A review of antibiotics and their use in periodontics.

1. ANTI-INFECTIVE
THERAPY
SEMINAR PRESENTED BY- SHASHI KIRAN
2/11/19
1

2. Contents
Introduction and terminology
Rationale for use in periodontics
Ideal requirements of an anti-infective agent
Classification of anti-infective agents
Choice of anti-infective agent
2

3. Contents
Principles of antibiotic dosage and duration
Guidelines for use of antibiotics
Systemic anti-infective agents in periodontics
Local anti-infective agents in periodontics
Conclusion
3

4. Introduction
Scaling and root planing has been considered the gold standard treatment for
periodontitis for almost 100 years.
Scaling and root planing leads to a reduction in the levels and proportion of
some periodontal pathogens, but does not seem to modify the composition of
the subgingival biofilm sufficiently for the new, beneficial, bacterial community
to become established in a more definitive manner.
Therefore, other forms of therapies, such as antibiotics, have been used in
conjunction with scaling and root planing in order to potentiate the effects of
this treatment.
4

5. Introduction
The term "antibiotic" was coined by Selman Waksman in
1939
An antibiotic is a word derived from the Ancient Greek
meaning: (anti, i.e., "against", and bios, i.e., "life")
It is a substance or compound that kills bacteria or inhibits
its growth
In 1909, Paul Ehrlich discovered that a chemical called
‘arsphenamine’ which was an effective treatment for
syphilis. (the first modern antibiotic)
5

6. Penicillin, the first natural antibiotic discovered by Alexander Fleming in 1928
Fleming found that a diffusible substance was elaborated by Penicillium notatum mould
which could destroy Staphylococcus on the culture plate.
Chain and Florey followed up this observation in 1939 developing the mass
production process that created the first mass produced antibiotic in 1941
6

7. Terminology
Chemotherapeutic agent is any chemical substance used to treat a disease
An antimicrobial is an agent that kills microorganisms or stops their growth. A
general term that encompasses antibiotics, antifungals, anti-protozoans and
antivirals.
An antibiotic is a naturally occurring, semisynthetic, or synthetic type of anti-
microbial agent that destroys or inhibits the growth of select microorganisms,
generally at low concentrations
7

8. Terminology
An antiseptic is a chemical antimicrobial agent that can be applied topically or
subgingivally to mucous membranes, wounds, or intact dermal surfaces to
destroy microorganisms and inhibit their reproduction or metabolism. (e.g.
Chlorhexidine, Dettol- Chloroxylenol)
Disinfectants (a subcategory of antiseptics) are antimicrobial agents that are
generally applied to inanimate surfaces to destroy microorganisms. (e.g.
Alcohols, Phenols)
8

9. Rationale for use in periodontics
Periodontitis is a plaque-induced inflammatory condition that affects the
periodontium; it is caused by the adherence to tooth surfaces of pathogenic
bacterial species organized in complex communities that form biofilms
Standard periodontal treatment- mechanical debridement to remove biofilm
and calculus from the affected root surfaces
However, mechanical debridement is a highly demanding procedure with some
limitations, such as the inability to access deep pockets, surface irregularities
and furcation areas
9

10. The rationale for using adjunctive antimicrobial agents is to eradicate or reduce the
numbers of pathogenic bacteria in deep pockets, root furcations and concavities or
those residing at or within the periodontal tissues at the biofilm–gingival interface
It is hoped that pathogenic organisms which are not accessible to mechanical removal
by hand or power driven instruments can be reduced in number or eliminated by
antimicrobial therapy
The current general consensus is that if antimicrobial therapy is considered, it should be
preceded by thorough mechanical debridement to disrupt the structured biofilm
10

11. Ideal requirements of an antibiotic
1. Toxic to microbes and not to humans
2. Bactericidal rather than bacteriostatic
3. Specific for periodontal pathogens
4. Should not cause allergic and hypersensitive reactions
5. Should be active in plasma, and other body fluids
6. Desired levels should be reached rapidly and maintained for adequate period of
time.
7. Should not cause drug resistance, long shelf life,
8. Inexpensive
11

12. Classification of anti-microbials
1. On the basis of chemical structure:
i. Sulphonamides and related drugs: Sulphadiazene
ii. Quinolones: Nalidixic acid, Norfloxacin
iii. β-lactam antibiotics: penicillins
iv. Tetracyclines
v. Aminoglycosides: Gentamycin, Streptomycin
vi. Macrolides: erythromycin, azithromycin
vii. Glycopeptide antibiotics: Vancomycin
viii. Nitroimidazole: Metronidazole, Tinidazole
Tripathi KD. Antimicrobial drugs: General considerations. In: Tripathi KD, editors. Essentials of medical pharmacology.
5th ed. New Delhi: Jaypee Publ ishers; 2003. p. 627-40.
12

13. 2. Mechanism of action
i. Inhibit cell wall synthesis –penicillins, vancomycin
ii. Cause leakage from cell membranes –polymyxins, bacitracin, nystatin
iii. Inhibit protein synthesis –tetracyclines, chloramphenicol, erythromycin
iv. Cause misreading of m-RNA code and affect permeability –aminoglycosides
v. Inhibit DNA gyrase –fluoroquinolones
vi. Interfere with DNA function –metronidazole, rifampicin
vii. Interfere with DNA synthesis –idoxuridine, acyclovir
viii. Interfere with intermediary metabolism –sulfonamides, trimethoprim
13

14. 3. Group of organisms against which primarily active
i. Antibacterial—penicillins, aminoglycosides
ii. Antifungal---griseofulvin, amphotericin-B
iii. Antiviral—idoxuridine, acyclovir
iv. Antiprotozoal—chloroquine, pyrimethamine
v. Antihelmintic---mebendazole, pyrantel
14

15. 4. On the basis of Spectrum of activity
i. Narrow spectrum- penicillin G, erythromycin
ii. Broad spectrum- tetracyclines, chloramphenicol
5. Type of action
i. Bacteriostatic: inhibit bacterial replication without killing the organism ---sulfonamides,
tetracyclines, erythromycin
ii. Bactericidal drugs, which cause death and disruption of the bacterial cell, ---penicillins,
aminoglycosides
15

16. Choice of an antimicrobial agent
1. Age of patient:
Patients at both extremes of age handle drugs differently, primarily due to differences in body
size and kidney function.
It may affect pharmacokinetics of many antibiotics e.g. tetracyclines accumulate in the
developing teeth and bone, Fluoroquinolones cause abnormal development of cartilage
2. Renal and hepatic function: Cautious use and modification of the dose of an antibiotic
becomes necessary when the organ of its disposal is defective.
Kapoor A, Malhotra R, Grover V, Grover D. Systemic antibiotic therapy in periodontics. Dental research journal. 2012
Sep;9(5):505. 16

17. 3. Local factors: The conditions prevailing at the site of infection greatly affect the action of
antibiotics like the presence of pus and secretions, necrotic material and foreign body, low pH.
Presence of pus and secretions (low pH) decrease the efficacy of most antibiotics esp.
sulfonamides and aminoglycosides
4. Drug allergy: History of previous exposure to an antibiotic and any allergic reaction should be
obtained.
5. Impaired host defense: In an individual with normal host defense, a bacteriostatic antibiotic
may achieve cure, while intensive therapy with bactericidal drugs is imperative in those with
impaired host defense.
17
Kapoor A, Malhotra R, Grover V, Grover D. Systemic antibiotic therapy in periodontics. Dental research journal. 2012
Sep;9(5):505.

18. 6. Pregnancy: Antibiotics should be avoided in the pregnancy because of risk to the developing
foetus.
Kapoor A, Malhotra R, Grover V, Grover D. Systemic antibiotic therapy in periodontics. Dental research journal. 2012
Sep;9(5):505. 18

19. 7. Organism related considerations:
Clinical diagnosis
Culture and sensitivity testing
8. Drug factors:
a. spectrum of activity (narrow/broad),
b. type of activity (bactericidal/ bacteristatic),
c. sensitivity of the organism (Minimal inhibitory concentration values),
d. relative toxicity,
Kapoor A, Malhotra R, Grover V, Grover D. Systemic antibiotic therapy in periodontics. Dental research journal. 2012
Sep;9(5):505. 19

20. Two critical factors should be specifically considered in selecting a systemic antibiotic in
periodontal therapy:
Gingival fluid concentration (C GCF) and
Minimum inhibitory concentration (MIC).
100 * (C GCF/MIC90) = antimicrobial activity
20

21. Antibiotic dosing
The proper dose of a drug is the amount that produces the maximum benefit with the least
attendant harm
Antibiotic dosing should achieve drug levels in infected tissue equal to or exceeding the minimal
inhibitory concentration of the target organism.
The blood concentration of the antibiotic should exceed the minimal inhibitory concentration
by a factor of 2-8 times to offset tissue barriers that restrict the access of the drug to the
infected site
21

22. Principles of antibiotic dosing
1. Employ high doses for a short duration
2. Use an oral antibiotic loading dose: Without a loading dose, it takes 6-12 hours to achieve
maximum therapeutic blood and tissue levels via oral administration.
3. Achieve blood levels of the antibiotic at 2-8 times the minimal inhibitory concentration:
Such blood levels are necessary to compensate for the tissue barriers that impede antibiotic
penetration to the site of the infection
4. Use frequent dosing intervals: so as to maintain relatively constant blood levels.
5. Determine the duration of therapy by the remission of disease: The antibiotic is terminated
when the patient host defenses have gained control of the infection and the infection is
reasonably certain to resolve or has resolved
Pallasch TJ. Pharmacokinetic principles of antimicrobial therapy. Periodontology 2000. 1996 Feb;10(1):5-11. 22

23. Antibiotic dosing variables
1. Lipid solubility:
Highly lipid-soluble antimicrobial agents like the tetracyclines, erythromycin and quinolones pass
better through tissue barriers than highly water-soluble agents such as the beta-lactams,
aminoglycosides and vancomycin
2. Plasma protein binding:
Only the antimicrobial agent not bound to plasma protein is free to diffuse through capillary walls
and other tissue barriers
The degree of plasma protein (serum albumin) binding of antibiotics can vary from 80 to 96%
(clindamycin and doxycycline), to 50-80% (erythromycin and tetracycline), to less than 25%
(ciprofloxacin, amoxicillin, metronidazole and aminoglycosides)
23

24. 3. The Inoculum effect: (loss of efficacy of antibiotics against dense microbial populations)
A larger mass of bacteria results in a decreased growth rate, less phagocytic activity, increased
betalactamase activity, more glycocalyx production and reduced pH
The deleterious effect of inoculum size can be reduced by early, vigorous antibiotic therapy and
by mechanical removal of the microorganisms (scaling and root planing, incision and drainage)
24

25. 4. Surface area to volume ratio
Ratio of the surface area of the vascular bed to the volume of the tissue compartment to be
supplied
With a high vascular bed to-volume ratio (high vascularity and low infection volume), as found in
areas of inflammation with minimal purulence or edema, the antimicrobial concentration (except
for beta-lactams) may be similar to that of blood
5. Altered patient physiology (age, kidney and liver function).
25

26. Duration of antibiotic therapy
Myths: Antibiotic use requires a “complete course” of therapy.
The ideal duration of antibiotic therapy is the shortest that will prevent both clinical and
microbiological relapse.
The only practical guide for determining the effectiveness of antimicrobial treatment, and hence
the duration of therapy, is clinical improvement of the patient as judged by remission of the
infection
When clinical evidence indicates that the infection is reasonably certain to resolve or is
resolved, the antibiotic therapy should be terminated.
Pallasch TJ. Pharmacokinetic principles of antimicrobial therapy. Periodontology 2000. 1996 Feb;10(1):5-11. 26

27. Time of administration
The optimal timing of antimicrobial drug administration has been a subject of controversy for
many years
Mombelli A. Antimicrobial advances in treating periodontal diseases. InPeriodontal Disease 2012 (Vol. 15, pp. 133-148).
Karger Publishers.
27

28. INDICATIONS FOR ANTIBIOTICS IN
PERIODONTAL THERAPY
1. Patients who do not respond to conventional periodontal therapy
2. Refractory periodontitis
3. Patients with acute periodontal infections (Abscesses) with systemic manifestations
4. Prophylaxis in medically compromised patients (Infective endocarditis)
5. As an adjunct to non-surgical periodontal therapy.
6. Aggressive periodontitis
7. NUP/NUG with systemic symptoms (AAP, 2001)
Eickholz P, Dannewitz B, Kim TS. Antibiotics in Periodontal Therapy. Periodontal Practice Today. 2005 Sep 1;2(4). 28

29. Guidelines for the use of antibiotics in
periodontal therapy
1. The clinical diagnosis and situation dictate the need for possible antibiotic therapy as an
adjunct for controlling active periodontal disease
2. Disease activity as measured by continuing attachment loss, purulent exudate, and bleeding
on probing may be an indication for periodontal intervention and possible microbial analysis
through plaque sampling
3. When they are used to treat periodontal disease, antibiotics are selected on the basis of the
patient’s medical and dental status and current medications and the results of microbial
analysis, if it is performed.
Jolkovsky DL, Ciancio S. Chemotherapeutic agents. In: Carranza FA, Newman MG, Takei HH, Klokkevold PR, editors. Clinical
periodontology. 10th ed. Philadelphia: WB Sa unders; 2006. p. 798-812 29

30. 4. A meta-analysis evaluating eight different antibiotics or antibiotic combinations showed that
only tetracycline and metronidazole significantly improved attachment levels when they were
used as adjuncts to scaling and root planing for patients with destructive periodontal diseases.
5. Microbiologic plaque sampling may be performed according to the instructions of the
reference laboratory. The samples are usually taken at the beginning of an appointment,
before instrumentation of the pocket
6. Should not be used as a stand-alone therapy. An antibiotic strength that is 500 times greater
than the systemic therapeutic dose may be required to be effective against bacteria that have
been arranged into biofilm. It is therefore important to disrupt the biofilm physically so that the
antibiotic agents can have access to the periodontal pathogens
Jolkovsky DL, Ciancio S. Chemotherapeutic agents. In: Carranza FA, Newman MG, Takei HH, Klokkevold PR, editors. Clinical
periodontology. 10th ed. Philadelphia: WB Sa unders; 2006. p. 798-812 30

31. Failure of antibiotic therapy
1. Inappropriate choice of antibiotic (the microorganism is not susceptible)
2. Emergence of antibiotic-resistant microorganisms (rebound infections,
superinfections and selection of resistant microbes)
3. Too low blood concentration (faulty dosing)
4. Slow growth rate of microorganisms (beta-lactams require dividing organisms
for activity; older abscesses have a slow microbial growth rate)
5. Impaired host defences (suboptimal activity of patient immune and
inflammatory systems)
Pallasch TJ. Pharmacokinetic principles of antimicrobial therapy. Periodontology 2000. 1996 Feb;10(1):5-11. 32

32. 6. Patient noncompliance (failure to take antibiotics properly)
7. Antibiotic antagonism (tetracycline and milk products)
8. Inability of the antibiotic to penetrate to the site of the infection
9. Unfavourable local factors (decreased pH or oxygen tension)
10. Failure to eradicate the source of the infection (lack of incision and drainage)
11. Limited vascularity or decreased blood flow
Pallasch TJ. Pharmacokinetic principles of antimicrobial therapy. Periodontology 2000. 1996 Feb;10(1):5-11. 33

33. Administration of antibiotics
Systemic administration
Local administration
34

34. Systemic administration
Advantages of systemic administration:
Simple, easy administration of drug to multiple sites of disease activity
Eliminate or reduce pathogens on oral mucosa and extra-dental sites
Disadvantages of systemic administration:
Inability to achieve high GCF concentration
Increased risk of adverse drug reactions
Increased selection of multiple antibiotic resistant micro-organisms
Uncertain patient compliance
35

35. Local administration
Advantages:
Less quantity of drug required
Can attain higher concentrations of an antimicrobial agent in sub gingival sites
No potential danger of resistant strains and super imposed infections
No risk of adverse drug reactions and systemic side effects
No dependence on patient compliance
Disadvantages:
Difficulty in placing into deeper parts of periodontal pockets and furcation lesions.
Time consuming
Re-infection from non-treated sites
36

36. Systemic antibiotics in
periodontics
37

37. Systemic antibiotics in periodontics
Eight principle antibiotic groups have been extensively evaluated for treatment of the
periodontal diseases;
1.Tetracycline
2.Minocycline
3.Doxycycline
4.Erythromycin
5.Clindamycin
6.Ciprofloxacin
7.Amoxicillin
8.Metronidazole
38

38. 40

39. Tetracycline
Produced naturally from certain species of Streptomyces or derived semi-synthetically
Tetracycline was patented in 1953 and came into commercial use in 1978
It is on the World Health Organization's List of Essential Medicines
Broad spectrum of antibiotic action (active against aerobic and anaerobic organisms, gram
positive and gram negative)
Bacteriostatic drug
C22H24N2O8
42

40. Concentration in the gingival crevice is 2-10 times than in serum
Possess unique non-antibacterial characteristics- collagenase inhibition, antiinflammatory
effects, inhibition of microbial attachment and root surface conditioning
Mode of action: Act by inhibition of protein synthesis by binding to 30 S ribosomes in the
susceptible organism
Clinical use:
1. Adjuncts in the treatment of localized aggressive periodontitis (LAP)
2. Arrest bone loss and suppress A. actinomycetemcomitans levels in conjunction with scaling
and root planing
3. Root bio-modification
43

41. Dosage regimen: 250 mg four times daily, lesser compliance
Common side effects:
Discolor permanent teeth (yellow-gray-brown)
Cause skin photosensitivity, so exposure to the sun or intense light is not recommended
Cause tinnitus
nausea, vomiting, diarrhea, loss of appetite
white patches or sores in mouth or on lips
44

42. Caution:
Affect bone growth of the fetus, so should be avoided during pregnancy
Be inactivated by calcium ions, so are not to be taken with milk, yogurt, and
other dairy products
Be inactivated by aluminium, iron, and zinc ions, not to be taken at the same time
as indigestion remedies (some common antacids and over-the-counter heartburn medicines)
45

43. Studies
Tetracycline administered via the systemic route suppressed A actinomycetemcomitans,
Capnocytophaga, and spirochetes to low or undetectable levels in all test periodontal pockets
and led to significant gain in clinical attachment levels (Slots et al, 1983)
Tetracycline administered during a 3‐week period concomitant with non‐surgical treatment
enhanced the outcome of mechanical therapy. 1 year after active therapy, average gain in
probing attachment that was almost 3× higher than Control group. (Ramberg et al, 2002)
Patients prescribed with Systemic tetracycline for 1 week showed significant gain in attachment
levels (mean = 1.4mm) and significantly reduced the levels of A actinomycetemcomitans
(Christersson et al, 1993)
46

44. Minocycline
Bacteriostatic
Mode of action: inhibition of protein synthesis
Dosage regimen: 100mg twice daily
In patients with adult periodontitis, it suppresses spirochetes and motile rods as effectively as
scaling and root planing, with suppression evident up to 3 months after therapy.
C23H27N3O7
47

45. Common side effects:
numbness, tingling;
hair loss;
discoloration of skin or nails.
Vertigo
Muscle or joint pain;
nausea, diarrhea, loss of appetite;
Brand names: Cynomycin, Divaine
48

46. Studies
Systemic Minocycline administration with or without periodontal scaling and root planing
resulted in major, long‐lasting shifts in the subgingival microflora and improvement in gingival
health (Ciancio et al, 1982)
Systemic Minocycline administration for 14 days as an adjunct to SRP resulted in significant
reduction in probing pocket depths in pockets greater than 6mm. (Attillla et al, 1993)
Systemic minocycline administration for 21 days as an adjunct to SRP led to significant gain in
clinical attachment levels. (Muller et al, 1993)
49

47. Doxycycline
Same spectrum of activity as Minocycline
Recommended dosage is 100 mg bid the first day, then 100 mg once daily
Compliance is favoured since it has to be taken once daily
Brand names: Lenteclin, Bidox-dt
C22H24N2O8
50

48. Clinical use: Adjuncts in the treatment of localized aggressive periodontitis (LAP)
Possess unique non-antibacterial characteristics- collagenase inhibition, antiinflammatory effects
Used as a systemic host modulating agent (SDD)
Common side effects:
Loss of appetite.
Nausea, vomiting and diarrhoea.
Skin rash.
Sensitivity to the sun.
Temporary discoloring of adult teeth
51

49. Studies
Significantly greater reduction in the prevalence of A. actinomycetemcomitans in LAP patients 8
months after treatment with doxycycline as compared with the placebo. (Saxen et al, 1990)
Systemic administration of doxycycline with full mouth SRP resulted in a better improvement of
periodontal parameters and elimination/suppression of putative periodontal pathogens such
as Aa, Pg, and Tf, than amoxicillin plus metronidazole in patients with LAP. (Nutalatapti et al,
2013)
Systemic doxycycline administration as an adjunct to SRP showed significant improvements in PI,
GI, CAL, PD when compared to patients receiving SRP alone (Vyas et al, 2009)
52

50. Metronidazole
A synthetic nitroimidazole compound with bactericidal effects primarily exerted on obligate
gram-positive and gram-negative anaerobes.
Spectrum of activity - for Fusobacterium and Selenomonas infections, the best candidate for
Peptostreptococcus infections, a reasonable candidate for P. gingivalis, P. intermedia and C.
rectus infections, a poor choice for A. actinomycetemcomitans and E. corrodens infections,
Bactericidal
53

51. Mode of action: Metronidazole acts by inhibiting DNA synthesis
Clinical use:
1. For treating acute necrotizing ulcerative gingivitis, chronic periodontitis, and aggressive
periodontitis.
2. As monotherapy, metronidazole is inferior, should be used in combination with root planing,
surgery or with other antibiotics.
The most commonly prescribed regimen is 400 mg tid for 7 days.
54

52. Brand names: Flagyl, Metrogyl
Common side effects: Common side effects include nausea, a metallic taste, loss of appetite,
and headaches
Caution: Consuming alcohol while taking metronidazole has been suspected in case reports to
cause a disulfiram-like reaction with effects that can include nausea, vomiting, flushing of the
skin, tachycardia, and shortness of breath
55

53. Studies
56

54. Penicillin
Natural and semi synthetic derivatives of broth cultures of the Penicillium mould
Bactericidal
Major activity in the gram positive spectrum. Only the extended spectrum penicillin, such as
ampicillin and amoxicillin, possess substantial antimicrobial activity for gram-negative species
57

55. Amoxicillin is a semisynthetic penicillin with an extended antiinfective spectrum that includes
gram-positive and gram-negative bacteria
Mode of action: Interfere with the synthesis of bacterial cell wall, inhibit the transpeptidases so
that cross linking does not take place
Clinical use: as an adjunct to SRP in LAP,
Recommended dosage is 500 mg tid for 8 days
Brand name: Novomox, Amoxil
58

56. Spectrum: Exhibits high antimicrobial activity at levels that occur in GCF for all periodontal
pathogens except E. corrodens, S. sputigena and Peptostreptococcus, inhibits the growth of the
gram positive facultative anaerobes
Common side effects:
Common adverse effects include nausea , diarrhoea and rash.
It may also increase the risk of yeast infections
59

57. Studies indicate that more than 60% of adult periodontitis patients sampled harbored
periodontal plaque that exhibited β-lactamase activity
For this reason, administration of β-lactamase sensitive Penicillin, including Amoxicillin alone, is
not generally recommended and, in some cases, may accelerate periodontal destruction
Amoxicillin-Clavulanate (Augmentin): The generally accepted strategy is to administer
amoxicillin with an inhibitor of beta-lactamase such as Clavulanic acid
60

58. Studies
61

59. Clindamycin
Effective against anaerobic bacteria, and in patients allergic to penicillin
Mode of action: Inhibition of protein synthesis by binding to 50 S ribosome
Bacteriostatic
Clinical use: as an adjunct to SRP in patients allergic to penicillins
Dosage: 300mg t.i.d 10 days
62

60. Common side effects: diarrhoea, pseudomembranous colitis, nausea, vomiting, abdominal pain
or cramps and/or rash.
Brand name: Cleocin, Clindacin
63

61. Ciprofloxacin
A fluorinated 4-quinolone antibiotic available for oral administration
Spectrum: A potent inhibitor of gram negative bacteria (all facultative and some anaerobic
putative periodontal pathogens), including Pseudomonas aeruginosa
Mode of action: Inhibition of bacterial DNA replication and transcription by inhibiting the
enzyme DNA gyrase, an enzyme unique to prokaryotic cells
Bacteriostatic
64

62. Clinical use: Fluoroquinolones are effective against the pasteurellaeae family, to
which Actinobacillus actinomycetemcomitans belongs.
At present, ciprofloxacin is the only antibiotic in periodontal therapy to which all strains of A.
actinomycetemcomitans are susceptible.
Also used in combination with Nitroimidazoles (metronidazole and tinidazole)
Dosage: 500mg b.i.d 8 days
Brand names: Cipro, Ciplox
65

63. Side effects: nausea, vomiting, diarrhea and rash.
Kleinfelder et al. (2000) reported that systemic ofloxacin in conjunction with open flap surgery
was able to suppress A. actinomycetemcomitans below detectable levels in 22 study patients for
a period of 12 months
66

64. Macrolides
Can be bacteriostatic or bactericidal, depending on the concentration of the drug and the
nature of micro organism
The macrolide antibiotics used for periodontal treatment include erythromycin and
azithromycin
Mode of action: Inhibit protein synthesis by binding to the 50 S ribosomal subunits of sensitive
microorganisms interfere with translation
67

65. Erythromycin: 400mg qid 7 days (Ery-tab, Ery-ped)
Clinical use: An extremely safe drug that has often been recommended as an alternative to
penicillin for allergic patients
Principle limitation of erythromycin is its poor tissue absorption.
Azithromycin: 500mg o.d 7 days (Zithromax)
It has been proposed that Azithromycin penetrates fibroblasts and phagocytes in
concentrations 100-200 times greater than that of extracellular compartment
The azithromycin is actively transported to sites of inflammation by phagocytes, then directly
released into the sites of inflammation as phagocytes rupture during phagocytosis
68

66. In addition to its antimicrobial effects, azithromycin modulates proinflammatory and anti-
inflammatory cytokine production in several systematic and periodontal diseases
Spectrum:
Azithromycin has bacteriostatic effects against a wide range of bacteria in vitro, including gram-
positive bacteria such as Staphylococcus aureus and Streptococcus pyogenes
Aggregatibacter actinomycetemcomitans have shown susceptibility to low dose azithromycin
Azithromycin is highly effective against Porphyromonas gingivalis (The minimal inhibitory
concentrations (MICs) were 0.25 micro g/mL)
Common side effects include abdominal cramps, vomiting, and diarrhea
69

67. Studies
Fujise et al, 2014 - The use of adjunctive azithromycin in scaling and root planing may be
effective for periodontal tissue regeneration. This property may be independent of the degree of
baseline gingival inflammation.
Sefton et al, 1996: Counts of spirochaetes were significantly reduced throughout the study in
patients who received azithromycin compared to placebo. Our microbiological study suggests
that azithromycin may be useful as an adjunct in the treatment of periodontal disease.
Herrera et al, 2010: Within the limitations of this study, the adjunctive use of systemic
azithromycin in the treatment of P. gingivalis periodontitis demonstrated significant clinical and
microbiological benefits when compared with SRP plus placebo.
70

68. Combination therapy
Since the subgingival microbiota in periodontal disease consists of various putative pathogens
that may differ in antimicrobial susceptibility, the use of a combination of two or more
antibiotics may represent a valuable approach in periodontal chemotherapy
71

69. Advantages
1. Broaden the antimicrobial range
2. Empirical treatment of severe infections
3. Treatment of polymicrobial infections
4. Prevention of the emergence of bacterial resistance
5. Increased effectiveness from antibiotic synergism (more than additive)
6. Lower the dose of individual antibiotics by exploiting possible synergy between two drugs
against targeted organisms
72

70. Disadvantages
Increased adverse reactions
Decreased patient compliance
Antagonistic drug interactions
Superinfections with Candida or other microbes owing to major suppression of the indigenous
microbiota.
73

71. Amoxicillin-metronidazole
Most common antibiotic combination in periodontics
Amoxicillin exerts antimicrobial synergy with metronidazole against periodontal pathogens
Dosage: 250 mg of amoxicillin and 250 mg of metronidazole, three times daily for 8 days
A-M combination therapy used as the sole periodontal treatment has yielded a clinical outcome
similar to that of scaling and root planning (Socransky et al, 2006)
74

72. Rams and Slots (2002) reviewed combination therapy involving the use of systemic
metronidazole along with amoxicillin, amoxicillin– clavulanate (Augmentin), or ciproloxacin.
The metronidazole– amoxicillin and metronidazole–Augmentin combinations provided excellent
elimination of many organisms in adults with LAP who had been treated unsuccessfully with
tetracyclines and mechanical debridement.
These drugs have an additive effect that involves the suppression of A.
actinomycetemcomitans.
Tinoco and colleagues found metronidazole and amoxicillin to be clinically effective for the
treatment of LAP, although 50% of patients who were treated with this regimen harbored A.
actinomycetemcomitans 1 year later.
75

73. .
76

74. Ciprofloxacin - metronidazole
500 mg of each drug, twice daily for 8 days
The metronidazole–ciprofloxacin combination is effective against A. actinomycetemcomitans;
metronidazole targets obligate anaerobes, and ciprofloxacin targets facultative anaerobes
This is a powerful combination against mixed infections.
This combination may provide a therapeutic benefit by reducing or eliminating pathogenic
organisms and a prophylactic benefit by giving rise to a predominantly streptococcal microlora
77

75. Serial antibiotics
Antibiotics that are bacteriostatic (e.g., tetracycline) generally require rapidly dividing
microorganisms to be effective. They do not function well if a bactericidal antibiotic (e.g.,
amoxicillin) is given concurrently.
When both types of drugs are required, they are best given serially rather than in combination
In one such study, six patients with recurrent progressive periodontitis were given the usual
adult dosage of doxycycline for 4 days followed by amoxicillin with clavulanate for 5 days. Five
similar patients were given doxycycline alone for 10 days. After 25 weeks, patients receiving the
sequential combination had significantly greater pocket depth reduction than those receiving
doxycycline alone (Roberto et al, 2006)
78

76. Therapeutic Uses of Systemic
Antimicrobial Agents
79

77. Local anti-infective
agents
80
Goodson et al in 1979 first proposed the concept of controlled delivery in the
treatment of periodontitis

78. Local administration
Advantages:
Less quantity of drug required
Can attain higher concentrations of an antimicrobial agent in sub gingival sites
No potential danger of resistant strains and super imposed infections
No risk of adverse drug reactions and systemic side effects
No dependence on patient compliance
Disadvantages:
Difficulty in placing into deeper parts of periodontal pockets and furcation lesions.
Time consuming
Re-infection from non-treated sites
81

79. Ideal requirements of
a Local Delivery Drug
1. It must deliver antimicrobial agent to the base of the pocket to target periodontal infections.
2. To deliver drug at a bacteriostatic or bactericidal concentration.
3. Ease of placement.
4. Retention of the medicament long enough to ensure an efficacious result.
6. Biodegradable.
7. Nontoxic and non-irritant.
8. No emergence of bacterial resistance.
9. Safe with minimal side effects.
10. Should be effective only against periodontal pathogens and not on commensal microflora.
82

80. Indications (Greenstein 1998)
1. As an adjunct to scaling and root planing.
2. Periodontal maintenance therapy
(in cases of recurrent periodontitis)
3. For whom surgery is not an option or those who refuse surgical treatment.
4. When localized diseased sites are present
5. During periodontal regenerative procedures
6. Around a failing implant (peri-implantitis)
83

81. Contraindications
1. Patients with known hypersensitivity reaction to any of the antimicrobials
2. Patients susceptible to infective endocarditis to avoid the risk of bacteremia by irrigation
devices
3. Pregnancy / lactating individuals
84

82. Classification Rams and Slots (1996)
1. Personally applied (in patient home self-care)
A. Nonsustained subgingival drug delivery(home oral irrigation)
2. Professionally applied (in dental office)
A. Nonsustained subgingival drug (professional pocket irrigation)
B. Sustained subgingival drug delivery (controlled- release device)
85

83. Local agents in periodontics
87

84. Tetracycline
PerioCol-TC: vial contains type I collagen (25 mg) impregnated with
approximately 2.0 mg of tetracycline hydrochloride
Releases tetracycline in vitro for 8 to 10 days. A periodontal dressing
should be placed to avoid dislodging the fibers.
Indicated for the treatment of adult periodontitis as an adjunct to SRP
for pockets more than 5 mm deep, and it can be administered every 3
months
The fibers are moistened with saline and placed into the periodontal
pocket to the depth of the pocket base; they are biodegradable and
do not have to be removed.
88

85. Periodontal Plus AB:
Periodontal Plus AB is a bio-resorbable tetracycline fiber. It has 25
mg of pure fibrillar collagen evenly impregnated with
approximately 2 mg of tetracycline hydrochloride
The fibers are packaged as a strip containing four individually
packed and separable sterile product packs.
The fiber biodegrades in the periodontal pocket within 7 days.
The fiber should be retained with a periodontal dressing for 10
days
89

86. ACTISITE:
FDA approved fibres
25% w/w tetracycline HCI
A thread of 0.5 mm in diam
and 23 cm in length.
1000 μg/ml for a period of
10 days
No longer available
90

87. Studies
Tonetti et al.(1994) reported that EVA fibres containing 25% tetracycline hydrochloride
maintained a constant drug level in the GCF above 600 mg/ml. Tetracycline fibre treatment
adjunctive to SRP showed significantly less periodontal disease recurrence (4%) compared with
SRP alone (9%).
Newman et al (1994), SRP Vs SRP and tetracycline fibers in maintenance patients. The
combination therapy showed significant clinical improvements including attachment levels at 1,
3 and 6 months than scaling root planing alone.
Freisen et al (2002) showed local delivery of tetracycline is superior to root planing alone in
reducing probing depth and bleeding on probing.
91

88. Doxycycline
Atridox: Doxycycline gel is a subgingival, controlled-release delivery product composed of a two-
syringe mixing system
92

89. Syringe A contains 450 mg of a bioabsorbable polymeric formulation of 36.7% poly(d,l,-lactide)
dissolved in 63.3% N-methyl-2-pyrrolidone.
Syringe B contains 50 mg of doxycycline hyclate, equivalent to 42.5 mg of doxycycline.
When mixed, the product is a viscous liquid of 500 mg, which contains 50 mg (10%) of
doxycycline hyclate
93

90. The gel has been reported to release doxycycline in the GCF
over 7 days.
The doxycycline gel is biodegradable and does not require
removal.
The doxycycline gel is used by injecting the mixed contents of
the two syringes directly into the pocket.
The pocket contents are then covered with a periodontal
dressing or a cyanoacrylate dental adhesive.
94

91. Studies
Garrett et al (1999) in 2 large, randomized controlled clinical trials. Doxycycline Vs scaling and
root planing indicated there was no difference between the therapies with regard to probing
depth reduction or gain in attachment.
Jorgensen et al (2004) : no significant additional reduction in the subgingival pathogenic
microbiota compared to thorough scaling root planing alone, thereby precluding the use of
doxycycline polymer.
Bogren et al (2008) : short-term effects on clinical parameters were found with the adjunctive
use of doxycycline, repeated applications annually had no clinical or microbiologic effects
beyond those observed with mechanical debridement alone in maintenance patients.
95

92. Minocycline
Arestin: is a subgingival, controlled release delivery system
containing the antibiotic minocycline hydrochloride
incorporated into a bioresorbable polymer in unit-dose
cartridges
Each cartridge delivers minocycline hydrochloride equivalent
to 1 mg of minocycline free base
Its bacteriostatic, antimicrobial activity results from the
inhibition of protein biosynthesis.
96

93. The minocycline microspheres are used by injecting the contents of a unit-dose cartridge into
the pocket. Neither a periodontal dressing nor an adhesive is needed
Patients should avoid hard or sticky foods at the treated teeth for 1 week and interproximal
cleaning devices for about 10 days. The minocycline microspheres formulation is biodegradable
and does not require removal
Paquette (2002) no increased incidence of adverse events or tetracycline resistance was
observed with minocycline-microsphere treatment, also indicate that minocycline microspheres
plus scaling root planing are safe and more effective than scaling root planing alone in reducing
the signs of chronic periodontitis.
97

94. Chlorhexidine
Perio-chip: The chlorhexidine chip is a small chip (4.0 × 5.0 × 0.35 mm)
that contains 2.5 mg of the active ingredient chlorhexidine gluconate
in a resorbable, biodegradable matrix of hydrolyzed gelatin that is
cross-linked with glutaraldehyde and packaged in individual foil
containers
The chlorhexidine chip is placed into the pocket directly from the foil
container using a forceps
After placement in the pocket, the chip has been reported to release
chlorhexidine into the gingival crevicular luid (GCF) over 7 to 10 days.
The chip is biodegradable and does not require removal, but dental
loss should be avoided for 10 days to avoid dislodging it.
98

95. PerioCol-CG :
PerioCol-CG is a small, 10-mg chip (4 × 5 × 0.25–0.32 mm)
designed as a collagen matrix into which chlorhexidine
gluconate (2.5 mg) is incorporated.
The chip is designed for insertion into the periodontal
pocket
It releases chlorhexidine in vitro at a rate of approximately
40% to 45% in the first 24 hours, followed by a linear
release for 7 to 8 days
99

96. Chlo-Site: Chlo-Site is a xanthan gel, consisting of a saccharide polymer as a three-
dimensional mesh containing 1.5% chlorhexidine in 0.5 mL of gel, which is injected into the
periodontal pocket
The gel contains two types of chlorhexidine: a slow-release chlorhexidine digluconate
(0.5%) and a rapid-release chlorhexidine dihydrochloride (1.0%)
Concentration in GCF of more than 100 µg/mL for an average of 6 to 9 days and to maintain
an effective concentration for at least 15 days
100

97. Studies
Soskolne et al (1997): compared chlorhexidine and SRP Vs SRP alone and found there is
improvement in attachment level in pockets even more than 7mm in the combination group.
Jeffcoat et al (1997) in a 9 month study, significant clinical improvement in periodontal
parameters when chlorhexidine chip was combined with SRP when compared to SRP alone.
Kasaj et al (2007) showed chlorhexidine chip application following SRP is beneficial in improving
periodontal parameters in patients under supportive periodontal therapy.
101

98. Metronidazole
Elyzol: is a bioabsosbable delivery device containing
25% Metronidazole benzoate in a matrix consisting of
a mixture of glyceryl mono-oleate and sesame oil.
The gel is subgingivally placed with a syringe and a
blunt cannula
It is potent and demonstrates low toxicity
It is not substantive.
Upon topical application, it is not readily adsorbed
into the tissues.
102

99. Studies
Klinge et al (1992) compared metronidazole gel administered once in a week for 2 weeks in
different concentrations Vs SRP alone. All the groups produced similar clinical effects with no
evidence of any adverse effects.
Stetzel and Flores-de-Jacoby (1996) showed that Metronidazole gel either alone or in
combination with mechanical debridement produced comparable results with mechanical
debridement alone.
103

100. Antibiotic prophylaxis
Recommended when these patients undergo procedures that are at risk for producing
bacteremia.
American Heart Association guidelines for dental procedures - - - - All dental procedures that
involve manipulation of gingival tissue on the periapical region of teeth or perforation of the
oral mucosa
CARDIAC CONDITIONS WITH HIGH RISK:
Prosthetic cardiac valve or prosthetic material used for cardiac valve repair
Previous infective endocarditis
Cardiac transplantation recipients who develop cardiac valvulopathy
Congenital heart disease
104

101. Procedures that do not need prophylaxis
Routine anesthetic injections through non-infected tissue
Taking dental radiographs
Placement of removable prosthodontic or orthodontic appliances
Bleeding from trauma to the lips or oral mucosa
105

102. Standard general prophylaxis
Amoxicillin
Adult dose: 2 g PO, 1 hour before procedure
Pediatric dose: 50 mg/kg PO; not to exceed 2 g/dose
Allergic to penicillin
Clindamycin
Adult dose: 600 mg PO
Pediatric dose: 20 mg/kg PO; not to exceed 600 mg/dose
106

103. Impact of antibiotic therapy
107

104. Conclusion
In conclusion, the slight additional benefits of adjunctive antimicrobials, which have been shown
for moderate forms of periodontitis, have to be balanced against their side effects, and
therefore their prescription should be limited as much as possible.
Therapists should be careful not to underestimate the effect of proper mechanical debridement
and modification of behavioral risk factors.
The patient’s overall risk for periodontitis must be considered, and exceptions that may indicate
antibiotic treatments include cases of early-onset disease if the periodontal infection needs to
be rapidly suppressed, localized deep sites with persistent or recurrent disease and patients
with uncontrolled diabetes.
108

105. References
Jolkovsky DL, Ciancio S. Chemotherapeutic agents. In: Carranza FA, Newman MG, Takei HH,
Klokkevold PR, editors. Clinical periodontology. 10th ed. Philadelphia: WB Saunders; 2006. pp.
798– 812
Tripathi KD. Antimicrobial drugs: General considerations. In: Tripathi KD, editor. Essentials of
medical pharmacology. 5th ed. New Delhi: Jaypee Publishers; 2003. pp. 627–40
Systemic antibiotic therapy in periodontics, Anoop Kapoor, Ranjan Malhotra, Vishakha Grover,
and Deepak Grover Dent Res J (Isfahan). 2012 Sep-Oct; 9(5): 505–515.
Slots J, MacDonald ES, Nowzari H. Infectious aspects of periodontal regeneration. Periodontol
2000. 1999;19:164–72
Haffajee AD, Socransky SS, Gunsolley JC. Systemic anti-infective periodontal therapy.A systematic
review. Ann Periodontol. 2003;8:115–81
109

106. References
Van Winkelhoff AJ, Rams TE, Slots J. Systemic antibiotic therapy in periodontics. Period ontol
2000 1996;10:45-78
Pallasch TJ. Pharmacokinetic principles of antimicrobial therapy. Periodontol 2000. 1996;10:5–11
Herrera D, Sanz M, Jepsen S, Needleman I, Roldan S. A systematic review on the effect of
systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J Clin
Periodontol. 2002;29:136–59
Ellen RP, Mcculloch CA. Evidence versus empiricism: Rational use of systemic antimicrobial
agents for treatment of periodontitis. Periodontol 2000. 1996;10:29–44.
THOMAES. RAMS & JBRGEN SLOTS Local delivery of antimicrobial agents in the periodontal
pocket Periodontology 2000, Vol. 10, 1996, 139-159
110

107. Thank you!
111

108. Tetracycline Root bio-modification
Two methods:
1. Passive application: (Bayko et al, 1980, Crigger et al, 1978, Froum et al. 1983)
2. Burnishing technique: Burnishing with saturated cotton pellets , vigorously rubbed using
root planning pressure (Sterrett et al, 1987, Sterrett et al, 1995, Sterrett et al, 1989).
Isik et al, 1997, conducted a study to compare various methods.
Group 1: Immersion in tetracycline HCl solution.
Group II: Placement of saturated cotton pellets
Group III: Burnishing with saturated cotton pellets , vigorously rubbed using root planning pressure.
Group IV: Camel hair brush application
112

109. The tetracycline HCl solution was prepared by slowly adding pure tetracycline HCl* into distilled
water until a saturated solution of 0.5%g/ml was obtained with constant stirring at 37°C for 10
min. This gave a pH 2.11 solution when checked with a pH meter.
The application time of the tetracycline HCl was 5 min and in the groups that the cotton pellets
were used, they were changed in every 30 s and then the areas were rinsed for 30 s with
distilled water.
“According to the results of this SEM study, it may be desirable to apply tetracycline HCl using
burnishing technique to expose maximum intertubular fibrils and for the tubular openings.”
113

110. Loading dose
In pharmacokinetics, a loading dose is an initial higher dose of a drug that may be given at the
beginning of a course of treatment before dropping down to a lower maintenance dose.
A loading dose is most useful for drugs that are eliminated from the body relatively slowly, i.e.
have a long systemic half-life. Such drugs need only a low maintenance dose in order to keep
the amount of the drug in the body at the appropriate therapeutic level,
but this also means that, without an initial higher dose, it would take a long time for the
amount of the drug in the body to reach that level
114

111. Post-surgical antibiotics
Periodontal surgical procedures by their nature carry with them an attendant risk of developing
complications, one among which includes infection
Various anti-infective measures have been advocated to improve clinical outcomes following
surgical intervention. These measures include:
(1) Meticulous professional mechanical debridement,
(2) application of antiseptics in dressings and/or rinses, and
(3) administration of systemic antibiotics.
115

112. Few studies support the concept of rapid healing and less discomfort when antibiotics are
used.[Ariuado et al 1969, Kidd et al 1974 ]
On the other hand, many well-conducted studies have not supported the routine use of
antibiotics after periodontal surgery and concluded that antibiotics should be used only when
there is a medical indication or when the infection has already set in.
[Powell et al, 2005; Scopp et al, 1975; Pack et al, 1983; Checchi et al, 1992; Mahmood et al,
1997; Tseng et al, 1993]
116

113. Studies
A prospective randomized double-blind cross over clinical study (Oswal et al, 2014)
All the patients included in the study for any periodontal surgery were randomly divided into
three categories: A total of 100 surgeries were carried out in 70 patients during the study
Group A (prophylactic): Prophylactic antibiotic (1 g amoxicillin 1 h before the surgery). No antibiotics were
given postoperatively.
Group B (therapeutic): Therapeutic antibiotics were prescribed. Amoxicillin 500 mg tid for 5 days after
surgery.
Group C (no antibiotics): No antibiotics given either prophylactically or postoperatively
117
Oswal S, Ravindra S, Sinha A, Manjunath S. Antibiotics in periodontal surgeries: A prospective randomised cross over clinical trial. Journal of
Indian Society of Periodontology. 2014 Sep;18(5):570.

114. Patients were followed up for 1-week after surgery on the day of suture removal and were
evaluated for pain, swelling, fever, infection, delayed wound healing and any other significant
findings.
“There was no postoperative infection reported in all the 90 sites operated in this study. The
prevalence of postoperative infections following periodontal surgery is <1% and this low risk
does not justify the routine use of systemic antimicrobials just to prevent infections.”
118

115. Studies
Forty-five systemically healthy patients with moderate to severe chronic periodontitis requiring
flap surgery were enrolled in the study. (Mohan et al, 2014)
Antibiotics were started 1 day prior to surgery and continued for 5 days thereafter, wherein
Group A patients were administered Amoxicillin 500 mg three times a day
Group B patients were administered Doxycycline 100 mg once daily.
Group C patients were controls without any antibiotic prescription.
Postoperative assessment of patient variables like swelling, pain, temperature, infection,
ulceration, necrosis, and trismus was performed at intervals of 24 h, 48 h, 1 week, and 3
months.
Changes in clinical parameters such as gingival index, plaque index, probing pocket depth, and
clinical attachment level were also recorded.
119
Mohan RR, Doraswamy DC, Hussain AM, Gundannavar G, Subbaiah SK, Jayaprakash D. Evaluation of the role of antibiotics in preventing postoperative
complication after routine periodontal surgery: A comparative clinical study. Journal of Indian Society of Periodontology. 2014 Mar;18(2):205.

116. There was no incidence of postoperative infection in any of the patients.
Though there was significant improvement in the periodontal parameters in all the groups, no
statistically significant result was observed for any group over the others
“Therefore, prophylactic antibiotics for patients who are otherwise healthy administered
following routine periodontal surgery to prevent postoperative infection are unnecessary and
have no demonstrable additional benefits”
120

117. Studies
The aim of the study is to evaluate the need of antibiotics in periodontal surgeries in
countering postsurgical complication. (Fenol et al, 2014)
The patients who were undergoing periodontal surgery were included in the study and were
randomly divided into two categories
a) Group A-Antibiotic was prescribed post operatively. Amoxicillin 500 mg thrice daily for 5 days
after surgery.
b) Group B -No antibiotic was given postoperatively. (15 patients).
121Fenol A, Boban NC, Jayachandran P, Rajan M. Effectiveness of Antibiotics on Post-Operative Complication after Periodontal Surgery.

118. Results: Assessment was done after 1 and 2 weeks following the periodontal surgical procedure.
It was observed that there was no significant difference in the post- operative outcome in both
the groups.
“The decision to administer antibiotic therapy following periodontal surgery must be case and
patient specific”
122

119. Various other factors are more important in protecting the patient from postoperative
infections. They include aseptic protocol, skill and experience of surgeon, tissue manipulation
and surgical technique, duration of surgery and control of systemic and local risk factors with
increased susceptibility to infections.
If such measures are taken, there is a very low rate of postoperative infection (less than 1%)
following periodontal surgery, thereby eliminating the need for using antibiotics as a
prophylactic measure.
Hence, use of antibiotics should be based on procedural outcomes and should not be
generalized or used blindly just to be extra cautious in preventing infection. (Oswal et al 2014)
123