ROLE OF ANTIBIOTICS IN PERIODONTAL THERAPY

DR. USHA.

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Contents

Various definitions Guidelines for use of antimicrobial therapy Indications of antibiotics Antibiotics used in periodontics Combination & serial therapy Local drug delivery system conclusion

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Various definitions

Chemotherapeutic agent : is a general term for a chemical substance that provides a clinical therapeutic benefit.

Anti-infective agent : is a chemotherapeutic agent that works by reducing the number of bacteria present.

Antibiotic : is a naturally occurring, semi synthetic, or synthetic type of anti infective agent that destroys or inhibits the growth of selective microorganisms, generally at low concentration 3

Guidelines for use of antimicrobial therapy

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Indications for Antibiotic Therapy

• Acute infections• Aggressive (early onset) forms ofperiodontitis• Recurrent (“refractory”) periodontitis

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Aggressive Periodontitis: Antibiotics Indicated

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Microorganisms Associated With Localized Aggressive Periodontitis

• Actinobacillus actinomycetemcomitans• Eikenella corrodens• Fusobacterium nucleatum

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Recurrent (refractory) Periodontitis: Antibiotics often indicated

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Microorganisms Associated WithRecurrent (“Refractory”) Periodontitis

• Porphyromonas gingivalis• Prevotella intermedia• Bacteroides forsythus• Treponema denticola• Eikenella corrodens• Campylobacter rectus• Fusobacterium nucleatum

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Acute Necrotizing Ulcerative Gingivitis: Antibiotics may be indicated

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Periodontal Abscess: Antibiotics may be indicated

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Chronic periodontitis is rarelytreated with antibiotics

• Scaling and root planing eliminates most speciesof subgingival bacteria associated with chronicperiodontitis• Host defense mechanisms are usually effective atcontrolling infections

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Key Pathogens

• Actinobacillus actinomycetemcomitans• Porphyromonas gingivalis• Prevotella intermedia• Bacteroides forsythus

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Requirements for EffectiveAntimicrobial Chemotherapy

• The drug must reach the site of action

• The drug’s concentration at the site of action must be sufficient to inhibit bacteria

• The duration of chemotherapy must be sufficient to allow the drug to act

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To inhibit subgingival bacteria, an antimicrobial agent must beable to reach the base of the periodontal pocket. Since somepathogens invade the soft tissue wall of the pocket, it is useful ifthe antibiotic can also reach this site.

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Systemic Antibiotics

• May have narrow or broad spectrumantimicrobial activity• Can potentially reach the pocket and its softtissue wall• Can potentially attain inhibitory levels inthe pocket• Can potentially be retained for an adequateduration

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MECHANISM OF ACTION

1. Inhibit cell wall synthesis

2. Cause leakage from cell membrane

3. Inhibit protein synthesis

4. Inhibit DNA gyrase

5. Cause misreading of m-RNA code and affect permeability.

6. Interfere with DNA function

7. Interfere with DNA synthesis, etc.

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Antibiotics Used in PeriodontalTherapy

Penicillins (e.g., amoxicillin Tetracyclines (e.g., doxycycline) Metronidazole Fluoroquinolones (e.g., ciprofloxacin) Clindamycin Erythromycin Azithromycin

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Penicillins

Bactericidal Reach effective levels in gingival fluid Don’t inhibit all A.a. Strains Inactivated by ß-lactamases Amoxicillin has enhanced tissue penetration and good activity against gram negatives Augmentin is as effective as amoxicillin, but resists inactivation by ß-lactamases

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Penicillins inhibit bacterial cell-wall synthesis,and the antimicrobial spectrum of natural penicillinsis narrow.

Amoxicillin is a semi-synthetic penicillin with broadened antimicrobial spectrum, and is used in periodontology because it is effective against some subgingival bacterial species such as P. micros and A. actinomycetemcomitans as well.

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It can be used in cases of acute infections, although it is most commonly used in combination with metronidazole.

Amoxicillin in combination with clavulonic acid isindicated in the presence of oral bacteria capableof producing β-lactamase

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Tetracyclines

Tetracyclines are a group of broad spectrum, bacteriostatic antibiotics. They are the first antimicrobial drugs which have been scientifically investigated in periodontology.

This group includes tetracycline hydrochloride, minocycline and doxycycline.

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Frequently used in treatment of refractory periodontitis including localised aggressive periodontitis.

Concentrate in periodontal tissues & inhibit the growth of a.a.

Also exert anticollagenase effect .

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Pharmacology – Obtained naturally from streptomyces sps. or

derived semisynthetically. More effective against gram +ve than gram -

ve bacteria. Their conc. in gingival crevice is 2 to 10 times

more than in serum.

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Specific agents

Tetracycline – Dose 250 mg four times daily (qid). Inexpensive but less patient compliance.

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Minocycline – Broad spectrum of activity. Dose 200 mg/day Given twice daily (bid) so better patient

compliance. Less side effects than tetracycline More efffective against spirochetes and

motile rods.

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Doxycycline – Same spectrum of activity as minocycline Given once daily so more patient compliance Dose as an anti infective agent is 100mg bid

the first day, then 100mg qd. as subantimicrobial dose ( to inhibit

collagenase) 20mg twice daily.

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Side effects LIVER DAMAGE KIDNEY DAMAGE PHOTOTOXICITY CHELATING EFFECTS-TEETH & BONES HYPERSENSITIVITY SUPER INFECTIONS

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Metronidazole

Metronidazole is a synthetic nitroimidazole.

Its action is bactericidal, acting on anaerobic bacteria, including gram- negative rods and spirochetes, through DNA synthesis blocking. Due to the susceptibility of the spirochetes, it is effective in cases of necrotising periodontal diseases.

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It seems relatively ineffective in the suppression of A. actinomycetemcomitans.

Periodontal abscesses can be successfuly treated with metronidazole, while for aggressive periodontitis treatment its antimicrobial spectrum is not wide enough

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Dose- 250mg/TDS/Oral FLAGYL,METROGYL

ADVERSE EFFECTS

ANOREXIA,NAUSEA,ABDOMINAL CRAMPSMETALLIC TASTEHEADACHE, GLOSSITIS,DRYNESS OF MOUTH

CONTRAINDICATION

IN NEUROLOGICAL DISEASE,Ist TRIMESTER OF PREGANANCY, CHRONIC ALCOHOLISM

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Fluoroquinolones (Ciprofloxacin)

It is a quinolone active against gram –ve rods.

Bactericidal

Extremely active against A.a., but less active against anaerobic bacteria

Reach higher levels in gingival fluid than in blood serum Penetrate epithelial cells-can kill invasive bacteria

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Ciprofloxacin is also effective in the treatment of periodontal superinfections caused by enteric bacteria, pseudomonas or staphylococci.

Another positive aspect is its inactivity towards streptococci, whose presence in the subgingival area is associated with periodontal health. Heightened streptococcal counts can postpone recolonisation of the pathogenic bacterial species.

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CiprofloxacinCIFRAN,CIPLOX-200,500mg tab

Side effects – GASTROINTESTINAL CNS EFFECTS HYPERSENSITIVITY REACTION

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Clindamycin

• Potent bacteriostatic activity against strictanaerobes• Less effective against facultative pathogens(A.a. and Eikenella)• Can induce ulcerative colitis• Often used as an alternative antimicrobialagent in penicillin-allergic patients

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DOSE150-300mg QID ORAL,200-600mg IV.8 HRLYDALCAP-150mg Cap

SIDE EFFECTS - RASHES URTICARIA ABDOMINAL PAIN PSEUDOMEMBRANOUS

ENTROCOLITIS

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Erythromycin

• Doesn’t reach effective concentrations ingingival fluid• Weak activity against A.a., Eikenella andFusobacterium

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Azithromycin

Azithromycin is an antibiotic from the macrolide group. it exerts bacteriostatic activity by blocking of bacterial proteins synthesis.

The spectrum is broad and covers gram-negative bacteria, including enteric bacteria.

Has good activity against A.a. and Eikenella and good activity against P. gingivalis and many other gram-negative anaerobes

Penetrates epithelial cells-can kill invasive bacteria38

Assessment of availability in periodontal tissues showed extremely high values in periodontal tissues, crevicular fluid and saliva.

Periodontally inflamed tissues exhibit concentrations significantly higher than healthy periodontal tissues, which is a very convenient characteristic of this antibiotic. Data from clinical investigations support the use of azithromycin in the treatment of advanced chronic, or aggressive periodontitis .

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Dose – therapeutic use requires a single dose of 250 mg/day for 5 days after an initial loading dose of 500mg.

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Deciding Which Antibiotic to Use

• Can use empirical approach

• Can identify pathogens at the site with culture or DNA probes, then prescribe an antibiotic that will presumably inhibit them

• Can culture isolated bacteria to identify them and determine their susceptibility to antibiotics

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Approaches for identifying periodontal bacteria

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Darkfield microscopy

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Bacterial culture

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Sampling deepest pockets with a paper point

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Systemic Antibiotic Regimens for Treating Aggressive and Recurrent Periodontitis

• Tetracycline HCl (250 mg QID) for 21 days (one of the oldest regimens)

• Amoxicillin (500 mg TID) and metronidazole (250 mg TID) for 8 days (most commonly prescribed-more effective than a single agent)

• Metronidazole (500 mg BID) and ciprofloxacin (500 mg BID) for 8 days (usually very effective for mixed infections)

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Limitations of Systemic Antibiotics in Periodontics

• Antibiotics rarely enhance the treatment of chronicperiodontitis• To eliminate bacteria in biofilms effectively,antibiotics must be used in conjunction withmechanical debridement• No single antibiotic can inhibit all periodontalpathogens• Antibiotics can have undesirable side effects whengiven systemically

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Adverse Side Effects AssociatedWith Systemic Antibiotics

• Induction of antibiotic resistance• Induction of microbial overgrowth• Inhibition of oral contraceptives (rare)• Hypersensitivity or toxicity (e.g., allergy,nausea, diarrhea, photosensitivity)

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Combined and serial antibiotic therapy

Subgingival microflora in periodontal diseases includes different pathogenic bacteria possessing differential sensitivity to antimicrobials, so the use of two or more antibiotics presents a useful option in the treatment of these diseases. The advantages of combined antibiotic therapy are broadened spectrum of antimicrobial activity, occurence of synergistic activity and prevention of bacterial resistance development.

Disadvantages of such a treatment are elevated incidence of adverse effects.

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Metronidazole in combination with amoxicillin or ciprofloxacin has been successfuly used in the treatment of advanced periodontitis, especially infections with A. actinomycetemcomitans .

Metronidazole and amoxicillin in vitro act synergistically on A. actinomycetemcomitans.

Combination of metronidazole with amoxicillin or amoxicillin and clavulonic acid can eliminate A. actinomyctemcomitans and other periodontal pathogens from the periodontal pockets for at least two years

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Metronidazole and ciprofloxacin can be effective in mixed periodontal infections, such as the presence of anaerobes, A. actinomycetemcomitans, enteric bacteriaand pseudomonades.

As this combination is ineffective against most gram-positive, facultative anaerobic bacteria, it can facilitate streptococcal colonisation of the pockets which have no periodontally pathogenic potential

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Serial use of antibiotics is indicated for a combination of antibiotics, in which one has bactericidal and the other bacteriostatic activity.

Combined administration would lead to antagonistic effects and therapeuticalfailure. This form of systemic antimicrobial therapy should be used in especially severe cases of recurrent or refractory periodontitis, where attachment loss was not arrested despite careful initial therapy, or in cases of disease reactivation during the supportive phase of therapy, occurring despite good oral hygiene and repeated mechanical subgingival instrumentation.

One of the combinations effective in the prevention of recurrent periodontitis in highrisk individuals is doxycycline and metronidazole

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Local delivery of antibiotics

Advantages Higher local drug concentrations Sustained therapeutic drug levels

(independent of patient compliance) Effective drug levels can be attained at sites

that are difficult to reach Adverse side effects are minimized

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Tetracycline –containing fibers(Actisite)

An ethylene/ vinyl acetate copolymer fiber (diameter, 0.5mm) containing tetracycline, 12.7mg per 9 inches.

For 10 days it sustained tetracycline conc. exceeding 1300 microgram/ml, well beyond the 32 to 64 microgram/ml required to inhibit pathogens.

In contrast GCF conc. of only 4-8 microgram/ml were reported after systemic administration, 250 mg qid for 10 days.

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Placement of Actisite fiber

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Subgingival doxycycline(Atridox)

The FDA approved 10% doxycycline in a gel system using a syringe ( Atridox) .

It is the only local delivery system accepted by ADA.

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Placement of atridox

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Sub gingival minocycline

The FDA recently approved a new, locally delivered, sustained release form of minocycline microspheres ( Arestin)

2% minocycline is encapsulated into bioresorbable microspheres in a gel carrier.

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Minocycline syringable gel

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Sub gingival metronidazole

A topical medication containing an oil based metronidazole 25% gel is used.

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Conclusion

Antimicrobial therapy is indicated in cases of disease where the periodontaldestruction continued, despite thoroughly performed mechanical therapy. In patients from high-risk groups, such as aggressive forms of periodontitis or periodontitis as a manifestation of systemic disease, the use of antibiotics is indicated as an adjunct to scaling and root planing. Antibiotics are never indicated in the treatment of chronic gingivitis.

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References : -

Carranza’s Clinical Periodontology 10th ediion.

www.google.com

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