Anti-infective therapy and
host modulating agents
Dr. Alaa M Attia
• The basic treatment of periodontitis is the
mechanical debridement of periodontal pockets
by scaling and root planing in combination with
effective plaque control.
• Certain periodontal pathogens can invade the
connective tissue e.g. Aa making it unreliably
removed with mechanical debridement alone.
• Systemic and local antimicrobial therapies aim
to help the mechanical and surgical periodontal
treatment by killing susceptible periodontal
pathogens that remain after conventional
Systemic Antimicrobial Therapy
General Guidelines for Antimicrobial Use
• Used as “adjunctive therapy”, never a substitute to
• They enhance the effect of debridement.
• Patients not responding to conventional mechanical therapy.
• Aggressive periodontitis.
• Refractory periodontitis (not respond to conventional ttt).
• Acute periodontal infections e.g. (abscesses and NPD).
• As an adjunct to surgical and non-surgical periodontal
A- Systemic Antimicrobial Therapy
• Allergic reactions
• Super infection, e.g. fungal infections, on
• Drug interactions
• Patient compliance is extremely important
• Bacterial resistance
Amoxicillin: Used for all aggressive
periodontitis cases 500mg/3/8.
Can be used for refractory and localized
aggressive periodontitis cases; 625
ttt : Localized aggressive P.
- Refractory periodontitis – P Abscess
• Broad spectrum antibiotic
• 4-8 µg/ml in the GCF (2-10 times more
than serum concentration)
• Bacteriostatic, Bactericidal (at high doses)
• Tetracycline, Doxycycline, and
Minocycline are the tetracyclines used for
• Dose: 250 mg, 4 times daily
• Stains teeth in children
• Absorption is impaired by antacids, milk &
calcium rich foods
• oral contraceptive effect
• Refractory cases
• Localized aggressive periodontitis
• Renal insufficiency (can use doxycycline)
• Liver dysfunction (can use minocycline)
• It suppresses the spirochetes
• Less photosensitivity and renal toxicity than
• May cause reversible vertigo
• Administered in a dose of 200 mg per day for
• Has the same spectrum as minocycline
• Its absorption is not affected by calcium, metal
ions or antacids.
• Given 100 mg once daily or 50 mg twice daily.
Mechanism of Action
• Bactericidal antimicrobial.
• Disrupts DNA synthesis
• Susceptible bacteria include Bacteroides, P. gingivalis,
Treponema, Campylobacter and Veillonellae.
• Necrotizing ulcerative gingivitis
• Refractory periodontitis (Combined with Amoxicillin or
• Localized aggressive cases (combined with amoxicillin or
• Ineffective against Aa except when combined with other drugs.
• Dose: 250 mg tid for 7-10 days or 500 mg bid for 1-2 weeks.
Action: active against gram-negative rods,
including all facultative and some anaerobic
putative periodontal pathogens.
• Indicated for use in refractory periodontitis
• May facilitate repopulation of pocket with
organisms associated with periodontal health
• Not for use in children as it disrupts the growth
• Side effect: Nausea, headache, metallic taste
in the mouth, and abdominal discomfort,
Action: against anaerobic bacteria and has a
strong affinity for osseous tissue
• Indicated: for refractory periodontitis especially
in cases that are non-responsive to tetracycline.
• Side Effects
- Pseudomembranous colitis- caused by clostridium
- Super infections
- Fungal overgrowth in oral cavity, intestine and
• Dose: 250-500 mg, tid, for 8 days
Azithromycin is a member of the azalide class of
Action: against anaerobes and gram-negative
For treatment of Aggressive periodontitis.
After an oral dosage of 500 mg qd for 3 days,
significant levels of azithromycin can be detected
in most tissues for 7 to 10 days.
Dose: 250 mg/day for 5 days after an initial
loading dose of 500 mg.
• Augmentin & Metronidazole
- 250 mg of each 3 times daily
- 8 days
• Ciprofloxacin & Metronidazole
- 500 mg of each twice daily
- 8 days
• Clindamycin & Ciprofloxacin
- 300 mg clindamycin
- 500 mg ciprofloxacin
- twice daily 8 days
Antibiotic treatment should be reserved for
specific subsets of periodontal patients who do
not respond to conventional therapy.
Selection of specific agents should be guided
by the results of cultures and sensitivity tests
for subgingival plaque microorganisms.
At this time, systemic antibiotics for the
treatment of periodontal diseases have been
indicated primarily for adjunctive use in the
treatment of aggressive periodontal diseases
Decision tree for selection of Antibiotics in PDs
B- Local Delivery Antimicrobials
• Facilitates prolonged drug delivery.
• GCF concentration greater than serum
• Reduces systemic effects.
• Enhances treatment results at specific
locations (i.e. acts on treated sites only).
• Improves clinical signs of periodontitis.
1- Tetracycline (Actisite)
• Fiber of 23 cm in length that has 12.7 mg tetracycline
• Pockets measuring 5 mm that bleed on probing.
• Localized treatment of sites not responding to mechanical
• Fiber is inserted into the pocket.
• Some control of saliva is needed.
• Should contact the pocket base.
• Surgical dressing is not necessary.
• Removed 7-10 days after placement.
2- Minocycline (Arestin)
sustained-release form of minocycline
microspheres (Arestin) is available for
subgingival placement as an adjunct to scaling
and root planing. The 2% minocycline is
encapsulated into bioresorbable microspheres
in a gel carrier.
• Do not eat hard or sticky foods for 1 week.
• Avoid of brushing for 12 hours.
• Do not use interproximal cleaning aids for 10 days
It is minocycline microencapsulated in in gel carrier.
Placement of minocycline
3- Doxycycline hyclate (Atridox)
It is an 10 % Doxycycline hyclate
• Released at minimal inhibitory
concentration levels for most
periodontal pathogens over a period of 7-8 days.
• A liquid polymer in one syringe and powdered
doxycycline hyclate in a second syringe, the two
syringes are mixed together just before use.
• The mixture is injected into the pocket using a blunt
needle and solidifies in contact with crevicular fluid
4- Metronidazole (Elyzol)
• Metronidazole. (Elyzol)
Is A topical medication containing an oil-
based metronidazole 25% dental gel
5- Chlorhexidine gluconate (Periochip)
• 34 % chlorhexidine gluconate in a cross-linked
• Each chip contains 2.5mg of chlorhexidine
• Chip is gently pushed into the pocket and it
biodegrades over 7-10 days.
• Chlorhexidine has been detected in gingival fluid
for one week following a single application.
• Absence of any bacterial resistance with
• Good substantively.
Chlorhexidine chip: (Periochip)
Placement of chlorhexidine gluconate chip
Mechanical plaque removal remains the
cornerstone of preventive and therapeutic
regimens in the management of gingivitis and
Specific subgroups of patients can significantly
benefit from an adjunctive antimicrobial agents.
Host Modulation: is the process that uses drugs
or chemicals, other than antimicrobials, to reduce
periodontal breakdown and enhance the immune
response of the host.
A- Systemically Administered Agents
B- Locally Administrating Agents
1- Subantimicrobial dose doxycycline
• Periostat is the first therapeutic agent
designed to modulate the host response and
helps to slow the progression of periodontal
• It is a doxycycline hyclate that is not used as an
antibiotic and has no detectable effect on
• Inhibits collagenase activity in gingival
crevicular fluid of patients with periodontitis.
Available as a 20 mg tablet to be taken
orally two times a day (about an hour
before, or two hours after meals). It
should be taken with plenty of fluids.
Typical treatments range from 3
months to 12 months.
Should not be used for children,
pregnant and nursing women or
anyone with tetracycline
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.
They are used to treat pain, acute
inflammation, and a variety of chronic
NSAIDs inhibit prostaglandins and therefore
reduce tissue inflammation.
Present in plasma membrane in inflammatory cells
COX-1 is constitutively expressed and has
antithrombogenic and cytoprotective functions.
Therefore, inhibition of COX-1 by nonselective NSAIDs
causes side effects such as gastrointestinal ulceration
and impaired hemostasis.
COX-2 is induced after stimulation by various
cytokines, growth factors, and LPS and results in the
production of elevated quantities of prostaglandins.
Inhibition of COX-2 by selective COX-2 inhibitors results
in reduction of inflammation.
Research shows that the periodontal benefits of taking
long-term NSAIDs are lost when patients stop taking the
drugs, with a return to or even an acceleration of the rate
of bone loss seen before NSAID therapy, often referred to
as a (rebound effect).
For these reasons, the long-term use of NSAIDs as an
adjunctive treatment for periodontitis has never really
developed beyond research studies.
NSAIDs (including the selective COX-2 specific inhibitors)
are presently not indicated as adjunctive human
modulators (HMTs) in the treatment of periodontal
The bisphosphonates are bone-seeking agents that inhibit
bone resorption by disrupting osteoclast activity.
Bisphosphonates interfere with osteoblast metabolism and
secretion of lysosomal enzymes.
Recent evidence has suggested that bisphosphonates also
possess anticollagenase properties.
In animal models of experimentally induced periodontitis,
bisphosphonates reduced alveolar bone resorption.
In human studies, these agents resulted in enhanced alveolar
bone status and density.
Side effect: ostenecrosis , oral ulcers , altered WBCs count
Dose: very small dose in comparison to anti-malignant dose
about (0.2 to 1 mg/kg/d).
B- Locally Administered Agents
1- NASID e.g. topical ketorolac mouthrinse
2- Periodontal bone regenerative agents:
A- Enamel Matrix Proteins
B- Growth Factors e.g.
(Platelet-derived growth factor, insulinlike g. factor).
C- Bone morphogenetic proteins (BMP-2, BMP-7).