Current Use of Antimicrobials Flashcards
Topical
Antiseptic rinses
2 Direct delivery
Subgingival irrigations/local antimicrobial delivery/laser therapy
3 Systemic administration
Adjunctive antibiotics
Periodontitis
* Is caused by —
* A — disease
* Recurs or —
— the disease
Alter the microflora to prevent —
Maintain the disease in an — state
bacteria
chronic
re-infects
Arrest
reinfection
arrested
Effective Antimicrobial
(5)
Kills or inhibits target microflora
Reaches the site
Has a sufficient duration
Has an adequate concentration
Does no harm
Crevicular levels Versus Blood levels
(3)
Cumulative oral dosage can have the problem
of side effects
* Small dose of local delivery antimicrobial leads
to high concentration at crevicular level
* An example of a 250 mg tablet of Tetracycline
Cumulative oral dosage can have the problem
of side effects
- Gastrointestinal problems or tolerance
An example of a 250 mg tablet of Tetracycline
* Delivered systemically:
* Delivered locally:
2ug in peripheral blood level; 16ug in GCF
1600 ug in GCF
An antibiotic strength 500 times greater than
the systemic therapeutic dose may be required
to be effective against the bacteria residing in
—
Disrupt the biofilm physically to allow …
plaque biofilms.
antibiotic agents gain access to the periodontal
pathogens and inhibit biofilm formation.
Never use antimicrobial agents in the absence of
mechanical debridement
Chlorhexidine gluconate (CHX)
(0.12-0.2%):
the most studied and
effective rinsing agent for plaque
inhibition and prevention of gingivitis
Chlorhexidine gluconate (CHX)
(0.12-0.2%):
(4)
- No systemic toxicity, rare hypersensitivity
- Active against most bacteria and fungi
- No microbial resistance reported
- Cannot reach the site subgingivally
Chlorhexidine gluconate (CHX)
(0.12-0.2%):
Sides effects
(3)
- Taste alteration, tooth discoloration, increased
supragingival calculus formation
- Extrinsic brown discoloration on the teeth from an individual
rinsing twice a day for 3 weeks with 0.2% chlorhexidine mouth
rinse (Europe). Can be alleviated with 0.12% formulation (US). - Beverages like tea, coffee and red wine will aggravate this
superficial staining. Can be removed using —
prophy paste.
Mechanisms
Chlorhexidine is a —-charged molecule that binds to
the —-charged sites on the cell wall; it destabilizes the
cell wall and interferes with —.
* Lower concentrations leads to increased…
* Higher concentrations leads to…
positively
negatively
osmosis
permeability and leakage.
precipitation of cytoplasmic contents
inducing microbial cell death.
Mechanisms
* High —
* Adhere to —
* Slow release over – hours
substantivity
soft and hard
tissues and then be released
over time
12
CHX
Application
* As adjunct to…
* Who?
* What? (2)
* — week post surgery
regular oral hygiene methods during Phase I therapy
(SRP) in high risk individuals (systemically compromised, refractory
cases, etc)
Mentally or physically challenged patients with low manual dexterity
Jaw fixation, BRONJ
1st - 2nd
2018 the first ‘—’ chlorhexidine supported by clinical evidence
non-staining
Anti-discoloration Formula
Essential Oils
- Mouth rinse with eucalyptol,
menthol, methyl salicylate, thymol
- Mouth rinse with eucalyptol,
menthol, methyl salicylate, thymol
Antiplaque effects and significant reduction
in —
gingivitis index
Essential Oils
Side effects
(2)
- Burning sensation and tooth staining
- Most anti-plaque rinses contains — as a vehicle to
deliver antiseptic ingredients.
alcohol
- Critical assessment of the literature does NOT support an
association of alcohol‐containing mouth rinses and —
cancer
- Most anti-plaque rinses contains alcohol as a vehicle to
deliver antiseptic ingredients. - Critical assessment of the literature does NOT support an
association of alcohol‐containing mouth rinses and cancer. - Not recommended in (2)
recovering alcoholics (craving for
alcohol), in patients taking metronidazole or disulfiram (drug
interaction).
Mechanisms
Multiple mechanisms proposed
(4)
- Cell wall disruption
- Inhibition of bacterial enzymes
- Extraction of endotoxins
derived from lipopolysaccharide
(LPS) of Gram-negative bacteria - Antiinflammatory action based
on antioxidant activity
Beneficial effects were seen with H2O2 levels above
1%.
* Prolonged use of H2O2 decreased plaque and gingivitis indices.
Conflicting results was shown on the effectiveness of
1.5% H2O2
rinse.
* Therapeutic delivery of H2O2 to prevent periodontal disease required
mechanical access to subgingival pockets.
–% H2O2 or less used daily showed occasional irritant effects.
(2)
3
- In small number of subjects with preexisting ulceration.
- When combined with high levels of salt solutions.
In animal model, –% H2O2 was referred to as a co-carcinogen; –%
or less, no co-carcinogenic activity/adverse effects were observed.
30
3
ADA and FDA have concerns regarding
long-term use
* Possible co-carcinogen and impaired wound healing
Subgingival Irrigation
* Significantly reduced monitored bacteria when used as
* — organisms doesn’t respond well
mono therapy, but not eliminated
Tissue invasive
Significantly reduced monitored bacteria when
used as mono therapy, but not eliminated.
* Microbiota rebound to baseline within — weeks after
short-term subgingival irrigation
1 to 8
Tissue invasive organisms doesn’t respond well.
* After 6 months of irrigation every 2 weeks with 3% hydrogen
peroxide,
limited success was achieved in reducing high
concentrations of Actinobacillus actinomycetemcomitans
Reaches the site with a sufficient concentration
* Achieved —% penetration in pockets of less than 6mm when
tip was place 1mm apical to the margin.
* —% penetration in deeper pockets when canula was placed
3mm apical to the margin.
90
70-80
Lack of substantivity
(2)
- Blood and protein can deactivate the drug
- The medicament may not be retained long enough to have an
efficacious effect
Lack of substantivity
(2)
- Blood and protein can deactivate the drug
- The medicament may not be retained long enough to have an
efficacious effect
- The medicament may not be retained long enough to have an
efficacious effect - 50% of a fluorescein labeled hydroxypropylcellulose gel injected
subgingivally was washed out of pockets within – minutes (Oosterwaal 1990) - The gingival crevicular fluid is replaced in a 5 mm pocket – times over an
hour period (Goodson 1989) - The half life of an antimicrobial irrigation concentration is – minute.
12.5
40
1
0.12% Chlorhexidine
* Single use to —; adjunctive use to —
* A (2) with a cannula were equally effective.
* — irrigation forces were effective.
reduce the bacterial load
gain the antiseptic effect
syringe and a jet irrigator
Low
Betadine® (10% povidone-iodine and 1% free
iodine)
* Can be used diluted as an —
- Do not use when there is history of – sensitivity
- Use with caution in — to prevent inducing
transient — in newborns.
irrigant
iodine
pregnancy and lactation
hypothyroidism
Local Antimicrobial Delivery
LAD is the medicament placed in a periodontal
pocket with a delivery system and released in a
controlled manner, allowing minimum inhibitory
concentration for 7 days.
Ideal Properties
(6)
- Effective against periodontal pathogens
- Low risk of bacterial resistance
- Low systemic absorption
- Biodegradable
- Easy to use
- Enhances scaling and root planing
- Effective against periodontal pathogens
(2)
- Kill the pathogens effectively
- Reach the site really well
- Low systemic absorption
(1)
- Good concentration and substantivity
Indications
When local sites with inflammation have not responded to periodontal or maintenance therapy
* Residual isolated pockets ≥5mm, not responding favorably to
initial SRP with BOP at —
* Residual pockets —
* Recurrent isolated pockets ≥5mm with BOP at —
re-evaluation.
after periodontal surgery.
maintenance.
When local sites with inflammation have not
responded to periodontal or maintenance therapy.
* Residual isolated pockets ≥5mm, not responding favorably to
initial SRP with BOP at re-evaluation.
* Residual pockets after periodontal surgery.
* Recurrent isolated pockets ≥5mm with BOP at maintenance.
Always as — therapy, never use —.
adjunct
alone
Brand name: PerioChip
Delivery platform
Active agent
Degradable film
Chlorhexidine gluconate
(2.5 mg)
Brand name: Atridox
Delivery platform
Active agent
Biodegradable gel
(two-syringe mixing)
Doxycycline hyclate
(50 mg)
Brand name: Arestin
Delivery platform
Active agent
Microspheres
(powder by syringe)
Minocycline hydrochloride
(1 mg)
Brand name: Acisite
Delivery platform
Active agent
Non-biodegradable
fibers
Tetracycline hydrochloride
(12.7 mg)
Perio-Chip®: bioresorbable polymer with 2.5 mg
Chlorhexidine
(4)
- Inserted in the pocket ≥ 5mm
- Release takes 7days
- Dissolves within 7-10 days, does not require removal.
- Significant improvement in CAL when used with SRP
Atridox®: 10 % doxycycline hyclate
(4)
- Delivered subgingivally by canula to flow to the base of the
pocket and adapt to root morphology - Controlled release over 21 days
- Significant improvement in CAL when used with SRP
- Do not use in patient with hypersensitivity to doxycycline or
drugs in the tetracycline class.
Arestin® : 1mg minocycline
hydrochloride in bioabsorbable
microspheres
(3)
- Bacteriostatic by inhibiting protein
synthesis - Broad spectrum
- Significantly reduced red complex
bacteria in smokers greater improvement
in PD, CAL regardless of smoking status.
Actisite®: Non-resorbable, monolithic
fiber (ethylene-vinyl acetate polymer)
contains 25% tetracycline-HCL powder
(4)
- Currently unavailable
- Slow release over 10 days
- Packed into the pocket and left in place for 7-12
days, need removal. - Improve PD, BOP, CAL when combined use with
SRP in 6 months (Wong 1999) but no difference after 5
years
Local Drug Delivery is not effective with
implants
* May partially detoxify the implants but no long-lasting effects
* May be used as a step in implant recovery for regeneration of
bone around implants in conjunction with grafting and GTR but
there is still no evidence in literature
Which following
statement is correct?
A. The active agent of PerioChip is minocycline
B. Use Atridox before mechanical debridement to
control inflammation
C. Arestin needs to be removed in 7-12 days after
application.
D. Actisite contains 25% tetracycline-HCL powder
Laser Therapy
3 basic structures
(3)
- An energy source,
- An active lasing medium
- Two or more mirrors that form
an optical cavity or resonator
Laser Therapy
Monochromatic light with a single wavelength
* The wavelength and other properties are determined primarily
by the
composition of an active medium
Laser Therapy
4 different interactions with a target tissue
absorbing chromophores
Absorbing chromophores
* Intraoral soft tissue: (3)
* Dental hard tissues: (2)
Melanin, Hemoglobin,
and Water
Water and
Hydroxyapatite
Light energy is converted into heat and
photochemical effects occur depending on the
— content of the tissues.
water
- –°C< temperatures <–°C, proteins
begin to denature without vaporization of
the underlying tissue. - When reaching –°C, vaporization of the
water within the tissue occurs (—) - At temperatures > –°C, the tissue is
dehydrated and then burned, resulting in
— (undesirable effect).
60, 100
100, ablation
200, carbonization
Different laser wavelengths have different
absorption coefficients with respect to these
primary tissue components, making the laser
selection —dependent
procedure
Diode Lasers
* Used in —
* Not effective for —
* Low-level laser has been recommended for
soft tissue treatments
calculus removal despite it’s bactericidal efficacy
pain reduction and
enhancing wound healing due to its anti-inflammatory effects.
Nd:YAG
* Highly absorbed by the — tissue
* Effective in —
* Used for —
pigmented
cutting and coagulating dental soft tissues
nonsurgical sulcular debridement in periodontal disease
control (Laser Assisted New Attachment Procedure (LANAP))
Erbium
(2)
- Laser of choice for treatment of dental hard tissues
- Can be used for soft tissue ablation (water vaporation)
Erbium
* Laser of choice for treatment of dental hard tissues
(2)
- High affinity for hydroxyapatite
- Highest absorption of water in any dental laser wavelengths
Ideal Properties
* Effective against ALL — pathogens
* — and —
* Not in general use for other diseases
periodontal
Substantive, non-toxic
No single antibiotic at
concentrations achieved in —
satisfies the above requirements
GCF
In phase I therapy
(4)
- Tetracyclines
- Penicillins
- Azithromicin
- Metronidazole
- Tetracyclines
(2) - Penicillins
(2)
- Tetracycline, Doxycycline
- Amoxicillin, Augmentin
Tetracyclines
* High concentration in
GCF (2-10 fold than serum)
Tetracyclines
Characteristics
* Broad spectrum —
* Antimicrobial effect:
* Anti-collagenolytic effects:
* Photosensitivity:
bacteriostatic
highly effective against A. actinomycetemcomitans, but resistant strains are now common
inhibit connective tissue destruction
and promote repair
severe skin burns
Tetracyclines
Doxycycline (DCN)
* Better compliance because it can be given
qd or bid
Penicillins
* A group of — antibiotics
* Amoxicillin+clavulanic acid=
* Up to –% of humans are allergic to penicillins
* Can be used in combination with —
β-lactam
Augmentin
10
metronidazole
Penicillins
* Characteristics
(2)
- Broad spectrum bactericidal
- Affected by beta-lactamases: can be protected by clavulanic acid
Penicillins
Up to 10% of humans are allergic to penicillins
* Substitute with (3)
ciprofloxacin, azithromycin or clindamycin
Azithromycin
* Better compliance because it is given –
* Can be used in combination with —
qd
metronidazole
Azithromycin
Characteristics:
* – for most pathogens
* Effective against
* Good — concentration
Bacteriostatic
most anaerobes, gram-positive and negative
bacteria.
tissue
Metronidazole
* Attain effective antibacterial concentration in
* Do not combine it with (4)
gingival tissue and GCF
warfarin, lithium, phenytoin,
cyclosporin.
Antibiotic Regiment
In phase I therapy
Metronidazole + Amoxicillin combination therapy
* van Winkelhoff cocktail:
* – mg of Amox. and – mg of Metro. TID
* – mg of Amoxicillin and – mg of Metronidazole TID or QID
* – days or – days of administration
375mg Amox+250mg Metro. TID 7 days
500, 500
250, 250
7, 14
Metronidazole
Characteristics
* Particularly effective against
*
* Adverse reaction (nausea, vomiting, cramping) when taken with
anaerobic bacteria and spirochetes
Bactericidal
alcohol
Host Modulation
* Aims to reduce tissue destruction by
modifying
the host response
Host Modulation
* Reduce excessive amounts or activity of —
* Increase — mediator amounts or activity
* Modulate (2) activity
* No impact on physiologic cell function; contribute to sustained control of —
* Promote (2)
lytic enzymes/cytokines/inflammatory mediators
anti-inflammatory
osteoblast and osteoclast
“harmful” bugs
connective tissue repair or regeneration and produce clinically significant results
NSAIDS
* Target (2)
* Selective (2) inhibitors
* (3) long term daily use (up to
3 years) can lead to slower disease
progression
* Serious side effects such as (3)
prostaglandins and
inflammation
COX-1 vs COX-2
Indomethacin, flurbiprofen and naproxen
GI irritation, liver and renal damage/
dysfunction.
Are NSAIDs adjuncts in periodontal therapy?
No
Bisphosphonates
* Disrupt — activity
* Can improve —
but the role in disease progression
in humans is unclear
* Serious side effects with
osteoclast
alveolar bone density
IV agents
(osteonecrosis of the jaw after oral
surgery)
Bisphosphonates
No approved application in
periodontal therapy
- Tetracyclines (TCs) inhibit
connective tissue breakdown
Tetracyclines
* Mediated by
(3)
- Mediated by extracellular mechanisms
- Mediated by cellular regulation
- Mediated by pro-anabolic effects
Tetracyclines
* Mediated by extracellular mechanisms
(3)
- Direct inhibition of active MMPs
- Inhibition of oxidative activation of Pro-MMPs
- Inhibition of MMPs indirectly decreases serine
proteinase activity
Tetracyclines
* Mediated by cellular regulation
* TCs decreases (3)
* Effects on
cytokines, iNOS, PLA, prostaglandin
synthase
protein kinases (MAPA)
Tetracyclines
* Mediated by pro-anabolic effects
(2)
- TCs increases collagen production
- TCs increases osteoblast activity and bone formation
Among tetracyclines, — has the best anticollagenolytic
activity and better GI absorption
* Currently the only FDA approved host modifier as adjunct to SRP
Doxycycline
SDD administration:
* – mg doxycycline twice daily or – mg once daily, for 6-9 months
* Adjunct to thorough and high-standard —
* SDD doesn’t result in
* Contraindicated in
* May reduce efficacy of —
20, 40
SRP
antibacterial effects/development of resistant strains/multiantibiotic resistance
pregnancy or children for the risk of permanent teeth discoloration
contraceptives
Subantimicrobial Dose
Doxycycline (SDD)
* Periostat (CollaGenex Pharmaceuticals) is a
host-modulating agent. It inhibits —
* FDA approved host modifier as adjunct to —
* DO NOT USE AS — THERAPY
host collagendegrading enzymes
SRP
STAND-ALONE
Subantimicrobial Dose
Doxycycline (SDD)
* Clinical significance?
* —mm difference in attachment gain
0.2-0.4
Antibiotic Prophylaxis
Heart conditions
Prosthetic joints
Apply only to dental procedures requiring manipulation of the
gingival
tissue or the periapical region of teeth, or perforation of the oral mucosa.
Only patients at the — risk of infective endocarditis
highest
In general, for patients with prosthetic joint
implants,
prophylactic antibiotics are NOT
recommended prior to dental procedures to
prevent prosthetic joint infection
- For patients with a history of complications associated with their joint replacement
who are undergoing dental procedures including gingival manipulation or mucosal
incision,
antibiotic prophylaxis should only be considered after consultation with the
patient and orthopedic surgeon.*
Regarding antibiotic therapy in
periodontal treatment, which
of the following is correct?
A. van Winkelhoff cocktail regimen contains 500mg
amoxicillin and 500mg metronidazole TID for 7days
B. Subantimicrobial dose doxycycline is used as 20mg
doxycycline once daily up to 9 months for host modulation.
C. Antibiotic prophylacsis is more essential to prevent
infective endocarditis than oral health maintenance and
regular dental care.
D. Metronidazole is contraindicated in patients taking warfarin
Prophylactic Regimens
Single dose 30-60 min before procedure
(3)
Amoxicillin (Amoxil®) of 2 g
Azithromycin (Zithromax®) of 500 mg
Clarithromycin (Biaxin®) of 500 mg
— is no loner recommended for dental
procedure antibiotic prophylaxis due to more frequent
and serious adverse effects associated with
clindamycin compared to other prophylactic options,
including C. difficile infections.
Clindamycin
- Consider 1 week of
antibiotic use following
bone
and soft tissue grafting
- Antibiotic prophylaxis before
— placement
implant
