Antibiotics used in dentistry


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Antibiotics used in dentistry

  1. 1. Antibiotics used in dentistry prepared by zirgi
  2. 2. DEFINATION Antibiotics are chemical substance elaborated by various species of micro- organism such as fungi, actinomycetes and bacteria. They suppress the growth of other micro-organism and may ultimately destroy them in low concentration.
  3. 3. History
  4. 4. Early history 3500 BC the Sumerian doctors would give patients beer soup mixed with snakeskins and turtle shells. Babylonian doctors would heal the eyes by using an ointment made of frog bile and sour milk. The Greeks used many herbs to heal ailments. All of these "natural" treatments contained some sort of antibiotic.
  5. 5. Modern history Louis Pasteur was one of the first recognized physicians who observed that bacteria could be used to kill other bacteria. In 1929 Sir Alexander Fleming a Scottish bacteriologist, went on a vaction and left a petri dish of staphylococci bacteria uncovered. When he returned, he noticed that there was mold growing on it. Upon further examination, he saw that the area around the mold had no bacteria growing. He named the mold Penicillium, and the chemical produced by the mold was named penicillin, which is the first substance recognized as an antibiotic.
  6. 6.  Almost immediately after penicillin was introduced, resistance in certain strains of staphylococci was noticed. In 1935, Domagkdiscovers synthetic antimicrobial chemicals (sulfonamides). During World War II, because of need for antibiotic agents, penicillin was isolated and further tested by injection into animals. It was found to be extremely useful in curing infections, and to have extremely low toxicity to the animals. Because of these findings, use of penicillin greatly increased. This also spurred a search of other chemical agents of similar use.
  7. 7.  the late 1940s through the early 1950s, streptomycin, chloramphenicol, and tetracycline were discovered and introduced as antibiotics. In 1953, during a Shigella outbreak in Japan, a certain strain of dysentery bacillus was found to be resistant to chloramphenicol, tetracycline, streptomycin, and the sulfanilamides. By the 1950s it was apparant that tuberculosis bacteria was rapidly developing resistance to streptomycin, which had commonly been used to treat it.
  8. 8. Classification of antibiotids
  9. 9. Classification of antibioticsClassification based on chemical structure & proposed mechanism of actions as fallows1. Agents that inhibits synthesis of bacterial cell wall these includes a) penicillin & cephalosporin which are structurally simillar b) Cycloserine vancomycin bacitracine & the azole antifungal agent ( e.g clotrimazole, fluconazole & itraconazole which are structurally dissimilar agent
  10. 10. 2.Agent that act directly on the cell membrane of the micro organism affecting permeablity & leading to leakage of intercelluar compounde.G polymyxin & polyene antifungal agent nystatinAmphotericin B which bind to cell wall sterolls
  11. 11. 3 .Agent that affect the function of 30 s or 50 s ribosomal subunit to cause or reversible inhibition of protein synthesise.G chloramphenicalTetracyclineErythromycinClindamycin
  12. 12. 4 .agent that bind to 30s ribosomal subunit &alter protein synthesis which eventually lead to cell deathE.g. aminoglycosides5.agent that affect bacterial nucleic acid metabolism such as rifamycin (e.g. rifampin ) which inhibit RNA polymerase & the quinilones which inhibit topoisomerase
  13. 13. 6 . agent that block essential enzymes of folate metabolisum E.g. trimethoprim& sulfonamide7 . Antiviral agent which are of several classes including e Nuclic acid analog such as acyclovir or gancyclovir that selectively inhibit viral DNA polymerase and zidovidine which inhibit reverse transcriptase Non nucleoside reverse transcriptase inhibitors such as nevirapine r Inhibitor of other essential viral enzyme. E.g. inhibitors of HIV protease or influenza neuraminidase
  14. 14. classification According to spectra 1.Antibiotic effective against gram positive bacteria a.For systemic infection, erythromycin, lincomycin, novobiocin. b. Those employed topically e.g. bacitracin 2.Antibiotic mainly against gram negative bacteria a.For sylstemic infection e.g. strepomycin & other aminoglycosides b.Those used locally in intestine e.g.paromomycin
  15. 15. 3.Antibiotic mainly effective against gram –ve & +ve bacteriaa.Used for systemic infectione.g. ampicillin, amoxycillin, cephalosporinb.For topical applicatione.g. neomycin4. Effective against rickettsial & chlamydiae.g. tetracycline & chloramphenicol5.Effective against acid fast bacillie.g. steptomycin, rifampicin & viomycin
  16. 16. 6.Effective against protozoae.g. paramomycin & tetracyclin7.Effective against fungie.g.nystatine, amphotericin B8.Effective against malignancye.g. actinomycin, mitomycin
  18. 18.  Following are the points by which the clinician can make a decision of when to use antibiotic, which are to select, and how to use both therapeutic and prophylactic situations. To do this one should atleast know about the following 1. Bacterial flora causing most odontogenic infections 2. The basic mechanism of host defenses 3. The variety of contemporary antibiotics and principles to choose
  19. 19. Bacterial flora causing mostodontogenic infections The indigenous microbial flora of the mouth is bacteria, which are almost always the cause of odontogenic infections. The usual flora is both aerobes and anaerobes
  20. 20. The basic mechanism of hostdefenses Host defense mechanism is the most important factor in the final outcome of a bacterial insult.Each patient has many defenses against infections. 1. Physiologic depression of host defence, Shock Disturbances of circulation caused by advanced age Obesity Fluid imbalance 2. Diseases and disease state that may inhibit host defense Malnutrition syndrome Patient with cancer and leukemia
  21. 21.  3 Congenital defect which causes defective host mechanism Agammaglobulinemia Multiple myeloma Total body radiation therapy Children who have had splenectomy 4. Therapeutic drugs that impares host defense mechanism Cytotoxic drugs Immunosuppressive drugs
  22. 22. principles to chooseAntibiotics Once the decision has been made to use antibiotics as an adjunct to treating infection the antibiotics should be properly selected. The followingguide lines are useful 1. Identification of causative organism 2. Determination of antibiotic sensitivity 3. Choice of antibiotics
  23. 23. 1. Identification of causative organism Causative organism can be isolated from pus blood, or tissue fluids. Based upon the knowledge of pathogenesis and clinical presentation of specific infection,antibiotic therapy will be either initial or definitive depending upon whether or not the organism is diagnosed previously.
  24. 24. 2. Determination of antibiotic sensitivity When treating an infection that has not responded to initial antibiotic therapy or when treating a postoperative wound ,the causative agent must be previously identified and the antibiotic sensitivity must also be determined.
  25. 25. 3 Choice of antibiotics Upon receipt of the culture and sensitivity report, there may be a choice of four or five antibiotics. Selection should be based on consideration of several factors like 1. Patients previous history of allergy 2. Antibiotics with narrow spectrum 3. Drug that cause fewest adverse reactions. 4. Drug which is least toxic 5. The well established still effective antibiotics 6. Bactericidal rather than bacteriostatic drug 7. The less expensive still effective antibotic 8. Combination antibiotics
  26. 26.  1. Patient`s history of allergy Allergic reaction to drugs should be considered first. When it exists, alternative drugs must be used. Example erythromycin or clindamycin is usually use if the patient is allergic to penicillin
  27. 27.  2. Antibiotics with narrow spectrum The only majour indication for use of broad spectrum antibiotics coverage is in severe life threatening infection where identification of causative agent is obsure. Each time bacteria are exposed to antibiotics, the opportunity for development of resistant strains is present. If narrow spectrum antibiotics is used ,fewer organisms have the opportunity to become resistant.
  28. 28.  3. Drug that cause fewest adverse reactions The goal of antibiotic therapy is to provide an effective Drug that causes least problem to the patient 4. Drug which is least toxic Toxicity reactions are those that occur as a result of excessive dose or duration of therapy, but can occur in individual patients with normal doses.
  29. 29.  5. The well established still effective antibiotics Since its initial availability, penicillin, has been used for oral infection and it has been very effective, with low incidence of adverse reaction. Newer antibiotics should be used only when they have proved advantage over the older ones .
  30. 30.  6. Bactericidal rather than bacteriostatic drug Bactericidal drugs are effective during the log phase of bacterial growth the time . If growth is slowed or brought to stop,cidal drugs have a greately diminished effect. As a result, in these situations, when combination drug therapy is to be used,cidal and static combination should not be used in combination.
  31. 31.  7. The less expensive still effective antibotic Most effective but less expensive drug should be considered first. 8. Combination antibiotics There are situations in which the use of antibiotic combination is clearly indicated. Example is when it is necessary to increase the antibacterial spectrum in patients with life threatening sepsis of unknown cause.
  32. 32. Bacterial resistance toantibiotic When the drug does not reach it’s target The drug is not active3. Target is altered.
  33. 33. Selection of antibiotics When an antibiotic is indicated the goal is to choose a drug that is selectivley active for the most likely infecting micro-org.& that has least potential to cause toxicity or allergic reaction in individual being treated. Antibiotic are used in three general ways as empirical therapy as definative therapy As prophylactic or preventive therapy
  34. 34. Pharamacokinetic factor thataffect the selection of antibiotic Location of the infection access of antibiotic to sites of infectione.g. if the infection in the CSF the drug must pass the blood brain barrier
  35. 35. Host factors Host factor for the selection of antibiotics Host defense mechanisms action in the immunocompetant host can be cure mearly by halting multiplication of micro organism { bacteriostatic effect} if host defense are impaired bacteriostatic activity may be inadequate and a berteriocidal agent may be required for curee.g. pt with bacterial endocarditis pt with AIDS
  36. 36. Local factors Antimicrobial activity may be significantly reduces in pus Large accumulation of Hb in infected hematomous cab bind penecillin and tetracycline & thus may reduce the effectiveness of other drug Penetration of antibiotic into infected areas such abscess is imparied because vascular supply is reduce
  37. 37. Genetic factors A no. of drug (e.g. sulfanamides, chloramphenicol and nalidixic acid ) may produces acute hemolysis in pt with glucose 6- phosphate dehydrogenase deficiency
  38. 38. pregnancy Pregnancy may impose an increased risk of reaction to antibiotic for both mother & fetus Hearing loss in child with administration of streptomycin to the mother during pregnancy Tetracycline can affect bones & teeth of fetus , may develop fatal acute fatty necrosis of liver pancreatitis & associated renal
  39. 39. Drug allergy A antibiotics especially- B-lactum are notorious or provoking allergic reaction Sulfonamides trimethoprim nitrofurapterin and erythromycin also has been associated with hypersentitivity reaction especially rash. Antimicrobial agent like othe drugs can caused drug fever
  40. 40. Therapy with combinedantimicrobial agent Indication Empirical therapy of severe infections in which a cause is unknown Treatment of polymicrobial infection Enhancement of antibacterial activity in the treatment of specific infection.
  41. 41. Disadvantage of combination ofantimicrobial agents Risk of toxicity from two or more agent The selection of multiple drug resistance micro organism Increased cost to the patient
  42. 42. Some commonly usedantibioticsPenicillinIt is the extract from mould penicilium notatumBelonging to group called beta lactum antibiotics
  43. 43. Classification1. natural penicillin E.g.penicillin g benzyl penicillin Procaine
  44. 44.  4.penicillin effective against gram +ve &some gram -ve organism  Ampicillin  Amoxicillin  Talampicin 5.extended spectram penicillin  a.carboxypenicilin  Carbenicillins  b.amidinopenicillin  Mecillinam
  45. 45. Mechanism of action Act by inhibiting cell walll synthesis in bacteria. they prevent sythesis & crosslinkage of peptidoglycans which is the integral part of bacterial cell wall.
  46. 46. Antibacterial spectrum ofpenicillin Effective mainly against gram +ve & gram – ve cocci &and some gram +ve bacilli.
  47. 47. Adverse effect of penicillin Intolerance Thrombophlebitis Allergy with manifestation like  rash  2.serum sickness like syndrome  3.renal disturabane  4.haemopoitic disturabance  5.anaphylaxis
  48. 48.  Jarish herxiheimer reaction on syphilitic pt treated with penicillin Superinfection e.g. candida hypermia
  49. 49.  Classification Usual adult Activity against Natural penicillin resgimen oral pathogens 250-500mg vk QID Gm+ve gm+ve Penicillinase gm–ve resistance Dicloxacillin 250mg 6 hrly Arobes anarobes anarobes  Nafcillin 500mg QID +ve +ve +- ve  Amoxicilline  Amox/ potassium 250-500mg clavulanate 8hrly (augmantin) 250-500mg  Ampicillin 8hrly 250-500mg QID stap.only -ve
  50. 50. AMINOGLYCOSIDES These are group of natural & semisynthetic drugs having polybasic amino groups & linked glycosidically to two or more amino sugars.
  51. 51. Mechanism of action The drugs combine with the bacterial ribosomes & interfares with m-RNA ribisomes combination which ultimately prevents protien synthesis.
  52. 52. Absorbtion fate and excreation It is excreted mainly by glomerular filtration &asmall portion in bile
  53. 53. spectrum Vibrio comma Proteus E-colli Enterobacteria Klebsiella H- influenza
  54. 54.  This group includes drug like  Streptomycine  Gentamycine  Kanamycine
  55. 55. Tetracycline They are naphthalene derivatives it’s nucleus is made up by the fusion of foci partialy unsaturated cyclohexiane radius and hence named tetracycline
  56. 56. Mechanism of action Interfer with protein synthesis by blocking the attachment of amino acyl transfer rna to acceptor site on m-RNA ribosome complex.
  57. 57. Absorption fate & excretion Tetracycline form insoluble complexes by chelation with calcium ,magnesium & aluminium Iron interferes with absorption excreted mainly in urine
  58. 58. Spectrum Includes both gram +ve & -ve orgamism Dose –  orally-250-500mg TDS  Parantally- 1-2gms in two equal doses 12hrly interval. Newer drug are-  Doxycycline  Demeclocycline  Methacycline  Minocycline  lymecycline
  59. 59. Disadvantages GI system  Diahrroea  Nausea  Vomiting Suprinfection  Candida infectionis comman  Fetal hepatic disfuction  Azotemia may be agrevated to renal impairment  Chelating effect in teeth & bone
  60. 60. Cephalosporins 1st generation They are highly effective against gram +ve but weaker against gram _ve bacteria These are cephalexim Cephalethin Cephaloridine Cephradine cefadroxil
  61. 61. Cephalexin Only orally active first generation cephalosporin with spectrum Strptococcus Staphylococci Gonococci Closridia C. diptheria Actinomyces Klebshiella Protease Salmonella shingella
  62. 62. Dose Adult – 25mg to 1gm 6 to 8 hrly. children – 25mg to 100mg/kg/day
  63. 63. Cefadroxil A it is close congener of cephalexim& has good tissue penetration B can be given 12 hrly C spectrum is same as cephalexim Dose 0.5gm -1gm BD.
  64. 64. SECOND GENARATION They are newer to first genaration. They have more activity against gram –ve organisms.  E.g. cefuroxime – it is higher activity against penicilliase producing organisms and all ampicillin resistant H-influenzae.
  65. 65. Other spectrum More active against klebsiella, E-coli, enterobacter, indole positive protiens. Dose – a. 0.75 – 1.5 gms/ IM or IV/9 hrly b.30- 100mg/kg/day. Available as- supacef.
  66. 66. Third generation These were developed in end of 1980’s. They have augmentation activity against –ve Endobactericeae. They are resistant to β lactamase. These are-  Cefotaxamine  Ceffizoxime  Ceftriaxone  Moxalactum  ceftazidium
  67. 67. Cefotoxamine Potent action on gram-ve as well as gram+ve It is not so active against anaerobic like bact. Fragillis, Staphylococcous aureus, Pseudomonas aerugemosa. It is very important drug in teratment of meningitis, hospital acquired diseases septicaemia and infection in immuno compromised pt. Dose –  A.1-2gms/Imor IV/6- 12hrly  50-100mg/kg/day
  68. 68.  Available as -  Omnatax  claforan
  69. 69. Ceftizaxone Long acing cephalosporin One daily dose is good enough and it has good CSF penetration Dose  Adult - 1-2gms/IM or IV /day  Child- 75-100mg/kg/day
  70. 70. Ceftazidime Most prominent feature is high activity againt pseudomonas. It is used in febrile pt including pt with burns. It is less effective to staphylococcus aureus. Dose  Adult-0.5-2gms/IM or IV/ every 8 hours  Child- 30mg/ kg/day
  71. 71. Forth generationcephalosporine E.g. cefepime(maxipime) and cefpirome It is new cephalosporine with properties like those of 3rd generation cephalosporine but more resistance to some beta-lactumase. It is active against streptococci and methyciline sensetive staphylococci but not against methyciline resistance staphylococci.
  72. 72. Spectrum It’s main use is in serious gram –ve infection (H- influenza, Neisseria- gonorrhoae and Neissera meningities) including infection of CNS inti which it has exelent penetration. Half life is of 2hrs. Dose -2gm I.V. every 12hrs
  73. 73. Fifth generationcephalosporine Ceftobiprole has been described as "fifth generation",though acceptance for this terminology is not universal. Ceftobiprole (and the soluble prodrug medocaril) are on the FDA fast-track. Ceftobiprole has powerful antipseudomonal characteristics and appears to be less susceptible to development of resistance.
  74. 74.  These cephems have progressed far enough to be named, but have not been assigned to a particular generation. Cefaclomezine Cefaloram Cefaparol Cefcanel Cefedrolor Cefempidone Cefetrizole Cefivitril
  75. 75.  Cefmatilen Cefmepidium Cefovecin Cefoxazole Cefrotil Cefsumide Ceftaroline Ceftioxide Cefuracetim
  76. 76. Adverse effect Pain after injection. Diarrhoea due disturbance in Gut ecology Hypersensitivity reaction- anaphylaxis, angiodema, asthma, urticaria. Nephrotoxicity Neutropenia or thrombocytopenia Hyperprothombinemia A flase +ve cmbs test may occur in as many as 60%of pt or cephalathin therapy.
  77. 77. Macrolides They are antibiotics having a macrocyclic lactone ring with attached sugars They are bacteriostatic drug
  78. 78. Erythromycin Used as aternative in penicillin sensitive individuals CONTRAINDICATIONS  Hypersensiivity  Liver dieases- ester salt is avoided Available as –tablet & syrup Dose ADULT- 250-500mgQID CHILDREN-30-50mg kg/day in form of divided doses.
  79. 79. Adverse reaction Nausea Vomiting Diahrroea Hypertention Cardiac arrythmias Revesible hearing loss ONSET OF ACTION- 2to4hrs
  80. 80. Azithromycin This new azalide longer of erytromicin has an expanded spectrum, hyper…, Pharmacokinetics, better tolerability and drugs interation profile however it is not effective against erythromycin resistant bacteria.
  81. 81. IndicationsRespiratory track infectionUrenary track infection.Otitis media
  82. 82. Contraindications Hypersensitivity Hepatic impairmentDOSE- ADULT-500mg OD for 3days OR 500mg OD on days one followed by 250mg OD for 4 days. CHILDREN- 10mg/kg/ day for 3 days OR 10mg/kg/day followed by 5mg/kg/day OD for 5day.ONSET OF ACTION- one to two hrs
  83. 83. Adverse effect Mild gastric upset Abdominal pain Headache Dizziness
  84. 84. Imidazoles Metronidazole  Prototype netroimidazole  Active against anarobes
  85. 85. Mode of action In anarobic micro-organisms metronidazole is converted into an active form by reduction of it’s nitro group. This binds to DNA and prevents formation of nuclic acid.
  86. 86. Absoption fate and excretion The drug is well absorbed after oral or rectal administration. It is elimanated urine, partly unchanged & party metabolized
  87. 87. Contraindications Neurogenic diseases Blood dyscrasias first trimester of pregnancy
  88. 88. Uses Acute ulcerative gingivitis Dental infections Amoebiasis Giardiasis Trichomoniasis
  89. 89. Dose Orally 400mg 8hrly IV infusion 0.5gms/8hrs. Treatment should be continue for 7 days.
  90. 90. Adverse effects Anorexia Nausea Metalic taste Headache Glossitis Dryness of mouth Thromphlebitis of injected veins
  91. 91. Indication for antibiotic used n Systemic indications i Congnital or acquired heart a. Rheumatic heart disease b. Valvular diseases c. Pt with ventricular defects 2. Severe kidney diseaes a. chronic glumerulonephritis b. pt undergoing dialysis
  92. 92. 3. Active leukemia, agranulocytosis, aplasia , anemia4. Metabolic disturbances – diabetes5. Pt on chemotherapeutic drugs6. Pt with vascular graft
  93. 93. B. Maxillo- facial trauma1.Hard tissue trauma-the consensus is that antibiotic convert should be used for any mandibular or maxillar fracture compented into mouth or paranasal sinus through mouth.2.Soft tissue trauma3.Orthognathic & recontructive maxillo- facial surgery.4.Odontogenig infection5.Pericoronities6.Osteomylitis
  94. 94. contraindication Minor chronic localised abscess. Well localised vesibular abscess . Localised ostitis For sterilizing root canal Pt with mild pericoronitis, minor gingival oedema & mild pain which do not required antibiotcs
  95. 95. Prophylactic antibiotic therapy Standard recommendation A cephalosporin cefadroxil preferred 1preoperatively 500 mg orally 1hr before surgery 2 post operatively 250 mg orally 6hr after initial dose or Clindamycin in penicillin allergic pt 1 pre operatively 300 mg orally 1 hr before surgery 2 post operatively 150 mg orally 6hr after initial dose
  96. 96. Principles of antibioticprophylaxis 1 antimicrobial agent t is chosen on basis of most likely micro organisum to cause infection 2 an antibiotic loading dose should be employed 3 antibiotic should present in sufficient concentration in blood and targate tissue prior to dissemination of offending micro organisum
  97. 97.  4 antibiotics should be continued only as long as microbial contamination from operative site persist 5 patient benefits from prophylaxis should out high risk of antibiotic included allergy , toxicity , superinfection.
  98. 98. Dental procedure that requireendocardititis prophylaxis Tooth extraction Periodontal suergery Subgingival dental prophylaxis Endodontic surgery Incision & Drainage of infection
  99. 99. do not require endocardiatisprophylaxis Supragingival prophylaxis Restorative tooth preparation Placement of orthodontic appliances Conserative endodontic theraphy
  100. 100. REASONS FOR ANTIBIOTICFAILURE INAPPROPIATE choice of antibiotics Too low blood concentration Poor penetration to infected site Limited or decreased vascularity Impaired host defence Unfavourable local factors
  101. 101.  Increased plasma protein binding Antibiotic antagonism Slow microbial growth Antibiotic resistant organisms Patient failure to take antibiotics Failure to eradicate sorce of infection
  102. 102. Myths &misconception inantibiotic th erapy Myth- antibiotics cure pt1 except in immunocompramised pt antibiotics are not curative but rather function to provide time for normal host defence initially overwhelmed by micro organisum to gain and control &eventually eliminate the in fectious process
  103. 103.  2 .Antibiotics are substitute for surgical drainage - never are antibiotics a substituted for eradication of the source of infection ( extraction, incision, drainage ) unless the infection is too diffuse (pericoronitis)
  104. 104.  3 culture and sensitivity test are required - orofacial infection are characteristically acute in nature, polymicrobial in cause, short in duration with proper treatment. These infection require immediate attention and a dealy of 18 to 36 hrs for result of culture & sensitivity tests prior to initiation of antibiotics therapy is usually not appropriate because the microbial cause Is commly such that common antibiotics are effective, incision &drainage are relatively easy.
  105. 105. Myth – antibiotics incresedhost defence to infection The followoing condition appear valid at present 1 antibiotic that can peenetrate into the mammelion cell (tetracycline , eryt hromycin) are more likely to affect host defence than those that can not (beta lactum) 2 tetracycline may supress white cell chemotaxis where as betta lactum do not 3 most antibiotics (except tetracycline) do not depress phagocytosis Tnb lymphocyte transformation may be depressed by trtracyclines
  106. 106. Multiple antibiotics aresuperior to as single antibiotics. It is often assume that antbiotic combination are superior to single antibiotic such as not commonly the case. The primary clilical indication for antibiotic conbination therapy is severe infection in which ofending organism is unknown and major conciquences may ensue if antibiotic therapy is not instituted immediatey before culture and sensetivity test are available.
  107. 107. Antibiotic prophylaxis usuallyeffective It is commonly assume that antibiotics administered prior to invasive surgical procedure remain post operative infection. The reality based on laboratoru studies is that antibiotic prophalaxis is only some time effective.
  108. 108. Bacteriocidal agents are alwayssuperior to bacteriostatic agent Bacteriocidal antimicrobials are required in pt with impaier host defenses (nutropenia, meningitis) but bacteriostatic agent are uaually satisfactory, if host defence against infection are adequqte.
  109. 109. Antimicrobials are effective inchronic infectious disease Antimicrobials are never been successful in the eradication of a chronic infection because the prolong exposure of micro-organism to chemical leads to eventual dominance of drug resistance organism
  110. 110. Antibiotics are safe and nontoxic Most antimicrobials are among safest drug yet all are associated with allergy, ecological damage to human and microbial environment.
  111. 111. Infection require a completecourse of therapy There is no such things as predetermine complete course of antibiotic therapy. The only guide for determining the effectiveness of antibiotic therapy and hence duration of treatment is related to clinical improvement of pt.
  112. 112. Misconceptions Prolong therapy destroy resistant micro-organism. Prolong therapy is necessary for rebound infection that recur as organism is suppresed but not eliminated (orofacial infections do not rebound if the sourse of infection is properly eliminated) Antibiotic doseges and duration of therapy can be extra polated from one infection to another
  114. 114. Antibiotic LoadedHAP/TCP Bone Substitute for Prophylactic Action: ATANTIK Genta – In Vivo Study
  115. 115. INTRODUCTION: Infections and their consequences are a considerable problem inorthopedic surgery. Despite systemic prophylaxis, infection rates after orthopedic surgery are above1%. Antibiotic loaded PMMA bone cements have been shown to enhance the efficiency of intravenous prophylactic treatments for total hipreplacement1. However, less than 10% of the load is released during the first 5-10 days ofimplantation2: the remaining antibiotic is released at low levels over many months3 and could select antibiotic-resistant strains2.
  116. 116. Methods A commercial bone substitute composed of 70% Hydroxyapatite and 30% β- Tricalcium Phosphate4 containing 125 mg of Gentamicin (ATLANTIK Genta, Medical Biomat, France) was used in this study. The release rate of Gentamicin from the bone substitute was investigated after implantation in the femoral condyle of 5 sheep. In order to investigate the local and systemic Gentamicin concentrations, synovial fluids and blood samples were assessed by immunoassay over a 5 day period.
  117. 117.  There were differences in local Gentamicin concentrations between individuals but for all animals, the local Gentamicin concentrations measured during the first 8 hours were higher than the minimal bactericidal concentration of the majority of the germs responsible for infections in orthopedic surgery, i.e. 6-12 μg/ml. After 48 hours, the concentration in blood and synovial fluids was less than 0.5 μg/ml.
  118. 118.  The mean Gentamicin concentration peak obtained in blood was 4.2 μg/ml and then mean local Gentamicin concentration obtained in synovial fluids during the first 8 hours was305 μg/ml The Gentamicin amount remaining in the implant explanted at day 8 was less than 0.003% of the initial amount
  119. 119. New era of antimicrobial therapeutics
  120. 120.  It is a fact that selection of multi-drug-resistant bacteria has occurred throughout history. Unfortunately, however, drug-resistant bacteria have been met with antibiotics that are nothing more than recapitulations of earlier drugs. There has been an urgent need for new avenues of therapeutic treatment, and a new era of prophalytic (preventative) treatment has begun. Here the most plausible approaches are described: bacterial interference
  121. 121.  bacteriophage therapy bacterial vaccines cationic peptides cyclic D,L-a-peptides
  122. 122. Bacterial interference
  123. 123. One way is to inoculate hostswith nonpathogenic bacteria. Bacterial interference, also known as bacteriotherapy, is the practice of deliberately inoculating hosts with nonpathogenic (commensal) bacteria to prevent infection by pathogenic strains. To establish an infection and propagate disease, pathogenic bacteria must find nutrients and attachment sites (adhesion receptors)..
  124. 124.  Infection by pathogenic bacteria is prevented by commensal bacteria, which compete with pathogenic bacteria for nutrients and adhesion receptors or spur attack through secretion of antimicrobial compounds
  125. 125.  This treatment has had promising results in infections of the gut, urogenital tract, and wound sites. The major advantage of using bacteria in a positive way to benefit health, known as “probiotic” usage, is that infection is avoided without stimulating the host’s immune system and decreases selection for antibiotic resistance. Understanding how bacterial species compete, an essential criterion for research, has been known for at least 20 years but its practical application has yet to be realized.
  126. 126. Bacteriophage therapy
  127. 127.  Bacteriophages (commonly called “phages”) are viruses that infect bacteria and were recognized as early as 1896 as natural killers of bacteria. Bacteriophages take over the host’s protein-making machinery, directing the host bacteria to make viral proteins of their own. Therapeutically, bacteriophages were used as a prophylaxis against cholera, typhoid fever, and dysentery from the 1920s to the early 1940s.
  128. 128.  The practice was abruptly stopped when synthetic antibiotics were introduced after World War II. Now that there is a plethora of multi-drug-resistant bacteria, bacteriophage therapy once again has become of keen interest.
  129. 129. Pathogens may be targetedthrough manipulation ofphage DNA. Bacteriophage therapy is quite attractive for the following reasons: phage particles are narrow spectrum agents, which means they posses an inherent mechanism to not only infect bacteria but specific strains
  130. 130.  Other pathogens may be targeted through manipulation of phage DNA exponential growth and natural mutational ability make bacteriophages great candidates for thwarting bacterial resistance. Development of bacterial vaccines has become an increasingly popular idea with the advent of complete genomic sequencing and the understanding of virulence regulatory mechanisms.
  131. 131. Bacterial vaccines
  132. 132.  Bacterial genomics allows scientists to scan an entire bacterial genome for specific sequences that may be used to stimulate a protective immune response against specific bacterial strains. This approach expedites the drug discovery process and, more importantly, provides a more rational, target-based approach. The best targets are essential bacterial genes that are common to many species of bacteria, which code for proteins with the ability to gain accesses through lipid membranes, and possess no homology to human genes.
  133. 133.  Regulatory genes that control virulence protein production are excellent vaccine candidates for priming the human immune system or inhibiting virulence production. Bacterial genomics can also detect conserved sequences from bacterial species and strains worldwide. This technology will inevitably yield superior clinical vaccine candidates.
  134. 134. Cationic peptides
  135. 135.  These diverse peptides are natural compounds that posses both hydrophobic and hydrophilic characteristics, which means portions of the molecule are water avoiding or water loving. Cationic peptides are found throughout nature in the immune systems of bacteria, plants, invertebrates, and vertebrates
  136. 136. Other Peptides are synthetic,and are engineered to killbacterial cells. These peptides are not the usual synthetic drugs encountered in pharmaceutical drug design; however, they do exhibit antibacterial effects. Cationic peptides have several mechanisms of action, all of which involve interaction with the bacterial cell membrane leading to cell death. From a therapeutic standpoint, these proteins have great promise, as they have coevolved with commensal bacteria yet have maintained the ability to target pathogenic bacteria.
  137. 137. Other peptides are synthetic,or engineered, to kill bacterialcells. Unlike cationic peptides, cyclic D,L-a-peptides are synthetic and amphipathic (molecules having both water loving and water hating characteristics) cell membrane disruptors. As the name implies these peptides are cyclic in nature and are composed of alternating D and L amino acids. Cyclic D,L-a- peptides are engineered to target gram-positive and negative membranes (not mammalian cell membranes).
  138. 138.  In contrast to any other known class of peptides, these peptides can self-assemble into flat ring shaped conformations forming structures known as nanotubes, which specifically target and puncture bacterial cell membranes resulting in rapid cell death