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1. ANTI INFECTIVE THERAPY
CONTENT
 Antibiotics
 Rationale
 Guidelines for using antibiotics
 Anti- infective therapy
 Anti –infective agents
 Systemic administration of antibiotics
 Serial or combination antibiotics
 Local delivery agents
Antibiotics
An Antibiotic is a natural occurring , semi synthetic or semi synthetic type of anti infective
agent that destroys or inhibits the growth of selective micro organisms, generally at low
concentrations.
An antiseptic is a chemical antimicrobial agent that can be applied topically or subgingivally to
mucous membranes, wounds or intact dermal surfaces to destroy micro organisms and to
inhibit their reproduction or metabolism.
Rationale for antibiotics
 Mechanical and surgical treatment combined with proper oral hygiene measures can arrest or
prevent further periodontal attachment loss in most individuals by reducing total supra-
subgingival bacterial mass
 Some individuals continue to experience periodontal breakdown, may be due to the
ability of major periodontal pathogens like
Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Fusobacterium-
nucleatum, Treponema denticola, bacteroids, to invade periodontal tissues or to reside in
furcations or other tooth structures outside the reach of periodontal instruments, or due to
poor host defense mechanisms.

2.  In addition, the putative periodontal pathogens (“red complex”) tend to reside in the
section of the biofilm attached to the epithelial surface of the periodontal pocket and
the patient cannot reach this site during the oral hygiene efforts.
Guidelines for using antibiotics:-
 Specific for periodontal pathogens
 Allogenic and non toxic
 Substantive
 Not in general use for treatment of other diseases
 Inexpensive
Anti Infective Therapy
Mechanical removal of plaque includes manual instrumentation (eg. scaling and root planning)
and machine driven instrumentation (eg. ultrasonic scalers) and these procedures considered
as Anti- infective therapy.
Anti infective agents
• An anti infective agent is a chemotherapeutic agent that acts by reducing the number
of bacteria present.
Common regimens used to treat
periodontal diseases are
• Tetracycline
• Metronidazole
• Penicillin
• Cephalosporins
• Clindamycin
LOCALLY SYSTEMIC

3. Effective intreating periodontal diseases
Because
theirconcentrationinthe gingival crevice is 2to 10 times that inserum.Thisallowshighdrug
concentrationtobe deliveredintoperiodontalpockets
• Ciprofloxacin
• Macrolides
TETRACYCLINE
Tetracyclines have the ability to concentrate in the periodontal tissues and inhibit the
growth of Aggregatibacter actinomycetemcomitans. In addition, exert an anti
collagenous effect that inhibits tissue destruction and may aid bone regeneration.
Pharmacology
 Broad spectrum
 Bacteriostatic
 Effective against G+ive>>>G-ive bacteria
 Studies suggested that tetracycline at low GCF
concentration (2 to 4 microgram/ml) effective
against many periodontal pathogens.
Clinical use
1. Refractory periodontitis
2. Localized aggressive periodontitis (LAP)
Specific agents – Tetracycline , Minocycline , Doxycycline are semisynthetic
members of tetracycline group used in periodontal therapy.
Tetracycline HCL
 Administration 250mg 4 times daily (qid)
 Inexpensive, but compliance may be reduced by having to take 4 capsules per day.

4. Side effects:
 GI disturbances
 photosensitivity
 hypersensitivity
 increased blood urea nitrogen(BUN)
 headache
 toothdiscolorationwhenadministered to children under 12 years.
Minocycline
Effective against broad spectrum of micro organisms
• In patients withadultperiodontitis, it suppresses spirochetes and motile rods as effectively as
scalig and root planning.
• Can be given twice daily(bid)
• Administered 200mg/day for 1 week
Reduction in number of bacteria
Complete elimination of spirochetes upto 2 months and
Improvement in all clinical parameters.
Side Effects
 Less renal toxicity
 Less phototoxicity
 Reversible vertigo
 Discolor permanently erupted teeth and gingival
tissue
Doxycycline
Same spectrum of activity as Minocycline.

5.  Can be given once daily(qd)
 Good compliance because it absorption form GI tract is slightly altered by Ca , Metal
ions or antacid.
 Side effects are similar, but is the most photosensitizing agent in this category.
Dosages
• 100 mg bid for 1st day.
• Then 100 mg qd.
• Sub Antimicrobial dose ( to inhibit collagenase) 20 mg twice daily
• To reduce GI upset, 50 mg bid.
METRONIDAZOLE
Pharmacology
 Nitroimidazole compound used to treat Protozoal infections
 Bactericidal to anaerobic organisms
 Effective against
1. P.gingivalis
2. P.intermedia
3. A.Actinomycetemcomitans
When used in combination with other
antibiotic
Clinical USES –
o Gingivitis
o NUG.
o Chronic periodontitis.

6. o Aggressive periodontitis
Doses:
250mg 3 times daily (tid) for a week.
Studies suggested that metronidazole combined with amoxicillin
or amoxicillin- clavulanate potassium (augmentin)
Used for LAP or Refractory Periodontitis
Side effects
 Antabuse effect, when alcohol is ingested (cramp, nausea, vomiting ).Products
containing alcohol should be avoided during & after therapy for at least one day.
 Inhibits warfarin metabolism an anticoagulant drugs.
 Avoided in patients on lithium (psychiatric
treatment).
 Metallic taste in mouth.
 Not recommended as mono-therapy.
PENICILLIN
Pharmacology
 Penicillins are natural and semi synthetic derivatives of broth cultures of the Penicillium
mold.
 β-lactam …Most widely used antibiotic.

7.  Inhibit bacterial cell wall production ie. bactericidal.
Side effect:
 Bacterial resistance
 10% patients may be allergic to penicillin
Amoxicillin
• Semisynthetic penicillin with extended anti-infective
spectrum (G+ve, G-ve)
• Demonstrates excellent absorption after oral
administration.
• Susceptible to penicillinase
Dose: 500mg 3 times/ day(tid) for 8 days.
Uses : for treatment of LAP & GAP.
Augmentin
Augmentin is combination of
Amoxicillin + Clavulanate potassuim.
(resist pencillinase enzyme)
Uses: Management of AP or refractory periodontitis.
(It also arrests alveolar Bone loss by BUENO et al )
Dose : 625mg/ml 3 times per day for 8 days
CEPHALOSPORINS
Pharmacology
 Beta lactam, similar in action and structure to penicillins
 Not used to treat dental infections, because the penicillins are SUPERIOR in action against
Periodontal pathogens

8. Side effect:
• Patients allergic to penicillins must be considered allergic to all beta-lactam products.
• Rashes, urticaria, fever, and GI upset.
CLINDAMYCIN
Pharmacology-
 Effective against anaerobic bacteria & has strong affinity for
osseous tissues.
 Effective in situations in which patient is allergic to penicillin.
Clinical Uses : Refractory Periodontitis
Dose: 300 mg 2 times/day(bid) for 8 days
Side effects: Pseudomembranous colitis.(cramps and diarrhea)
CIPROFLOXACIN
Pharmacology
Quinolone active against G-ve rods , including all facultative and some anaerobic putative
pathogens.

9. Clinical uses
• It has minimal effect on Streptococcus species, which facilitates the establishment of a
microflora associated with periodontal health.
• The only antibiotic that affects all strains of A.actinomycetemcomitans.
• It also used in combination with Metronidazole.
Side effect:
• Nausea , headache and abdominal discomfort.
• Metallic taste
• Inhibit the metabolism of theophylline
(branchodilatotor)and caffeine, concurrent administration
can produce toxicity.
• Enhance warfarin effect and other anticoagulants.
Macrolides
Pharmacology
 Many membered lactone ring to which one or more deoxy sugars are attatched.
 Inhibit protein synthesis by binding to 50S ribosomal subunits of sensitive micro
organisms.
 Bacteriostatic or Bactericidal depending on drug conc. and nature of micro organisms.
 Macrolides used in periodontal therapy include Erythromycin, Spiramycin ,and
Azithromycin.

10. DOSES:250mg/day for 5 days after an initial loading dose of 500mg.

11. Spiramycin
Minimal effect on increasing attatchment levels.
Azithromycin
 Member of the azalide class of macrolides.
 Effective against anaerobes and G-ive bacilli.
 Effective in increasing attatchment levels.
MOA– It penetrates fibroblasts and phagocytes in conc. 100 to
200 times greater than that of extracellular component.
Dosage – 250mg/day for 5 days after an initial leading dose of 500mg
Serial and Combination Antibiotic Therapy

12. Rationale
Periodontitis is a mixed infection
Treatment requires more than one antibiotics
 Before combinations of antibiotics are used , the periodontal pathogens being treated
must be identified and antibiotic susceptibility testing performed.
Clinical Use
 Antibiotics that are bacteriostatic (eg. Tetracycline) generally require rapidly dividing
micro organisms to be effective. They do not function well if a bactericidal antibiotic (eg.
Amoxicillin) is given concurrently.
 When both types of drugs are required , they are best given serially rather than in
combination.
Examples
Metronidazole+amoxicillin excellent elimination of
Metronidazole+Augmentin micro oraganisms in
LAP (+ mechanica debridement)
Metronidazole + Ciprofloxacin powerful in the treatment of Refractory Periodontitis
 Eliminate pathogenic organisms
 keep streptococcal microflora
 A combination of metronidazole and amoxicillin (MA) has shown to be an
effective antibiotic regime to combat Aggregatibacter actinomycetemcomitans
and Porphyromonas gingivalis-associated periodontal infections.
 One important clinical finding in a study by Winkel et al. was the observation that
patients with subgingival P.gingivalis at baseline who were treated with
metronidazole+amoxicillin showed approximately half the number of >5 mm pockets
Dose 500mg BID for 8
days

13. after therapy compared with P. gingivalis positive patients treated with placebo.
Guerreo et al used a comparable treatment protocol in patients with aggressive
periodontitis and showed significantly better improvement of all periodontal
parameters in the antibiotic treated patients compared to placebo treated subjects 6
months post-treatment.
 Metronidazole andclindamycinappeartobe more efficientineradicatingthe anaerobic
periodontopathic bacteria than doxycycline or mechanical therapy alone
 Metronidazole ciprofloxacin combination is effective against A.
actinomycetemcomitans. Metronidazole targets obligate anaerobes, and ciprofloxacin
targetsfacultative anaerobes.Thisisa powerful combination against mixed infections.
Studies of this drug combination in the treatment of refractory periodontitis have
documented marked clinical improvement.
Local Delivery Agents
Indications
 Available as adjunct to scaling and root planing
 Aids in control of growth of bacteria on barrier mambranes.
 When placed in periodontal pockets, reduces subgingival microflora, probing depth and
clinical signs of inflammation.
 Use when probing depth greater than 5mm
 Chlorhexidine has been shown to be an effective agent in plaque inhibition.

14.  Reacting reversibly with receptors in the mouth due to its affinity for hydroxyapatite
and acidic salivary glands.
 Its antibacterial action is due to an increase of the cellular membrane permeability
followed by the coagulation of intracellular cytoplasmic macromolecule.
Subgingival Chlorhexidine
• Available in the form of mouth rinses, gels,
varnishes and chips.
Mechanism of action
• By binding to anionic acid groups on salivary
glycoproteins thus reducing pellicle formation
and plaque colonization.
• By binding to salivary bacteria and interfering with their adsorption of teeth.
PERIOCHIP
• Periochip (4.0 X 5.0 X 0.35mm) composed of a
biodegradable hydrolyzed gelatin matrix, cross
linked with glutaraldehyde also containing
glycerine and water, in which 2.5 mg of
chlorhexidine incorporated per chip.
• Perio chip releases chlorhexidine in vitro in a
biphasic manner.
• Initially releasing approx 40% of chlorhexidine
within 24hrs then remaining in an almost linear
fashion for 7 to 10 days.
Tetracycline Containing Fibers
• Tetracycline fibers applied with or without scaling and root planing reduces-
1. probing depth
2. bleeding on probing

15. 3. periodontal pathogens and
4. provided gains in clinical attachment level.
• Non resorbable, biologically inert, safe plastic copolymer (ethylene &vinyl acetate)
loaded with 25% w/w tetracycline HCl powder packed as thread of 0.5mm diameter &
23cm length
• It maintains constant concentrations of active drug in the crevicular fluid in excess of
1300 μg/mL for a period of 10 days.
Subgingival Minocycline
 A bacteriostatic antibiotic has been tried clinically via in three different modes i.e. film,
microspheres, and ointment.
Film:
 Ethyl cellulose film containing 30% of
Minocycline were tested as
 sustained release
 complete eradication of pathogenic flora
from the pocket after
 14 days
Microsphere:
 A new, locally delivered, sustained release
form of minocycline microspheres
(ARESTIN) for subgingival placement is
available.
 The 2% minocycline is encapsulated into bioresorbable microspheres (20-60 μm in
diameter) in a gel carrier and has resorption time of 21 days.
 Gingival crevicular fluid hydrolyses the polymer and releases minocycline for a period of
14 days or longer before resorbing completely.

16. Subgingival Doxycycline
• Doxycycline is a bacteriostatic agent
• Has the ability to down regulate MMP’s .
• The only ADA approved 10% Doxycycline in a
gel system ATRIDOX (42.5 mg Doxycycline) is
a Subgingival controlled release product
composed of a 2 syringe mixing system.
• Doxycycline levels in GCF peaked to 1,500 -
2000 μg/ml in 2 hours following treatment
with ATRIDOX.
• Local levels of Doxycycline have been found to remain well above the MIC for
periodontal pathogens (6.0μg/ml) through Day 7.
• 95% of the polymer is bio absorbed or expelled from the pocket naturally within 28
days.
• Locally applied controlled release DOX gel may partly counteract the negative effect of
smoking on periodontal healing following no surgical therapy
Subgingival Metronidazole
• Elyzol 25%
• Metronidazole concentrations of above100
μ/ml were measurable in the periodontal
pocket for at least 8 hours and concentrations
above 1 μ/ml were found at 36 hours.
• Applied in viscous consistency to the pocket,
where it is liquidized by the body heat and
then hardens again, forming crystals in contact
with water.
There were no statistically significant differences between the
groups.
Ointment
 2% minocycline hydrochloride in a matrix of hydroxyethyl-
cellulose, amino alkyl- methacrylate, triacetine & glycerine.

17.  DENTOMYCIN –european union
 PERIOCLINE –JAPAN
 The concentration of minocycline in the periodontal pocket is about 1300μg/ml, 1 hr
after single topical application of 0.05 ml ointment (1mg of minocycline) and is reduced
to 90μg/ml after 7 hrs
SUMMARY
Misuse or overuse of prophylactic anti infective agent
Increase bacterial resistance
USELESS

18. Conclusion
Scaling and root planig alone are effective for reducing pocket depths, gaining increases in
periodontal attatchment levels and decreasing inflammation levels. When scaling and root
planning are combined with the subgingival placement of sustained release vehicles, additional
clinical benefits are possible including further reduction of pockets, additional gains in clinical
attatchment levels and further decrease in inflammation.
REFERENCES :
Carranza’s Clinical Periodontology