7. Chemical Plaque Control and Anti-infective Periodontal Therapy

Question 1

Contemporary Model of Pathogenesis of Periodontitis

• The development of periodontal disease
• Start from a state of clinical health
• minimal bleeding, minimal plaque, gingival margin is scalloped, etc.
• There is still biofilm but it is in ____ with the host (no host response)
• Poor brushing, development of diabetes
• Now you accumulate more plaque, and you start to develop ____
• The composition of the biofilm changes
• 10-15% of those with gingivitis develop ____
• Moving to a more pathogenic biofilm (increase in certain pathogenic organisms, including red complex)
• Everything starts with the ____. Before there is a host response or any clinical outcome, you have the biofilm microbiome. This is why we will be talking about control of plaque.
• There are certain things that increase the risk of moving from health –> periodontitis
• ____
• Diabetes
• ____ factors (interleukin-1 polymorphisms) • It all starts with the bacteria

Answer 1

symbiosis
gingivitis
periodontitis
biofilm
smoking
genetic

Question 2

Treatment Goals
• ____ of pain
• Individually satisfactory ____ and function
• Control of local risk factors: improper ____ control
• Reduction or resolution of gingivitis: ____ of <25%
• Reduction in PPD: ____ mm should be present (risk of progression)
• Elimination of open ____ in multirooted teeth: only if it can be achieved without ____ the tooth
• If possible, control of systemic risk factors: cigarette ____, and uncontrolled diabetes mellitus

Answer 2

absence
esthetics
plaque
BoP
4
5
furcations
compromising
smoking

Question 3

Phases of Treatment

o If we see a patient that has periodontal disease and we are making a plan
____, diagnosis, do they smoke, do they have other conditions that need to
be addressed?
o Then the patient receives initial ____, then ____
o Some patients may not cooperate or may not respond –> they may need other modalities of treatment (not the focus of today)
Today we focus on PHASE 1 (plaque control and antibiotics)

Answer 3

assessment
phase
re-eval

Question 4

Non-surgical phase
Anti-infective Therapy:
ü ____
ü Systemic ____

Chemical plaque control:
ü ____
ü Mouthrinses

Maintenance phase
Anti-infective Therapy:
ü ____
ü ____

Chemical plaque control:
ü ____
ü Mouthrinses

• Maintenance Phase
• Once treated, the patient goes into the maintenance phase. It is now time to use more ____ drugs (rather than systemic antibiotics like in the non-surgical phase)

Answer 4

SRP
antibiotics
toothpastes

SPT
LDD
toothpastes

local

Question 5

• What is the #1 selling toothpaste in the US?
• ____
• Sensodyne
• Crest 3D White

Answer 5

colgate total

Question 6

Chemical Plaque Control: Toothpastes

• There are many options as to what we should recommend to our patients. What should we recommend?
• Colgate Total and Crest have the ____ seal (have been scientifically analyzed)
• Colgate Total
• Besides fluoride, the key ingredients in Colgate is ____, as well as the ____ copolymer
• Triclosan = ____ (controls inflammation). However it does not have ____ (meaning you need to reapply it every few hours, it does not last all that long)
• PVM/MA Copolymer = this helps with ____ to help the toothpaste last for a long time
• Crest
• This is popular due to the ____ component

Answer 6

ADA

triclosan
PVM/MA
antigingivitic
substantivity
substantivity

fluoride

Question 7

• How do we know the best toothpaste to use? Meta-analysis to review many research studies that compared toothpastes

• He compared different agents and mouth rinses.
• Whenever the whisker is more towards the right –>, it favors the active agent (rather than the
control). So if we focus on the toothpaste category (see missing slide), we can see that ____ had a substantial favoring for the active agent (meaning that Colgate total did have an anti-gingivitis effect)
• The ____ one (Crest) was also good, but not as good as Colgate Total

Answer 7

triclosan + copolymer

stannous fluoride

Question 8

• Controversy about triclosan
• Triclosan is also found in antibacterial ____, and there were claims that it could be ____, disruptive to hormonal pathways, etc.
• FDA then issues a rule on the safety of triclosan, and recommended it should be removed from
____, but it still remains in the toothpaste

Answer 8

soaps
cancerous
soaps

Question 9

Chemical Plaque Control: Mouthrinses

• Mouth Rinses
• These fall in one of three categories:
1. CPC (Cetylpyridiniu Chloride)
This is an agent that disrupts ____ cells, perforating their membranes and leading
to cell death
• Very good at killing ____ bacteria
• If used a lot, it can cause ____ staining on the teeth
• None of these products had the ____ seal of approval (suggesting they are not as
good as the others we have)

Answer 9

bacterial
gram +
brown
ADA

Question 10

Chemical Plaque Control: Mouthrinses

2. Essential Oils
   • See next slide
   • Eucalyptol, menthol, etc.
   • The most popular is Listerine, and it does have the ____ seal (has anti plaque and anti-gingivitis effects)
3. Chlorhexidine (Peridex)
   • See next slide
   • This is a ____ mouth wash
   • The most effective in killing ____, yeast, viruses, etc.
   • Good ____ (must reuse every 12 hours)
   • If used for more than 1-3 months, you get ____, ulcerations, etc. (but it is all
   ____)

Answer 10

ADA

prescription
bacteria
substantivity
staining
reversible

Question 11

• Studies done on mouth rinses (meta-analysis)
• They compared different types of mouth washes
• The ones that had the most evidence for working are those with ____, as
well as ____
• All of the mouthwashes do NOT REPLACE ____ CLEANING. By themselves
they cannot penetrate the ____ (must be combined with mechanical plaque
control, aka toothpaste and toothbrush)
• In patients with ____ disease (5mm + pockets), the mouthwash will not
penetrate the depth of the pocket. It only remains at the marginal level where the plaque begins to form.

Answer 11

esstential oils
chlorhexidine
mechanical
biofilm
periodontal

Question 12

• Summary:
• Best toothpaste = ____
• Best mouth rinse = ____

Answer 12

colgate total

perifex and listerine/essential oils

Question 13

Microbiological Goals of Periodontal Therapy

• kill or suppress ____ pathogen(s)
• foster survival of host compatible species
• do not permit the establishment of uncommon pathogens or encourage ____ species
• create a new, stable climax community
• We use antibiotics to try and control bacteria, to change the biofilm making it more ____ with health (to decrease the number of red complex species in the biofilm)
• We want to change the balance of the biofilm to have the “____” bacteria which are beneficial
• We want to create a new homeostasis, an environment compatible with health

Answer 13

periodontal
antibiotic resistant
compatible

Question 14

Microbiological goals of periodontal therapy

• Microbiological Goals of Perio Therapy
• You have compatible species (yellow complex, actinomyces, green complex, etc.) and you have pathogenic species. We want to increase compatible, and decrease the pathogenic (red complex). So we want changes in the ____ (the percentage of pathogens) and we want to decrease the ____ of the pathogens.

Answer 14

proportions

prevalence

Question 15

Advantages in the use of Systemic Antibiotics

• There are a number of challenges in trying to achieve these goals via SRP alone:
• Shown we have the tooth, cementum, epithelium, and CT
• The cementum is not intact in this inflammatory situation. The epithelium is very fragile, so when you probe, you go right into the CT which is why you get a lot of ____.
• There are many areas in this inflammatory state that are good for bacteria to be, and hard to reach via SRP
• They could be in ____, in epithelial cells, in CT, in dentinal tubules
• So even after SRP there are still bacteria ____ behind that will multiply and cause disease after therapy
• We are not trying to CURE, but rather to monitor, and to control (similar to diabetes)
• Top pic:
• This is a case where we would need ____ (SRP alone will not be enough). There are many reservoirs for bacteria allowing them to avoid SRP treatment. This includes ____ tongue, roof of mouth, and other areas. Using systemic antibiotics allows all these bacteria to be treated as well, decreasing the # of pathogenic organisms.
• What antibiotics should we use for periodontal disease?
• ____
  
  • See next slide

Answer 15

bleeding
biofilms
left
antibiotics
metronidazole

Question 16

• Metronidazole
• Paper from 1962 – a case report talking about a physician that treated a
woman with vaginal infection (by using metronidazole which is specific for anaerobes).
• At the end of the week, her ____ was cured, and ____ was relieved
as well
• He then gave this antibiotic to 6 other patients with gingivitis and they all
showed improvement
• Many studies we will look at used this antibiotic

Answer 16

vaginitis

gingivitis

Question 17

Adjunctive Systemic Antibiotics Aggressive Periodontitis RCTs 2002-2012

• Historically it was very well accepted to give systemic antibiotics for ____ periodontitis cases (they are hard to treat, progress rapidly, etc.).
• Shown here is a summary of studies from around the world following patients for up to 1 year after giving one round of metronidazole combined with amoxicillin and sometimes doxycycline
• ____ = more specific
• ____ = more broad

Answer 17

aggressive
metro
amox

Question 18

Adjunctive Systemic Antibiotics Chronic Periodontitis RCTs 2002-2012

• Studies from around the world looking at ____ (moderate to severe) following patients up to 2 years after metro/amoxicillin

Answer 18

chronic periodontitis

Question 19

Meta-analysis: Aggressive Periodontitis

• All these studies show good results (positive clinic changes)
• Improved ____, clinical attachment level, etc.
• How do we put all the studies together and form a conclusion? ____
• Meta-analysis for aggressive periodontitis
• Comparing changes in pocket depth and clinical attachment with SRP alone vs
SRP + antibiotics
• The further away the whisker is to the right, the more in favor it is in the test we
are looking at.
• All of these studies led to CAL gain and PD reduction.

Answer 19

pocket depth

meta-analysis

Question 20

• Meta-analysis for chronic periodontitis
• We see a similar trend as above – using ____ along with systemic ____
had an advantage in PD reduction and CAL gain

Answer 20

SRP

antibiotics

Question 21

• This is a ____-blind study (dentist and patient both do not know what they are giving/receiving) by a leader in periodontology and usage of systemic antibiotics.
• They compared patients who only had SRP, patients who had SRP + metronidazole, and those who had SRP + metro + amox

• We will focus just on bleeding on probing (red box)
• Everyone started with roughly the same level of ____ (between 63-70% of sites
with BOP)
• At 3 months, ____ improved (reduced BOP)
• The group that received the combo antibiotics (SRP + metro + amox) had even
further ____
• 1 year after giving the one course of antibiotics, they all maintained low levels of
bleeding, but even less bleeding for those on the ____ antibiotics.

Answer 21

BOP
everyone
reduction
combo

Question 22

• They classified individuals as either low, moderate, or high risk of further disease progression (based on the number of sites with 5mm+ and BOP)
• Nobody in this study ____ or had diabetes
• The patients that remained at high risk at the end of the study were 62% of those that
had ____ only, and 23% of those with ____ antibiotics
• Those with pockets of 6mm + (sites that need additional therapy) had elimination of
those pockets in 60% of those with ____ therapy, and only 20% in those that had ____ only
• The point: you decrease the risk and decrease the need for additional treatment by using SRP + ____ therapy

Answer 22

smoked
SRP
combo
antibiotic
SRP
combo

Question 23

• This study was done in the US and Sweden. It allowed for the ____ of all therapies available at the time (SRP, systemic metro and amox, low dose doxycycline, surgery, and the combo of all of them)

• Patients would receive SRP, ____, low dose ____, etc. and then they would be seen again later on
• Certain patients received surgery at this point
• ____ months later and ____ months later they were re-examined

Answer 23

chlorhexidine
tetracycline
6
24

Question 24

Changes in Clinical Parameters

• Measured the changes in clinical parameters over time
• ____ reduction
• ____
• ____
• # of sites with ____
• SRP Group had some reduction of PD, some improved AL (attachment levels), decreased in number of sites that were deep and bleeding, and an increase in sites that had loss attachment

Answer 24

pocket depth
clinical attachment level
POB
attachment loss

Question 25

Changes in Clinical Parameters

• Those who had SRP + systemic antibiotics (blue dot) had a further reduction in ____, they gained more attachment, they had further reduction of sites that were ____ and bleeding, and fewer sites that loss attachment over time (when compared to SRP alone). So the results were much better!
• They also had a group that had modified wing flap surgery (red dot). Not much ____ for pocket depth, they often lose ____ due to the surgery, it was not much better for deep bleeding sites, and they had more attachment loss (so not as good results as the systemic antibiotics)

Answer 25

PD
deep
better
attachment

Question 26

• All the studies we’ve looked at were for periodontitis, but not smokers/diabetics.
• Some studies also looked at the use of metro and amox in diabetic patients and smoking patients

• Diabetic study
• LEFT: Looking at the reduction of sites that are 5mm +
• SRP + Placebo
• Reduction by ____ sites
• SRP + Combo Antibiotics
• Reduction by ____ sites (11 more than the placebo)
So in the diabetic patients, the use of ____ led to fewer deep sites
after therapy

• RIGHT: Looking at the number of periodontal pathogen bacteria
• Reductions in ____ complex pathogens were more significant in the group that had antibiotics as compared to those that did not

Answer 26

17
28
antibiotics

red

Question 27

• After a patient stops smoking, it takes them ____ YEARS to get to the same risk of disease as someone who has never smoked
• Smoking primes people for disease

Answer 27

11

Question 28

Adjunctive Systemic

• Smoking study
• A group that received SRP, SRP + Metro, and SRP + combined antibiotics
• The use of antibiotics (metro alone AND combo antibiotics both) led to further ____ in pocket depth and improved attachment, as well as
reduced BOP than SRP alone.

• Why do they study metronidazole, as well as metronidazole in combo with
amoxicillin?
• Because clinically, we may have patients with ____ to penicillin (they could
take metronidazole, but not amoxicillin)

Answer 28

reduction

allergy

Question 29

How do antibiotics affect bacteria living in biofilms?

• Right: you take an antibiotic pill, it goes to the liver, and it is distributed everywhere (including oral cavity
soft tissues and GCF). You can use a ____ to collect GCF and measure the amount of antibiotic in
the periodontal pocket.
• Use of antibiotics has a good effect in ____ pockets (likely because there is lots of GCF in these pockets).
It is brought from the blood/serum –> pocket, and the first thing it encounters is the ____ complex
bacteria (see my red arrow)
• It affects red complex not only in the ____ sites, but the ____ sites as well

Answer 29

paper point
deep
red
deep
shallow

Question 30

Microbiological effects of SA

• Use of Systemic Antibiotics
• Shown is 40 types of bacteria in the oral cavity (the most common). They are
measured in amounts
• At baseline, the three groups (SRP, MTZ, and MTZ + AMX) had similar composition
(lots of red complex)
• At 3 months, the biggest differences occurred in the groups that received
____ compared to those that received SRP only. Same with 6 and 12 months
• The group that had antibiotics sustained lower levels of ____ complex species
throughout the study whereas SRP only started to have a rebound of these species at 3 months.

Answer 30

antibiotics

red

Question 31

Adjunctive systemic antibiotics lead to microbiological benefits

• Smoker Study
• Again, much more significant reduction of ____ complex bacteria at 3 months for antibiotics compared to SRP alone

Answer 31

red

Question 32

Adjunctive systemic antibiotics lead to microbiological benefits

• Smoker Study
• Again, much more significant reduction of ____ complex bacteria at 3 months for antibiotics compared to SRP alone

Answer 32

red

Question 33

• This is a more recent study that looks at progression of periodontitis
• Investigated the impact of combo antibiotics and disease progression
• All received ____ + ____, and then measured changes in AL, and % of sites
that had changed levels of attachment

Answer 33

amox

metronidazole

Question 34

Results
• Percentage of pockets >=5mm:
– Placebo: ____%
– Antibiotics: ____%
• N of subjects X number of teeth/subjectX6 sites/tooth:
–Placebo: 200 x 24 x 6 = 28,000 x 0.055 = ____
– Antibiotics: 206 x 24 x 6 =29,664 x 0.021 = ____
• Difference: ____ deep pockets

• % of pockets that were 5mm or more:
• The patient that had placebo had 5.5% of the pockets that were 5mm +, and
those who received antibiotics were 2.1%.
• The ~3% differences is actually very significant (think about the number of
possible sites it could affect– 1584 sites remained deep in placebo, and only
623 sites remained deep in the antibiotic patients!)
• So the 3% difference is actually a difference of 961 deep pockets

Answer 34

5.5
2.1
1584
623
961

Question 35

Who should receive antibiotics

Who should receive antibiotics? Patients with:
• ____ periodontitis
• ____ periodontitis (moderate to severe)
When should we give antibiotics? • next

Answer 35

aggressive

chronic

Question 36

When use antibiotics?

• Study done on localized aggressive periodontitis
• Some people had ____ treatment (antibiotics after the evaluation) and
some were ____ (antibiotics at time of SRP)
• The patients who received delayed treatment did not have as good of a
____ as those who received them immediately
• So when should we give antibiotics? Around the same time as we do the ____

Answer 36

delayed
immediate
response
SRP

Question 37

Timing of Drug Administration

• American academy of Periodontology (2004) – Patients with ____ and/or progressing periodontitis after re- examination (Slots 2004)
• Kaner et al. 2007 – Timing affects the clinical outcome of adjunctive ____ antibiotics
• Griffiths et al. 2011 – Initial ____ vs. re- treatment

• More recent studies also show initial therapy (at time of ____) provide better clinical results

Answer 37

unresolved
systemic
therapy
SRP

Question 38

Dose, Dosage and Duration of Systemic MTZ + AMOX

• These are a summary of the studies and their dosages/durations of antibiotics
• The dosages are not ____ (they all vary from each other slightly).
The drug works in a range of ____mg of amoxicillin, and from ____mg in metronidazole
• Duration ranges from ____ days to ____ days (most are either 7, 10, or 14)

Answer 38

standardized
250-500
200-500
7
14

Question 39

Metronidazole
• Effective against strict ____ only
• Upon entry into an anaerobic organism, metronidazole is reduced by ____ metabolic pathways
• These reductive pathways can only be found in strict ____
• Resistance to Metronidazole is ____
• May induce a ____ taste and interfere with hepatic enzymes which metabolize ____
• Increases the effect of ____

• Metronidazole
• This is not ____ when you take it. The drug becomes active once inside the
bacterial cell. When it enters, it is reduced via metabolic pathways (anaerobes only), causing it to become activated. This is why it is so specific to the ____ complex
• It is rare to find bugs that are resistant to metronidazole
• DO NOT TAKE ____ when on this – it interferes with alcohol
metabolism
• It also can have an affect on anti-coagulants

Answer 39

anaerobes
anaerobic
anaerobes
rare
metallic
ethanol
anticoagulants

active
red
alcohol

Question 40

Amoxicillin
• Among all drugs penicillins are the most likely to induce \_\_\_\_ reactions (0.02 to 0.04%)
• Common side effects: 
– \_\_\_\_
– Vomiting 
– \_\_\_\_
– Stomach pain
– \_\_\_\_ itching or discharge
 – Headache
– \_\_\_\_

Answer 40

anaphylactic
nausea
diarrhea
vaginal
rash

Question 41

• Several studies looking at amoxicillin side effects. This is a meta-analysis of those studies, looking at the main side effects
• ____ symptoms
• Dizziness
• ____ taste
• Intraoral tissue alteration
• Overall, there was no major difference for getting these ____ when looking at placebo vs antibiotics

Answer 41

GI
metallic
symptoms

Question 42

Antibiotic Resistance

• There is fear of prescribing these due to the possibility of antibiotic resistance
• Shown is two mechanisms bacteria use to gain resistance:
• Mechanisms of resistance
• Efflux pump that pumps the ____ out
• Enzymes that ____ the antibiotic when it enters

• Horizontal Gene Transfer
• Communication among bacteria, allowing them to share genes via
____, conjugation, or ____

Answer 42

drug
alter/degrade

transformation
transduction

Question 43

How to avoid antibiotic resistance

• Prudent antibiotic use:
• Only when patient outcome can be ____
• Use of ____-spectrum antibiotics
• Save last ____ antibiotics for serious, life threatening infections
• Therapy should be stopped as ____ as possible
• Prophylaxis
• Use ____ courses (single dose for surgery)
• Give at correct time (time of surgical ____)

How do we avoid antibiotic resistance?
• Be mindful/prudent. Only use them when the outcome of the patient can be
improved, use narrow spectrum when possible, and only use last generation
antibiotics in extreme cases
• Therapy should be stopped ASAP (remember the duration is 7, 10, and 14 days.
If we can end therapy in 7 days, it would be much better than going longer)
• Another way to use antibiotics prudently in the context of prophylaxis.

Answer 43

improved
narrow
generation
soon

short
incision

Question 44

Local Drug Delivery (LDD)

• Flow of the gingival crevicular fluid (GCF) is replaced ____ times per hour leading to rapid clearance of subgingivally placed ____

• The idea is that instead of having the systemic side effects (dizziness, GI issues, etc.) we can deliver the drug in specific areas where it is needed.
• The challenge is that we need to give it in pockets that have varying anatomy, and we need to ensure the drug stays there/does not get ____ away by GCF.

Answer 44

40
drugs
washed

Question 45

PerioChip® - Chlorhexidine

• EachPerioChip weighs approximately 6.9 mg and contains 2.5 mg of ____ in a ____ matrix of hydrolyzed gelatin

• PerioChip
• This is a gel that contains chlorhexidine, as well as a matrix that is degraded
over time. This allows the chlorhexidine to be released over time into the
pocket
• This did not achieve great clinical results, so it was ____ in practice

Answer 45

chlorhexidine
biodegradable
discontinued

Question 46

Atridox® - Doxycycline

Composed of a two syringe mixing system
• Syringe A - 450 mg of a bioabsorbable formulation of 36.7% ____
dissolved in 63.3% ____
• Syringe B contains 50 mg of ____

• This is a derivative of doxycycline that comes in a dual syringe
• You use the whole ____ in the pockets
• This was not as practical as some other options we have now

Answer 46

poly(DLIactide) (PLA)
N-methyl-2-pyrrolidone (NMP)
doxycycline hyclate

cartridge

Question 47

Arestin® - Minocycline
• 1 mg of ____ incorporated into a bioresorbable polymer, Poly (glycolide-co- dl-lactide) or PGLA

• This is the most commonly accepted/used today
• In the minocycline family
• ____ deposited directly into the pocket. It stays there and is ____ over time
• This is one of the most studied LDDs

Answer 47

minocycline hydrochloride
microspheres
degraded

Question 48

• The first study published for the microspheres
• Treatment of periodontitis via microspheres – this study was the benchmark for FDA approval of Arestin
• You had three groups: SRP alone, SRP + microspheres, SRP + drug
• Pocket depth reduction was sustained over time in the group with the
____. The sites that received microspheres had a greater reduction in deep ____ compared to those that had SRP.

Answer 48

microspheres

pocket depth

Question 49

• In a subsequent study they did a microbiological analysis, and found a significant reduction in ____ complex bacteria (comparing microspheres to SRP alone)

Answer 49

red

Question 50

Adjunctive Local Minocycline Enhances effects of SRP

• This is a study looking at periodontitis in smokers – pocket depth was reduced in individuals that smoked for ____ time, but not so much for those that smoked >____ years
• In addition, individuals that received microspheres had much more improvement when looking at ____, smokers with CV, etc.)

Answer 50

less
20
smokers

Question 51

Questions Remaining:
Who Should Receive Systemic Antibiotics?
• Some authors have suggested that this therapeutic approach should be recommended for ____ or Aa-associated periodontitis (van Winkelhoff et al 1992, Winkel et al 2001)
• Added clinical benefits have been suggested even in the absence of ____ periodontal pathogens (Cionca et al 2010, Feres et al 2012, Goodson et al 2012)
• Identification of a ____ population can avoid overprescription
• ____ in knowledge remains as to which patients truly benefit from systemic antibiotics
What are best therapies for what patients? What about patients that do not respond? How exactly does SA affect microbiome? Any other taxa not affected?

There is enough evidence in the literature that aggressive periodontitis and moderate to severe chronic periodontitis should receive ____
We still need to find a way to better tailor the treatment to our patients to avoid ____

Answer 51

Pg
classic
target
gap

antibiotics
overprescritpion

Question 52

Concluding Remarks

• ____ are useful in the delivery of chemical plaque control during all phases of periodontal therapy
• Systemic ____ provide additional clinical benefits as an adjunct to non-surgical therapy
• Most of the evidence is based on the use of ____
• ____ provides additional clinical benefits
• Most of the evidence is based on the use of ____

• Note that typically we use the LDD (arrestin) in the ____
PHASE (after we treat, we use this on pockets/areas that did not respond)

Answer 52

toothpastes and mouthrinses
antibiotics
AMOX+METRO
LDD
arrestin
maintenance