Microbial agents for perio tx

• What are benefits of antimicrobials?

  • stops infection spreading
  • eliminates infectious microorganisms
• What are justifications for the use of antimicrobials?

  • infective element: specific/non-specific
  • host: side effects, adverse reactions, drug eimination
  • nature of infection: aerobe/anaerobe, facultative anaerobe, biofilm, tissue invasion
  • antimicrobial: Mode of action, Bacteriostatic, Bactericidal, Site of action, Microbial reservoirs
• What microbes are strongly associated with disease?

  Principle periodontopathogens, RED COMPLEXES

  • Porphyromonas Gingivalis
  • Treponema Denticola
  • Tannerella Forsythia
• What is the nature of infection?

  • Aerobe

  • Anaerobe

  • Facultative Anaerobe

  • Virulence Factors

  • Resistance

  
• What types of micro-organism are there?

  Gram +ve

  • Staph/strep

  • More susceptible topenicillin

  Gram –ve

  Periodontopathogens

  • Presence of LPS triggers immune response

  • Resistant to penicillin
• What is the common environment for the micro-organism?

  • Biofilm

  • Planktonic

  • Tissue invasion

  • Tongue

  • Tonsil

  
• What are the efficacy of antimicrobials?

  • Minimum Inhibitory Concentration[Lowest concentration that stops replication of the microbe]
  • Minimum Lethal Concentration[Lowest concentration that kills the microbe]
  • Need to achieve at very least a MIC in: Blood/Serum (Tissue invasion microbes) or GCF (Pocket microbes)
  • Biofilm interferes with GCF delivery
• What are the key considerations for a drug to kill a bug?

  Systemic Delivery

  Select appropriate drug– Microbe is sensitive and not resistant

  Prescribe drug at dose that is high enough for long enough

  Must achieve Minimum Inhibitory Concentration (MIC) at:– Serum level– GCF level

  Compliance of patient to take as prescribed

  What about microbial reservoirs – tongue/tonsil/tooth grooves?
• How can the full mouth be disinfected?

  Microbial reservoirs (tongue, tonsil, opercula)

  
  

  • Chlorhexidine Rinse

  
  

  • Gargle (tonsils)

  
  

  • Brush tongue

  
  

  • Chlorhexidine gel subgingivally
• What is the spectrum of activity of the antimicrobial?

  Broad - Acts against wide range of bacteria, both gram +ve and gram -ve bacteria e.g. Amoxicillin, Tetracyclines

  
  

  Narrow - Limited activity against particular species of organisms, both gram +ve and gram –ve organisms e.g. Penicillin, Metronidazole
• How are some microbes antimicrobial resistant?

  
• What are examples of penicillin/tetracycline/metronidazole resistance drugs?

  
• How many strains do certain microbes have?

  
• What is the outcome of evidence base for testing influenced by?

  • Correct sampling technique

  
  

  • Correct transport

  
  

  • Standardisation of methodologies (or lack of)

  
  

  • Integrity of small specimens with diverse populations of anaerobic bacteria
• What are the four main microbes associated with perio?

  
• Why is drug elimination important?

  What is the health status of the organ of elimination

  - Effect of drug on diseased organ

  - Effect on host of ineffective elimination

  
• What can be adverse reactions to the use of antimicrobials?

  Microbial resistance

  – The right antimicrobial (? Culture & Sensitivity)

  – The right dose & duration (M I C)

  – Patient who will comply

  Superinfections

  Candidal infection(careful if immunosuppression) consider simultaneous anti-fungal

  Stevens Johnson Syndrome Penicillin Tetracycline
• When are antimicrobials taken?

  Antimicrobials to be taken on last day of treatment

  
  

  Biofilm has been disturbed/removed

  
  

  Remaining bacteria in pocket more accessible by antimicrobial in GCF

  
  

  Bacteria invaded into tissue accessible by antimicrobial in blood supply
• Periostat?

  • doxycycline hyclate
  • Subantimicrobial dose (not acting as an antimicrobial)
  • Anticollagenase effect
  • Host neutrophil/osteoblast– Inhibits osteoclast function
• How is Periostat taken?

  • 20mg 2x day

  • 1-3 months

  • Break 3/12 before repeat

  • No more than 3 courses
• What are the risk of using antimicrobials?

  • microbial resistance
  • adverse reactions
• How might a pathogen be resistant to Penicillin?

  • B lactamase (penicillinase)

  • Alteration to penicillin binding proteins (streptococci)

  • Interspecies transfer of resistance (plasmids)
• How may a pathogen be resistant to Metronidazole?

  Mutations

   Decreased entry of drug into cell

   Increased efflux of drug

   Affect enzymes that reduce drug to active form
• How may a pathogen be resistant to tetracyclines?

  Tet Genes (27 types in oral bacteria)

   Ribosome protection proteins

   Enzyme modification of antibiotic

   Synthesis of efflux proteins
• What bacteria are resistant to chlorhexadine?

  • S. Aureus & Strep. Sanguis
  • Plasmid mediated
• Impact of microbial resistant?

  • right antimicrobial
  • right dose and durations
  • compliance from patient
• Superinfections (adverse reaction)?

  • candidal infections - immunosupressent patient
  • Stevens Johnson Syndrome - penicillin, tetracycline
• Adverse reactions - Gastrointestinal?

  • diarrhoea
  • gut flora
  • pseudomembrane colitis
• Allergy Adverse reactions?

  • skin allergy
  • anaphylaxis
• Teteracycline group - adverse reactions?

  • photo-sensitivity: within mins, unexpected sunburn, rash (dry, blistering, itchy)
  • iatrogenic intracranial hypertension: pulsatile headache and tinnitus, visual disturbances (perm damage)
• Adverse reaction rg pregnancy?

  • contraceptive failure
  • risk to dev foetous (avoid tetracyclines, co-amoxiclav, metronidazole)
  • lactation (avoid tetracyclines, co-amoxiclav, metronidazole, clindamycin)
• How may antimicrobials cause contraceptives to fail?

  • diminishes enterophepatic re-circulation: by eliminating gut bacteria, reduced regeneration of active oestrognes from conjugated oestrogens in gut.
  • induction of liver cytochrome P450 enzyme, faster catabolism of drugs
• Drug interactions:

  Warfarin - penicillin, metronidazle, tetracycline, miconazole

  Phenytoin - inhibits metronidazole, and potentiates causing unconsciousness and death

  Lithium - potentiates causing tremour, seizures and death
• Treatment of acute infection?

  • drain via swelling or pocket
  • if unable to drain, prescribe amoxicillin 500mg, 3x day, 5 days or metronidazole 400mg, 3x day, 5 days
• NUG Treatment?

  • chlorhexadine mw
  • metronidazole 400mg 3x daily, 3 days
  • if immunosupressed antifungal?
  • then review and OHI
  • smoking cessation?
  • investigate underlying cause - substance abuse, blood dyscrasias, immunodeficiency
• When may systemic antimicrobials be indicated?

  minimal plaque, little/no calculus, tissue invasion of bacteria
• alternative antimicrobials if allergic?

  • doxycycline 200mg 1st dose (loading dose), then 100mg 1x day for 3 weeks
  • azithromycin 500mg 1 x day for 3 days
• Systemic antimicrobials tx post antibiotics?

  • antimicrobials taken on last day of tx
  • biofilm disturbed/removed
  • remaining bacteria more accessible by antimicrobials in GCF
  • bacteria invaded into tissue accessible by antimicrobials in blood
• Periostat?

  • doxycycline hyclate
  • anticollagenase effect
  • inhibits osteoclasts function
  • 20mg 2x day 1-3 months, break for 3/12 then repeat, no more that 3 courses
• REMEMBER

  • use must be evidence based
  • not first line of tx
  • use evidenced based regime
  • side effects and drug resistant serious consequences