CHEMOTHERAPEUTICS:

SYSTEMIC AND TOPICAL USE AS AN

ADJUNCT TO THERAPY

Beatriz Bezerra, DDS, PhD

University of Rochester
Eastman Institute for Oral

Management of Periodontal
Diseases
Patient education in the etiology of periodontal
disease and self-performed plaque control
Trainingin the use of plaque control devices and aids
Scaling and root planing
Periodontal surgery
Pharmacotherapy
Combination of methods

Goals of
Chemotherapeutics
Chemotherapeutic agent: A chemical substance that provides
a clinical therapeutic benefit.
Reduce/eliminate pathogens
Alter disease progression
Repair/regenerate periodontium

Chemotherapeutics
o Oral rinses
o Systemic antibiotics
o Local drug delivery

Chlorhexidine
Broad spectrum antimicrobial activity
o Binds cell walls and alters osmotic equilibrium
o Bactericidal
o Effective against Gram positive, Gram negative
and Yeast organisms
o High substantivity
o Binds to plaque, oral mucosa, and restorations
o Major effect lasts up to 12 hrs

Chlorhexidine
Low toxicity
Side effects
o Staining of soft tissue, teeth and restorations
o Altered taste sensation

Chlorhexidine
Twice daily rinse with 10 ml 0.2% CHX for 1 min results in
complete plaque elimination.
Loe et. al. 1970
Significant plaque (33%) and gingivitis (26%) reduction
CHX+Plaque control vs Plaque control alone.
Van Strydonck et al. 2012
However, due to taste alterations and staining, as well as a
lack of long term studies not recommended for daily use.
Greenstein et. al. 1986

Phenolics/Essential Oils
Listerine
Thymol, menthol, eucalyptol, and methyl salicylate in
an alcohol carrier
o Alters bacterial cell wall causing lysis
o 25-35% Reduction in gingivitis
o 20-35% reduction in plaque

Cetylpyridinium Chloride
Crest Pro-Health, Colgate Total, ACT Advanced Care
o Alters bacterial cell wall causing lysis
o Effective at reducing plaque and gingivitis
oTooth staining

Which rinse do we
recommend?
o No differences in anti-plaque and anti-gingivitis benefits of Crest Pro-Health
and Listerine mouth rinses over a 6-month period
Albert-Kiszely et al 2007
o CHX was significantly better at reducing plaque accumulation than EOMW in
short-and long-term studies. Staining and calculus accumulation were greater
among CHX users compared to EOMW. CHX and EOMW were not different with
respect to long-term control of gingival inflammation. CHX remains the first
choice when plaque control is the focus of therapy.
Neely 2012

Which rinse do we
recommend?

Essential oil rinses (listerine) are effective but to a lesser degree than
chlorhexidine. Advantageous because they have fewer side effects and are
available without a prescription.

Interproximal plaque
control?
OR

Which rinse do we
recommend?
Caton et al 1993
o 3 month study
o Compared 3 groups:
o 1: toothbrushing + CHX vs
o 2: toothbrushing + stim-u-dent vs
o 3: toothbrushing alone

o Showed that only mechanical interdental plaque

removal + toothbrushing is effective at reducing or
preventing inflammation at interdental sites

When to recommend?

Answer: When mechanical removal is not possible (ie: acute gingivitis, post-op
surgery) or as an adjunct to initial therapy.

QUESTIONS ?

Antibiotics

Systemic
ProsAntibiotics
o Reach the base of the pocket
o Penetrate tissue
o Several different drugs available
for use

Cons
o May have adverse systemic
response
o Bacterial resistance
o Opportunistic infections

o Ease of use/delivery

vs Local antibiotics
Pros
oHigh concentrations at base of the
pocket, with low systemic effects
oSeveral different drugs available
for use

Cons
o

Delivery more difficult than

systemic

Systemic Antibiotics
Indications:
o Active Infection
o Patients who didnt respond to initial therapy
o Regenerative therapy

Systemic Antibiotics
Penicillin VK
o Inhibits cell wall synthesis
o Indicated for acute infections
o High incidence of allergic reaction and increase
number of bacteria presenting resistance

Systemic Antibiotics
Amoxicillin
o Inhibits cell wall synthesis (broader spectrum)
o Indicated for acute infections
o High incidence of allergic reaction
Augmentin (Amoxicillin/clavulanic acid)
o Effective against beta-lactamase producing
microorganisms
o Still incidence of allergic reaction
o Rarely used for perio management

Systemic Antibiotics
Clindamycin
o Inhibits protein synthesis
o Effective against anaerobic bacteria
o Risk of pseudomembranous colitis (C.
difficile)

Systemic Antibiotics
Tetracycline
o Broad spectrum antibiotic
o Bacteriostatic
o Inhibits bacterial protein synthesis
o Regenerative procedures
Tetracycline contraindications:
o Children under 8 years old
o Hepatic or renal disease

Systemic Antibiotics
Chemically modified Tetracyclines
o Minocycline and Doxycycline
o Antibiotic and anticollagenase activity (MMPs)
o Same spectrum of activity as tetracycline
o Lower dosing (100mg QD) achieves equal antibiotic
concentration in the GCF
o Higher patient compliance

Systemic Antibiotics
Metronidazole
o Mechanism of action: DNA degradation within the
organism
o Bactericidal
o Metronidazole could be used in combination with
other antibiotics for aggressive periodontitis
o Avoid consumption of alcohol!

Systemic Antibiotics
Ciprofloxacin
o Inhibits DNA gyrase
o Broad spectrum bactericidal agent
o Some indication for refractory cases
o Promotes periodontal pocket repopulation by
streptococci which are non-periodontopathic
Slots et al., 1990

Systemic Antibiotics
Azythromycin
o Bacteriostatic - Inhibits protein synthesis
o Effective against anaerobes and gram-negative bacilli
o Reaches high concentrations in inflamed periodontal
tissues
o Zithromax: 2 stat, then one tablet QD for 3 days

Systemic Antibiotics
Low Dose Doxycycline
Periostat
o Long term, low dose Doxycycline
o 20mg 2X day for 3 months or more
o Only effect is through anticollagenase activity
o Not antimicrobial: Subantimicrobial Dose
Doxycycline

Systemic Antibiotics
Low Dose Doxycycline
Indications:
o Continuous or recurrent breakdown despite good plaque
control and mechanical and/or surgical therapy
o Does this work? (Caton et al., 2000)
o 4-6mm: the PD reduction was 0.26mm greater than
placebo at 9 months (34-38% greater)
o >7mm: the PD reduction was 0.48mm greater than
placebo at 9 months (40-67% greater)

Summary of Systemic Antibiotic

Rx

Slots et al., 2004

Local Antibiotics Sustained release

devices
Local delivery
High concentrations at the base of the
pocket
Substantivity
Overall low dosage systemically

Local Drug Delivery

Subgingival placement
o Doxycycline (Atridox)
o Chlorhexidine (PerioChip)
o Minocycline Microspheres (Arestin)

Local Drug Delivery: Indications

Patients that do not respond to non-surgical therapy
Patients not interested in- or not a candidate for
periodontal surgery
Post surgical isolated sites

Atridox
10% Doxycycline in bioresorbable polymer
Sustained-release over 21 days
As effective as SRP alone at sites >5mm over a 9
month period in patient under SPT
1.3mm PD reduction and 0.9mm clinical attachment
gain
It was applied at baseline and 4 months

Garrett et al. 2000

PerioChip
2.5mg Chlorhexidine in biodegradable
matrix of hydrolyzed gelatin
Sustained release over 10 days
Combined therapy had a better
probing depth reduction (0.95 vs.
0.64mm)
Combined therapy had a better gain in
clinical attachment (0.75 vs. .51mm)
It was applied multiple times
Is this clinically significant???

Arestin
1mg Minocycline HCL in bioresorbable polymer
Drug is encapsulated in microspheres which completely dissolve
over 28 days
Arestin placed at sites with >5mm PD
Over 9 months there were statistically significant PD reductions
over SRP alone:1.32mm vs. 1.08mm
It was applied 3x

Williams, 2001

Arestin

AAP Statement
Insufficient data to conclude that LDA can reduce need for surgery or
improve long-term tooth retention
Recommendations:
Localized residual pockets >5mm
Decision should be based on:
Clinical findings, dental and medical hx, patients preferences

Conclusions
Chemotherapeutic rinses serve an important part in plaque reduction
post-surgically when the patient should not perform plaque removal at
the site of surgery.
There is no evidence to support the use of antibiotics as a monotherapy
to treat periodontal disease.
Antibiotics, systemic and local delivery, could decrease probing depths
and increase attachment levels to an extent when sites do not respond
to conventional therapy.
The AAP position paper indicates that antibiotics might be a useful
adjunct to treat periodontal disease, however it has not been determined
which antibiotic should be used, the optimum dosage to use, or for how
long it should be used.

Conclusions
Antimicrobials andantibiotics, whether administered topically or
systemically to a healthy patient, should be limited to the following
situations:
1. Appropriate treatment of acute periodontal infections
2. Adjunct to improve the clinical attachment level and/or long term tooth
retention potential when compared to conventional treatment alone

Questions?