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 antibioticsAntibiotic era
4 Overview Antimicrobial compounds AntiviralAntifungalAntibacterialSelective Toxicity: the drug can be administered to humans with reasonable safety while having a marked lethal or toxic effect on a specific microbe.
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 InfectionPatients host defensesTreating the infection surgically (I&D)Treating with antibiotics
8 Indications of Antibiotic Use Temperature >101F with malaiseSpreading cellulitisChronic infection resistant to previous TXAnatomical space involvementTrismusLyphadenopathyPt with co-morbiditiesAcute pericornitis, osteomyelitis, ANUG, ect…
9 Antibiotics Use Not Indicated Minor, chronic, well localized abscessToothachePeriapical abscessDry socketMultiple extractions in healthy patientSurgical extraction (drill and sutures)Mild pericoronitisDrained alveolar abscess
11 Rational Antibiotic Therapy: Is the ideal method for deciding on which antibiotic to administer, and is based on:C&S of organisms involvedSite of infectionSafety of agentPatients statusCost of therapy
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. StaticBactericidal 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’Bactericidaldisrupts the cell wall synthesis-killing the bacteriaLess reliance on host resistanceDrug works faster than ‘static’More flexibility with dosage intervalBacteriostaticinhibits the RNA synthesis/reproductionInhibit growth and reproduction of bacteriaHelp the host defenses to take over
16 Therapeutic SpectraRefers 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 Broad spectrumAmoxicillinAugmentin (Amoxicillin with clavulanic acid)AzythromycinTetracyclineMoxifloxacinNarrow spectrumPenicillinCephalosporin (1st generation)ClindamycinMetronidazole
19 Combination TherapyThe use of more that one agent is not advisable, in most dental situations because:Risk of increased side-effectsCompetitive antagonism of agentsCo$tHowever, there are certain situations where this is appropriate:Adding Metronidazole to Penicillin that the patient is already taking.
20 Clinical ScenarioPt was I&D’d 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&DInappropriate antibiotic therapyPresence of local factorsImpaired host responsePoor patient compliancePoor perfusionUnusual 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 pumpingModification of the Active Site of the Drug
25 Complications of Antibiotic Therapy HypersensitivityAnaphylactoid type reactions (IV)ToxicityUsually due to high serum levelsSuperinfectionsMost commonly due to broad-spectrum or combination therapy.Idiosyncratic reactionsranging from nausea to fatal aplastic anemiaInteractions
26 Side effects Allergy- manifested as Hives Itching Wheezing Clindamycin Pseudomemberanous colitis
27 Principles of Antibiotic Administration DoseSufficient to achieve desired therapeutic effectsTime intervalPlasma Half lifeRoute of AdministrationIV, IM, Oral
28 Principles of Antibiotic Administration Use least toxic antibioticPatients drug historyPatient’s drug reactionDrug/drug interactions
29 Effective Antibiotics for Oral Surgery PenicillinsPen VKAmoxicillinAugmentinCephalosporinsClindamycinMetronidazole (Flagyl)Azithromycin
30 Mechanism of Action Classification Eight Categories:Blocks cell wall synthesis (inhibition of peptidoglycan cross-linkingBlock peptidoglycan synthesisDisrupt cell membraneBlock nucleotide synthesisBlock DNA topoisomerasesBlock mRNA synthesisBlock protein synthesis (50S subunit)Block protein synthesis (30S subunit)
33 Penicillins Most commonly prescribed antibiotic in dentistry. Are extremely effective against most oral/odontogenic pathogens.BactericidalSide 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..
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 AmoxicillinIs an extended spectrum, oral, agent used primarily for premedication and in situations where minor “sinus” pathogens are present and/or suspected.Amoxicillin > AmpicillinSpectrum of action:Similar to pen VKGram- (Haemophilus and Proteus)
39 Amoxicillin Resistance is a drawback, via β-lactamase. Dosing for adult ,premed is at 2000mg, 1 hour prior to TXOtherwise 500 mg, tid for 7-14 days
40 AugmentinPotassium 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 1st generation agent Cephalexin (Keflex).
42 Cephalosporins Uses in dentistry: Dosing “anti-staphylococci”Orthopedic premedSecond-line odontogenicDosingPremed is 2000mg, 1 hour prior500mg qid, for 7-10 daysAround 10% cross-sensitivity with penicillins.
43 ClindamycinIt 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 highMetabolized in liver, excreted in urine and fecesEXCELLENT abscess penetration but poor CSF penetrationInfections with rapid deep spread, resistant to Penn VK, Penn allergic.
44 Clindamycin Dosing: Side effects are primarily with the GI tract Uses in dentistry:Premed (Penn allergic)Infections where significant anaerobic colonization is suspected.Dosing:Premed is 600 mg, 1 hour priorInfection is mg, tid or qid for 7 daysSide effects are primarily with the GI tractDiarrhea, Pseudomembranous Colitis (C. difficile).Clostridium difficile produces toxin a and b.
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: Side Effects: Dosing: Primary agent in ANUG.Used with penicillin VK (“poor-man’s augmentin)Side Effects:Metallic tasteDisulfram reactionDosing:500 mg, tid for 5-7 days (caution use over 7 days at this dose).
48 AzithromycinIt 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 useBetter sterile and clean technique of treatmentNew antibioticsModify existing antibioticsAgents to “cure” resistance plasmidsDevelop inhibitors of antibiotic-modifying enzymes
50 Current TrendsIncreased incidence of Beta lactamase producing BacteriaIncrease in s. aureus (Methicillin-resistant Staphylococcus aureus )-MRSA
51 Vancomycin Narrow spectrum bactericidal Not absorbed from GI tract – Must be given iv for systemic infectionUseful for treatment of C. DifficileExcreted by kidneys as active drugUse in serious penicillin allergic infections, methicillin resistant infections (mrsa)
52 Mechanism to Reduce Antibiotic Resistance Control and reduce useBetter sterile and clean technique of treatmentNew antibioticsModify existing antibioticsAgents to “cure” resistance plasmidsDevelop inhibitors of antibiotic-modifying enzymes
53 ReferencesLe, Tao, et al. First Aid for the USMLE: Step New York: McGraw Hill Medical, 2008.Mycek, Mary, Richard Harvey, and Pamela Champe. Illustrated Reviews: Pharmacology 2nd Edition. New York: Lippincott’s, 2000.Peterson, Larry, et al. Contemporary Oral and Maxillofacial Surgery: Forth Edition. New York: Mosby, 2006.Samaranayake, L.P., Brian Jones, and Crispian Scully. Essential Microbiology for Dentistry. New York: Churchill Livingstone, 2002.