Common Antibiotics : Used in periodontal therapy, easy approach for therapeutic use.


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An antibiotic is an agent that either kills or inhibits the growth of a microorganism.
The term antibiotic was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.[3] This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic mass units.

With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds.[4] These include, for example, the beta-lactam antibiotics, which include the penicillins (produced by fungi in the genus Penicillium), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. In accordance with this, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification, antibacterials are divided into two broad groups according to their biological effect on microorganisms: Bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth.Before the early 20th century, treatments for infections were based primarily on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago.[5] Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infections.[6][7] More recent observations made in the laboratory of antibiosis between micro-organisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics". The term 'antibiosis', meaning "against life," was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial drugs.[9][10] Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis. These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942. Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Ehrlich noted that certain.

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Common Antibiotics : Used in periodontal therapy, easy approach for therapeutic use.

  2. 2. Contents  Various definitions  Guidelines for use of antimicrobial therapy  Indications of antibiotics  Antibiotics used in periodontics  Combination & serial therapy  Local drug delivery system  conclusion 2
  3. 3. Various definitions  Chemotherapeutic agent : is a general term for a chemical substance that provides a clinical therapeutic benefit.  Anti-infective agent : is a chemotherapeutic agent that works by reducing the number of bacteria present.  Antibiotic : is a naturally occurring, semi synthetic, or synthetic type of anti infective agent that destroys or inhibits the growth of selective microorganisms, generally at low concentration 3
  4. 4. Guidelines for use of antimicrobial therapy 4
  5. 5. Indications for Antibiotic Therapy • Acute infections • Aggressive (early onset) forms of periodontitis • Recurrent (“refractory”) periodontitis 5
  6. 6. Aggressive Periodontitis: Antibiotics Indicated 6
  7. 7. Microorganisms Associated With Localized Aggressive Periodontitis • Actinobacillus actinomycetemcomitans • Eikenella corrodens • Fusobacterium nucleatum 7
  8. 8. Recurrent (refractory) Periodontitis: Antibiotics often indicated 8
  9. 9. Microorganisms Associated With Recurrent (“Refractory”) Periodontitis • Porphyromonas gingivalis • Prevotella intermedia • Bacteroides forsythus • Treponema denticola • Eikenella corrodens • Campylobacter rectus • Fusobacterium nucleatum 9
  10. 10. Acute Necrotizing Ulcerative Gingivitis: Antibiotics may be indicated 10
  11. 11. Periodontal Abscess: Antibiotics may be indicated 11
  12. 12. Chronic periodontitis is rarely treated with antibiotics • Scaling and root planing eliminates most species of subgingival bacteria associated with chronic periodontitis • Host defense mechanisms are usually effective at controlling infections 12
  13. 13. Key Pathogens • Actinobacillus actinomycetemcomitans • Porphyromonas gingivalis • Prevotella intermedia • Bacteroides forsythus 13
  14. 14. Requirements for Effective Antimicrobial Chemotherapy • The drug must reach the site of action • The drug’s concentration at the site of action must be sufficient to inhibit bacteria • The duration of chemotherapy must be sufficient to allow the drug to act 14
  15. 15. To inhibit subgingival bacteria, an antimicrobial agent must be able to reach the base of the periodontal pocket. Since some pathogens invade the soft tissue wall of the pocket, it is useful if the antibiotic can also reach this site. 15
  16. 16. Systemic Antibiotics • May have narrow or broad spectrum antimicrobial activity • Can potentially reach the pocket and its soft tissue wall • Can potentially attain inhibitory levels in the pocket • Can potentially be retained for an adequate duration 16
  17. 17. MECHANISM OF ACTION 1. Inhibit cell wall synthesis 2. Cause leakage from cell membrane 3. Inhibit protein synthesis 4. Inhibit DNA gyrase 5. Cause misreading of m-RNA code and affect permeability. 6. Interfere with DNA function 7. Interfere with DNA synthesis, etc. 17
  18. 18. Antibiotics Used in Periodontal Therapy  Penicillins (e.g., amoxicillin  Tetracyclines (e.g., doxycycline)  Metronidazole  Fluoroquinolones (e.g., ciprofloxacin)  Clindamycin  Erythromycin  Azithromycin 18
  19. 19. Penicillins  Bactericidal  Reach effective levels in gingival fluid  Don’t inhibit all A.a. Strains  Inactivated by ß-lactamases  Amoxicillin has enhanced tissue penetration and good activity against gram negatives  Augmentin is as effective as amoxicillin, but resists inactivation by ß-lactamases 19
  20. 20. Penicillins inhibit bacterial cell-wall synthesis, and the antimicrobial spectrum of natural penicillins is narrow. Amoxicillin is a semi-synthetic penicillin with broadened antimicrobial spectrum, and is used in periodontology because it is effective against some subgingival bacterial species such as P. micros and A. actinomycetemcomitans as well. 20
  21. 21.  It can be used in cases of acute infections, although it is most commonly used in combination with metronidazole. Amoxicillin in combination with clavulonic acid is indicated in the presence of oral bacteria capable of producing β-lactamase 21
  22. 22. Tetracyclines Tetracyclines are a group of broad spectrum, bacteriostatic antibiotics. They are the first antimicrobial drugs which have been scientifically investigated in periodontology. This group includes tetracycline hydrochloride, minocycline and doxycycline. 22
  23. 23.  Frequently used in treatment of refractory periodontitis including localised aggressive periodontitis.  Concentrate in periodontal tissues & inhibit the growth of a.a.  Also exert anticollagenase effect . 23
  24. 24. Pharmacology –  Obtained naturally from streptomyces sps. or derived semisynthetically.  More effective against gram +ve than gram -ve bacteria.  Their conc. in gingival crevice is 2 to 10 times more than in serum. 24
  25. 25. Specific agents Tetracycline –  Dose 250 mg four times daily (qid).  Inexpensive but less patient compliance. 25
  26. 26. Minocycline –  Broad spectrum of activity.  Dose 200 mg/day  Given twice daily (bid) so better patient compliance.  Less side effects than tetracycline  More efffective against spirochetes and motile rods. 26
  27. 27. Doxycycline –  Same spectrum of activity as minocycline  Given once daily so more patient compliance  Dose as an anti infective agent is 100mg bid the first day, then 100mg qd.  as subantimicrobial dose ( to inhibit collagenase) 20mg twice daily. 27
  29. 29. Metronidazole  Metronidazole is a synthetic nitroimidazole.  Its action is bactericidal, acting on anaerobic bacteria, including gram- negative rods and spirochetes, through DNA synthesis blocking. Due to the susceptibility of the spirochetes, it is effective in cases of necrotising periodontal diseases. 29
  30. 30. It seems relatively ineffective in the suppression of A. actinomycetemcomitans. Periodontal abscesses can be successfuly treated with metronidazole, while for aggressive periodontitis treatment its antimicrobial spectrum is not wide enough 30
  32. 32. Fluoroquinolones (Ciprofloxacin)  It is a quinolone active against gram –ve rods.  Bactericidal  Extremely active against A.a., but less active against anaerobic bacteria  Reach higher levels in gingival fluid than in blood serum  Penetrate epithelial cells-can kill invasive bacteria 32
  33. 33.  Ciprofloxacin is also effective in the treatment of periodontal superinfections caused by enteric bacteria, pseudomonas or staphylococci.  Another positive aspect is its inactivity towards streptococci, whose presence in the subgingival area is associated with periodontal health. Heightened streptococcal counts can postpone recolonisation of the pathogenic bacterial species. 33
  34. 34. Ciprofloxacin CIFRAN,CIPLOX- 200,500mg tab Side effects –  GASTROINTESTINAL  CNS EFFECTS  HYPERSENSITIVITY REACTION 34
  35. 35. Clindamycin • Potent bacteriostatic activity against strict anaerobes • Less effective against facultative pathogens (A.a. and Eikenella) • Can induce ulcerative colitis • Often used as an alternative antimicrobial agent in penicillin-allergic patients 35
  37. 37. Erythromycin • Doesn’t reach effective concentrations in gingival fluid • Weak activity against A.a., Eikenella and Fusobacterium 37
  38. 38. Azithromycin Azithromycin is an antibiotic from the macrolide group. it exerts bacteriostatic activity by blocking of bacterial proteins synthesis. The spectrum is broad and covers gram-negative bacteria, including enteric bacteria.  Has good activity against A.a. and Eikenella and good activity against P. gingivalis and many other gram-negative anaerobes  Penetrates epithelial cells-can kill invasive bacteria 38
  39. 39.  Assessment of availability in periodontal tissues showed extremely high values in periodontal tissues, crevicular fluid and saliva. Periodontally inflamed tissues exhibit concentrations significantly higher than healthy periodontal tissues, which is a very convenient characteristic of this antibiotic.  Data from clinical investigations support the use of azithromycin in the treatment of advanced chronic, or aggressive periodontitis . 39
  40. 40. Dose – therapeutic use requires a single dose of 250 mg/day for 5 days after an initial loading dose of 500mg. 40
  41. 41. Deciding Which Antibiotic to Use • Can use empirical approach • Can identify pathogens at the site with culture or DNA probes, then prescribe an antibiotic that will presumably inhibit them • Can culture isolated bacteria to identify them and determine their susceptibility to antibiotics 41
  42. 42. Approaches for identifying periodontal bacteria 42
  43. 43. Darkfield microscopy 43
  44. 44. Bacterial culture 44
  45. 45. Sampling deepest pockets with a paper point 45
  46. 46. Systemic Antibiotic Regimens for Treating Aggressive and Recurrent Periodontitis • Tetracycline HCl (250 mg QID) for 21 days (one of the oldest regimens) • Amoxicillin (500 mg TID) and metronidazole (250 mg TID) for 8 days (most commonly prescribed-more effective than a single agent) • Metronidazole (500 mg BID) and ciprofloxacin (500 mg BID) for 8 days (usually very effective for mixed infections) 46
  47. 47. Limitations of Systemic Antibiotics in Periodontics • Antibiotics rarely enhance the treatment of chronic periodontitis • To eliminate bacteria in biofilms effectively, antibiotics must be used in conjunction with mechanical debridement • No single antibiotic can inhibit all periodontal pathogens • Antibiotics can have undesirable side effects when given systemically 47
  48. 48. Adverse Side Effects Associated With Systemic Antibiotics • Induction of antibiotic resistance • Induction of microbial overgrowth • Inhibition of oral contraceptives (rare) • Hypersensitivity or toxicity (e.g., allergy, nausea, diarrhea, photosensitivity) 48
  49. 49. Combined and serial antibiotic therapy Subgingival microflora in periodontal diseases includes different pathogenic bacteria possessing differential sensitivity to antimicrobials, so the use of two or more antibiotics presents a useful option in the treatment of these diseases. The advantages of combined antibiotic therapy are broadened spectrum of antimicrobial activity, occurence of synergistic activity and prevention of bacterial resistance development.  Disadvantages of such a treatment are elevated incidence of adverse effects. 49
  50. 50. Metronidazole in combination with amoxicillin or ciprofloxacin has been successfuly used in the treatment of advanced periodontitis, especially infections with A. actinomycetemcomitans . Metronidazole and amoxicillin in vitro act synergistically on A. actinomycetemcomitans. Combination of metronidazole with amoxicillin or amoxicillin and clavulonic acid can eliminate A. actinomyctemcomitans and other periodontal pathogens from the periodontal pockets for at least two years 50
  51. 51. Metronidazole and ciprofloxacin can be effective in mixed periodontal infections, such as the presence of anaerobes, A. actinomycetemcomitans, enteric bacteria and pseudomonades.  As this combination is ineffective against most gram- positive, facultative anaerobic bacteria, it can facilitate streptococcal colonisation of the pockets which have no periodontally pathogenic potential 51
  52. 52. Serial use of antibiotics is indicated for a combination of antibiotics, in which one has bactericidal and the other bacteriostatic activity. Combined administration would lead to antagonistic effects and therapeutical failure. This form of systemic antimicrobial therapy should be used in especially severe cases of recurrent or refractory periodontitis, where attachment loss was not arrested despite careful initial therapy, or in cases of disease reactivation during the supportive phase of therapy, occurring despite good oral hygiene and repeated mechanical subgingival instrumentation. One of the combinations effective in the prevention of recurrent periodontitis in highrisk individuals is doxycycline and metronidazole 52
  53. 53. Local delivery of antibiotics Advantages  Higher local drug concentrations  Sustained therapeutic drug levels (independent of patient compliance)  Effective drug levels can be attained at sites that are difficult to reach  Adverse side effects are minimized 53
  54. 54. Tetracycline –containing fibers(Actisite)  An ethylene/ vinyl acetate copolymer fiber (diameter, 0.5mm) containing tetracycline, 12.7mg per 9 inches.  For 10 days it sustained tetracycline conc. exceeding 1300 microgram/ml, well beyond the 32 to 64 microgram/ml required to inhibit pathogens.  In contrast GCF conc. of only 4-8 microgram/ml were reported after systemic administration, 250 mg qid for 10 days. 54
  55. 55. Placement of Actisite fiber 55
  56. 56. Subgingival doxycycline(Atridox)  The FDA approved 10% doxycycline in a gel system using a syringe ( Atridox) .  It is the only local delivery system accepted by ADA. 56
  57. 57. Placement of atridox 57
  58. 58. Sub gingival minocycline  The FDA recently approved a new, locally delivered, sustained release form of minocycline microspheres ( Arestin)  2% minocycline is encapsulated into bioresorbable microspheres in a gel carrier. 58
  59. 59. Minocycline syringable gel 59
  60. 60. Sub gingival metronidazole  A topical medication containing an oil based metronidazole 25% gel is used. 60
  61. 61. Conclusion Antimicrobial therapy is indicated in cases of disease where the periodontal destruction continued, despite thoroughly performed mechanical therapy. In patients from high-risk groups, such as aggressive forms of periodontitis or periodontitis as a manifestation of systemic disease, the use of antibiotics is indicated as an adjunct to scaling and root planing. Antibiotics are never indicated in the treatment of chronic gingivitis. 61
  62. 62. References : - Carranza’s Clinical Periodontology 10th ediion. 62