Antihelminthic Mebendazole, nicosamide, diethyl carbamazine etc
  13. 13. CLASSIFICATION (v) TYPE OF ACTION: 13 Primarily Bacteriostatic Primarily Bactericidal Sulfonamides Tetracyclines Chloramphenicol Erythromycin Ethambutol Penicillins , Cephalosporins, Aminoglycosides, Vancomycin, Ciprofloxacin, Isoniazid , Rifampin, Cotrimoxazole,
  14. 14. SOURCE  Fungi  Penicillin, Cephalosporin, Griseofulvin.  Bacteria  Polymyxin B, Colistin, Bacitracin, Tyrothricin Aztreonam.  Actinomycetes  Aminoglycosides, Tetracyclines, Chloramphenicol, Macrolides, Polyenes.
  15. 15. PRINCIPLES OF ANTIBIOTIC THERAPY PRINCIPLE 1: TO DETERMINE THE SEVERITY OF INFECTION PRINCIPLE 2: TO EVALUATE STATE OF PATIENT’S HOST DEFENSE MECHANISMS PRINCIPLE 3:TO DETERMINE WHETHER PATIENT SHOULD BE TREATED BY GENERAL DENTIST OR SPECIALIST PRINCIPLE 4:TO TREAT INFECTION SURGICALLY
  16. 16. PRINCIPLE 5 :TO SUPPORT THE PATIENT MEDICALLY PRINCIPLE 6 : CHOOSE AND PRESCRIBE APPROPRIATE ANTIBIOTIC PRINCIPLE 7 : PROPER ANTIBIOTIC ADMINISTRATION PRINCIPLE 8 :MONITORING THE PATIENT
  17. 17. DETERMINATION OF THE SEVERITY OF INFECTION  Complete history-Time of onset -Duration of infection -Rapidity of progress  Eliciting patient’s symptom  Physical examination
  18. 18. DIFFERENCES BETWEEN CELLULITIS AND ABSCESS CHARACTERISTIC CELLULITIS ABSCESS Duration Acute Chronic Pain Severe and generalized Localized Size Large Small Localization Diffuse borders Well circumscribed Palpation Doughy to indurated Fluctuant Presence of pus No Yes Bacteria Aerobic Anaerobic
  19. 19. 2)TO EVALUATE STATE OF PATIENT’S HOST DEFENSE MECHANISMS  Uncontrolled metabolic diseases e.g. – uremia, alcoholism, malnutrition, severe diabetes (decreased function of leucocytes, decreased chemotaxis, decreased phagocytosis, decreased bacterial killing)  2- Immuno Suppressing diseases Interfere with host defense mechanism e.g.- leukemias, lymphomas, malignant tumours  3- Immuno Supressing drugs e.g.- cancer chemotherapeutic drugs Immunosuppressive agents
  20. 20. 3)TO DETERMINE WHETHER PATIENT SHOULD BE TREATED BY GENERAL DENTIST OR SPECIALIST  Criteria for referral to a specialist : 1.Rapid progressive infection 2.Difficulty in breathing 3.Difficulty in swallowing 4.Fascial space involvement 5.Elevated temperature(>101 degree F) 6.Severe jaw trismus(<10mm) 7.Toxic appearance
  21. 21. 4)TO TREAT INFECTION SURGICALLY GOALS : 1.To remove the cause of infection 2.To provide drainage of accumulated pus and necrotic debris MODES : 1.Endodontic treatment 2.Extraction 3.Incision and drainage +extraction endodontic treatment Drainage of pus Reduction in tissue tension Improved local blood supply and increased delivery of host defenses
  22. 22. 5)TO SUPPORT THE PATIENT MEDICALLY Odontogenic infection Pain and swelling No adequate fluid and nutritional intake Depressed host defenses Adequate analgesics and fluid intake
  23. 23. 6)CHOOSE AND PRESCRIBE APPROPRIATE ANTIBIOTIC PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC Identification of causative organism  Scientifically determined either in the laboratory, where the organism can be isolated from pus, blood or tissue or  Empirically based upon the knowledge of the pathogens and clinical presentation of specific infection.
  24. 24. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (I) IDENTIFICATION OF THE CAUSATIVE ORGANISM:-  Scientifically - laboratory  Emperically – knowledge of the pathogenesis & clinical presentation.  Initial emperical therapy instituted with a fair degree of reliability. 24
  25. 25. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC  Typical odontogenic infection is caused by a mixture of aerobic & anaerobic bacteria (70%)  Aerobic bacteria – 5% (gm positive cocci)  Pure anaerobic bacteria – 25% (gm positive cocci – 30% & gm negative rods – 50%)  All are sensitive to penicillin & penicillin like drugs, but Fusobacterium frequently resistant to erythromycin (apprx. 50%) 25
  26. 26. Oral and Maxillofacial Surgery Clinics of NA :2003 TYPE OF INFECTION MICROORGANISMS ODONTOGENIC CELLULITES/ABS CESS STREPTOCOCCUS MILLERI GROUP PEPTOSTREPTOCOCCI PREVOTELLAAND PORPHYROMONAS FUSOBACTERIA RHINOSINUSITIS ACUTE STREPTOCOCCUS PNEUMONIAE HAEMOPHILUS INFLUENZAE HEAD AND NECK ANAEROBES (PEPTOSTREPTOCOCCI, PREVOTELLA PORPHYROMONAS, FUSOBACTERIA) GROUP A BETA-HEMOLYTIC STREPTOCOCCI STAPHYLOCOCCUS AUREUS MORAHELLA CATARRHALIS VIRUSES CHRONIC HEAD AND NECK ANAEROBES FUNGAL ASPERGILLUS RHIZOPUS SP. (MUCOR) NOSOCOMIAL (ESPECIALLY IF INTUBATED) ENTEROBACTERIACEAE (ESPECIALLY PSEUDOMONAS, ACINETOBACTER, ESCHERICHIA COLI) S. AUREUS YEASTS (CANDIDA SPECIES) Major pathogens of head and neck infections
  27. 27. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC Pathobiology of mixed odontogenic infection:- 27 Entry of organisms (aerobic) Effects underlying tissues Cellulitis develops Condtion resolves on treatment Hypoxic acidotic condition Tissue destruction and abscess formation (anaerobic) Production of enzymes and toxins
  28. 28. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC CULTURES SHOULD BE PERFORMED:- 1. Pt. with an infection has compromised host defenses 2. Received appropriate treatment for 3 days without improvement 3. Postoperative wound infection 4. Recurrent infection 5. Actinomycosis is suspected, or 6. Osteomyelitis is present 28
  29. 29. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (II) DETERMINATION OF ANTIBIOTIC SENSITIVITY:-  Not responded to initial antibiotic therapy or a postoperative wound infection – causative agent identified & the antibiotic sensitivity determined. 29
  30. 30. DISK DIFFUSION METHOD RATIONALE :  Antibiotics diffuse into the agar and inhibit the growth of sensitive bacteria in a semicircular zone around the disc.  When the resistance to a given agent is present, the zone radius will be reduced or these will be no zone at all.
  31. 31. Advantages :  Simple to perform  Inexpensive  Provides data within 18 to 24 hours Disadvantages :  It is only semi quantitative and is not useful for many flow growing or fastidious organisms.  It has not been adequately standardized for anaerobic bacteria.
  32. 32. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC  The result of these studies provide the information needed to prescribe the most appropriate antibiotic.  Penicillin is excellent for treatment of streptococcus infection & is good to excellent for the major anaerobes of odontogenic infections.  Erythromycin - Streptococcus, Peptostreptococcus & Prevotella but is ineffective against Fusobacterium. 32
  33. 33. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC  Clindamycin – streptococcus & major anaerobic groups.  Cephalexin – moderately active against streptococcus & is good to excellent against anaerobes.  Metronidazole – no activity against streptococcus but has excellent activity against anaerobes. 33
  34. 34. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (III) USE OF A SPECIFIC, NARROW SPECTRUM ANTIBIOTIC:- Advantages -  less chances of developing resistant organisms. E.g. streptococcus sensitive to penicillin , cephalosporin and tetracycline.  Minimizes the risk of super infections. E.g. moniliasis and gram negative pneumonias 34
  35. 35. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (IV) USE OF THE LEAST TOXIC ANTIBIOTIC:-  Equally effective but less toxic drugs have to be used. E.g. bacteria causing odontogenic infection susceptible to both penicillin and chloramphenicol.  More toxicity present with the latter drug. 35
  36. 36. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (V) PATIENT DRUG HISTORY:-  Previous allergic reactions  Previous toxic reactions  Allergy rate to penicillin - 5 %  Cross sensitivity Penicillins and cephalosporins.  Toxic reactions - identify the drug and precise reaction  Likely to happen again. 36
  37. 37. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (Pharmacologic factors in antibiotic selection) (VI) USE OF A BACTERICIDAL RATHER THAN A BACTERIOSTATIC DRUG:- Advantages: 1. Less reliance on the host resistance 2. killing of the bacteria by the antibiotic itself 3. Faster results 4. Greater flexibility with dosage intervals. Used especially when the host defenses are low. 37
  38. 38. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (VII) USE OF THE ANTIBIOTIC WITH A PROVEN H/O SUCCESS:- Critical observation of the clinical effectiveness over a prolonged period -----assessment of  Frequency of treatment success and failures Frequency of adverse reactions Frequency of side effects Standards for use 38
  39. 39. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (VIII) COST OF THE ANTIBIOTIC:-  Difficult to place a price tag on health.  In some situations, more expensive antibiotic is the drug of choice.  In other situations, there may be a substantial difference in price for drugs of equal efficacy.  Surgeon should consider the cost of the antibiotic prescribed. 39
  40. 40. PRINCIPLES FOR CHOOSING APPROPRIATE ANTIBIOTIC (IX) ENCOURAGE PATIENT COMPLIANCE:-  Dosage interval that encourages compliance OD 80% BID 69% TID 59% QID 35%  Non-compliant start feeling better 3-5 days 50% >7 days 20%  Antibiotic that would have the highest compliance would be the drug given OD for 4 or 5 days. 40
  41. 41. Indications for use of antibiotics  Rapidly progressive swelling  Diffuse swelling  Compromised host defenses  Involvement of facial spaces  Severe pericoronitis  Osteomyelitis
  42. 42. Use of antibiotics is not necessary  Chronic well localized abscess  Minor vestibular abscess  Dry socket  Mild pericoronitis
  43. 43. INDICATIONS OF EMPIRICAL ANTIBIOTIC THERAPY :  The site and feature of the infection have been well defined.  The circumstances leading to the infection are well known.  Organisms that most commonly cause such infections.
  44. 44. EMPIRIC ANTIBIOTIC TREATMENT Early infection (first 3 days of symptoms and mildly immunocompromised)  Penicillin  Clindamycin  Cephalexin Late infection (After 3 days of symptoms or moderately to severely immunocompomised)  Clindamycin  Revicillin and metranidazole.  Ampicillin and sulbactam.  Cephalosporin (first or second generation). -Mild, moderate and severe compromised based on CD4 / viral loads, glycemic control, and the degree of alcoholic related disease.
  45. 45. 7)PROPER ANTIBIOTIC ADMINISTRATION  Proper dose.  Proper time interval.  Proper route of administration.  Combination antibiotic therapy.  It is indicated in few situations like in:  Situations of life threatening situations of unknown cause.  To increase the bactericidal effect of a specific organism.  Prevention of the rapid emergence of resistant bacteria. - Empiric therapy of certain odontogenic infections like when the infection progresses to the lateral and retropharyngeal spaces and caused by aerobes and anaerobes.
  46. 46. PRINCIPLES OF ANTIBIOTIC DOSING  GOAL : 1.To aid the body’s defenses to clear the tissues of microbial pathogen by achieving antibiotic levels in the infected area to or greater than the MIC
  47. 47. ANTIBIOTIC DOSING VARIABLES  PHARMACOKINETIC FACTORS Diffusion to the site of action 1.Tissue pH. 2.Lipid and water solubility 3.Plasma protein binding  INOCULUM EFFECT- It is defined as a laboratory phenomenon that results in significantly increased MIC required of an antibiotic. When the number of inoculated organisms increases. It generally occurs in case b-lactum antibiotics and b-lactamase producing bacteria (review of infectious diseases vol.2 number.3 may- june 1989)  SURFACE AREA TO VOLUME RATIO
  48. 48. Lipophilic antibiotics Tetracyclines,macrolides,fluoroquinolones Pass better through tissue barriers Effective against intracellular pathogens Drug depot within macrophages
  49. 49. Hydrophilic antibiotics Beta-lactams,vancomycin,aminoglycosides Confined to ECF Poor diffusion through capillaries
  50. 50. PLASMA PROTEIN BINDING Limited plasma protein binding Diffuse easily through capillary walls and other barriers
  51. 51. PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE (I) PROPER DOSE:-  Dose – 3 to 4 times the MIC for e.g. penicillinase producing staphylococcus - MIC 6 µg/ ml , plasma level - 18µg /ml  Administration of doses above this level – increases the likelihood of toxicity & is wasteful.  Sub therapeutic levels - mask the infection ,recurrence. 51
  52. 52. DRUG DOSE CALCULATION  BASED ON BODY SURFACE AREA Individual dose = BSA[m2] x adult dose 1.7  BASED ON BODY WEIGHT Individual dose = BW[kg] x average 70 adult dose
  53. 53. IN PEDIATRICS YOUNG’S FORMULA : CHILD DOSE = Age x adult dose Age + 12 DILLING’S FORMULA : CHILD DOSE = Age x adult dose 20
  54. 54. NEONATES AND INFANTS  Greater percentage of body weight compared with body water Greater volume of distribution Increased serum half lives  Reduced gastric emptying  Reduced plasma protein binding  Reduced GFR
  55. 55. ELDERLY  Reduced host defenses  Underlying illness  Reduced total body water  Lean body mass  Reduced cardiac output  Reduced gastric emptying time  Decreased renal function
  56. 56.  LOADING DOSE; This is a single or few quickly repeated doses given in the beginning to attain target concentration capacity.  MAINTAINANCE DOSE: This is the dose repeated at specific interval after attainment of target cycles per second
  57. 57. ANTIBIOTIC LOADING DOSES  INDICATIONS : 1.The half-life of the antibiotic is longer than 3-hours. 2. A delay of longer than 12-hours to achieve therapeutic blood levels is unacceptable. Because most acute orofacial infections begin and peak rapidly
  58. 58. DURATION OF ANTIBIOTIC DOSING  The ideal antibiotic duration is the shortest time that will prevent both clinical and microbiological relapse. Clinical improvement of the patient Remission of infection.
  59. 59. MISCONCEPTIONS IN LONGER DURATION OF ANTIBIOTICS  Prolonged antibiotic therapy destroys resistant bacteria.  Prolonged antibiotic therapy is necessary to prevent rebound infections.  The dosage and duration of therapy can be extrapolated from one infection to another.  The prescriber knows how longer the infection will last.
  60. 60. PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE (II) Proper time interval:-  Established plasma t 1/2 – one half of the absorbed dose is excreted.  Usual dosage interval for therapeutic use of antibiotics - Four times the half life. E.g. cefazolin t 1/2 - 2 hours. 60
  61. 61. PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE (III) Proper route of administration:- In some infections , only the parenteral route produces necessary serum level of antibiotic For e.g. Penicillin V oral - 2 gm Plasma level - 4 µG/ mL Oral route - variable absorption. Serious well established infection - parenteral route 61
  62. 62. PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE (IV) Consistency in Route of Administration:- After initial response , immediate discontinuation of parenteral route - Recurrence Maintenance of peak blood levels of antibiotic for an adequate period is important – max. tissue penetration & effective bactericidal action. After the 5th day of parenteral administration, the blood levels achievable with oral administration are usually sufficient. 62
  63. 63. PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE (V) Combination Antibiotic therapy:-  Life threatening sepsis of unknown cause  Increased bactericidal effect against a specific µorg is desired. E.g. treatment of infections caused by enterococcus  Prevention of rapid emergence of resistant bacteria E.g. tuberculosis  Empiric treatment of certain odontogenic infections E.g. Penicillin G & Metronidazole 63
  64. 64. COMBINATION ANTIBIOTIC THERAPY Combination therapy with two or more antibiotics is used in special cases:  Prevent the emergence of resistant strains  To treat emergency cases during the period when an etiological diagnosis is still in progress  To take advantage of antibiotic synergism
  65. 65. ADVANTAGES vs DISADVANTAGES  Broad antibacterial spectrum  Reduced dose for each agent.  Antibiotic synergism  Decreased adverse drug reactions  Greater likelihood of adverse reactions  Antibiotic antagonism  Increased financial costs  Greater microbial resistance  Resistance genes  Increased risk of superinfection
  66. 66. SYNERGISTIC ANTIBIOTIC COMBINATION  Cell wall inhibitors and aminoglycosides  Beta-lactams with beta-lactamase inhibitors  Beta-lactams that act on different PBPs  Sulfonamides and trimethoprim
  67. 67. PRINCIPLES OF ANTIBIOTIC THERAPEUTIC DOSE  Should be avoided when not specifically indicated.  Usual result – broad spectrum exposure that leads to depression of the normal host flora & inc opportunity for resistant bacteria to emerge.  For routine infections, the disadvantages of combination therapy outweigh the advantages. 67
  68. 68. FACTORS INFLUENCING  Minimal Inhibitory Concentration  Post-antibiotic effects  Microbial persistence and regrowth.  Dosing and resistance  Antibiotic loading dose  Duration of antibiotic dosing  Incision and Drainage  Special conditions
  69. 69. MINIMAL INHIBITORY CONCENTRATION  Is the lowest antibiotic concentration that prevents growth of microorganism after an incubation period of 18 – 24 hours incubation period with a standard inoculum of 104 to 105 cfu/ml MINIMAL BACTERICIDAL CONCENTRATION  Is the lowest concentration of drug that causes the complete destruction of the organisms or permits survival of less than 0.1% of the inoculum
  70. 70. ADVANTAGES IN DETERMINING MIC  DETERMINES: 1.The ratio of the peak drug concentration in the serum to the MIC 2.The duration of the time the serum drug concentration exceeds the MIC 3.The ratio of the 24-hour area under the curve [AUC] to the MIC The AUC is the measure of the drug exposure to the bacteria over time
  71. 71. DISADVANTAGES WITH MIC  Is only a point in time and tells nothing about the true antibiotic activity at the locus of infection  The concentration of organisms at the site of infection is 108-1010 cfu/ml – greater than that used to determine the MIC in the laboratory.  Exponential growth in vitro  Differing variables- temperature, inoculum Size, pH and growth period.
  72. 72. RULE OF THUMB  The concentration of the antibiotic in the blood should exceed the MIC by a factor of 2-8 times to offset the tissue barriers that restrict access to the infected site.
  73. 73. CONCENTRATION DEPENDENT Vs TIME DEPENDENT ANTIBIOTICS CONCENTRATION DEPENDENT TIME DEPENDENT ANTIBIOTICS 1. Aminoglycosides, metronidazole, fluroquinolones 2. Bactericidal activity depends on the drug concentration 1. Beta-lactams and vancomycin 2. Long time of exposure of the organisms 3. Better the bactericidal concentration 4. Require organisms in the process of cell division
  74. 74. POSTANTIBIOTIC EFFECTS  Is the persistent supression of microbial growth after short time exposure to an antimicrobial agent.  MECHANISM : Is the time necessary to recover from sublethal structural and metabolic alterations that prevents resumption of bacterial regrowth.
  75. 75. FACTORS INFLUENCING PAE  The particular organism  Inoculum size  Growth medium  Organism growth phase  Mechanism of action of antibiotic  Duration of exposure to the drug
  76. 76. MICROBIAL PERSISTENCE AND REGROWTH.  The subpopulation of organisms that is not inhibited or killed during a given dose interval which can then reestablish themselves and continue growth.  FACTORS DETERMINING : 1.Initial inoculum size 2.Bactericidal activity 3.Organism MIC 4.Post-antibiotic effects 5.Antibiotic pharmacokinetics 6.Doubling time of the organism.
  77. 77. 8)MONITORING THE PATIENT 1)Response to treatment. Reasons for treatment failure: -Inadequate surgical treatment. -Depressed host defences. -Presence of foreign body. -Antibiotic problems – Drugs not reaching infection. Dose not adequate Wrong bacterial diagnosis. Wrong antibiotic. 2)Development of adverse reactions: 3)Superinfection and recurrent infection:
  78. 78. ANTIBIOTIC SIDE EFFECTS Side effects are unwanted but often unavoidable pharmacodynamic effects that occur at therapeutic doses. 1) HAEMATOLOGIC EFFECTS a) Leucopenia and thrombocytopenia: Beta lactams sulfonamides(Cotrimazole) b) Anaemia: Beta lactam- Autoimmune anaemia Cotrimazole- Folate deficiency- Megaloblastic anaemia Chloramphenicol- Aplastic anaemia. c) Platelet dysfunction: Anti pseudomonal penicillins- Impaired platelet aggregation. d) Clinical bleeding: Moxalactam- Interferes with vit.K depended clotting factor synthesis. Trovafloxacin- Increases prothrombin time.
  79. 79. 2) HYPERSENSITIVITY EFFECTS Drug fever: 10-15% of unexplained fever in hospitalized patients. Beta lactams, Sufonamides. Drug rashes: Itching, urticaria, maculo popular rashes. Beta lactams, sulfonamides. Anaphylactic reactions: Beta lactams, rare in Sulfonamides. Serum sickness: Develops 2 weeks after exposure- Beta lactams. Photosensitivity reactions: Tetracycline, Sparfloxacin Rare with Doxycyclin, minocycline Drug induced Systemic Lupus Erythematosus(SLE): Minocyclin, Isoniazide, Nitrofurantoin, Griseiofulvin.
  80. 80. 3) NEUROLOGIC EFFECTS a) Encephalopathy: Trovafloxacin- Mental confusion Clarithromycin b) Seizures: Ciprofloxocin, Imipenem, Trovafloxacin. It depends on seizure threshold of patient. c) Neuromuscular blockade: Aminoglycosides d) Peripheral neuropathy: Isoniazide, Griseiofulvin e) Muscular tremors and myalgias: Trovafloxacin f) Ototoxicity: Aminoglycisides, Parenteral Erythromycin g) Blindness: Ethambutol, Chloroquine.
  81. 81. 4) PULMONARY EFFECTS a) Acute pulmonary reactions: Rifampicin- Flu like illness. Nitrofurantoin: Varying degrees of respiratory Insufficiency, Pleural effusion. b) Chronic pulmonary reaction: Nitrofurantoin- Pulmonary fibrosis. 5) CARDIAC EFFECTS a) Ventricular arrhythmias: Erythromycin b) Hypotension: Trovafloxacin, Amphotericin-B
  82. 82. 6) GASTROINTESTINAL EFFECTS a)Nausea and vomiting Clarithromycin,Amoxicillin/Clavulanate,Azithromycin, Doxicycline,Minocycline. b) Non-clostridium difficile diarrhea: Macrolides,Ampicillin, Trovafloxacin c)Cl. Difficile diarrhoea Beta lactums, Quinolones d)Anti pancreatitis Trovafloxacin.
  83. 83. 7)HEPATIC SIDE EFFECTS a) drug induced hepatitis -Isoniazide- elevates serum transaminas, Trovafloxacin,Oxacillin b) Cholestasis -Erythromycin,Nitrofurantoin c) Hepatic necrosis -PAS, Ketoconazole or Trovafloxacin 8)NEPHROTOXIC SIDE EFFECTS a) Nephrotoxicity Aminoglycosides-Tubular toxicity. Tetracyclines, Polymyxin –B b) Interstitial nephritis Beta lactamase therapy.
  84. 84. ANTIBIOTIC RESISTANCE  The organisms continue to multiply even in the presence of antibiotic.  Resistance to an antimicrobial can arise (1) Mutation in the gene that determines sensitivity/resistance to the agent or (2) Acquisition of extrachromosomal DNA (plasmid) carrying a resistance gene. (3) Bacteriophages. (4) Mosaic genes Mutation: random, undirected, heritable variation caused by an alteration in the nucleotide sequence at some point of the DNA of the cell
  85. 85. CROSS RESISTANCE Single mechanisms confers resistance to multiple antimicrobial agents MULTIPLE RESISTANCE Multiple mechanisms Cross resistance - closely related antimicrobial agents Multiple resistance - unrelated antimicrobial agents.
  86. 86. ANTIBIOTIC RESISTANCE MECHANISMS 1.ENZYMATIC ANTIBIOTIC INACTIVATION a.Beta-lactams - beta lactamases b.Aminoglycosides - aminoglycosides modifying enzymes c.Chloramphenicol - acetyl transferases 2.MODIFICATION PROTECTION OF TARGET SITE a.Beta-lactams-altered PBPs b.Fluoroquinolones:altered DNA gyrases c.Rifampin:altered RNA polymerase d.Sulfonamides: altered dihydropteroate synthase
  87. 87. 3.LIMITING ACCESS OF ANTIBIOTIC Beta-lactams and fluoroquinolones Altered outer membrane porins 4.ACTIVE ANTIBIOTIC EFFLUX 5.FAILURE TO ACTIVATE ANTIBIOTIC Metronidazole - flavodoxin production
  88. 88. 6.USE OF ALTERNATE GROWTH REQUIREMENTS 7.OVERPRODUCTION OF TARGET SITES a.Sulfonamides:overproduction of PABA b.Entericbacilli:overproduction of beta- lactamases
  89. 89. ANTIBIOTIC FAILURES Common reasons for antibiotic failure: 1.Failure to surgically eradicate - source of infection 2.Too low - blood antibiotic concentration 3.Inability to penetrate the site of infection 4.Impaired host defenses 5.Patient failure to take the antibiotic
  90. 90. 6.Inappropriate choice of antibiotic 7.Limited vascularity or blood flow 8.Decreased tissue ph or oxygen tension 9.Antibiotic resistance 10.Delay or incorrect diagnosis 11.Antibiotic antagonism
  91. 91. MISUSE OF ANTIBIOTICS  1) Treatment of untreatable infections  2) Therapy of fever of unknown origin  3) Improper dosage  4) Inappropriate reliance on chemotherapy alone  5) Lack of adequate bacteriological information
  92. 92. DEVELOPMENT OF DRUG RESISTANCE  Refers to unresponsiveness of a microorganism to an AMA  Natural Resistance  Acquired Resistance . 92
  93. 93. DEVELOPMENT OF DRUG RESISTANCE  Single step mutation E.g. Enterococci to Streptomycin, E.coli & Staphylococci to rifampin  Multistep mutation E.g. resistance to erythromycin, tetracyclines & chloramphenicol by many organisms. 93
  94. 94. DEVELOPMENT OF DRUG RESISTANCE  Gene Transfer:- from organism to another can occur by, (i) Conjugation:- E.g. Chloramphenicol – typhoid bacilli, Streptomycin – E.coli, Penicillin – Haemophilus & Gonococci (ii) Transduction:- E.g. Penicillin, Erythromycin & Chloramphenicol (iii) Transformation:- E.g. pneumococcal resistance to Penicillin G 94
  95. 95. PRINCIPLES OF PROPHYLACTIC ANTIBIOTICS It is the use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. ADVANTAGES: 1.Prevention of infection. 2.Decrease patient morbidity and mortality. 3.Decrease hospital stay. 4.Decreased medical cost. 5.Decreased total antibiotic usage. 6.Decrease numbers of resistant bacteria – because of short term course.
  96. 96. DISADVANTAGES  No reduction of infection.  Development of increased number of resistant bacteria.  Delay in onset of infection.  Adverse effect on surgical technique
  97. 97. THE PRINCIPLES FOR PROPHYLACTIC ANTIBIOTICS  Increased risk of significant bacterial contamination and a high incidence of infection.  Organism must be known.  Antibiotic susceptibility must be known.  To be effective and to minimize adverse effects the antibiotic must be in the tissue at the time of contamination (operation) and it must be continued for not more than 4 hours after cessation of contamination.  Four times the MIC of the causative organisms.  Timing the antibiotic correctly.  Shortest effective antibiotic exposure.
  98. 98. PRINCIPLE 1: PROCEDURE SHOULD HAVE A SIGNIFICANT RISK OF INFECTION 1.Bacterial inoculum of sufficient size 2.Extensive and prolonged surgery 3.Insertion or presence of foreign body 4.Depressed host resistance
  99. 99. Type I. Clean wounds (no opening of mucosa in the oral cavity): Confirmed infection rate of 1 to 4%. Antibiotic prophylaxis not required. Type II. Clean-contaminated wounds (opening of mucosa in the oral cavity, insertion of dental implants or intervention on inflammatory pathology): Confirmed infection rate of 5 to 15%. These require antibiotic prophylaxis with drugs covering Gram positive and anaerobic micro-organisms. Type III. Contaminated wounds (oncological pathology in which there is simultaneous action on the oral cavity and the neck): Confirmed infection rate of 16 to 25%. Antibiotic prophylaxis must be carried out to cover Gram negative organisms whose coverage in clean and cleancontaminated surgeries is disputed. Type IV. Dirty and infected wounds. Confirmed infection rate of above 26%. These always need adequate antibiotic treatment. CLASSIFICATION OF SURGICAL WOUNDS
  100. 100. PRINCIPLE 2: TO CHOOSE CORRECT ANTIBIOTIC 1.Effective against the most likely organism 2.Narrow spectrum antibiotic 3.Least toxic antibiotic 4.Bactericidal antibiotic
  101. 101. PRINCIPLE 3: ANTIBIOTIC PLASMA LEVEL MUST BE HIGH  To ensure diffusion of antibiotic into all fluid and tissue components  USUAL RECCOMENDED DOSE: Two times the usual therapeutic dose
  102. 102. PRINCIPLE 4: TO TIME ANTIBIOTIC ADMINISTRATION CORRECTLY  Antibiotic must be administered before the surgery begins Prolonged surgery Additional antibiotic is required Intraoperative dose intervals should be one half the usual therapeutic dose interval
  103. 103. PRINCIPLE 5: USE OF SHORTEST EFFECTIVE ANTIBIOTIC EXPOSURE  Continued antibiotic administration - no benefit once the surgical procedure is complete  Hence the final dose of the antibiotic - after surgical operation Procedure lasts for Short procedure more than two hours 2nd dose of antibiotic is Single preop dose is required adequate
  104. 104. ANTIBIOTIC PROPHYLAXIS AGAINST INFECTIVE ENDOCARDITIS  GOALS : 1.To reduce the intensity of bacteremia. 2.Assist the RES in killing the bacteria. 3.Decrease the bacterial adherence to the damaged heart valves and vegetations.
  105. 105. CONDITIONS CONSIDERD FOR ANTIBIOTIC PROPHYLAXIS  Antibiotic prophylaxis recommended : High risk condition 1.Prosthetic cardiac valves 2.Bioprosthetic valves 3.Previous bacterial endocarditis 4.Complex congenital CHD Moderate risk condition 1.Acquired valvular dysfunction 2.Hypertrophic cardiomyopathy 3.Other congenital cardiac malformation
  106. 106. ANTIBIOTIC PROPHYLAXIS NOT RECOMMENDED  LOW RISK CONDITION: 1.Isolated atrial septal defect 2.Previous coronary artery bypass graft surgery. 3.Mitral valve prolapse without valvular regurgitation 4.Cardiac pacemakers and defibrillators 5.Previous rheumatic fever without valvular regurgitation
  107. 107. 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
  108. 108. ANTIBIOTICS USEFUL FOR OROFACIAL INFECTIONS:  Penicillins.  Cephalosporins.  Erythromycins.  Clindamycin and Lincomycin.  Metronidazole.  Aminoglycosides.  Fluoro quinolones – ciprofloxacin.  Sulfonamides and trimethoprim
  109. 109. PENICILLINS  Discovered in 1929, it was first antibiotic drug to be used.  The drug of choice for the initial empirical management of odontogenic infections remains penicillin  Bactericidal  Narrow but appropriate spectrum  Little or no toxicity
  110. 110. CLASSIFICATION OF PENICILLIN I) Natural penicillins : Penicillin G (Benzyl penicillin) II) Acid resistant penicillins : Phenoxymethyl penicillin (penicillin V) III) Penicillinase – resistant penicillins : Acid labile : Methicillin, nafillin, cloxacillin, dicloxacillin IV) Penicillins effective against gram +ve and some gram –ve organisms : Ampicillin V) Extended spectrum penicillins : Carboxypenicillins : Carbenicillin, tiocillin
  111. 111. PENICILLIN-G ( Benzyl Penicillin ) -Narrow spectrum activity Spectrum of activity- Streptococci except enterococci, Staph. aureus, N. gonorrhoea, N. meningitides, Anthracis, C.diphtheriae, Clostridia, Listeria. PHARMACOKINETICS: PnG is acid liable destroyed by gastric acid. -Absorption of sodium PnG from i.m. site is rapid and complete. -Distributed extracellularly, penetration into serous cavity and CSF is poor. -Plasma T1/2 is 30 min. -Extreted through kidneys by glomerular filtration.
  112. 112.  PREPARATION AND DOSE: 1) Sod. PnG or Crystallin penicillin injection: 0.5-5 MU i.m. 6-12 hrly  Repository PnG injections: These are insoluble salts must be given deep i.m. never given i.v. Drug is released slowly from the injection site.  Procaine PnG: 0.5-1MU i.m.12hrly  Fortified Procaine PnG : Contains 3lakhU  Procaine PnG and 1lakhU Sod. PnG  Benzathine PnG : 0.6-2.4MU i.m. every 2-4 weeks. It releases drug very slowly and effective for prophylactic purposes.
  113. 113. AMPICILLIN Semi synthetic penicillin belongs to aminopenicillins. Spectrum: Active against all organisms sensitive to PnG, H.Influenza, E.Coli, Proteus, Salmonella, Shigella, Strepto. Viridans, Enterococci, Pseudomonas, Klebsiella. Kinetics : Not degraded by gastric acid. Oral absorption is incomplete but adequate. Food interferes with absorption. Plasma T1/2 is 1 hr, excreted through kidneys. Dose: 0.5-2g oral /i.m. /i.v. every 6th hrly. Children 25-50mg /kg /day.
  114. 114. Uses: Urinary tract infections, Respiratory tract infections, Meningitis, Gonorrhoea, Typhoid fever, Bacillary dysentery, Cholecystitis, SABE. Adverse effects: Diarrhea is frequent after oral administration, rashes Avoided in patients with a H/O hypersensitivity to PnG. AMOXICILLIN It is a close congener of Ampicillin, similar to it except - Oral absorption is better food does not interferes - Incidence of diarrhea is less. - Less active against Shigella, H.Influenza. Dose: 0.25-1g orally /i.m /i.v. TDS.
  115. 115. BROAD SPECTRUM EFFECT WITH CLAVULANIC ACID  Clavulanic acid- streptomycet clavuligerous- inhibiting β lactamase enzymes  Broaden antibacterial spectrum of amoxicillins
  116. 116. SULBACTAM  Semisnythetic betalactamase inhibitor  Related chemically in activity to clavulanic acid  Progressive inhibitor ,highly active against betalactamase  2-3 times < potent  Oral absorption- inconsistent,preferably im/iv  Sulbactam+ ampicillin=Dicapen  SULBACIN, AMPITUM 1g+ 0.5g per vial im/iv 6-8hourly 1g+500mg tab
  117. 117.  ADVERSE EFFECTS : a) Local irritancy and direct toxicity b)Jarisch-Herxheimer reaction c) Hypersensitivity or drug allergy(1-10%) Defn: An allergic drug reaction is defined as any noxious, unintended, and undesired effect of a drug that occurs at doses used in humans for prevention, diagnosis, or treatment. 2types predictable unpredictable PENICILLIN ALLERGY SKIN TESTING Reagents: Concentration -Penicilloate 0.01 mol/L -Penilloate 0.01 mol/L -Penicillin G 10,000U/ml -Ampicillin/Amoxicillin 1-20mg/ml PROCEDURE: 1) Epcutaneous or (scratch or prick) 2) Intradermal test
  118. 118. DESENSITIZATION IN PENCILLIN ALLERGIC PATIENTS  Administration of a penicillin to a allergic patient, who requires penicillin for clearly defined medical reasons. Ex; Endocarditis, meningitis. -Done in Intensive care setting… -Penicillin doses of 1,5,10,100 and 1000U administered intradermally ,60 mints interval b/n doses. -well tolerated- 10000U-50,000U given s.c.
  119. 119. Therapeutic Uses :  Streptococcal infections  Pneumococcal infections  Meningococcal infections  Staphylococcal infections  Gonorrhoea  Syphilis  Diphtheria  Tetanus and gas gangrene  Antibiotic prophylaxis
  120. 120. CEPHALOSPORINS  These are a group of semisynthetic antibiotics derived from "cephalosporin – C" obtained from a fungus cephalosporium.  They are chemically related to penicillins, the nucleus consists of a -lactam ring fused to a dihydrothiazine ring.
  121. 121. CEPHALOSPORINS 1ST GENERATION CEPHALOSPORINS Good against methicillin sensitive S. aureus, streptococci and many Enterobacteriaceae. Members include: Cephalexin (Keflex), Cefazolin (Ancef), Cephapirin (Cefadyl) and Cephalothin (Keflin) Cefadroxil. 2ND GENERATION CEPHALOSPORINS More stable to Gram negative b-lactamase and less active against S. aureus. Members include: Cefuroxime (Ceftin [oral] and Zinocef), Cefotetan (Cefotan), and Cefoxitin (Mefoxin).
  122. 122. 3RD GENERATION CEPHALOSPORINS Broader activity against Gram negatives. Members include: Cefdinir (Omnicef), Cefoperazone (Cefobid), Ceftazidime (Fortaz), and Ceftriaxone (Rocephin), and Cefotaxime (Claforan). 4TH GENERATION CEPHALOSPORINS More resistant to destruction by chromosomal b- lactamases, but not completely resistant to the b-lactamases of Serratia, Enterobacter and Pseudomonas. Cefepime (Maxipime).
  123. 123. Adverse effects :  Pain  Diarrhoea  Hypersensitivity  Nephrotoxicity  Neutropenia  Thrombocytopenia
  124. 124. USES :  As alternatives to PnG in patients developing rashes or other allergic reactions with PnG.  Respiratory, urinary and soft tissue infections caused by gram negative organisms.  Penicillinase producing staphylococcal infection.  Septicaermias caused by gram negative organisms : an aminoglycotide may be combined with a cephalosporin.  Surgical prophylaxis; surgical prosthesis such as artificial heart valves, artificial joints etc. The first generation drugs are used.  Meningitis caused by H.influenzae, enterobacteriaceae.  Gonorrhoea caused by penicillinase producing organisms.  Typhoid : as alternative to fluoroquinolones (specially in children)  Mixed aerobic – anaerobic infections seen in cancer patients those undergoing colorectal surgery, obstetric complications.  Prophylaxis and treatment of infections in neutropenic patients.
  125. 125. MACROLIDES (ERYTHROMYCIN), LONG ACTING MACROLIDES (AZITHROMYCIN), LINCOSAMIDES (CLINDAMYCIN) AND STREPTOGRAMINS (SYNERCID)  Bind to the 50s ribosomal subunit.  Block chain elongation.  Bacteriocidal or bacteriostatic depending upon the organism.
  126. 126. ERYTHROMYCIN USES Gram positive organisms. Used to treat Legionella, Mycoplasma, syphilis, diphtheria carriers and pertussis. Safe in pregnancy. SIDE EFFECTS Erythromycin estolate - cholestatic hepatitis (1/1000). Ototoxic in high doses.
  127. 127. CLARITHROMYCIN A.Uses Spectrum is similar erythromycin and respiratory Gram-negative pathogens Clarithromycin can be used - H. pylori and atypical mycobacteria infections. B.Side Effects Teratogenic. Ototoxic in high doses.
  128. 128. CLINDAMYCIN  A.USES Used against Gram positive cocci and anaerobes, both Gram-positive and Gram- negative rods.  B.SIDE EFFECTS Significant risk of pseudo- membranous colitis due to the overgrowth of C. difficile.
  129. 129. AMINOGLYCOSIDES  MECHANISM : Works by binding to a specific protein, S12, on the 30s ribosomal subunit. Blocks normal activation of the initiation complex. At low concentrations - the mRNA is misread and the wrong amino acid is inserted. At higher concentrations - inhibit translation.
  130. 130. METABOLISM  Excreted by glomerular filtration.  Aminoglycosides have a low toxic to therapeutic ratio. Blood levels need to be monitored to insure safety and efficacy.  If the GFR falls below 70mL/min, the daily dose must be reduced to prevent toxicity.
  131. 131. SIDE EFFECTS  Ototoxicity  Nephrotoxicity  Very high concentrations - neuromuscular blockade.
  132. 132. GENTAMICIN  It is effective against gram positive and negative bacteria including penicillinase resistant staphylococci.  Gentamicin and ampicillin should be administered separately because gentamicin gets destroyed.  It is indicated in severe anaerobic infections.  Dose – Adult – 3-7mg/kg/day in 2-3 divided dose. Child – 1-3mg/kg/day in 2-3 divided dose.  Toxicity – It causes ototoxicity (vestibular and cochlear). If serum concentrations exceeds 10mg/ml transient tinnitus may occur.  When used over a weak, nephrotoxicity occurs.  Allergic reactions – not recommended in lactating mothers.
  133. 133. QUINOLONES CLASSIFICATION First generation: Cinoxacin, Oxalinic acid, Nalidixic acid. Second generation: Ciprofloxacin, Ofloxacin, Norfloxacin, Levofloxacin Third generation: Gatifloxacin, Sparfloxacin, Tosulfioxacin Fourth generation: Gemifloxacin, Moxifloxcin, Torvafloxacin.
  134. 134. QUINOLONES  Mechanism Interfere with the activity of DNA gyrase. Prevent winding of the DNA helix into the supercoiled form. Actions are bacteriocidal.
  135. 135. THERAPEUTIC USES  Used against Enterobacteriaceae.  Ciprofloxacin most active against Pseudomonas.  Fluoroquinolones used for UTIs Pneumonia Atypical pneumonia and Bacterial gastroenteritis.
  136. 136. SIDE EFFECTS  High drug levels are neurotoxic.  Prolonged use leads to tendon damage (rupture of Achilles tendon).  Not approved for children causes cartilage damage.  Safety in pregnancy is not established
  137. 137. METRONIDAZOLE Belongs to Nitroimidazole group. Mechanism -In a reducing environment, metronidazole is reduced to a substance - inhibits bacterial DNA synthesis. -Its action is broadspectrum bacteriocidal -Its use is limited to anaerobic organisms. * Plasma t1/2 is 8hrs.
  138. 138. SIDE EFFECTS  Anorexia nausea and abdominal cramps.  Produces metallic taste in the mouth.  Peripheral neuropathy, seizures and ataxia have been seen with prolonged use.  Thromboflebitis of injected vein occurs if the solution is not well diluted.
  139. 139. CONTRAINDICATIONS -Neurological disease. -Blood dyscrasias. -First trimister of pregnancy. -Chronic alcoholism. Preparations: Tab Metrogyl 200mg 400mg 200mg/5ml susp 500mg/100ml i.v. infustion
  140. 140. USES  Amoebiasis  Giardiasis  Trichomonas vaginitis  Anaerobic bacterial infections  Pseudomembranous enterocolitis  Ulcerative gingivitis, trench mouth  Helicobacter pylori gastritis/peptic ulcer
  141. 141. SULFONAMIDES AND TRIMETHOPRIM:  These are bacteriostatic agents.  inactivated by presence of pus.  They act by inhibition of bacterial synthesis of folic acid from para amino benzoic acid (PABA).  The concentration of sulfonamides in the urine is greater than in blood this leads to formation of crystals of sulfonamides termed as crystalluria and leads to renal damage.
  142. 142. Toxic effects:  Allergic reactions  Prolonged therapy can lead to macrocytic anemia  Also cause kernicterus by displacing bilirubin from plasma albumin in babies during intrauterine life. They may also cause foetal malformation.  Sulfadizine: It penetrates blood brains barrier. It is commonly used in traumatic meningitis.
  143. 143. COTRIMOXAZOLE (SULFAMETHOXAZOLE AND TRIMETHOPRIM)  This agent inhibits the conversion of folic acid to folinic acid which is important for bacterial synthesis of DNA and RNA.  It is active against strep pyogens and most staphylococci and haemophili.  It is indicated in acute exacerbations in post irradiation osteomyelitis secondary to osteoradionecrosis. It is also used in mixed actinomycotic infections along with penicillin.  Dose 80 mg of Trimethoprim + 400 mg of sulfamethoxazole 2 tablets 12 hourly Child : 20 mg + 100 mg
  144. 144. USES : Cotrimoxazole is widely used  Urinary tract infections  Respiratory tract infections  Typhoid  Bacterial diarrhoeas and dysentery  Chancroid  Granuloma inguinale  It is an effeictive alternative to penicillin for protecting agranulocytosis patients and treating respiratory and other infections in them.  Pneumocystitis carinii.
  145. 145. TOPICAL ANTIBIOTICS These are the antibiotics used for external application of drugs to the surface for local action. POLYPEPTIDE ANTIBIOTICS  Low molecular weight cationic drugs.  Powerful bactericidal  Toxic when used systemically.  They are: Polymyxin-B, Colstin, Bacitran, Tyrothricin. POLYMYXIN-B & COLISTIN  Active against g-ve bacteria.  They have a detergent like action on cell membrane causing leak in cell constituents. No cross resistance with other drugs.  Adverse effects: No systemic absorption after oral or topical administration.  Given orally causes G.I.T. disturbances.  Systemic effects are flushing, paraesthesia, renal and CNS disturbance.
  146. 146. Uses: 1. Topically used in combination with other anti microbials for skin infections, burns, otitis externa, conjunctivitis, corneal ulcers. 2. Orally for g-ve bacillary dysentery, diarrhea in children and infants. Preparation and dose: 1. Neosporin powder: 5000u polymyxin with neomycin sulphate 3400u and bacitracin 400u per g.  Neosporin eye drops.  Neosporin-H ear drops. BACITRACIN  Discovered from Bacillus Subtilis.  Active against g+ve organisms like Neisseria, H.Influenza, Staph, Strepto, Clostridium, Corynebacterium.  Not absorbed orally and does not penetrate the intact skin.  Commonly combined with Neomycin and Polymyxin-B.
  147. 147. NEOMYCIN It is an aminoglyciside, obtained from Steptomyces Fradiaea. Binds to ribosomal 30S subunit to inactivate DNA polymerase cause misreading of genetic code. Spectrum: Active against g+ve and g-ve bacteria less active against Pseudomonas, Strepto. Pyogens. It is not used systemically because of nephro and ototoxicity. No systemic absorption from topical and oral administration. Uses: a) Topical: Combined with Polymyxin-B & Bacitracin for infected wound, ulcers, burns, external ear infection, conjunctivitis.  Oral: -For preparation of bowel before surgery to decrease post operative infection. In hepatic coma to reduce nitrogen producing bacteria in G.I.T.
  148. 148. FOUR CATEGORIES BASED ON HOW SAFE OR RISKY IT IS TO USE ANTIBIOTICS DURING PREGNANCY. Category A – No evidence of foetal harm. Eg : Nystatin Category B – No known association with birth defects Eg : Amoxicillin, Augmentin, Metronidazole Category C – Information only from animal studies Eg : Bactrim, isoniazid, rifampin Category D – Clear - cut problems Eg : Tetracyclines, minocycline, sulfa drugs. SPECIAL CONDITIONS-PREGNANCY
  149. 149. DRUG ADMINISTRATION DURING PREGNANCY AND BREAST FEEDING : Drug Use during pregnancy Risk Use during Breast feeding Antibiotics Pencillins YES - YES Erythromycin YES - Avoid estolate form - YES Cephalosporins YES - YES Tetracylines AVOID Tooth discoloration inhibits bone formation Avoid Metronidazole YES - YES Clindamycin YES - YES
  150. 150. RENAL FAILURE  Concentration-dependent antibiotics Dosage interval should be increased  Time-dependent antibiotics Dose is decreased
  151. 151. ANTIMICROBIALS NEED DOSE REDUCTION IN RENAL FAILURE - Aminoglycosides - Cotrimoxazole - Cephalexin - Carbenicillin - Ethambutol - Cefotaxime - Vancomycin - Norfloxacin - Amphotenicin –B - Metronidazole
  152. 152. DRUGS TO BE AVOIDED IN CHRONIC RENAL FAILURE :  Cephalothin  Cephaloridine  Talampicillin  Tetracycline (except doxycline).
  153. 153. LIVER  ATTENTION IN LIVER DISEASE :  Antimicrobials to be avoided or used at lower dose in liver disease are :  Drugs to be avoided Dose reduction needed  Erythromycin estolate Chloramphenicol Pyrazinamide Metronidazole Talampicillin Clindamycin Tetracycline Isoniazid Nalidixic acid Rifampin Pefloxacin  The biliary concentration of ampicillin may be significantly reduced in patients with hepatic disease, rendering the antibiotic less effective.
  154. 154. THE DIABETIC PATIENT  Antibiotic prophylaxis.  Amoxicillin is better choice.  Uncontrolled diabetes.  PRECAUTION;Gatifloxacilin- causes both hypoglycemia and hyperglycemia.  Compared with macrolides- Gatifloxacilin 4.3 times higher risk hypoglycemia 16.7times higher risk hyperglycemia
  155. 155. MANAGEMENT OF HEAD AND NECK INFECTIONS IN THE IMMUNOCOMPROMISED PATIENT :  The immunocompromised host has a potential risk for severe head and neck infections that usually require aggressive antimicrobial therapy and prolonged hospitalization.
  156. 156. Management steps  Airway monitoring and possible surgical airway establishment.  Comprehensive history and physical examination.  Obtaining appropriate laboratory and imaging studies.  Empiric antimicrobial therapy.  Surgical debridement and irrigation, as needed.  Culture and antibiotic sensitivity testing of infectious organisms to appropriately adjust antibiotic therapy.  Close follow-up to monitor for resolution and recurrence.
  157. 157. NEWER ANTIBIOTICS 1. MEROPENEN  It is a beta-lactam, belongs to the subgroup of carbapenem.  Ultra broad spectrum injectable antibiotic.  Inhibits bacterial cell wall synthesis.  Action against gram positive and gram negative bacteria and some anaerobic bacteria.  Administered intravenously.
  158. 158. CLINICAL USES  Cystic fibrosis  Infections in immunocompromised patients.  Intra abdominal infections.  Urinary tract infections.  Septicaemia.  Skin infections  ADVERSE EFFECTS : Diarrhoea, Nausea, Vomiting, headache, rash, thrombophlebitis.
  159. 159. 2. CEFEPIME  Fourth generation cephalosporin.  Extended spectrum of activity against gram +ve and gram –ve microbes compared to third generation cephalosporins.  Administrated intramuscularly or intravenously dose – 1 gm to 2 gm every 12 hourly. PHARMACOKINETICS :  Peak plasma concentration after i.m. administration is 1.0 to 1.6 hour.  It is distributed throughout the body tissues and fluids.  Primarily excreted unchanged in urine.
  160. 160. USES  Lower respiratory tact infections.  Urinary tract infections.  Skin and skin structure infections.  Sepsis and bacteremia  Febrile neutropenia  Meningitis. ADVERSE EFFECTS :  Headache, nausea, vomiting, rash, diarrhoea, dizziness.
  161. 161. 3. QUINUPRISTIN / DALFOPRISITIN (SYNERCID)  Synercid is the brand name of combination of quinupristin and dalfopristin antibiotics.  These are semisynthetic pistinamycin derivatives.  Active against methicillius sensitive staphylococcus aureus, group A streptococci, Enterococcus faecium.  500 mg strength of synercid contains 150 mg of quinupristin and 350 mg of Dalfopristin.  Administration – intravenously.
  162. 162. USES  In life threatening infections and certain skin infections.  Adverse effects :  Pain, swelling and irritation at the injection site.  Muscle and joint pain, nausea, vomiting, rash, diarrhoea, headache, itching.
  163. 163. 4. LINEZOLID  New antibacterial drug belongs to class oxazolidones.  Inhibits protein synthesis – 70s ribosomes.  Active against methicillin resistant and sensitive staphylococci, and streptococci enterobacteria faecalis.  400 – 600 mg orally twice daily (12 hrly) parenteral route for severely ill patients. Dosage is same as that of oral route  Metabolized by oxidation and hence can safely used in renal failure.
  164. 164. 5. MOXIFLOXACIN  It is a synthetic fluoroquinolone agent.  Inhibits topoisomerase II and IV, there by affects the replication and repair of bacterial DNA.  It is active against following organisms :  Step. aureus, staph Epidermides, strepto pneumonias, H. influenzae, Klebsiella, Enterobacilus, mycobacterium, Bacillus anthracis.  Administrated both oral and intravenous route.  Dose : 400 mg daily orally or i.v. infusion.
  165. 165. USES  Acute sinusitis.  Acute exacerbation of chronic bronchitis.  Pneumonia.  Skin and skin structure infections.  Second – line agent in T.B. CONTRAINDICATIONS :  Known hypersensitivity, in QT prolongation.  Pregnancy and lactation. SIDE EFFECTS :  G.I. disturbances – Nausea vomiting anorexia, bloating.
  166. 166. 6. GATIFLOXACIN  It is a fourth generation fluro-quinolone agent.  Greater affinity for topoisomerase IV.  Active against gram +ve cocci.  Oral and intravenous route.  Dose – 200 to 400 mg orally or i.v. once daily (+½ shown)  Active against – Streptococcus pneumonias.  Chlamydia pneumonias.
  167. 167. INTERCALATING AGENTS  The reversible inclusion of a molecule between two other groups, most commonly seen in DNA  Inhibits DNA replication in rapidly growing cells
  168. 168. ANTHRACYCLINES  First anthracycline antibiotics were isolated from Streptomyces peucetius in 1958  Interact with DNA by intercalcation and inhibit topsoimerase  Some of the most effective cancer drugs available  Very wide spectrum
  169. 169. Common Anthracyclines  Daunorubicin (Cerubidine)  Doxorubicin (Adriamycin, Rubex)  Epirubicin (Ellence, Pharmorubicin)  Idarubicin (Idamycin)
  170. 170. DOX vs. DNR  Daunomycin (DNR) for acute lymphocytic and myeloid leukenmia  Doxorubicin (DOX) for chemotherapy for solid tumors including breast cancer, soft tissue sarcomes, and aggressive lymphomas
  171. 171. MECHANISMS OF ACTION  Disrupt DNA  Intercalate into the base pairs in DNA minor grooves  Inhibits topoiosomerase II enzyme, preventing the relaxing of supercoiled DNA, thus blocking DNA transcription and replication  Cause free radical damage of ribose in the DNA
  172. 172. Negative Effects  Causes cardiotoxicity due to free radical formation  Interference with ryanodine receptors of the sarcoplasmic reticulum in the heart muscle cells  Free-radical formation in the heart  Leads to forms of congestive heart failure, often years after treatment  Counteract with dexrazoxane
  173. 173. Bleomycins (BLM)  Natural glycopeptidic antibiotics produced by Streptomyces verticillus  Efficacy against tumors  Mainly used in therapy in a combination with radiotherapy or chemotherapy  Commonly administered as Blenoxane, a drug that includes both bleomycin A2 and B2.
  174. 174. History of Bleomycins  First discovered in 1966 by Hamao Umerzawa from Japan when screening cultures of S. verticullus  Launched in Japan by Nippon kayaku in 1969  Initially marketed by Bristol-Myers Squibb under brand name-Blenoxance
  175. 175. Structure
  176. 176. Mechanism  Induction of DNA strand breaks  Medicate DNA strand scission of single and double strand breaks dependent on metal ions and oxygen
  177. 177. Side effects  Pulmonary fibrosis and impaired lung function  Age and dose related  Capillary changes, atypical epithelial cells
  178. 178. Resistance to Anticancer Agents  Resistance mechanisms can operate to  Prevent agents from entering cells, as in loss of plasma membrane carriers for nucleoside analogs  Enhance their extrusion, as exemplified by energy-dependent pumps such as ABC transporters
  179. 179. ANTIBIOTICS NEEDED,NOT NEEDED WHAT TO DO WHAT TO GIVE HOW TO DOPROBLEMS OF MISUSE
  180. 180. WHEN THE QUESTION OF USING ANTI BIOTICS ARISES IN MAXILLOFACIAL SURGERY????  SURGICAL EXTRACTIONS  SURGIAL MANAGEMENT OF LESIONS  SPACE INFECTIONS  TRAUMA  ORTHOGNATHIC SURGERY  OSTEOMYELITIS
  181. 181. [ ASIAN J OMFS : VOL 18 : NO. 4 : 272-278 ] MOST ORAL INFECTIONS ARE ODONTOGENIC IN ORIGIN SEQUELAE OF DEEP CARIOUS LESION / PERIODONTAL / PERICORONAL INFECTIONS MANAGEMENT EXTRACTION / ENDO TREATMENT / SURGICAL DRAINAGE WITHOUT ANTIBIOTICS
  182. 182. CONCLUSION UNCOMPLICATED EXTRACTION,SURGERIES + OTHERWISE HEALTHY LOW INFECTION RATE ANTIBIOTICS NOT NEEDED [ JIDA VOL.69 : SEPT-DEC 1998 : 274 – 277]
  183. 183. CONCLUSION  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.
  184. 184.  NEVER ACCEPT CONCEPT OF ANTIBIOTICS ON DEMAND  NEVER USE A BROAD SPECTRUM ANTIBIOTICS WHEN NARROW SPECTRUM IS INDICATED  NO LONG COURSE OF ANTIBIOTICS  NO NEED OF ANTIBIOTIC PROPHYLAXIS FOR SIMPLE SURGICAL PROCEDURES or WHEN THERE IS LESS CHANCE OF POST SURGICAL INFECTION  WHEN NO SIGNS OF INFECTIONS SUCH AS SWELLING,LYMPHADENOPATHY, ELEVATED TEMPERATURE  ALWAYS MAKE SURE THE SOURCE OF INFECTION IS ELIMINATED- EXTRACTION OF TOOTH INCISION AND DRAINAGE
  185. 185. REFERENCES  Medical pharmacology - Satoskar  Medical pharmacology. - K.D. Tripathi.  Contemporary oral and maxillofacial surgery. - Lary J. Peterson 4th Edition.  Pharmacology and therapeutics and dentistry. - Yogiela Dowd Neidle  OMFS Clin N Am -2003  Oral and maxillofacial infections Topazian  Internet
  186. 186. Thank you

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