Role of Antibiotics in Periodontal Therapy

Dentistry 664 Textbook: Chapter 23 (pp 494-511)

Aggressive Periodontitis: Antibiotics Indicated

Recurrent (refractory) Periodontitis: Antibiotics often indicated

Acute Necrotizing Ulcerative Gingivitis: Antibiotics may be indicated

Periodontal Abscess: Antibiotics may be indicated

Chronic periodontitis is rarely treated with antibiotics

Scaling and root planing eliminates most species of subgingival bacteria associated with chronic periodontitis Host defense mechanisms are usually effective at controlling infections Controlled clinical trials show little or no statistical evidence that antibiotics significantly enhance the reduction of probing depths by SRP

Indications for Antibiotic Therapy

Acute infections Aggressive (early onset) forms of periodontitis Recurrent (refractory) periodontitis

Requirements for Effective Antimicrobial Chemotherapy

The drug must reach the site of action The drugs 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

To inhibit subgingival bacteria, an antimicrobial agent must be able to reach the base of the periodontal pocket. Since some pathogens invade the soft tissue wall of the pocket, it is useful if the antibiotic can also reach this site.

Stratification of subgingival plaque biofilm. Bacteria in biofilm can be difficult to kill with antibiotics

Antimicrobial mouthrinses
Possess broad spectrum antimicrobial activity Do not attain adequate concentrations at the base of the periodontal pocket Are not retained for an adequate duration

Systemic Antibiotics
May have narrow or broad spectrum antimicrobial activity Can potentially reach the pocket and its soft tissue wall Can potentially attain inhibitory levels in the pocket Can potentially be retained for an adequate duration

Mechanisms of Antibiotic Action

Microorganisms Associated With Localized Aggressive Periodontitis

Actinobacillus actinomycetemcomitans Eikenella corrodens Fusobacterium nucleatum

Microorganisms Associated With Recurrent (Refractory) Periodontitis

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

Key Pathogens
Actinobacillus actinomycetemcomitans Porphyromonas gingivalis Prevotella intermedia Bacteroides forsythus

Antibiotics Used in Periodontal Therapy

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

Penicillins
Bactericidal Reach effective levels in gingival fluid Dont inhibit all A.a. Strains Inactivated by -lactamases Amoxicillin has enhanced tissue penetration and good activity against gram negatives Augmentin is as effective as amoxicillin, but resists inactivation by -lactamases

Metronidazole
Bacteriocidal activity against strict anaerobes Less active against facultative pathogens (A.a. and Eikenella corrodens)

Tetracyclines
Have bacteriostatic activity against most periodontal pathogens. Can reach higher levels in gingival fluid than in blood serum. Inhibit collagenase, which mediates collagen breakdown in inflammatory disease.

Doxycycline levels are less variable in gingival crevicular fluid than in blood serum
3
serum level GCF level

[doxycycline] in g/ml

1 48 50 52 54 56 58 60

hours after initial dose of doxycycline

Fluoroquinolones (Ciprofloxacin)
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

At steady-state, the levels of systemically-administered doxycycline and ciprofloxacin are higher in gingival connective tissue (GCT) and gingival fluid (GCF) than in serum.

3.0

*
concentration, g/ml
2.5

serum (in g/ml) GCT (in g/g) GCF (in g/ml)

*
2.0

* *

1.5

1.0

0.5

0.0

Doxycycline

Ciprofloxacin

Clindamycin
Potent bacteriostatic activity against strict anaerobes Less effective against facultative pathogens (A.a. and Eikenella) Can induce ulcerative colitis Often used as an alternative antimicrobial agent in penicillin-allergic patients

Erythromycin
Doesnt reach effective concentrations in gingival fluid Weak activity against A.a., Eikenella and Fusobacterium

Azithromycin
Macrolide derivative related to erythromycin Has better tissue distribution and longer half-life than erythromycin Has good activity against A.a. and Eikenella. Has good activity against P. gingivalis and many other gram-negative anaerobes Penetrates epithelial cells-can kill invasive bacteria

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

Approaches for identifying periodontal bacteria

Darkfield microscopy

Bacterial culture

Advantages of Culturing Techniques

Reflects viable bacteria in the pocket Can assess the predominance of a particular bacterial pathogen Can grow and study unusual bacteria Facilitates determination of antibiotic susceptibility

Disadvantages of Culturing Techniques

Very costly Very time consuming Problems with transport to the lab Difficult to grow some organisms (e.g., spirochetes) Accuracy dependent on good sampling technique Not very sensitive

DNA Probe Tests for Microbial Evaluation

Permits reliable detection of specific pathogens in subgingival plaque specimens Available as a reference laboratory service

Sampling deepest pockets with a paper point

Laboratory processing of bacterial samples with DNA probes

DMDx test vs micro-Dent test

A.a. P. gingivalis P. intermedia B. forsythus F. nucleatum E. corrodens C. rectus T. denticola A. a. P. gingivalis P. intermedia B. forsythus T. denticola

Advantages of DNA Probe Tests

Plaque specimens are easy to collect. Plaque collection is noninvasive. Tests are specific for A.a., P.g., P.i., F.n. and C.r. More sensitive than culture methods. Tests quantify bacteria at physiologically relevant ranges. Tests require DNA, not live cells.

How to best use microbiological tests?

Complete initial periodontal therapy before testing. Assess the response to initial therapy. If not ideal, sample deepest pockets and test for presence of pathogens with DNA probes. Prescribe an antimicrobial regimen that is active against pathogens identified by test.

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)

Limitations of Systemic Antibiotics in Periodontics

Antibiotics rarely enhance the treatment of chronic periodontitis To eliminate bacteria in biofilms effectively, antibiotics must be used in conjunction with mechanical debridement No single antibiotic can inhibit all periodontal pathogens Antibiotics can have undesirable side effects when given systemically

Adverse Side Effects Associated With Systemic Antibiotics

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

Local antibiotic delivery into pockets avoids adverse side effects

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