O-Med: Antibiotic Therapies (lecture 3)

  1. Normal microbial flora develops             through environmental exposure of the newborns via what 3 ways?
    • ¡Passage from the birth canal
    • ¡Nursing
    • ¡Interaction with the adult family members
  2. what is the role of normal flora?
    • - role is unclear
    • - Potentially prevents colonization of the non-indigenous bacteria
  3. how many microbial species colonize adult human oral cavity?
    > 300

    - Same microbial density as large intestine 10^11/g wet tissue weight
  4. what type of bacteria colonize mouth....

    few days after newborn?
    after tooth eruption?
    after puberty?
    few days after newborn: strep.

    after tooth eruption: s. mutans & s.sanguis, actinomyces, bacteroides, fusobacterium

    after puberty: spirochetes
  5. How to choose the correct antibiotic?
    • 1. selective toxicity
    • 2.Consider agent’s activity & concentration
    • 3. Use drug dosing & schedule with respect to in-vitro MIC
  6. How to choose correct abx? Consider agent’s activity & concentration

    bactericidal agents vs bacteriostatic?
    combo tx and effects?
    - Use bactericidal agents over bacteriostatic

    - If using combination tx:

    • - Bacteriostatic + bacteriostatic: additive effect (1+1=2)
    • - Bacteriostatic + bacteriocidal: antagonism (1+1<1)
    • - Bacteriocidal + bacteriocidal: synergism (1+1>2)

    - Whenever possible, determine the sensitivity of pathogen
  7. How to choose the correct antibiotic: Use drug dosing & schedule with respect to in-vitro MIC

    what is concentration-dependent drugs?
    time dependent drugs?
    ¡Concentration-dependent drugs – the more you increase the dose, the higher the killing rate nDoses used achieve peak plasma levels that are 8-10x the in-vitro MIC - Metronidazole and quinolones

    ¡Time-dependent drugs – once concentration threshold has been reached increasing drug concentration will not increase the killing rate nDoses used achieve plasma levels that are 4-5x the in-vitro MIC - Penicillins & cephalosporins - to ensure threshold has been reached use a loading dose
  8. How to choose the correct antibiotic? Other factors to consider
    • Correct diagnosis of the infection
    • Choice of most specific and effective drug (antibiotic spectrum)
    • Adverse effects (allergy Hx, & toxicity)
    • Cost  
    • Bacterial resistance
  9. Treatment of Orofacial Infections: General Principles
    - Use an agent with a spectrum appropriate for the type of infection

    - Employ high doses for a short duration

    - Use the oral route

    - Use dosing intervals appropriate for drug half-life

    - Determine the duration of therapy by the remission of disease + 48 hrs

    - Consider host factors; adjust for renal and hepatic diseases
  10. Orofacial Infections: Odontogenic infections

    what bacteria are present?
    1.Odontogenic infections involve a mix of g+, g-, facultative anaerobes.

    Strict anaerobes are found in:

    • ~ 60% of pulp necrosis (non-intact teeth)
    • ~ 90% of pulp necrosis (intact teeth)
  11. Orofacial Infections: Periodontal pockets

    what bacteria are present?
    involves g+ and g- organisms;

    g- anaerobes (Porphyromonas & Bacteroides) predominate as pockets deepen
  12. Orofacial Infections: Osteomyelitis

    what bacteria are the most common cause?
    Staph. aureus and epidermis are the most common causes
  13. Orofacial Infections: Acute Salivary Infections

    what bacteria are the most common cause?
    may be due to S. aureus or any commensal organism
  14. Orofacial Infections: Oral malodor

    what bacteria are present?
    mix of superficial anaerobic infections
  15. Antimicrobial Agents
  16. Inhibitors of Cell wall synthesis: Beta-Lactam Antibiotics

    bacteriocidal? bacteriostatic?
    cleared through what system?
    cross placenta?
    resistance issues?
    side effects?
    • Bacteriocidal antibiotics
    • Include penicillins and cephalosporins
    • Good diffusion in organic fluids, infected tissues
    • All cleared through the renal system
    • Most cross the placenta; excreted in breast milk
    • Resistance is an issue
    • Hypersensitivity, GI disturbance, anemia, renal damage
  17. Name examples of beta-lactams abx?
    • penicillins
    • - broad spectrum
    • - narrow spectrum

  18. Beta-Lactam: Penicillins

    - name some extended spectrum drugs?
    • - Amoxicillin
    • - ampicillin
    • - carbenicillin
    • - ticarcillin
    • - mezlocillin
    • - piperacillin
  19. Beta-Lactam: Penicillins

    - name some narrow spectrum drugs? (2 types)
    • 1. Beta lactamase sensitive:
    • - Penicillin G (benzylpenicillin)
    • - Penicillin V (phenoxymethyl penicillin)

    • 2. Beta lactamase resistant/inhibitor:
    • - Cloaxacillin, oxacillin, methicillin, clavulanic acid
  20. Beta-lactam: cephalosporines

    - examples
    - spectrum
    - used for?
    - First through 5th generations: cefazolin, cefriaxone…

    - broad – similar to broad spectrum penicillins plus pseudomonas & Klebsiella

    - used for: Hospital-acquired pneumonia & GI infections
  21. inhibitors of protein synthesis

    - name 3 classes of drugs
    - bacteriostatic? bacteriocidal?
    - which one has poor tissue [ ] ?
    - excreted via?
    - which one binds to Ca? and not used in pregnant women?
    - which is secreted in breast milk?
    - side effects of each?
    - tetracyclines, clindamycin and macrolides

    - Mostly bacteriostatic (except clindamycin)

    - Some have poor tissue concentration (esp erythromycin)

    - Excreted via kidney and hepatic bile

    - Teracyclines bind to Ca; inhibited by anti-acids & dairy, not used in pregnancy

    - All secreted in breast milk

    • Side effects:
    • - Can cause GI symptoms (esp erythromycin)
    • - Over growth of Clostridium difficile w/ clindamycin
    • - Candida superinfection w/ tetracyclines (oral, vaginal)
  22. Examples of ABx inhibitors of protein synthesis

    - Tetracycline: short acting? long acting?
    - macrolides: name 3
    - clindamycin
    • 1. tetracyclines
    • - Short acting: tetracycline
    • - Long acting: doxycycline and minocycline

    • 2. macrolides
    • - Erythromycin
    • - Semi-synthetic erythromycins: clarithromycin, azithromycin

    3. Clindamycin
  23. Inhibitors of Protein Synthesis – Bacterial Spectrum

    - spectrum?
    - target which type of bacteria?
    - used for?
    - broad spectrum

    - most g+ and g- bacteria including many anaerobes (chlamydiae, rikettsia, spirochetes), even some protozoa¡

    - used for: Acne, rosacea, intestinal infections, PID, UTI & spirochetal infections (syphilis, lyme disease, periodontitis)
  24. Inhibitors of Protein Synthesis – Bacterial Spectrum

    - spectrum?
    - target which type of bacteria?
    - used for?
    - narrow spectrum

    - streptococci, staphylococci, pneumococci and very specific for anaerobes (fusobacterium, bacteroides, porphyromonas, prevotella)

    - used for: Anaerobic dental & periodontal infections, acne, infections of the soft tissues and respiratory tract
  25. Inhibitors of Protein Synthesis – Bacterial Spectrum


    - spectrum?
    - target which type of bacteria?
    - used for?
    - narrow spectrum

    – streptococci, staphylococci, mycobacteria (M. pneumonia) and some anaerobes (chlamydia, haemophilus, spirochetes)

    - Skin infections, pharyngitis/tonsillitis/sinusitis, bronchitis, pneumonias, chlamydial infections
  26. Inhibitors of Nucleic Acid Synthesis

    - name 2 classes
    1. Metronidazole

    2. Quinolones - Ciprofloxacin
  27. Inhibitors of Nucleic Acid Synthesis

    - spectrum? targets which type of bacteria?
    - used for?
    - crosses placenta?
    - mutagenic?
    - excretion?
    - interferes with what process?
    - Spectrum: narrow, strict anaerobes        

    - used for: trichomonal infections, brain & lung abscesses, periodontitis)

    - Crosses placenta & is mutagenic

    - Excretion: renal

    - Interferes w/ anticoagulants, potentiates alcohol
  28. Inhibitors of Nucleic Acid Synthesis:

    Quinolones (ciprofloxacin)

    - used for?
    - crosses placenta?
    - secretion in what?
    - excretion?
    - Chlamydial infections, hospital acquired pneumonias

    - Crosses placenta & secreted in breast milk

    - Excretion: renal
  29. What are classified as odontogenic infections?
    Odontogenic infections range from:

    • - periapical abscesses
    • - superficial and deep infections of orofacial spaces
  30. Signs of regional spread of odontogenic infections beyond the dentoalveolar structures:
    • ¡Excessive extraoral swelling
    • ¡Trismus
    • ¡Dysphagia
    • ¡Drooling
    • ¡Voice changes
    • ¡Infraorbital or periorbital swelling
    • ¡Descending swelling to the neck & airway compromise
    • ¡Deviation of the uvula, fever, chills, malaise
    • ¡Potential for spread to facial spaces
  31. Treatment of Puplal Infections

    - target what class of bacteria?
    - tx when no soft tissue involvement?
    - tx when soft tissue involved? narrow vs broad spectrum? examples of what you would use?
    - tx for facial spaces?
    - Target facultative cocci w/some anaerobes

    - When no soft tissue involvement, chemomechanical debridement of root canals can be effective

    - w/ soft tissue involvement, use systemic ABs (Because broad spectrum ABs alter the gut flora, have more side effects and select resistant strains, use narrow spectrum

    - Penicillins V, clarithromycin; although extended spectrum, amoxicillin is also a good choice

    - For facial spaces use surgical intervention & ABs against anaerobes (clindamycin, metronidazole) & Klebsiella(first generation cephalosporins)
  32. Periodontal Therapy

    name 4 abx
    • 1. Tetracyclines
    • 2. Doxycycline
    • 3. Metronidazole
    • 4. Clindamycin
  33. Perio therapy: tetracycline

    - short or long acting? [drug] in GCF vs serum?

    - used for?
    - Short –acting; drug conc. in GCF is 7x higher than serum

    - Useful for aggressive tx of periodontitis in young pts, Juvenile periodontitis, rapidly advancing disease or those refractory to tx
  34. Perio therapy: Doxycycline

    - what special activity?
    - short or long acting?
    - how is it used dosage-wise?
    - The greatest anti-collagenase activity

    - Because it is long acting

    - used as once daily low dose
  35. Perio therapy: Metronidazole

    - spectrum? effective against?
    - used for?
    - side effects?
    - Narrow spectrum, effective for g- anaerobes

    - used in tx of periodontitis in combination w/ conventional tx methods

    - Can cause metallic taste, HA, vertigo and peripheral neuritis
  36. Perio therapy:Clindamycin

    - spectrum? targets what?
    - used for?
    - good at penetrating what?
    - Narrow spectrum targeted to g- anaerobes,

    - useful for disease refractory to tetracycline & metronidazole

    - Very good at penetrating bone
  37. Acute Salivary Gland Infections

    - most common cause?
    - clinical signs of partial obstruction?
    - clinical signs of full obstruction?
    - of major salivary glands is the most common cause

    - Partial obstruction causes intermittent swelling at mealtime

    - Full obstruction leads to infection & painful swelling of the affected gland

    Patients with decreased salivary flow have an increased risk for sialadenitis
  38. Salivary Gland Infections: clinical presentation

    - swelling location 
    - describe skin overlying gland??
    - describe gland?
    - clinical signs if infection in Stensen's/Wharton's duct?
    • Swelling is in:
    • - submandibular triangle when it involves the submandibular glands
    • - preauricular area when it involves the parotid glands.

    Skin overlying the gland may be erythematous

    Gland is tender to palpation

    There may also be purulent discharge from the Stensen’s or Wharton’s duct
  39. Salivary Gland Infections: diagnostic process

    - describe dx process?
    - tx in abcence of stone?
    - abx tx?
    - Radiographic examination to rule out sialoliths

    - Culture and sensitivity

    In the absence of stones a lacrimal probe may be utilized to dilate the stricture or to relieve blockage

    A broad-spectrum antibiotic such as tetracycline or Cephalexin may also be used
  40. NUG

    - what is it?
    - organism involved?
    - An acute periodontal infection, involves a number of organisms including:

    • - Fusobacterium nucleatum
    • - Borrelia vincenti
  41. NUG: treatment

    - tx?
    - abx tx? which one?

    - Gentle local debridement (3% hydrogen peroxide)

    - Systemic tx if there is evidence of deep or systemic involvement (gingival destruction, masticatory dysfunction and palpable lymph nodes)

    - Use metronidazole in severe cases
  42. NUG tx

    - name 2
    - spectrum? 
    - mech?
    - lung term uses?
    1. Chlorohexidine gluconate 0.12% is a broad spectrum Bis-Biguanide that acts on bacterial and fungal cell membrane permeability

    - Long term use: exogenous staining and calculus accumulation

    2. Povidone Iodine 10% has bactericidal and virucidal activity

    - Used for disinfection of wounds, burns, and tx of LGE
  43. Oral malodor:

    how did the patient find out?
    who refers?
    • How did patient find out?
    • - Patient feels bad taste
    • - Patient’s contacts react
    • - Patient’s dentist notices

    • Who refers?
    • - 84% of patients came spontaneously
    • - 7% were referred by their general practitioner
    • - 5% referred by various specialists
    • - 1% sent by their dentists
  44. Oral Malodor Diagnostic Process (3)
    • Assess Pt’s Hx:
    • - PMH, SHx, DHx, h/o oral malodor, diet

    • PE
    • - Head & neck structures, intraoral tissues

    Breath analysis
  45. Oral Malodor: Relevant Dental History
    • - Poor restorations
    • - Poor oral hygiene practices
    • - Malpositioned teeth
    • - Impactions
    • - Periodontal disease
    • - Oral ulcers (Autoimmune disorders, Reactive lesions, Neoplasms)
    • - Oral infections (Odontogenic bacterial infections, Recurrent viral infections, Fungal infections)
    • - Xerostomia (aging, drug induced/cancer/systemic dz/taste alterations)
  46. Oral Malodor: Relevant Med Hx
    • nGastrointestinal diseases¡Esophageal reflux¡Pyloric stenosis¡Hiatal hernia¡Malabsorption¡CarcinomasnLiver/gallbladder diseasesnKidney diseases nDiabetes mellitusnHemorrhagic diseases¡Hematopoietic neoplasms
    • nPulmonary Diseases¡Anaerobic infections¡Tuberculosis¡NeoplasmsnNose and Sinus Diseases¡Chronic sinusitis/post-nasal dripnTonsillitis¡TonsillolithsnPharyngitisnTrimethylaminuria
  47. Oral Malodor: Relevant Psychosocial Hx
    nTobacco historynAlcohol intakenIllicit substancesnPsychogenic factors¡Individuals’ variations in odor perception¡Depression, phobias, Obsessive/Compulsive Disorder, Body Dysmorphic Disease, psychotic disorders
  48. Oral Malodor: The Role of Diet
    nOdoriferous foods (transient)¡Garlic, onion, spices, herbsnOdorigenic foods¡High protein diets provide a continuous source of aminoacids for bacterial breakdown nSulfur containing aminoacids (cysteine, cystine, methionine) and other types of amino acids (tryptophan, ornithine, arginine) undergo putrefaction by gram negative bacteria producing sulfur containing volatiles
  49. Oral Malodor: Clinical Examination

    Name the 5 steps
    1. Evaluate Head & Neck (lymph nodes, nasal and paranasal sinuses

    2. evaluate oral tissues (salivary flow, dentition)

    3. Periodontium (AL, mobility, BOP, abcesses)

    4. Oral mucosa (atrophy, desquamation, ulcers, necorsis, masses, pseudomembrane)

    5. Oral Hygiene (plaque, gross debris, tongue coating)
  50. Oral Malodor:

    Breath Analyses Odor Judge Tests (name 3)
    Organoleptic tests:

    • Examination of the expired air
    • Wrist-Lick test
    • Spoon test
  51. Oral Malodor:Breath Analyses Objective Methods

    Name 3
    1. Volatile Sulfur Compounds (VSCs) detection test (Halimeter)

    - Measurement of VSCs in ppb in the air collected from the anterior mouth, posterior tongue and each of the nostrils

    2. Gas chromatography

    Identification and quantification of the specific VSCs in the headspace air sample

    3. The electronic nose

    Identification of the specific odorous bacterial species in the headspace air sample
  52. Treatment Strategies for Oral Malodor
    1. Reduce the bacterial reservoir:

    - Antibacterials (Cetylpyridium chloride, Benzethonium chloride, Chlorine dioxide)

    Mechanical removal (tongue scraper)

    2. Transform odorous gases into non volatile form (zinc salts)

    3. Reduce levels of nutrients available for use by the bacteria (avoid high protein diets)

    4. Restore to normal the salivary flow
  53. Patients with Post-Nasal Drip
    • Are there any accompanying symptoms?
    • (Cough, mildly productive cleansing of the throat, heavy coating on the posterior dorsal tongue, obstruction and congestion)

    • If suspect chronic sinusitis refer for ENT evaluation
    • Allergy vs obstruction
    • Rhinoscopic examination w/ flexible endoscope
    • Sinus series of radiographs & MRI
    • Appropriate Tx (allergy vs obstruction)

    Nasal irrigation
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O-Med: Antibiotic Therapies (lecture 3)
O-Med D3 Spring