11/1/2022

Anti-infective Therapy

Division of Periodontology
College of Dentistry

Outline
• Definition
• Systemic Administration Of Antibiotics
• Serial And Combination Antibiotic Therapy
• Local Delivery Agents

1
 11/1/2022

Definition
➢ Anti-infective agent is a chemotherapeutic agent that acts by
reducing the number of bacteria present

➢ It can be administered locally or orally

SYSTEMIC ADMINISTRATION
OF ANTIBIOTICS
➢ Most effective agent should be selected using antibiotic-
sensitivity tests

Ideal antibiotic should be;

▪ Specific for periodontal pathogens

▪ Nontoxic
▪ Inexpensive

2
 11/1/2022

➢ Currently, an ideal antibiotic for the treatment of periodontal diseases

does not exist

3
 11/1/2022

Treatment of The Individual Patient

Treatment of the individual patient must be based on;

▪ Patient’s clinical status
▪ Nature of the colonizing bacteria
▪ Ability of the agent to reach the site of infection
▪ The risks and benefits associated with the treatment plan

Some adverse reactions include;

▪ Anaphylactic reactions
▪ Superinfections of opportunistic bacteria
▪ Development of resistant bacteria
▪ Interactions with other medications
▪ Stomach upset, nausea, and vomiting

Tetracyclines
Clinical use :
➢ Refractory periodontitis, LAP (Grade C)
➢ Systemic tetracycline can eliminate tissue bacteria and arrest bone
loss
➢ Inhibit the growth of AA (A. Actinomycetemcomitans)
➢ Exert an anticollagenase effect that can inhibit tissue destruction
and may aid bone regeneration

Pharmacology:
➢ These antibiotics are bacteriostatic and are effective against
rapidly multiplying bacteria
➢ Effective against gram-positive than gram-negative bacteria
➢ Concentration in the GCF is 2 to 10 times that in serum

4
 11/1/2022

Tetracyclines Cont.
➢ Because of increased resistance to tetracyclines;

▪ Metronidazole or amoxicillin with metronidazole has

been found more effective;
✓ In treating aggressive periodontitis(Grade C) in
children

▪ Metronidazole combined with amoxicillin–clavulanic acid

is the preferable antibiotic

Specific Agents
Tetracycline : Tetracycline HCL
➢ Inexpensive
➢ Compliance is reduced (Because have to take 250 mg 4 cap /day – 7
days)

Side effects :
➢ Gastrointestinal (GI) disturbances, Photosensitivity,
Hypersensitivity, Blood dyscrasias, dizziness, headache
➢ Increased blood urea nitrogen (BUN)

➢ Tooth discoloration occurs, when administered to children who are

12 years old or younger

10

5
 11/1/2022

Minocycline
Use: Effective against a broad spectrum of microorganisms

➢ Minocycline – 100 mg /twice daily for 1 week;

▪ Results in a reduction in total bacterial counts

➢ There is complete elimination of spirochetes for up to 2 months;

▪ There is improvement of all clinical parameters

11

Minocycline Cont.

Side Effects;

➢ Similar to those of tetracycline HCL

➢ Less phototoxicity and renal toxicity than tetracycline
➢ It may cause reversible vertigo

➢ It is the only tetracyline that can discolor;

▪ Permanently erupted teeth and gingival tissue when
administered orally

12

6
 11/1/2022

Doxycycline
Use: Effective against a broad spectrum of microorganisms;

➢ Because doxycycline can be given only once daily, patients may be

more compliant

Doxycycline - Dosage
200 mg / first day( 2 tablets)
Then 100 mg /daily ( 1 tablet)

13

Doxycycline Cont.
Sub- antimicrobial dose to inhibit collagenase; 20-mg dose twice daily
(periostat)
➢ Prevent the destruction of the periodontal attachment by;

▪ Controlling the activation of matrix metalloproteinases,

primarily collagenase and gelatinase

▪ From both infiltrating cells and resident cells of the

periodontium, primarily the neutrophils

Side effects;
➢ Similar to those of tetracycline HCL
➢ It is the most photosensitizing agent in the tetracycline category

14

7
 11/1/2022

Metronidazole
Pharmacology:

➢ Disrupt bacterial DNA synthesis

➢ Bactericidal to anaerobic organisms

➢ Effective against with P. gingivalis and P. intermedia

➢ Effective against A. Actinomycetemcomitans;

▪ When used in combination with other antibiotics

15

Metronidazole Cont.
Clinical Use
Used to treat
➢ Gingivitis, NG, Periodontitis, Aggressive periodontitis(Grade C)

➢ Used as monotherapy and also in combination with both;

▪ Root planing and surgery or with other antibiotics

➢ Used in combination with augmentin for patients with Grade C

Periodontitis or refractory periodontitis

16

8
 11/1/2022

Metronidazole Cont.

Side Effects:

➢ It has an antabuse effect when alcohol is ingested, result in severe

cramps, nausea, and vomiting

➢ Products containing alcohol should be avoided during therapy;

▪ For at least 1 day after therapy is discontinued

➢ Inhibits warfarin metabolism

17

Metronidazole Cont.

➢ Patients undergoing anticoagulant therapy;

▪ Should avoid metronidazole because it prolongs
prothrombin time

➢ Avoided in patients who are taking lithium;

▪ Produces a metallic taste in the mouth, which may affect

compliance

18

9
 11/1/2022

Penicillins
Pharmacology:
➢ Penicillins are natural and semisynthetic derivatives

➢ They inhibit bacterial cell wall production and therefore are

bactericidal

Side Effects:
➢ Allergic reactions
➢ Bacterial resistance

19

Penicillins Cont.
1) Amoxicillin: Used for;
➢ Gram-positive and gram-negative bacteria
➢ Aggressive periodontitis, in both Localized and generalized forms

➢ Amoxicillin is susceptible to penicillinase, a β-lactamase produced

by certain bacteria;
▪ That breaks the penicillin ring structure and thus renders
penicillins ineffective

2) Amoxicillin–Clavulanate Potassium (Augmentin)

➢ Resistant to penicillinase enzymes produced by some bacteria
➢ Useful in LAP or refractory periodontitis

20

10
 11/1/2022

Clindamycin
Pharmacology:
➢ Effective against anaerobic bacteria
➢ Has a strong affinity for osseous tissue
➢ Effective in patients who are allergic to penicillin

Clinical Use: In patients with periodontitis refractory to tetracycline

therapy

Side Effects:
➢ Pseudomembranous colitis
➢ Diarrhea or cramping

21

Ciprofloxacin
Pharmacology:
➢ Active against gram-negative rods;
▪ Including all facultative and some anaerobic, putative
periodontal pathogens
➢ All strains of A. Actinomycetemcomitans are susceptible

Clinical Use:
➢ Used in combination with metronidazole
➢ Demonstrates minimal effect on streptococcus species;
▪ Which are associated with periodontal health

22

11
 11/1/2022

Ciprofloxacin Cont.
Side Effects:

➢ Nausea, headache, metallic taste in the mouth

➢ Abdominal discomfort
➢ Inhibit the metabolism of theophylline, caffeine
➢ Enhance the effect of warfarin and other anticoagulants

23

Macrolides
Pharmacology :

➢Bacteriostatic or bactericidal depending on the concentration of the

drug and the nature of the microorganism

➢ Macrolide Derivatives: Erythromycin, spiramycin, and

azithromycin

24

12
 11/1/2022

Macrolides Cont.
➢ Erythromycin does not concentrate in GCF;
▪ It is not effective against most putative periodontal
pathogens
▪ For these reasons, erythromycin is not recommended as an
adjunct to periodontal therapy

➢ Spiramycin is active against gram-positive organisms;

▪ It is excreted in high concentrations in saliva
▪ It is used as an adjunct to periodontal treatment

25

Macrolides Cont.
➢ Azithromycin is effective against anaerobes and gram-negative
bacilli
➢ Therapeutic use requires a single dose of 250 mg/day for 5 days
after an initial loading dose of 500 mg

Clinical use: Azithromycin;

➢ Effective adjunctive therapy for increasing attachment levels in
patients with aggressive periodontitis (Grade C)
➢ Effective in reducing the degree of gingival enlargement

26

13
 11/1/2022

Serial And Combination

Antibiotic Therapy
Rationale;
➢ Because periodontal infections may contain a wide diversity of
bacteria, no single antibiotic is effective against all putative pathogens

Clinical Use;
➢ Metronidazole-Amoxicillin
➢ Metronidazole-Augmentin combinations;

▪ Used in LAP (localized aggressive periodontitis)

27

Serial And Combination Antibiotic

Therapy Cont.
Metronidazole - Ciprofloxacin combination;

➢ This is a powerful combination against mixed infections

➢ Effective against A. Actinomycetemcomitans

➢ Metronidazole targets obligate anaerobes

➢ Ciprofloxacin targets facultative anaerobes

➢ Used in refractory periodontitis

28

14
 11/1/2022

LOCAL DELIVERY AGENTS

Use of local delivered agents is based on;
➢ Clinical findings
➢ The patient’s dental, medical history
➢ Advantages and disadvantages of alternative therapies

➢ Available as adjuncts to scaling and root planing;

▪ As aids for the control of growth of bacteria on barrier
membranes

➢ Use of local delivered agents may be of value when probing

depths are greater than 5 mm

29

Subgingival Chlorhexidine
➢ Resorbable delivery system for subgingival placement

➢ PerioChip : Small chip (4.0 × 5.0 × 0.35 mm)

Composition:

➢ Biodegradable Hydrolyzed gelatin matrix cross linked with

glutaraldehyde
➢ Glycerin and water
➢ 2.5 mg of chlorhexidine gluconate has been incorporated per chip
➢ This delivery system releases chlorhexidine
➢ Maintains drug concentrations in the GCF greater than 100 μg/ml
for at least 7 days

30

15
 11/1/2022

Subgingival Chlorhexidine Cont.

➢ These concentrations are well above the tolerance of most oral
bacteria
➢ Chip biodegrades in 7 to 10 days
➢ The proportion of pocket sites with a probing depth reduction of 2
mm or more;
▪ Was increased when chlorhexidine chip was placed

Placement of chlorhexidine gluconate chip (PerioChip)

31

Tetracycline-Containing Fibers
Composition :
➢ Ethylene/vinyl acetate copolymer fiber (diameter, 0.5 mm)
containing tetracycline (12.7 mg per 9 inches)

➢ When packed into a periodontal pocket, it was well tolerated by the

oral tissues

➢ For 10 days it sustained tetracycline concentrations exceeding 1300

µg/ml;
▪ Which was well beyond the 32 to 64 µg/ml required to
inhibit the growth of pathogens

32

16
 11/1/2022

Tetracycline-Containing Fibers Cont.

➢ Tetracycline fibers applied with or without scaling and root
planing;
▪ Reduced probing depth, bleeding on probing and periodontal
pathogens
▪ Provided gains in clinical attachment level

Tetracycline fibers
33

Subgingival Doxycycline
➢ It is the only local delivery system accepted by the ADA
➢ A gel system involving the use of a syringe with 10%
doxycycline (Atridox)
Clinical parameters significantly improved in;
▪ Clinical attachment level, probing depth, bleeding on
probing

Placement of 10% doxycycline (Atridox) gel

34

17
 11/1/2022

Subgingival Minocycline
➢ A locally delivered sustained-release form of minocycline
microspheres (Arestin)
➢ 2% minocycline is encapsulated into bioresorbable microspheres in
a gel carrier

➢ Significant increase in the clinical attachment levels among

patients;
▪ who presented with pockets with probing depths of 6 mm or
more

Placement of minocycline microspheres (Arestin)

35

Subgingival Metronidazole
➢ A topical medication that contains an an oil-based metronidazole;
▪ 25% dental gel (glyceryl monooleate and sesame oil)
( Elyzol 25 %)

➢ It is applied in a viscous consistency to the pocket

➢ where it is liquidized by the body heat and then hardens again;

▪ Forming crystals when it comes in contact with water

36

18
 11/1/2022

Subgingival Metronidazole Cont.

➢ Preparation contains Metronidazole-benzoate;

▪ Which is converted into the active substance by
esterases in GCF

➢ Two Metronidazole 25% gel applications at 1-week interval

was used;

▪ Treatment effectively reduced;

✓ Probing depth and bleeding with probing over
the 6 month period

37

Subgingival Moxifloxacin
➢ Moxifloxacin is a fourth generation synthetic fluoroquinolone;
▪ With broadspectrum antibacterial activity

➢ Local delivery of 0.4% moxifloxacin may be of benefit as an

adjunct to scaling and root planning;
▪ For the treatment of periodontitis

➢ There is significant reduction in probing depth

38

19
 11/1/2022

Local delivery of antimicrobial agents and

Periimplant mucositis/implantitis

Peri - implantmucositis Peri - implantitis

39

Local delivery of antimicrobial agents and

Periimplant mucositis/implantitis Cont.

➢ Tetracycline-containing fibers for periimplant mucositis;

▪ Improved clinical and microbiologic parameters around

infected implants

➢ Doxycycline (Atridox) for periimplant mucositis;

▪ Showed significant increased attachment levels;

✓Lesser pocket probing depth, lesser bleeding index

40

20
 11/1/2022

Local delivery of antimicrobial agents and

Periimplant mucositis/implantitis Cont.

➢ Minocycline microspheres (Arestin) for periimplantitis;

▪ Showed significant reduction in pocket depth and

bleeding on probing

➢ Periochip (chlorhexidine) for periimplant mocositis;

▪ Shows limited reduction of bleeding scores

41

• TEXT BOOK: Carranza’s Clinical Periodontology,

13th Edition

42

21