Sequence of treatment plan.

Dr. Omar Soliman

 Sequence
of
treatment
plan.

Dr. Omar Soliman

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 Anti-infective Therapy
And
Host Modulation

Dr. Omar Soliman

Lecturer of Oral medicine and Periodontology,
South Vally University

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 Anti-infective Therapy

An anti-infective agent is a chemotherapeutic agent that acts by reducing the

number of bacteria present.
An antibiotic is a naturally occurring, semisynthetic, or synthetic type of
anti-infective agent that destroys or inhibits the growth of selective
microorganisms, generally at low concentrations.
An antiseptic is a chemical anti-microbial agent that can be applied
topically or subgingivally to mucous membranes, wounds, or intact dermal
surfaces to destroy microorganisms and to inhibit their reproduction or
metabolism. In dentistry, antiseptics are widely used as the active ingredient
in antipla︎que and anti-gingivitis oral rinses and dentifrices.
Disinfectants (a subcategory of antiseptics) are antimicrobial agents that are
generally applied to inanimate surfaces to destroy microorganisms.
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 Anti-infective Therapy

Anti-infective agents can be administered locall︎y or systemically.

The s︎ystemic a︎dministration of antibiotics may be a necessary adjunct for
the controlling of bacterial infection, because bacteria can invade
periodontal tissues, thereby making mechanical therapy alone sometimes
ineffective. Systemic administration have a dual mechanism of action. For
example, tetracyclines (especially doxycycline) are chemotherapeutic agents
that can reduce collagen and bone destruction via their ability to inhibit the
enzyme collagenase (Host modulation) and as antibiotic agents, they can
also reduce periodontal pathogens in periodontal tissues.
The local a︎dministration of anti-infective agents, generally directly to the
pocket, has the potential to provide greater concentrations directly to the
infected area and thus reduce possible systemic side effects.
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 Systemic Administration of Antibiotics.

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 1. Tetracyclines

Tetracyclines have been widely used for the treatment of periodontal

diseases. They have been freqeuently used to treat refractory
periodontitis, including locali︎zed aggressive perio︎ontitis (LAP).
Tetracyclines have the ability to concentrate in the periodontal tissues and
to inhibit the growth of ︎aggregatibacter actinom︎ycetemcomitans︎, in
addition, tetracyclines exert an anti-collagenase effect that can inhibit
tissue destruction and that may help with bone regeneration.

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 1. Tetracyclines

Pharmacology.
These antibiotics are bacteriostatic, and they are effective against
rapidly multiplying bacteria. They generally are more effective against
gram-positive bacteria than gram-negative bacteria.
Tetracyclines are effective for the treatment of periodontal diseases in
part because their concentration in the gingival crevice is 2 to 10 times
that found in serum. This allows a high drug concentration to be
delivered into the periodontal pockets. In addition, several studies have
demonstrated that tetracyclines at a low GCF concentration (i.e., 2 μg/ml
to 4 μg/ ml) are very effective against many periodontal pathogens.

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 Clinical Use.
Tetracyclines have been investigated as adjuncts for the treatment of LAP. ︎
(A.actinom︎ycetemcomitans is a fre︎quent microorganism that is associated
with LAP, and it invades tissue). Therefore, the mechanical removal of
calculus and plaq︎ue from root surfaces may not eliminate this
bacterium from the periodontal tissues. Systemic tetracycline can
eliminate tissue bacteria, and it has been shown to arrest bone loss and to
suppress ︎ A. actinom︎︎ycetemcomitans levels in conjunction with scaling and
root planing.
This combination therapy allows for the mechanical removal of root surface
deposits and for the elimination of pathogenic bacteria from within the
tissues. Increased post treatment bone levels have been noted with the use of
this method.
As a result of increased resistance to tetracyclines, metronidazole or
amoxicillin with metronidazole has been found to be more effective for the
treatment of aggressive periodontitis in children. Some investigators think
that metronidazole in combination with amoxicillin︎ clavulanic acid is the
preferable antibiotic. 16
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 Specific Agents.

1. Tetracycline.
Treatment with tetracycline hydrochloride req︎ u ires the
administration of 250 mg four times daily.
It is inexpensive, but compliance may be reduced by the need to
take the medication so freq︎uently.
Side effects include gastrointestinal disturbances,
photosensitivity, hypersensitivity, increased blood urea nitrogen
levels, blood dyscrasias, dizziness, and headache. In addition,
tooth discoloration occurs when this drug is administered to
children who are 12 years old or younger.
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 2. Minocycline.
Minocycline is effective against a broad spectrum of microorganisms. In
patients with adult periodontitis, it suppresses spirochetes and motile rods
as effectively as scaling and root planing, with suppression evident up to 3
months after therapy.
Minocycline can be given twice daily, thereby facilitating compliance as
compared with tetracycline. Although it is associated with less
phototoxicity and renal toxicity than tetracycline, minocycline may cause
reversible vertigo.
Minocycline administered at a dose of 200 mg/day for 1 week results in a
reduction in total bacterial counts, the complete elimination of spirochetes
for up to 2 months, and the improvement of all clinical parameters.

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 3. Doxycycline.
Doxycycline has the same spectrum of activity as minocycline, and it may
be eq︎ually as effective. Because doxycycline can be given only once daily,
patients may be more compliant. Compliance is also favored because its
absorption from the gastrointestinal tract is only slightly altered by calcium,
metal ions, or antacids, as is absorption of other tetracyclines. Side effects
are similar to those of tetracycline hydrochloride︎ however, it is the most
photosensitizing agent in the tetracycline category.
The recommended dosage when doxycycline is used as an anti- infective
agent is 100 mg twice daily the first day, which is then reduced to 100
mg daily. To reduce gastrointestinal upset, 50 mg can be taken twice daily
after the initial dose.
When given as a sub-antimicrobial dose (to inhibit collagenase), 20 mg of
doxycycline twice daily is recommended (Periostat).

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 Metronidazole
Pharmacology.
Metronidazole is a nitroimidazole compound treat protozoal infections. It is
bactericidal to anaerobic organisms, and it is thought to disrupt bacterial DNA
synthesis in conditions with a low reduction potential. Metronidazole is not the
drug of choice for treating ︎ A. actinom︎ycetemcomitans infections. However,
metronidazole is effective against ︎ A. actinom︎ycetemcomitans when it is used in
combination with other antibiotics. Metronidazole is also effective against
anaerobes such as Porph︎romonas gingivalis and Prevotella intermde︎ia.
Clinical Use.
Metronidazole has been used clinically to treat gingivitis, acute necrotizing
ulcerative gingivitis, chronic periodontitis, and aggressive periodontitis. It has
been used as monotherapy and also in combination with both root planing and
surgery or with other antibiotics. Metronidazole has been used successfully to
treat necrotizing ulcerative gingivitis.
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 Side Effects.
Metronidazole has an Antabuse effect when alcohol is ingested. The
response is generally proportional to the amount ingested, and it can result
in severe cramps, nausea, and vomiting. Products that contain alcohol
should be avoided during therapy and for at least 1 day after therapy is
discontinued.
Metronidazole also inhibits warfarin metabolism. Patients who are
undergoing anticoagulant therapy should avoid metronidazole, because it
prolongs prothrombin time.
It also should be avoided in patients who are taking lithium.
Metronidazole also produces a metallic taste in the mouth, which may
affect compliance.

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 Penicillins

Pharmacology. They inhibit bacterial cell wall production and therefore

are bactericidal.
Clinical Use. Amoxicillin and amoxicillin︎ clavulanate potassium
(Augmentin) have can be used in periodontal therapy.
Side Effects. Penicillins may induce allergic reactions and bacterial
resistance︎.
Amoxicillin is susceptible to penicillinase, which is a β-lactamase
produced by certain bacteria that breaks the penicillin ring structure and
thus renders penicillins ineffective.

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 Amoxicillin may be useful for the management of patients with aggressive
periodontitis in both localized and generalized forms. The recommended
dosage is 500 mg three times daily for 8 days.

Amoxicillin–Clavulanate Potassium.
The combination of amoxicillin with clavulanate potassium makes this
anti-infective agent resistant to penicillinase enzymes produced by some
bacteria. Amoxicillin with clavulanate (Augmentin) may be useful for the
management of patients with LAP or refractory periodontitis.

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 Clindamycin

Pharmacology.
Clindamycin is effective against anaerobic bacteria, and it has a strong
affinity for osseous tissue. It is effective for situations in which the
patient is allergic to penicillin.
Clinical Use.
Clindamycin has demonstrated efficacy in patients with periodontitis that is
refractory to tetracycline therapy.
Side Effects.
Clindamycin can be used with caution, but it is not indicated for patients
with a history of colitis. Diarrhea or cramping that develops during
clindamycin therapy may be indicative of colitis.
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 Serial and Combination Antibiotic Therapy

Rationale
Because periodontal infections may contain a wide diversity of
bacteria, no single antibiotic is effective against all putative
pathogens.
These ︎mixed︎ infections can include a variety of aerobic, and
anaerobic bacteria, which may be both gram negative and gram
positive. In these cases, it may be necessary to use more than one
antibiotic, either serially or in combination. Before combinations of
antibiotics are used, however, the periodontal pathogens being treated
must be identified and antibiotic-susceptibility testing performed.

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 Serial Therapy. Antibiotics that are bacteriostatic (e.g., tetracycline)
generally req︎uire rapidly dividing microorganisms to be effective. They do
not function well if a bactericidal antibiotic (e.g., amoxicillin) is given
concurrently. ︎When both t︎ypes or︎ ︎drugs are req︎uire︎︎ the︎y are best given
seriall︎ rather than in combination︎.

Combination therapy involving the use of systemic metronidazole along

with amoxicillin, amoxicillin︎ clavulanate (Augmentin). The metronidazole︎
amoxicillin and metronidazole and ︎Augmentin combinations provided
excellent elimination of many organisms in adults with LAP who had been
treated unsuccessfully with tetracyclines and mechanical debridement.
These drugs have an additive effect that involves the suppression of ︎ A.
actinom︎ycetemcomitans. This is a powerful combination against mixed
infections.

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 Guidelines for the use of antibiotics in periodontal therapy:

1. The clinical diagnosis and situation dictate the need for possible antibiotic
therapy as an adjunct for controlling active periodontal disease. The patient’s
diagnosis can change over time. For example, a patient who presents with
generalized, mild chronic periodontitis can return to a diagnosis of
periodontal health after initial therapy. However, if this patient has been
treated and continues to have active disease, the diagnosis may change to
generalized severe chronic periodontitis.
2. Disease activity as measured by continuing attachment loss, purulent
exudate, and bleeding on probing may be an indication for periodontal
intervention and possible microbial analysis through pla︎que sampling.
3. When they are used to treat periodontal disease, antibiotics are selected on
the basis of the patient’s medical and dental status, his or her current
medications, and the results of microbial analysis, if it is performed.
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4. Microbiologic pla︎que sampling may be performed according to the
instructions of the reference laboratory.
The samples are usually taken at the beginning of an appointment before
instrumentation of the pocket.
Supragingival pla︎que is removed, and an endodontic paper point is inserted
subgingivally into the deepest pockets present to absorb bacteria in the
loosely associated pla︎que.
This endodontic point is placed in reduced transfer ︎fluid or a sterile transfer
tube and sent overnight to the laboratory. The laboratory will then send the
referring dentist a report that includes the pathogens that are present and any
appropriate antibiotic regimen. At this time, there are scant data to suggest
that microbial identification from a pla︎que sample can be used to clinically
improve the periodontal condition of the patient.
5. Systemic antibiotics can improve attachment levels when they are used as
adjuncts to scaling and root planing. The same benefits could not be
demonstrated when antibiotics were used as a stand-alone therapy.
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6. When systemic antibiotics were used as adjuncts to scaling and root planing,
improvements were observed in the attachment levels of patients with chronic
and aggressive periodontitis, although patients with aggressive periodontitis
experienced greater benefits.

7.Debridement of root surfaces, optimal oral hygiene, and freq︎uent periodontal

maintenance therapy are important parts of comprehensive periodontal
therapy. As mentioned previously, an antibiotic strength that is 500 times
greater than the systemic therapeutic dose may be re︎quired to be effective
against bacteria that has been arranged into biofilms. It is therefore
important to disrupt this biofilm physically so that the antibiotic agents
can have access to the periodontal pathogens.

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 Local Delivery Agents

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 Local Delivery Agents

Locally delivered antimicrobial agents are available as adjuncts to scaling and root
planing and as aids for the control of growth of bacteria on barrier membranes.

1. Subgingival Chlorhexidine
A resorbable delivery system has been tested for
the subgingival placement of chlorhexidine
gluconate with positive clinical results.
The PerioChip is a small chip (4.0 mm × 5.0 mm
× 0.35 mm) that is composed of a biodegradable
hydrolyzed gelatin matrix. It is cross-linked with
glutaraldehyde, and it also contains glycerin and
water into which 2.5 mg of chlorhexidine
gluconate has been incorporated per chip.

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1. Subgingival Chlorhexidine

This delivery system releases chlorhexidine and

maintains drug concentrations in the GCF of more
than 1000 μg/ml for at least 7 days these
concentrations are well above the tolerance of
most oral bacteria.
Because the chip biodegrades within 7 to 10 days,
a second appointment for removal is not
needed.

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2. Tetracycline-Containing Fibers (Arestin).
The first local delivery product available in the
U︎nited States︎ an ethylene/vinyl acetate copolymer
fiber (diameter, 0.5 mm) that contained tetracycline
(12.7 mg per 9 inches)︎was extensively studied.
When packed into a periodontal pocket, it was well
tolerated by the oral tissues. For 10 days, it
sustained tetracycline concentrations that exceeded
1300 μg/ml, which was well beyond the 32 μg/ml
to 64 μg/ml re︎uqired to inhibit the growth of the
pathogens that had been isolated from periodontal
pockets.
Studies demonstrated that tetracycline fibers applied with or without scaling and root
planing reduced probing depth, bleeding with probing, and periodontal pathogens and
provided gains in clinical attachment level. Such effects were significantly better than
those attained with scaling and root planing alone or with placebo fibers. No change in
antibiotic resistance to tetracycline was found after tetracycline fiber therapy among the
tested putative periodontal pathogens. However, these fibers are no longer commercially
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3. Subgingival Doxycycline (Atridox).
A gel system involving the use of a syringe with 10% doxycycline (Atridox) is
available. It was the only local delivery system accepted by the American Dental
Association.

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4. Subgingival metronidazole.
A topical medication that contains an oil-based metronidazole 25︎ dental gel
(glyceryl monooleate and sesame oil) has been tested in a number of studies.
It is applied in a viscous consistency to the pocket, where it is li︎quidized by the
body heat and then hardens again, forming crystals when it comes in contact
with water.

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 Host Modulation

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 Host Modulation Treatment.

HMT is a means o︎f treating the host si︎te or︎ the host︎bacteria interaction.
The host response is responsible for most of the tissue breakdown that
occurs, leading to the clinical signs of periodontitis (i.e., loss of connective
tissue attachment and bone).
HMTs offer the opportunity for modulating or reducing this destruction by
treating aspects of the chronic infl︎ammatory response.
HMTs do not ︎switch off︎ normal defense mechanisms or in︎flammation︎
instead, they ameliorate excessive or pathologically elevated infl︎ammatory
processes to enhance the opportunities for wound healing and periodontal
stability.

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 HMT can be used to reduce excessive levels of enzymes, cytokines, and
prostanoids and should not reduce levels below constitutive levels.
HMTs can also modulate osteoclast and osteoblast function but should not
impact normal tissue turnover.
HMT is key to addressing many of the risk factors that have adverse effects
on the host response, which are either not easily managed (e.g., smoking,
diabetes) or cannot be changed (e.g., genetic susceptibility). In addition,
host modulatory agents might be used to increase the levels of a person’s
own protective or anti-in︎flammatory mediators.
The use of systemic HMTs for treatment of a patient’s periodontal condition
may also provide benefits for other infl︎ammatory disorders such as arthritis,
cardiovascular disease, dermatologic conditions, diabetes, rheumatoid
arthritis, and osteoporosis.

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 Systemically Administered Agents.

1. Nonsteroidal Antiinflammatory Drugs .

NSAIDs inhibit the formation of prostaglandins, including PGE2, which is
produced by neutrophils, macrophages, fibroblasts, and gingival epithelial
cells in response to the presence of LPS, a component of the cell wall of
gram-negative bacteria.
PGE2 has been extensively studied in periodontal disease because it
upregulates bone resorption by osteoclasts. Levels of PGE2 have been
shown to be elevated in patients with periodontal disease compared with
healthy patients. PGE2 also inhibits fibroblast function and has inhibitory
and modulatory effects on the immune response.
NSAIDs include the salicylates (e.g., aspirin), indomethacin, and the
propionic acid derivatives (e.g., ibuprofen, ︎urbiprofen, and naproxen).
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 Systemically Administered Agents.

The prostaglandins (PGs) are a group of lipid compounds derived from

arachidonic acid, a polyunsaturated fatty acid found in the plasma
membrane of most cells.
➢ Arachidonic acid is metabolized by cyclooxygenase-1 and -2 (COX-1 and COX-2) to
generate a series of related compounds called the prostanoids, which includes the
PGs, the thromboxanes, and the prostacyclins.
➢ PGs are important mediators of inflammation, particularly prostaglandin E2(PGE2),
which results in vasodilation and induces cytokine production by a variety of cell types.
➢ COX-2 is upregulated by IL-1β, TNF-α, and bacterial LPS, resulting in increased
production of PGE2 in inflamed tissues. PGE2 is produced by various types of cells and
most significantly in the periodontium by macrophages and fibroblasts. PGE2 results in
the induction of MMPs and osteoclastic bone resorption, and it has a major role in
contributing to the tissue damage that characterizes periodontitis.
➢ Prostaglandins are inhibited by nonsteroidal antiinflammatory drugs (NSAIDs),
researchers have investigated the use of NSAIDs as potential host–response
modulators in the management of periodontal disease.
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2. Bisphosphonates
The bisphosphonates inhibit bone resorption by disrupting osteoclast
activity. Bisphosphonates interfere with osteoclast metabolism and
secretion of lysosomal enzymes and also possess anticollagenase properties.
The ability of bisphosphonates to modulate osteoclast activity clearly may
be useful in the treatment of periodontitis.
Some bisphosphonates have the unwanted effects of inhibiting bone
calcification and inducing changes in white blood cell counts. Also, there
have been recent reports of avascular necrosis of the jaws following
bisphosphonate therapy, with the resultant risk of bone necrosis following
dental extractions.
The recent reports of bisphosphonate-related osteonecrosis of the jaw
(BRONJ), although primarily associated with intravenous
administration of bisphosphonates rather than oral administration.
At present there are no bisphosphonate drugs that are approved and
indicated for treatment of periodontal diseases.
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 3. Sub-Antimicrobial-Dose Doxycycline (Periostat).

Sub-antimicrobial-dose doxycycline (SDD) is a 20-mg dose of doxycycline

(Periostat) that is approved and indicated as an adjunct to SRP in the
treatment of chronic periodontitis.
It is taken twice daily for, 3 months up to a maximum of 9 months of
continuous dosing.
The 20-mg dose exerts its therapeutic effect by enzyme, cytokine, and
osteoclast inhibition rather than by any antibiotic effect.
At present, SDD (Periostat) is the only systemically administered HMT
specifically indicated for the treatment of chronic periodontitis that is
approved by Food and Drug Administration (FDA) and accepted by
the American Dental Association (ADA).

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BONE DESTRUCTION CAUSED
BY SYSTEMIC DISORDERS.

bone loss initiated by local inflammatory processes may be

magnified by systemic influence on the response of alveolar
bone.

This is termed . The bone factor concept .