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Antibiotic Chemotherapy for Oral & Maxillofacial Surgery.

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Presentation on theme: "Antibiotic Chemotherapy for Oral & Maxillofacial Surgery."— Presentation transcript:

1 Antibiotic Chemotherapy for Oral & Maxillofacial Surgery

2 History of Antibiotics-Early History Ayurveda-Oldest medicine system (over 5000 years old) used Sesame paste, Honey, Skin from the stem of many antiseptic herbs e.g. Neem (azadirachta indica),Turmeric root etc. In 3500 BC the Sumerian doctors would give patients beer soup mixed with snakeskins and turtle shells. (yummy!!) 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.

3 Modern History Louis Pasteur Sir Alexander Fleming-Penicillin Domagk- discovers synthetic antimicrobial chemicals (sulfonamides). Late 1940's through the early 1950's, streptomycin, chloramphenicol, and tetracycline were discovered and introduced as antibiotics Antibiotic era

4 Overview Antimicrobial compounds –Antiviral –Antifungal –Antibacterial Selective Toxicity: the drug can be administered to humans with reasonable safety while having a marked lethal or toxic effect on a specific microbe.

5 Decision to Use Antibiotics

6 Would you like to treat this patient with antibiotics John a 30 year old patient has painful tooth #29 but no swelling, no trismus or increase in temperature. His general health is Good. –Would you administer antibiotics to him following an extraction, WHY ?

7 Principles of appropriate Antibiotic use Evaluate the patient carefully and in this order: –Severity of Infection –Patients host defenses –Treating the infection surgically (I&D) –Treating with antibiotics

8 Indications of Antibiotic Use Temperature >101F with malaise Spreading cellulitis Chronic infection resistant to previous TX Anatomical space involvement Trismus Lyphadenopathy Pt with co-morbidities Acute pericornitis, osteomyelitis, ANUG, ect…

9 Antibiotics Use Not Indicated Minor, chronic, well localized abscess Toothache Periapical abscess Dry socket Multiple extractions in healthy patient Surgical extraction (drill and sutures) Mild pericoronitis Drained alveolar abscess

10 Selection of Antimicrobial Agents

11 Rational Antibiotic Therapy: Is the ideal method for deciding on which antibiotic to administer, and is based on: –C&S of organisms involved –Site of infection –Safety of agent –Patients status –Cost of therapy

12 Cost NAMEIntervalCost per week Pen VK 500mg 1 tab qid$10.99 Clindamycin 150 mg 2 tabs qid$49.00 Augmentin 875mg I tab bid$

13 Empirical Antibiotic Therapy: Broad-spectrum antimicrobials can be administered on a educated guess basis, considering: - Site of infection - Most probable pathogens - Antibiotic sensitivity pattern - C&S is not always cost and time effective

14 Cidal vs. Static Bactericidal Agents: Kills bacteria and reduces the total number of viable organisms. Bacteriostatic Agents: Arrest the growth and replication of bacteria, thus allowing the host immune system to complete pathogen elimination.

15 Bactericidal vs. Bacteriostatic Prefer Bactericidal to Bacteriostatic –Bactericidal disrupts the cell wall synthesis-killing the bacteria Less reliance on host resistance Drug works faster than static More flexibility with dosage interval –Bacteriostatic inhibits the RNA synthesis/reproduction Inhibit growth and reproduction of bacteria Help the host defenses to take over

16 Therapeutic Spectra Refers to a particular drugs species of organisms affected. Antimicrobial agents are categorized: - broad-spectrum: acts against both Gram- positive and Gram-negative bacteria. -narrow-spectrum: effective against only specific families of bacteria.

17 Therapeutic Spectra Examples of Antibiotics Narrow spectrum –Penicillin –Cephalosporin (1 st generation) –Clindamycin –Metronidazole Broad spectrum –Amoxicillin –Augmentin (Amoxicillin with clavulanic acid) –Azythromycin –Tetracycline –Moxifloxacin

18 Therapeutic Spectra

19 Combination Therapy The use of more that one agent is not advisable, in most dental situations because: –Risk of increased side-effects –Competitive antagonism of agents –Co$t However, there are certain situations where this is appropriate: –Adding Metronidazole to Penicillin that the patient is already taking.

20 Clinical Scenario Pt was I&Dd and given a Rx of Penn VK 500mg on Mon. due to significant vestibular swelling status post 5 days extraction of #19. Pt. returns to clinic today (Fri.) with diffuse indurated swelling on his left submandibular space. What TX should be considered.

21 Why is TX failing Consider if no response within 48 hours: –Inadequate I&D –Inappropriate antibiotic therapy –Presence of local factors –Impaired host response –Poor patient compliance –Poor perfusion –Unusual pathogen and/or no infective etiology.

22 Antibiotic Resistance This is a major problem for patients and healthcare providers in the hospital setting. Resistance develops when progeny of resistant bacteria proliferate via selective advantage. As long as the antibiotic is being taken, this proliferation will continue.

23 Types of Antibiotic Resistance Primary Resistance: Organism is naturally resistant to the drug. Acquired Resistance: Mutation within the same species or gene transfer between different species (plasmids). Cross-Resistance: Resistance to one drug confers resistance to another similar drug.

24 Mechanism of Antibiotic Resistance Inactivation of the Drug: very common, bacteria produces a product to inactivate. (ex. β-lactamase production) Altered Uptake: drug is not allowed to reach its target by either altered permeability or reverse pumping Modification of the Active Site of the Drug

25 Complications of Antibiotic Therapy Hypersensitivity –Anaphylactoid type reactions (IV) Toxicity –Usually due to high serum levels Superinfections –Most commonly due to broad-spectrum or combination therapy. Idiosyncratic reactions –ranging from nausea to fatal aplastic anemia Interactions

26 Side effects Allergy- manifested as Hives Itching Wheezing Clindamycin –Pseudomemberanous colitis

27 Principles of Antibiotic Administration Dose –Sufficient to achieve desired therapeutic effects Time interval –Plasma Half life Route of Administration –IV, IM, Oral

28 Principles of Antibiotic Administration Use least toxic antibiotic Patients drug history –Patients drug reaction –Drug/drug interactions

29 Effective Antibiotics for Oral Surgery Penicillins –Pen VK –Amoxicillin –Augmentin Cephalosporins Clindamycin Metronidazole (Flagyl) Azithromycin

30 Mechanism of Action Classification Eight Categories: 1.Blocks cell wall synthesis (inhibition of peptidoglycan cross-linking 2.Block peptidoglycan synthesis 3.Disrupt cell membrane 4.Block nucleotide synthesis 5.Block DNA topoisomerases 6.Block mRNA synthesis 7.Block protein synthesis (50S subunit) 8.Block protein synthesis (30S subunit)

31 50S 30S A C T Cell wall synthesis Cycloserine Vancomycin Bacitracin Penicillins Cephalosporins Monobactams Cell membrane Polymyxins DNA replication (DNA gyrase) Nalidixic acid Quinolones DNA-dependent RNA polymerase Rifampin DNA mRNA Protein synthesis (30S inhibitors) Tetracycline Spectinomycin Streptomycin Gentamicin, tobramycin Amikacin Protein synthesis (50S inhibitors) Erythromycin Chloramphenicol Clindamycin Folic acid metabolism Trimethoprim Sulfonamides

32 2 nd GENERATION 1 st GENERATION 3 rd GENERATION 4 th GENERATION PENICILLINS MONOBACTAMS CARBAPENEMS CEPHALOSPORINS -LACTAM ANTIBIOTICS -LACTAM ANTIBIOTICS OTHER ANTIBIOTICS OTHER ANTIBIOTICS INHIBITORS OF CELL WALL SYNTHESIS INHIBITORS OF CELL WALL SYNTHESIS -LACTAMASE INHIBITORS -LACTAMASE INHIBITORS Vancomycin Bacitracin Tazobactam Sulbactam Clavulanic acid Imipenem/Cilastatin Aztreonam CefadroxilCephalexinCephalothinCephapirinCephradine Cefazolin Cefamandole Cefaclor CefonicidCefmetazoleCefotetanCefoxitinCefuroxime CefdinirCefepime MoxalactamCeftriaxoneCeftibutenCeftazidimeCeftizoximeCefotaximeCefoperazoneCefixime Penicillin G Penicillin VMethicillinOxacillinCloxacillinAmpicillinCarbenicillinAmoxicillinn

33 Penicillins Most commonly prescribed antibiotic in dentistry. Are extremely effective against most oral/odontogenic pathogens. Bactericidal Side effects occur frequently and range from minor rash to anaphylaxis. If allergic to one type of penicillin it will be share by all the penicillins.

34 Cloxacillin Dicloxacillin Methicillin Nafcillin Oxacillin Amoxicillin + clavulanic acid Ampicillin + sulbactam Ticarcillin + clavulanic acid Piperacillin + tazobactam Stable to penicillinase Stable to acid permitting oral administration Stable to acid permitting oral administration Natural penicillins Penicillin G* Penicillin V Antistaphylococcal Extended spectrum Ampicillin Amoxicillin Antipseudomonal Azlocillin Carbenicillin Mezlocillin Piperacillin Ticarcillin

35 Pen V K Phenoxymethylpenicillin Should be your first consideration for dental related infections. Inhibits cell wall synthesis via disruption of the cross-linking structure of the peptidoglycan portion of the cell wall. Very cost effective

36 Pen V K Phenoxymethylpenicillin Spectrum of activity include a majority of α- hemolytic streptococci and some penicillianse- negative staphylococci. Gram + sensitive include: Actinomyces, Eubacterium, Bifidobacterium and Peptostreptococcus. Gram – sensitive include: Prevotella, Porphyromonas, Fusobacterium and Veillonella

37 Pen V K Phenoxymethylpenicillin Resistance is common due to β-lactamase production by bacteria (Staph. aureus) Penicillinase is a specific type of β- lactamase, showing specificity for penicillins. Dose is 500 mg for adults, qid for 7-10 days.

38 Amoxicillin Is an extended spectrum, oral, agent used primarily for premedication and in situations where minor sinus pathogens are present and/or suspected. Amoxicillin > Ampicillin Spectrum of action: –Similar to pen VK –Gram- (Haemophilus and Proteus)

39 Amoxicillin Resistance is a drawback, via β- lactamase. Dosing for adult, –premed is at 2000mg, 1 hour prior to TX –Otherwise 500 mg, tid for 7-14 days

40 Augmentin Potassium Clavulanate can be incorporated with amoxicillin to form Augmentin. This blocks the action of β-lactamase. Dose is 500mg tid or 875mg bid, for 7-14 days. Beta lactam ring

41 Cephalosporns β-lactams similar to Penicillins Relatively stable to staphylococcal penicillinase. Classified as first, second, third and fourth generation. Spectrum changes with generations. As dentist we will be concerned with a 1 st generation agent Cephalexin (Keflex).

42 Cephalosporins Uses in dentistry: –anti-staphylococci –Orthopedic premed –Second-line odontogenic Dosing –Premed is 2000mg, 1 hour prior –500mg qid, for 7-10 days Around 10% cross-sensitivity with penicillins.

43 Clindamycin It is bacteriostatic via inhibition of protein synthesis by binding to the 50 S ribosomal protein. Spectrum favors anaerobic bacteria (Bacteroides/Prevotella), but does have some aerobic coverage. Static in low concentraations, cidal in high Metabolized in liver, excreted in urine and feces EXCELLENT abscess penetration but poor CSF penetration

44 Clindamycin Uses in dentistry: –Premed (Penn allergic) –Infections where significant anaerobic colonization is suspected. Dosing: –Premed is 600 mg, 1 hour prior –Infection is mg, tid or qid for 7 days Side effects are primarily with the GI tract –Diarrhea, Pseudomembranous Colitis (C. difficile).

45 Clindamycin Contraindications –hypersensitivity to lincosamides –history of inflammatory bowel disease

46 Metronidazole Bactericidal Spectrum is effective against strict anaerobes (Bacteroides and Clostridia). Anaerobic bacteria convert into active metabolite, which inhibits DNA synthesis.

47 Metronidazole Dental uses: –Primary agent in ANUG. –Used with penicillin VK (poor-mans augmentin) Side Effects: –Metallic taste –Disulfram reaction Dosing: –500 mg, tid for 5-7 days (caution use over 7 days at this dose).

48 Azithromycin It is bacteriostatic via inhibition of protein synthesis by binding to the 50 S ribosomal protein. Spectrum: –Weak to Strep. and Staph. –Active against respiratory infections. Uses are limited to penicillin allergic sinus situations. Dosed as a Z-pack, 5 day course.

49 Mechanism to Reduce Antibiotic Resistance Control and reduce use Better sterile and clean technique of treatment New antibiotics Modify existing antibiotics Agents to cure resistance plasmids Develop inhibitors of antibiotic-modifying enzymes

50 Current Trends Increased incidence of Beta lactamase producing Bacteria Increase in s. aureus (Methicillin- resistant Staphylococcus aureus )-MRSA

51 Vancomycin –Narrow spectrum bactericidal – Not absorbed from GI tract – Must be given iv for systemic infection – Useful for treatment of C. Difficile – Excreted by kidneys as active drug –Use in serious penicillin allergic infections, methicillin resistant infections (mrsa)

52 Mechanism to Reduce Antibiotic Resistance Control and reduce use Better sterile and clean technique of treatment New antibiotics Modify existing antibiotics Agents to cure resistance plasmids Develop inhibitors of antibiotic-modifying enzymes

53 References Le, Tao, et al. First Aid for the USMLE: Step New York: McGraw Hill Medical, Mycek, Mary, Richard Harvey, and Pamela Champe. Illustrated Reviews: Pharmacology 2 nd Edition. New York: Lippincotts, Peterson, Larry, et al. Contemporary Oral and Maxillofacial Surgery: Forth Edition. New York: Mosby, Samaranayake, L.P., Brian Jones, and Crispian Scully. Essential Microbiology for Dentistry. New York: Churchill Livingstone, 2002.

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