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Antibiotic Chemotherapy for Oral & Maxillofacial Surgery. 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.
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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.
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
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.
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 ?
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
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…
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
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
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
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.
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
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.
Narrow spectrum Penicillin Cephalosporin (1st generation) Clindamycin Metronidazole Broad spectrum Amoxicillin Augmentin (Amoxicillin with clavulanic acid) Azythromycin Tetracycline Moxifloxacin Therapeutic SpectraExamples of Antibiotics
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.
Clinical Scenario • Pt 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.
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.
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.
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.
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
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
Allergy- manifested as Hives Itching Wheezing Clindamycin Pseudomemberanous colitis Side effects
Principles of Antibiotic Administration • Dose • Sufficient to achieve desired therapeutic effects • Time interval • Plasma Half life • Route of Administration • IV, IM, Oral
Principles of Antibiotic Administration • Use least toxic antibiotic • Patients drug history • Patient’s drug reaction • Drug/drug interactions
Effective Antibiotics for Oral Surgery • Penicillins • Pen VK • Amoxicillin • Augmentin • Cephalosporins • Clindamycin • Metronidazole (Flagyl) • Azithromycin
Mechanism of Action Classification • Eight Categories: • Blocks cell wall synthesis (inhibition of peptidoglycan cross-linking • Block peptidoglycan synthesis • Disrupt cell membrane • Block nucleotide synthesis • Block DNA topoisomerases • Block mRNA synthesis • Block protein synthesis (50S subunit) • Block protein synthesis (30S subunit)
Cell wall synthesis Cycloserine Vancomycin Bacitracin Penicillins Cephalosporins Monobactams 50S 50S 30S 30S Folic acid metabolism Trimethoprim Sulfonamides A T C DNA Protein synthesis (50S inhibitors) Erythromycin Chloramphenicol Clindamycin mRNA DNA-dependent RNA polymerase Rifampin Cell membrane Polymyxins DNA replication (DNA gyrase) Nalidixic acid Quinolones Protein synthesis (30S inhibitors) Tetracycline Spectinomycin Streptomycin Gentamicin, tobramycin Amikacin
Cefazolin Carbenicillin Imipenem/Cilastatin Cefadroxil Cephalexin Cephalothin Cephapirin Cephradine Cefamandole Cefaclor Ampicillin Cloxacillin Oxacillin Methicillin Penicillin V Penicillin G Amoxicillinn Cefoperazone Cefotaxime Ceftizoxime Ceftazidime Ceftibuten Ceftriaxone Moxalactam Cefixime Cefepime Cefdinir Cefuroxime Cefoxitin Cefotetan Cefmetazole Cefonicid INHIBITORS OF CELL WALL SYNTHESIS -LACTAMASE INHIBITORS Clavulanic acid Sulbactam -LACTAM ANTIBIOTICS OTHER ANTIBIOTICS Tazobactam Vancomycin Bacitracin PENICILLINS CEPHALOSPORINS CARBAPENEMS MONOBACTAMS Aztreonam 1st GENERATION 2nd GENERATION 3rd GENERATION 4th GENERATION
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.
Stable to acid permitting oral administration Natural penicillins Penicillin G* Penicillin V Antistaphylococcal Cloxacillin Dicloxacillin Methicillin Nafcillin Oxacillin Amoxicillin + clavulanic acid Ampicillin + sulbactam Ticarcillin + clavulanic acid Piperacillin + tazobactam Stable to penicillinase Extended spectrum Ampicillin Amoxicillin Antipseudomonal Azlocillin Carbenicillin Mezlocillin Piperacillin Ticarcillin
Pen V KPhenoxymethylpenicillin • 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
Pen V KPhenoxymethylpenicillin • 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
Pen V KPhenoxymethylpenicillin • 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.
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)
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
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
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).
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.
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
Clindamycin • Uses in dentistry: • Premed (Penn allergic) • Infections where significant anaerobic colonization is suspected. • Dosing: • Premed is 600 mg, 1 hour prior • Infection is 150-300 mg, tid or qid for 7 days • Side effects are primarily with the GI tract • Diarrhea, Pseudomembranous Colitis (C. difficile).
Clindamycin • Contraindications • hypersensitivity to lincosamides • history of inflammatory bowel disease
Metronidazole • Bactericidal • Spectrum is effective against strict anaerobes (Bacteroides and Clostridia). • Anaerobic bacteria convert into active metabolite, which inhibits DNA synthesis.
Metronidazole • Dental uses: • Primary agent in ANUG. • Used with penicillin VK (“poor-man’s augmentin) • Side Effects: • Metallic taste • Disulfram reaction • Dosing: • 500 mg, tid for 5-7 days (caution use over 7 days at this dose).
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.
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
Current Trends • Increased incidence of Beta lactamase producing Bacteria • Increase in s. aureus (Methicillin-resistant Staphylococcus aureus )-MRSA