This document discusses antibiotics used in periodontics. It defines key terms like antibiotic, antimicrobial, and provides classifications of antibiotics based on chemical structure, mechanism of action, spectrum of activity, and source. It outlines guidelines for antibiotic use in periodontal disease, including indications, choosing an antibiotic based on patient and microbe factors, dosing principles, and duration of therapy. Systemic and local antibiotic administration methods are discussed. Common antibiotics used in periodontics that have been extensively evaluated are also listed.

1. Antibiotics used in
periodontics
SHASHI KANT CHAUDHARY
JR I
DEPT OF PERIODONTOLOGY AND ORAL
IMPLANTOLOGY

2. Contents
 Introduction
 Rationale
 Systemic antibiotics used in periodontics
 Local drug delivery
 Conclusion
 References
2

3. Introduction
 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
 The term "antibiotic" was coined by Selman Waksman in 1942
3

4.  Penicillin, the first natural antibiotic discovered by
Alexander Fleming in 1928
 Originally known as antibiosis,
 The term antibiosis, which means "against life," was
introduced by the French bacteriologist Vuillemin as
a descriptive name of the phenomenon exhibited by
these drugs
4

5.  Fleming found that a diffusible substance was
elaborated by Penicillium mould which could
destroy Staphylococcus on the culture plate in 1929
 Chain and Florey followed up this observation in
1939 which culminated the use of Penicillin in
clinical use in 1941
5

6. Terminologies
 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
 Antimicrobial agents: Designate synthetic as well as naturally
obtained drugs that attenuate micro-organisms.
7

7.  Antibiotics: A naturally occurring , semisynthetic, or
synthetic type of anti-infective agent that destroys or
inhibits the growth of selective microorganisms, generally
at low concentrations.
8

8.  Antiseptic: A chemical antimicrobial agent applied
topically or subgingivally to mucous membranes,
wounds or intact dermal surfaces to destroy
microorganisms and inhibit their reproduction or
metabolism.
 Disinfectants: A subcategory of antiseptics, are
antimicrobial agents that are generally applied to
inanimate surfaces to destroy microorganisms
9

9. ANTIBIOTICS IN PERIODONTAL
THERAPY
 The value of administering antimicrobial agents as a quick and
inexpensive means of augmenting mechanical periodontal
debridement is worthy of consideration.
 Periodontitis patients may benefit from systemic antibiotics,
topical antibiotics and topical antiseptics.
10

10.  The microbial etiology of inflammatory periodontal diseases
provides the rationale for use of antibiotics in periodontal
therapy.
 The ability of the organism to cause a disease depends upon
the characteristic end products of bacterial metabolism, the
chemical composition of bacterial components and its
ability to overwhelm host.
 Systemic antibiotics may be a necessary adjunct in
controlling bacterial infection because bacteria can invade
periodontal tissues, making mechanical therapy alone
sometimes in effective.
Rationale 11

11. Ideal antibiotics
 Toxic to microbes and not to humans
 Bactericidal rather than bacteriostatic
 Specific for periodontal pathogens
 Should not be allergic and hypersensitive reactions
 Should be active in plasma, and other body fluids
 Desired levels should be reached rapidly and maintained
for adequate period of time.
 Should not cause drug resistance, long shelf life,
 Inexpensive
12

12. Classification
1. On the basis of chemical structure:
 Sulphonamides and related drugs: Sulphadiazene
 Quinolones: Nalidixic acid, Norfloxacin
 β-lactam antibiotics: penicillins
 Tetracyclines
 Aminoglycosides
 Macrolides
 Glycopeptide antibiotics: Vancomycin
 Nitroimidazole: Metronidazole, Tinidazole
13

13. 2. Mechanism of action
 Inhibit cell wall synthesis
–penicillins, cephalosporins, vancomycin
 Cause leakage from cell membranes
–polymyxins, bacitracin, nystatin
 Inhibit protein synthesis
–tetracyclines, chloramphenicol, erythromycin
 Cause misreading of m-RNA code and affect
permeability –aminoglycosides
14

14.  Inhibit DNA gyrase
–fluoroquinolones
 Interfere with DNA function
–metronidazole, rifampicin
 Interfere with DNA synthesis
–idoxuridine, acyclovir
 Interfere with intermediary metabolism
–sulfonamides, trimethoprim
15

15. 16

16. 3. Group of organisms against which primarily active
•Antibacterial—penicillins, aminoglycosides
•Antifungal---griseofulvin, amphotericin-B
•Antiviral—idoxuridine, acyclovir
•Antiprotozoal—chloroquine, pyrimethamine
•Antihelmintic---mebendazole, pyrantel
17

17. On the basis of Spectrum of activity
 Narrow spectrum- penicillin G, erythromycin
 Broad spectrum- tetracyclines, chloramphenicol
18

18. Type of action
 Bacteriostatic---sulfonamides, tetracyclines, erythromycin
 Bactericidal---penicillins, aminoglycosides, cephalosporins
Bacteriostatic
 Antimicrobial agents that reversibly inhibit growth of bacteria
are called as bacteriostatic
Bactericidal
 Those with an irreversible lethal action on bacteria are known
as bactericidal
19

19. On the basis of Source of antibiotics
 Fungi—penicillin, griseofulvin, cephalosporin
 Bacteria—polymyxinB, bacitracin
 Actinomycetes—aminoglycosides, macrolides,
tetracyclines, chloramphenicol
20

20. INDICATIONS FOR ANTIBIOTICS IN
PERIODONTAL THERAPY
 Patients who do not respond to conventional periodontal
therapy,
 Patients with acute periodontal infections with systemic
manifestations,
 Prophylaxis in medically compromised patients
 As an adjunct to surgical and non-surgical periodontal
therapy.
AJ Van Winkelhoff, TE Rams, J Slots. Systemic antibiotics in periodontics.
Periodontol2000. 1996; 10: 45-78
21

21. GUIDELINES FOR USE OF ANTIBIOTICS
IN PERIODONTAL DISEASE
 The clinical diagnosis and situation dictate the need for possible
antibiotic therapy
 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.
 Antibiotics are selected based on the patient's medical and
dental status, current medications, and results of microbial
analysis, if performed
22

22.  Microbial plaque samples may be obtained from
individual pockets with recent disease activity or from
pooled subgingival sites.
 Studies have shown that systemic antibiotics can
improve attachment levels when they are used as
adjuncts to scaling and root planing.
23

23.  systemic antibiotics were used as adjuncts to scaling and root
planing, improvements were observed in the attachment
levels of patients with chronic and aggressive periodontitis,
although patients with aggressive periodontitis experienced
greater benefits
24

24.  The identification of which antibiotics were most effective for
the treatment of destructive periodontal diseases (only
tetracycline and metronidazole were shown to significantly
improve attachment levels)
 Debridement of root surfaces, optimal oral hygiene, and
frequent periodontal maintenance therapy are important
parts of comprehensive periodontal therapy
25

25. Guidelines for use of antimicrobial therapy
27

26. 28

27. ADVERSE EFFECTS OF ANTI
MICROBIAL AGENTS:
 Allergic/anaphylactic
 Superinfection of opportunistic
 Development of resistant
 Interaction with other drugs
 Stomach upset, nausea, vomiting
 Most common GIT upset
29

28. CHOICE OF AN ANTIMICROBIAL AGENT
1. PATIENT FACTORS
 Age
May affect kinetics of many AMAs. Eg: tetracycline
accumulate in developing teeth and bones. Hence are
contraindicated < 8 yrs
 Renal and hepatic function
•Renal failures: aminoglycosides, vancomycin,
cephalosporin, metronidazole
•Liver disease: erythromycin, tetracycline,
nalidixicacid, chloramphenicol
30

29.  LocalFactors
•Presence of pus and secretions decrease the efficacy
of most AMAs esp. sulfonamides and
aminoglycosides
•Presence of necrotic material and foreign body
makes eradication of infection practically impossible
•Hematomas foster bacterial growth eg: tetracycline,
penicillin and cephalosporin get bound to degraded
Hb in the hematoma
31

30. •Lowering of pH at site of infection reduces activity of
macrolide and aminoglycosides
•Anaerobic environment in the Center of an abscess
impairs bacterial transport processes which concentrate
aminoglycosides in the bacterial cell
•Penetration barrier may hamper the access of the AMA to
the site of infection in sub acute bacterial endocarditis
32

31.  Drug allergy: History of previous exposure to an AMA
 Impaired host defense : Cidal drugs is imperative in those
with impaired host defense, normal host defense, a
bacteriostatic antibiotic
 Pregnancy: safety of the drug
33

32. 2. ORGANISM RELATED CONSIDERATIONS
 Clinical diagnosis
 Culture and sensitivity testing
When bacteriological services not available, empirical
therapy to cover all likely organisms with abroad spectrum
drug may be used
34

33. MICROBIAL TESTING
 Should be completed initially to determine which species
are present and the most effective antibiotic for targeting
them
(Shaddox and Walker, 2009; Fine, 1994)
 Re-testing
•to ensure that the antibiotic is successful;
•At an interval of 3months
35

34. 3. DRUG FACTORS
Based on the specific properties of the AMAs—
 Spectrum of activity— narrow spectrum drug is
preferred
 Type of activity— bactericidal preferred over
bacteriostatic
 Sensitivity of the organism determined on the basis of
MIC values
 Relative toxicity— a less toxic drug is preferred
36

35. DRUG FACTORS
 Pharmacokinetic profile— to be present at the site of
infection insufficient concentration for an adequate
length of time
 Route of administration— oral or parenteral
 Evidence of clinical efficacy—the drug, its optimum
dosage and duration of treatment are based on
comparative clinical trials
 Cost—less expensive drug preferred
37

36. FACTORS THAT PLAY A ROLE IN THE
EFFICACY IN THE PERIODONTAL AREA
 Drug binding to tissues
 Protection of key organisms thru binding and/or
consumption of the drug by non-target microorganisms
 Microbial invasion of periodontal tissues and root
surfaces
 Total bacterial load in the periodontal pocket in relation
to maximum achievable antibiotic concentration
38

37.  Periodontal pathogens may reside on buccal surfaces, tongue
tonsils and gingiva
 Microorganisms in biofilms are more resistant to bactericidal
actions of antibiotics in comparison to planktonic cells
 Bacteriostatic tetracycline can suppress susceptible
pathogens but are notable to completely eradicate some key
subginigval pathogens
 Penicillin and other B –lactam antibiotics may be inactivated
by bacterial derived B-lactamases especially inpatients with
recent penicillin exposure
Arie jan van winkelhoff, Thomas e. rams & Jorgen slots. Systemic antibiotic
therapy in periodontics. Periodontology 2000, 1996 ; 10: 45-78
39

38. ANTIBIOTIC DOSING PRINCIPLES
1) Employ high doses for a short duration: High concentrations are
more critical with aminoglycosides, metronidazole and
quinolones
2) Use an oral antibiotic loading dose
3) Achieve blood levels of the antibiotic at 2-8 times the minimal
inhibitory concentration
4) Use frequent dosing intervals: so as to maintain relatively
constant blood levels.
5) Determine the duration of therapy by the remission of disease
Pallasch TJ. Pharmacokinetic principles of antimicrobial therapy.
Periodontol 2000 1996;10:5-11
40

39. ANTIBIOTIC DOSING VARIABLES
 Diffusion to site of infection, lipid solubility,
 Plasma protein binding,
 Inoculum effect,
 Surface area to volume ratio
 Altered patient physiology (pregnancy, age, kidney
and liver function).
41

40.  Two critical factors should be specifically
considered in selecting a systemic antibiotic
in periodontal therapy
1. Gingival fluid concentration
2. Minimum inhibitory concentration
Goodson JM. Antimicrobial strategies for treatment of
periodontal diseasesa. Periodontol 2000 1994;5:142-68
42

41.  The gingival fluid concentration (CGCF) provides
information on the peak levels achieved by systemic
delivery at the primary ecological niche for periodontal
pathogens, the periodontal pocket.
43

42.  The 90% minimum inhibitory concentration (MIC90) is an
in vitro determination of the concentration that will inhibit
growth of 90% of the bacterial strains of a species that are
tested.
 Antimicrobial activity can be defined as a relationship
between CGCF and MIC90
44

43. POST-ANTIBIOTIC EFFECT
 Short dosing intervals to maximize the time of exposure
of microorganism are preferred for time dependent
antibiotics with no significant post-antibiotic effects.
45

44. DURATION OF ANTIBIOTIC THERAPY
 The ideal duration of antibiotic therapy is the shortest
that will prevent both clinical and microbiological relapse
46

45.  Slots et al. described a series of steps using anti-infective
agents for enhancing regenerative healing. They
recommend starting antibiotics 1-2 days before surgery
and continuing for a total of at least 8 days, however, the
value of this regimen has not been well documented.
47

46.  Acute orofacial infections have a rapid onset and
relatively short duration of 2-7days or less
(Van Winkelhoff and Winkel, 2005)
48

47. Administration
 Systemic administration
 Local administration
49

48. ADVANTAGES OF SYSTEMIC
ANTIBIOTIC THERAPY
 Simple, easy administration of drug to multiple
sites of disease activity
 Eliminate or reduce pathogens on oral mucosa
and extra-dental sites
50

49. DISADVANTAGES OFSYSTEMIC
ANTIBIOTIC THERAPY
 In ability to achieve high GCF concentration
 Increased risk of adverse drug reactions
 Increased selection of multiple antibiotic resistant
micro-organisms
 Uncertain patient compliance
51

50. 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.Ampicillin
7.Amoxicillin 8.Metronidazole
Goodson JM. Antimicrobial strategies for treatment of periodontal diseases.
Periodontol 2000. 1994;5:142–68
52

51. Tetracycline
 Produced naturally from certain species of Streptomyces or
derived semi-synthetically
 Bacteriostatic drugs, effective against rapidly multiplying
bacteria and gram positive bacteria than gram negative
bacteria
 Concentration in the gingival crevice is 2-10 times than in
serum
 Possess unique non-antibacterial characteristics-collagenase
inhibition, inhibition of neutrophil chemotaxis, anti-
inflammatory effects, inhibition of microbial attachment and
root surface conditioning
54

52.  Mode of action
 Act by inhibition of protein synthesis by binding to 30 S
ribosomes in the susceptible organism
 Clinical use
 Adjuncts in the treatment of localized aggressive
periodontitis (LAP)
 Arrest bone loss and suppress A. actinomycetemcomitans
levels in conjunction with scaling and root planing
 Dosage regimen
 250 mg four times daily, inexpensive, lesser compliance
55

53.  Minocycline and Doxycycline are semisynthetic
members of the tetracycline group that have been
used in periodontal therapy
56

54. Minocycline
 Effective against a broad spectrum of microorganisms
 Suppresses spirochetes and motile rods as effectively as
scaling and root planing, with suppression evident up to 3
months after therapy
 Can be given twice daily, thus facilitating compliance
57

55.  Although associated with less phototoxicity and renal
toxicity than tetracycline, may cause reversible vertigo
 Yields gingival fluid levels 5 times blood levels
 Except for the effect of minocycline on actinomycetes, none
of the tetracyclines substantially inhibit the growth of oral
gram-positive organisms by systemic delivery
 Dosage of administration: 200 mg/day
58

56. Doxycycline
 Same spectrum of activity as Minocycline
 Compliance is favored since it has to be taken once daily, absorption
from gastrointestinal tract is only slightly altered by calcium, metal
ions, or antacids
 The recommended dosage is 100 mg bid the first day, then 100 mg
o.d
 To reduce gastrointestinal upset, 50 mg can be taken bid
59

57. Metronidazole
 A synthetic nitroimidazole compound with bactericidal effects
primarily exerted on obligate gram-positive and gram-negative
anaerobes
 Campylobacter rectus is the only facultative anaerobe and
probable periodontal pathogen that is susceptible to low
concentrations of metronidazole
 Spectrum of activity-outstanding treatment for Fusobacterium
and Selenomonas infections
60

58.  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, does not substantially suppress growth
beneficial species
 The concentrations measured in gingival fluid are generally
slightly less than in plasma
61

59.  Mode of action
 Metronidazole acts by inhibiting DNA synthesis
62

60. Clinical use
 For treating gingivitis, acute necrotizing ulcerative gingivitis,
chronic periodontitis, and aggressive periodontitis
 As monotherapy, Metronidazole is inferior, should be used
in combination with root planing, surgery or with other
antibiotics
 The most commonly prescribed regimen is 250 mg tid for 7
days
63

61. In a study by Haffajee et al., sites with initial pocket depth
≥6 mm showed significantly greater pocket depth
reduction and greater attachment gain in subjects
receiving Metronidazole or Azithromycin than in subjects
who received Doxycycline
64

62.  Side effects
 Severe cramps
 Nausea
 Vomiting and metallic taste
 Avoid in patients with history of alcohol taking,
patients on anticoagulant therapy
65

63. Penicillin
 Natural and semi synthetic derivatives of broth cultures of
the Penicillium mould
 Narrow spectrum and bactericidal in nature
 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
66

64.  Mode of action
 Interfere with the synthesis of bacterial cell wall, inhibit the
transpeptidases so that cross linking does not take place
 Clinical use
 In the management of patients with aggressive periodontitis,
in both localized and generalized forms
 Recommended dosage is 500 mg tid for 8 days
 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
67

65.  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
68

66.  Amoxicillin alone is not effective for treatment of chronic
and aggressive periodontitis but effective in combination
with metronidazole
(Soaresetal.,2012; Rabeloetal.,2015)
69

67. Amoxicillin-Clavulanate (Augmentin)
 The generally accepted strategy is to administer amoxicillin with an
inhibitor of beta-lactamase such as Clavulanic acid
 Beta-lactamase producing strains are generally sensitive to this preparation
 Augmentin may be useful in the management of patients with refractory or
localized aggressive periodontitis patients
 In guided tissue regeneration, systemic amoxicillin-Clavulanic acid therapy
has been used to suppress periodontal pathogens and increase the gain of
clinical attachment
70

68. Cephalosporin
 Used for infections that might otherwise be treated with
penicillin
 Resistant to a number of β-lactamases normally active
against penicillin
 Mode of action
 Same mode of action as penicillin, i.e., inhibition of
bacterial cell wall synthesis
 However, they bind to different proteins than those which
bind penicillin
71

69.  Clinical use
 Cephalexin is a cephalosporin available for administration in
an oral dosage form
 Achieves high concentrations in GCF
 Effectively inhibits growth of gram-negative obligate
anaerobes, fails to inhibit the gram-negative facultative
anaerobes
 Newer Cephalosporin with extended gram-negative
effectiveness could be of value in treatment of periodontal
disease conditions
72

70. Clindamycin
 Effective against anaerobic bacteria, and in patients
allergic to penicillin
 Mode of action
 Inhibition of protein synthesis by binding to 50 S
ribosome
 Clinical use
 Clindamycin achieves higher levels of antimicrobial
activity than other antibiotics
73

71.  Gordon et al observed a mean gain of clinical attachment of 1.5
mm and a decrease of disease activity in patients 24 months
after adjunctive Clindamycin therapy
 Walker et al. showed that Clindamycin assisted in stabilizing
refractory patients
 Dosage was 150 mg qid for 10 days
 Jorgensen and Slots recommended a regime of 300 mg bid for 8
days
74

72. Ciprofloxacin
 A fluorinated 4-quinolone antibiotic available for oral
administration
 A potent inhibitor of gram negative bacteria (all
facultative and some anaerobic putative periodontal
pathogens), including Pseudomonas aeruginosa, with
MIC90 values ranging from 0.2 to 2 μg/ml
75

73.  Mode of action
 Inhibition of bacterial DNA replication and
transcription by inhibiting the enzyme DNA gyrase, an
enzyme unique to prokaryotic cells
76

74.  Clinical use
 Facilitates the establishment of a microflora associated with
periodontal health, minimal effects on streptococcus species,
which are associated with periodontal health
 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)
77

75. Macrolides
 Contain a poly-lactone ring to which one or more deoxy
sugars are attached
 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, spiramycin, and azithromycin
78

76.  Mode of action
 Inhibit protein synthesis by binding to the 50 S
ribosomal subunits of sensitive microorganisms
interfere with translation
79

77. Erythromycin
 Clinical use
 An extremely safe drug that has often been
recommended as an alternative to penicillin for allergic
patients
 Gingival fluid levels suggest that only a small portion
reaches the periodontal pocket by oral route
80

78.  Principle limitation of erythromycin is its poor tissue
absorption
 Preparations for systemic administration are available as
pro-drugs (erythromycin estolate, erythromycin stearate or
erythromycin ethyl succinate) to facilitate absorption
 The pro-drug has little antibacterial activity until
hydrolyzed by serum esterases
81

79. Spiramycin
 It is excreted in high concentrations in saliva
 The results of various clinical trials have revealed good
efficacy of spiramycin in the treatment of periodontitis and
meta-analysis of these studies revealed high levels of
evidence supporting its efficacy
 It has been shown to reduce gingival crevicular fluid volume,
pocket depth and subgingival spirochete levels
82

80.  Herrera et al. in a meta analysis evaluating Spiramycin,
amoxicillin plus Metronidazole, and Metronidazole showed a
statistically significant additional effect of Spiramycin in
comparison to other antibiotics with regard to probing pocket
depth reduction for sites with initial probing depth of more
than 6 mm
 Clinical use
 Effective against gram positive organisms, has minimal effect
on increasing attachment levels
83

81. Azithromycin
 Effective against anaerobes and gram negative bacilli
 After an oral dosage of 500 mg o.d for 3 days, significant
levels of Azithromycin can be detected in most tissues for 7-
10 days
 It has been proposed that Azithromycin penetrates
fibroblasts and phagocytes in concentrations 100-200 times
greater than that of extracellular compartment
84

82.  The azithromycin is actively transported to sites of
inflammation by phagocytes, then directly released into
the sites of inflammation as phagocytes rupture during
phagocytosis
 Therapeutic use requires a single dose of 250 mg/day for
5 days after initial loading dose of 500 mg
85

83. Aminoglycosides
 Inhibit protein synthesis by binding irreversible to a
particular protein or proteins of the 30 S ribosomal subunit
 Are inactive under anaerobic conditions because intracellular
transport is severely impaired in the absence of oxygen
 Therefore, all anaerobic bacteria are markedly resistant even
though they contain ribosomes that are sensitive to these
antibiotics
86

84. Therapeutic Uses of Systemic
Antimicrobial Agents for Various
Periodontal Diseases
87

85. There are five daunting problems that have
slowed progress of antibiotic therapy are
 Periodontal diseases are heterogeneous
 Clinical diagnoses are made on the basis of clinical signs, not
molecular pathology
 The actual causal factor(s) have not been definitively identified
 No microbiological sampling
 There are many different antibiotic protocols but few well
designed, randomized controlled trials that test the efficacy of
these protocols
Ellen RP, Mcculloch CA. Evidence versus empiricism: Rational use of systemic
antimicrobial agents for treatment of periodontitis. Periodontol 2000.
1996;10:29–44
88

86. Serial systemic therapy
 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 or metronidazole) is given concurrently
 When both types of drug are required, they are best given serially,
not in combination, to avoid unfavourable interaction yet derive
the benefit of both
89

87. 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
van Winkelhoff AJ, Rams TE, Slots J. Systemic antibiotic therapy
in periodontics. Period ontol 2000 1996;10:45-78
90

88. Advantage
(i) empirical treatment of severe infections
(ii) treatment of polymicrobial infections
(iii) prevention of the emergence of bacterial resistance
(iv) increased effectiveness from antibiotic synergism (more than
additive)
91

89. Disadvantages
 increased adverse reactions
 antagonistic drug interactions with improperly
selected antibiotics
 Superinfections with Candida or other microbes owing
to major suppression of the indigenous microbiota
Rybak MJ, McGrath BJ. Combination antimicrobial therapy for bacterial
infections. Guidelines for the clinician. Drugs 1996: 52: 390–405.
92

90. Amoxicillin-metronidazole
 most common antibiotic combination in periodontics
 Amoxicillin exerts antimicrobial synergy with metronidazole
against periodontal pathogens
 250 mg of amoxicillin and 250 mg of metronidazole, three
times daily for 8 days
 A-M is particularly effective against A.a infections (Slots et
al.2002)
93

91.  A-M combination therapy used as the sole periodontal
treatment has yielded a clinical outcome similar to that
of scaling and root planing
Lo´pez NJ, Socransky SS, Da Silva I, Japlit MR, Haffajee AD Effects of metronidazole
plus amoxicillin as the only therapy on the microbiological and clinical parameters of
untreated chronic periodontitis. J Clin Periodontol 2006: 33: 648–660
94

92.  the most promising drugs for the treatment
of periodontal diseases are metronidazole
or the combination of metronidazole +
amoxicillin
95

93. Ciprofloxacin - metronidazole
 500 mg of each drug, twice daily for 8 days
 valuable alternative for penicillin-allergic periodontitis patients
 Unique antimicrobial benefit
 Non periodontopathic viridans streptococci exhibit resistance to
both and dominate the periodontal micro-biota post-treatment
 delay pocket colonization by pathogenic species
96

94. Clinical reasons for antibiotic failure
 Inappropriate choice of antibiotic
 Emergence of antibiotic-resistant microorganisms
 Too low a blood concentration of the antibiotic
 Slow growth rate of microorganisms
 Impaired host defenses
Pallasch TJ, 1996
97

95.  Patient noncompliance
 Antibiotic antagonism
 Inability of the antibiotic to penetrate to the site of the infection
 Limited vascularity or decreased blood flow
 Unfavorable local factors (decreased tissue pH or oxygen tension)
 Failure to eradicate the source of the infection (lack of incision
and drainage)
98

96. LOCAL DRUG DELIVERY
Goodson et al in 1979 first proposed the concept of
controlled delivery in the treatment of periodontitis.
The first delivery devices involved hollow fibers of cellulose
acetate filled with tetracycline. They were primarily local
delivery devices with minimal control of drug release
However ,Tetracycline fibers are no longer commercially
available
99

97. LOCAL DRUG DELIVERY
 provides long-term retention of a highly concentrated drug at
the base of the periodontal pocket
 Periodontal pockets provide natural reservoir bathed by
gingival crevicular fluid that is easily accessible for the insertion
of a delivery device.
 Controlled drug delivery-more prolonged availability and
sustained action.
100

98. For local chemotherapy (drug delivery) to be effective, it
must meet 3 requirements:
 Reach the site of disease activity namely the base of
the pocket,
 Be delivered at a bacteriostatic or bactericidal
concentration,
 Remain in place long enough to be effective
101

99. INDICATIONS FOR LDD
 As an adjunct to Scaling and Root planing
 Periodontal maintenance therapy: Recurrent periodontitis
usually involves only a few teeth. These sites are ideal for the
treatment with this device.
 Medically compromised patients for whom surgery is not an
option or those who refuse surgical treatment.
 To halt the progression of periodontal disease in patients with
moderate periodontitis.
102

100. Classification
1. Personally applied (in patient home self-care)
A. Nonsustained subgingival drug delivery(home oral
irrigation)
B. Sustained subgingival drug delivery(none developed to
date)
2. Professionally applied (in dental office)
A. Nonsustained subgingival drug (professional pocket
irrigation)
B. Sustained subgingival drug delivery (controlled- release
device)
103

101. ADVANTAGES OF LOCAL DRUG
DELIVERY
 Can attain 100-fold 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 dependence of patient
compliance
 May employ antimicrobial agents not suitable for systemic
administration.
104

102. DISADVANTAGES
 Difficulty in placing into deeper parts of periodontal pockets
and furcation lesions.
 Lack of adequate manual dexterity limited understanding of
periodontal anatomy, & poor compliance limits the use as
home self-care procedures
 Time-consuming and labor-intensive.
 Do not markedly affect periodontal pathogens residing within
adjacent gingival connective tissues and on extra pocket oral
surfaces, which increases the risk of reinfection.
105

103. LOCAL DELIVERY AGENTS
•Tetracycline
•Doxycycline
•Minocycline
•Metronidazole
•Moxifloxacin
•Azithromycin
•Chlorhexidine
106

104. TETRACYCLINE CONTAINING FIBER
 The first local delivery product
 Tetracycline fibers with 12.7mg per 9 inches, an
ethylene/vinyl acetate copolymer fiber 0.5mm diameter
and 23 cm long
 It was well tolerated in oral tissues and concentration
reach 1300μg/ml for 10 days
 No change in antibiotic resistance to tetracycline was
found
 ACTISITE, PERIODONTAL PLUS AB
 These fibers are no longer commercially available
107

105. DOXYCYCLINE
 A gel system using a syringe with 10% doxycycline
(Atridox).
 only local delivery system accepted by the American
Dental Association
 1500mcg/ml in 2 hrs and remains >1000mcg/ml
through18 hrs
109

106.  The combined use of systemically delivered
doxycycline hyclate (20 mg twice daily) plus locally
delivered doxycycline hyclate gel (10%) in
combination with scaling and root planning provided
statistically significantly greater clinical benefits
Novak MJ, Dawson DR, 3rd, Magnusson I, et al: Combining host modulation and
topical antimicrobial therapy in the Management of moderate to severe
periodontitis: a randomized multicenter trial. J Periodontal 79(1):33, 2008.
110

107. MINOCYCLINE
 A locally delivered sustained release form of
minocycline microspheres (arestin).
 The 2% minocycline is encapsulated into
bioresorbable microspheres in gel carrier.
112

108.  Grace et al evaluated topical locally delivered minocycline
as an adjunctive to non-surgical periodontal treatment
and found advantageous outcome for nonsurgical
periodontal treatment in terms of probing attachment
level and bleeding on deep probing.
113

109. METRONIDAZOLE
 A topical medication containing an oil based
metronidazole 25% dental gel. (glyceryl monooleate
and sesame oil)
 Two 25% gel application at a 1- week interval have
been used.
115

110.  Studies have shown that metronidazole gel is
equivalent to scaling and root planing, but they have
not shown adjunctive benefits with scaling and root
planing
 Bleeding on probing was reduced by 88% of cases.
116

111. Moxifloxacin
 fourth-generation synthetic fluoroquinolone with
 broad-spectrum antibacterial
 Antimicrobial activity against aerobic and anaerobic bacteria,
including a number of periodontal pathogens
 the local delivery of 0.4% moxifloxacin may be of benefit as
an adjunct to scaling and root planning for the treatment of
periodontitis
118

112. AZITHROMYCIN
 Has a wide antimicrobial spectrum of action towards an
aerobic bacteria & Gram-negative bacilli. It is effective
against periodontal pathogens such a s A.a & P.g
119

113. Tyagi et al investigated the clinical effectiveness of AZM at a
concentration of 0.5%In an indigenously prepared
bioabsorbable controlled release gel as an adjunct to non
surgical mechanical therapy in the treatment of chronic
periodontitis. Although both treatment strategies seem to
benefit patients, the adjunctive use of 0.5%ofAZM showed
better results.
120

114. Choice of LDD
Several local anti-infective agents combined with SRP appear to
provide additional benefits in PD reduction and CAL gain compared
to SRP alone. The decision to use local anti-infective adjunctive
therapy remains a matter of individual clinical judgment, the phase
of treatment, and the patient's status and preferences
Hanes PJ, Purvis JP. Local anti-infective therapy: pharmacological agents. A
systematic review. Ann Periodontol. 2003 Dec;8(1):79-98.
121

115. Comparative study
In a study, attempted to compare LDD devices doxycycline
polymer, metronidazole gel, and PerioChip were compared in 47
periodontal patients. The study found that all controlled-release
polymer devices increased gingival attachment levels but there
was a slightly greater improvement with the doxycycline
polymer
Salvi GE, Mombelli A, Mayfield L, et al: Local antimicrobial therapy after
initial periodontal treatment. J Clin Periodontol 29:540, 2002
122

116. CHLORHEXIDINE
 A resorbable delivery system resorbs in 7-10 days.
 No signs of staining were noted in any of the studies!!
 PERIOCHIP, PERIOCOL-CG
123

117.  Studies have shown suppression of pocket flora for
upto11 weeks following treatment with periochip
Paquette DW, Ryan ME, Wilder RS 2008
 Largest effect on PPD reduction—tetracycline fibres,
doxycycline, minocycline
 Highest effect for CAL gain—CHX xanthan gel
Matesanz-Pe´rezP 2013
124

118. COMPARISON OF SYSTEMIC AND
LOCAL ANTIBIOTIC THERAPY-
Issue Systemic administration Local delivery
Drug distribution Wide distribution Narrow effective range
Drug concentration Variable levels in
different body
compartments
High dose at treated
low levels else where
Therapeutic potential May reach widely
distributed micro-
organisms
may act locally on
biofilm associated
bacteria better
Problems Systemic side effect Re-infection from non-
treated sites
Clinical limitation s Requires good patient
compliance
infection limited to the
treated site
Mombelli,2012
125

119. Antibiotic prophylaxis
 Recommended when these patients undergo
procedures that are at risk for producing bacteremia.
 incidence of infections such as IE ranges from 5.0 to 7.9
per 100,000 person-years with a significant increasing
trend among women
126

120. RECENT AHA REVISION IN
ANTIBIOTIC PROPHYLAXIS
 Only an extremely small number of cases of IE might be
prevented by antibiotic prophylaxis for dental procedures
even if such prophylactic therapy were 100% effective.
 IE prophylaxis for dental procedures is reasonable only for
patients with underlying cardiac conditions associated with
the highest risk of adverse out-come
127

121. 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
129

122.  Congenital heart disease(present from birth)
 unrepaired cyanotic congenital heart disease, including palliative
shunts and conduits
 a completely repaired congenital heart defect with prosthetic
material or device, whether placed by surgery or by catheter
intervention, during the first six months after the procedure
 any repaired congenital heart defect with residual defect at the site
or adjacent to the site of a prosthetic patch or a prosthetic device
(that inhibit endothelialization)
 Except for the conditions listed above, antibiotic prophylaxis
is no longer recommended for any other form of congenital
heart disease.
130

123. American Heart Association guidelines for dental
procedures for which endocarditis prophylaxis is
recommended
 All dental procedures that involve manipulation of
gingival tissue on the periapical region of teeth or
perforation of the oral mucosa
132

124. Procedures do not need prophylaxis
 Routine anesthetic injections through non-infected tissue
 Taking dental radiographs
 Placement of removable prosthodontic or orthodontic appliances
 Adjustment of orthodontic appliances
 Placement of orthodontic brackets
 Shedding of deciduous teeth
 Bleeding from trauma to the lips or oral mucosa
135

125. Antibiotic prophylaxis for infective
endocarditis
 Standard general prophylaxis
 Amoxicillin
 Adult dose: 2 g PO
 Pediatric dose: 50 mg/kg PO; not to exceed 2 g/dose
 Unable to take oral medication
 Ampicillin
 Adult dose: 2 g IV/IM
 Pediatric dose: 50 mg/kg IV/IM; not to exceed 2 g/dose
Antibiotic Prophylactic Regimens for Endocarditis , Mary L Windle, PharmD; Karlheinz Peter, MD,
PhD (13 jan 2015)
136

126.  Allergic to penicillin
 Clindamycin
 Adult dose: 600 mg PO
 Pediatric dose: 20 mg/kg PO; not to exceed 600 mg/dose
 Cephalexin or other first- or second-generation oral
cephalosporin in equivalent dose
 Pediatric dose: 50 mg/kg PO; not to exceed 2 g/dose
 Azithromycin or Clarithromycin
 Adult dose: 500 mg PO
 Pediatric dose: 15 mg/kg PO; not to exceed 500 mg/dose
137

127.  Allergic to penicillin and unable to take oral medication
 Clindamycin
 Adult dose: 600 mg IV
 Pediatric dose: 20 mg/kg IV; not to exceed 600 mg/dose
 Cefazolin or ceftriaxone
 Adult dose: 1 g IV/IM
 Pediatric dose: 50 mg/kg IV/IM; not to exceed 1 g/dose
138

128. Additional Considerations
 “If the dosage of antibiotic is inadvertently not
administered before the procedure, the dosage may be
administered up to 2 hours after the procedure.”
 patients who require prophylaxis but are already taking
antibiotics for another condition. In these cases, the
guidelines for infective endocarditis recommend that the
dentist select an antibiotic from a different class than the
one the patient is already taking
139

129. Concluding with few queries
What is the significance of the periodontal biofilm when
prescribing systemic antibiotics?
 Periodontitis is an infection caused by bacteria residing
in biofilms
 within a mature biofilm structure they have a reduced
susceptibility to antimicrobials compared to planktonic
or free floating bacteria concentration of 500 time more
is needed
 mechanical debridement - critical to disrupt the biofilm
140

130. Should antibiotics be used as a monotherapy in the treatment
of periodontitis?
 Haffajee et al the effect of the antibiotic alone was minimal
and short term.
 Lopez et al showed similar clinical results for scaling and root
planing as for antibiotics (amoxicillin plus metronidazole)
prescribed as a monotherapy
 But the majority of studies do not support the concept of
monotherapy with inferior results
141

131. Do adjunctive systemic antibiotics offer an advantage over
non-surgical mechanical therapy alone for the treatment of
chronic periodontitis?
 The majority of case can be successfully treated following
mechanical debridement, adequate oral hygiene and
regular maintenance care
 Hererra et al. concluded that systemic antibiotics used in
conjunction with SRP can offer an additional benefit over
SRP alone
 Haffajee et al.also reported similar finding
142

132. Choice of systemic antibiotic – which antibiotic is the best
to use?
 Periodontitis is a mixed microbial infection making the
choice of antibiotic regimen difficult
 the literature does not provide a clear indication of the
superiority of one antibiotic regimen over another and
the choice of antibiotic should be made on an individual
basis
143

133. What is the ideal duration and dosage of the antibiotic?
 there is no consensus on the ideal regimen
 In principle important to prescribe in sufficient dose
for adequate duration.
144

134. Common Antibiotic Regimens Used to Treat
Periodontal Diseases
145

135. In which phase of the mechanical treatment should the
antibiotic be prescribed?
 Two different questions
 (i) should the antibiotic(s) be administered during the
active phase of therapy or on re-evaluation (i.e. 3 or 6
months after active treatment);
 (ii) should the antibiotic(s) be administered on the first
or last day of the scaling and root planing procedure
146

136.  Indirect evidence suggests that antibiotic intake
should start on the day of debridement completion
and debridement should be completed within a short
period of time (< 1 week)
147

137. How critical is patient compliance when using adjunctive
antibiotics?
 studies have shown that as little as 20 per cent of
patients comply with antibiotic regimens prescribed
 If a patient is non-compliant with oral hygiene measures
and maintenance protocols
 Prescription of antibiotics is no substitute for adequate
debridement, good oral hygiene and regular
maintenance care
148

138. Are adjunctive systemic antibiotics useful for the
treatment of aggressive periodontitis?
 Frequently associated with A.a and P.g which have
potential to invade the periodontal tissue
 adjunctive antibiotics may be required to eradicate or
suppress these pathogens
 In the systematic review by Hererra et al. it was
concluded that adjunctive systemic antibiotics should
be considered in cases of aggressive periodontitis
149

139. Should antibiotics be used when regenerative periodontal
therapy is attempted?
 limited evidence for the additional benefit of systemic
antibiotics for the regenerative outcome
 The rationale for use of the antibiotics is to prevent
postsurgical infection, particularly if membrane exposure
occurs and to optimize the potential for regeneration.
150

140. Periodontal abscess – should systemic antibiotics be
prescribed?
 The role of systemic antibiotics is controversial.
 Some authors advocate use of systemic antibiotics as
adjunct
 Others recommend only if a clear systemic involvement is
present ( lymphadenopathy, fever or malaise or when the
infection is not well localized)
 Mechanical debridement and drainage through the
periodontal pocket usually effective
151

141.  most prevalent bacterial species is Porphyromonas
gingivalis, with a range in prevalence of 50–100%
 The drug with the most appropriate profile is
metronidazole (250 mg, three times daily).
 Azithromycin (500 mg, once per day)
 Amoxicillin plus clavulanate (500 + 125 mg, three times
daily)
 The duration, restricted to the duration of the acute lesion,
which is normally 2–3 days.
152

142. 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
154

143.  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
155

144. Thank you
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