An antibiotic is an agent that either kills or inhibits the growth of a microorganism.
The term antibiotic was first used in 1942 by Selman Waksman and his collaborators in journal articles to describe any substance produced by a microorganism that is antagonistic to the growth of other microorganisms in high dilution.[3] This definition excluded substances that kill bacteria but that are not produced by microorganisms (such as gastric juices and hydrogen peroxide). It also excluded synthetic antibacterial compounds such as the sulfonamides. Many antibacterial compounds are relatively small molecules with a molecular weight of less than 2000 atomic mass units.
With advances in medicinal chemistry, most modern antibacterials are semisynthetic modifications of various natural compounds.[4] These include, for example, the beta-lactam antibiotics, which include the penicillins (produced by fungi in the genus Penicillium), the cephalosporins, and the carbapenems. Compounds that are still isolated from living organisms are the aminoglycosides, whereas other antibacterials—for example, the sulfonamides, the quinolones, and the oxazolidinones—are produced solely by chemical synthesis. In accordance with this, many antibacterial compounds are classified on the basis of chemical/biosynthetic origin into natural, semisynthetic, and synthetic. Another classification system is based on biological activity; in this classification, antibacterials are divided into two broad groups according to their biological effect on microorganisms: Bactericidal agents kill bacteria, and bacteriostatic agents slow down or stall bacterial growth.Before the early 20th century, treatments for infections were based primarily on medicinal folklore. Mixtures with antimicrobial properties that were used in treatments of infections were described over 2000 years ago.[5] Many ancient cultures, including the ancient Egyptians and ancient Greeks, used specially selected mold and plant materials and extracts to treat infections.[6][7] More recent observations made in the laboratory of antibiosis between micro-organisms led to the discovery of natural antibacterials produced by microorganisms. Louis Pasteur observed, "if we could intervene in the antagonism observed between some bacteria, it would offer perhaps the greatest hopes for therapeutics". The term 'antibiosis', meaning "against life," was introduced by the French bacteriologist Jean Paul Vuillemin as a descriptive name of the phenomenon exhibited by these early antibacterial drugs.[9][10] Antibiosis was first described in 1877 in bacteria when Louis Pasteur and Robert Koch observed that an airborne bacillus could inhibit the growth of Bacillus anthracis. These drugs were later renamed antibiotics by Selman Waksman, an American microbiologist, in 1942. Synthetic antibiotic chemotherapy as a science and development of antibacterials began in Germany with Paul Ehrlich in the late 1880s. Ehrlich noted that certain.
2. Contents
Various definitions
Guidelines for use of antimicrobial therapy
Indications of antibiotics
Antibiotics used in periodontics
Combination & serial therapy
Local drug delivery system
conclusion
2
3. Various definitions
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.
Antibiotic : is a naturally occurring, semi
synthetic, or synthetic type of anti infective
agent that destroys or inhibits the growth of
selective microorganisms, generally at low
concentration 3
12. Chronic periodontitis is rarely
treated with antibiotics
• Scaling and root planing eliminates most species
of subgingival bacteria associated with chronic
periodontitis
• Host defense mechanisms are usually effective at
controlling infections
12
14. Requirements for Effective
Antimicrobial Chemotherapy
• The drug must reach the site of action
• The drug’s concentration at the site of
action must be sufficient to inhibit bacteria
• The duration of chemotherapy must be
sufficient to allow the drug to act
14
15. To inhibit subgingival bacteria, an antimicrobial agent must be
able to reach the base of the periodontal pocket. Since some
pathogens invade the soft tissue wall of the pocket, it is useful if
the antibiotic can also reach this site.
15
16. Systemic Antibiotics
• May have narrow or broad spectrum
antimicrobial activity
• Can potentially reach the pocket and its soft
tissue wall
• Can potentially attain inhibitory levels in
the pocket
• Can potentially be retained for an adequate
duration
16
17. MECHANISM OF ACTION
1. Inhibit cell wall synthesis
2. Cause leakage from cell membrane
3. Inhibit protein synthesis
4. Inhibit DNA gyrase
5. Cause misreading of m-RNA code and
affect permeability.
6. Interfere with DNA function
7. Interfere with DNA synthesis, etc.
17
19. Penicillins
Bactericidal
Reach effective levels in gingival fluid
Don’t inhibit all A.a. Strains
Inactivated by ß-lactamases
Amoxicillin has enhanced tissue penetration
and good activity against gram negatives
Augmentin is as effective as amoxicillin, but
resists inactivation by ß-lactamases
19
20. Penicillins inhibit bacterial cell-wall synthesis,
and the antimicrobial spectrum of natural penicillins
is narrow.
Amoxicillin is a semi-synthetic penicillin with
broadened antimicrobial spectrum, and is used in
periodontology because it is effective against some
subgingival bacterial species such as P. micros
and A. actinomycetemcomitans as well.
20
21. It can be used in cases of acute infections,
although it is most commonly used in combination
with metronidazole.
Amoxicillin in combination with clavulonic acid is
indicated in the presence of oral bacteria capable
of producing β-lactamase
21
22. Tetracyclines
Tetracyclines are a group of broad spectrum,
bacteriostatic antibiotics.
They are the first antimicrobial drugs which
have been scientifically investigated in
periodontology.
This group includes tetracycline hydrochloride,
minocycline and doxycycline.
22
23. Frequently used in treatment of refractory
periodontitis including localised aggressive
periodontitis.
Concentrate in periodontal tissues & inhibit
the growth of a.a.
Also exert anticollagenase effect .
23
24. Pharmacology –
Obtained naturally from streptomyces sps. or
derived semisynthetically.
More effective against gram +ve than gram
-ve bacteria.
Their conc. in gingival crevice is 2 to 10 times
more than in serum.
24
26. Minocycline –
Broad spectrum of activity.
Dose 200 mg/day
Given twice daily (bid) so better patient
compliance.
Less side effects than tetracycline
More efffective against spirochetes and
motile rods.
26
27. Doxycycline –
Same spectrum of activity as minocycline
Given once daily so more patient compliance
Dose as an anti infective agent is 100mg bid
the first day, then 100mg qd.
as subantimicrobial dose ( to inhibit
collagenase) 20mg twice daily.
27
29. Metronidazole
Metronidazole is a synthetic nitroimidazole.
Its action is bactericidal, acting on anaerobic bacteria,
including gram-
negative rods and spirochetes, through DNA synthesis
blocking.
Due to the susceptibility of the spirochetes, it is effective
in cases of necrotising periodontal diseases.
29
30. It seems relatively ineffective in the suppression
of A. actinomycetemcomitans.
Periodontal abscesses can be successfuly
treated with metronidazole, while for aggressive
periodontitis treatment its antimicrobial spectrum is
not wide enough
30
32. Fluoroquinolones (Ciprofloxacin)
It is a quinolone active against gram –ve rods.
Bactericidal
Extremely active against A.a., but less
active against anaerobic bacteria
Reach higher levels in gingival fluid than in blood serum
Penetrate epithelial cells-can kill invasive bacteria
32
33. Ciprofloxacin is also effective in the treatment of
periodontal superinfections caused by enteric bacteria,
pseudomonas or staphylococci.
Another positive aspect is its inactivity towards
streptococci, whose presence in the subgingival area is
associated with periodontal health. Heightened
streptococcal counts can postpone recolonisation of the
pathogenic bacterial species.
33
35. Clindamycin
• Potent bacteriostatic activity against strict
anaerobes
• Less effective against facultative pathogens
(A.a. and Eikenella)
• Can induce ulcerative colitis
• Often used as an alternative antimicrobial
agent in penicillin-allergic patients
35
37. Erythromycin
• Doesn’t reach effective concentrations in
gingival fluid
• Weak activity against A.a., Eikenella and
Fusobacterium
37
38. Azithromycin
Azithromycin is an antibiotic from the macrolide group.
it exerts bacteriostatic activity by blocking of bacterial
proteins synthesis.
The spectrum is broad and covers gram-negative
bacteria, including enteric bacteria.
Has good activity against A.a. and Eikenella and
good activity against P. gingivalis and many other
gram-negative anaerobes
Penetrates epithelial cells-can kill invasive bacteria
38
39. Assessment of availability in periodontal tissues showed
extremely high values in periodontal tissues, crevicular fluid
and saliva.
Periodontally inflamed tissues exhibit concentrations
significantly higher than healthy periodontal tissues, which is
a very convenient characteristic of this antibiotic.
Data from clinical investigations support the use of
azithromycin in the treatment of advanced chronic, or
aggressive periodontitis .
39
40. Dose – therapeutic use requires a single dose of 250 mg/day
for 5 days after an initial loading dose of 500mg.
40
41. Deciding Which Antibiotic to Use
• Can use empirical approach
• Can identify pathogens at the site with culture or
DNA probes, then prescribe an antibiotic that will
presumably inhibit them
• Can culture isolated bacteria to identify them
and determine their susceptibility to antibiotics
41
46. Systemic Antibiotic Regimens for Treating
Aggressive and Recurrent Periodontitis
• Tetracycline HCl (250 mg QID) for 21 days (one of the
oldest regimens)
• Amoxicillin (500 mg TID) and metronidazole (250 mg
TID) for 8 days (most commonly prescribed-more effective
than a single agent)
• Metronidazole (500 mg BID) and ciprofloxacin (500 mg
BID) for 8 days (usually very effective for mixed infections)
46
47. Limitations of Systemic Antibiotics in
Periodontics
• Antibiotics rarely enhance the treatment of chronic
periodontitis
• To eliminate bacteria in biofilms effectively,
antibiotics must be used in conjunction with
mechanical debridement
• No single antibiotic can inhibit all periodontal
pathogens
• Antibiotics can have undesirable side effects when
given systemically
47
48. Adverse Side Effects Associated
With Systemic Antibiotics
• Induction of antibiotic resistance
• Induction of microbial overgrowth
• Inhibition of oral contraceptives (rare)
• Hypersensitivity or toxicity (e.g., allergy,
nausea, diarrhea, photosensitivity)
48
49. Combined and serial antibiotic therapy
Subgingival microflora in periodontal diseases includes
different pathogenic bacteria possessing differential
sensitivity to antimicrobials, so the use of two or more
antibiotics presents a useful option in the treatment of
these diseases.
The advantages of combined antibiotic therapy are
broadened spectrum of antimicrobial activity, occurence of
synergistic activity and prevention of bacterial resistance
development.
Disadvantages of such a treatment are elevated
incidence of adverse effects.
49
50. Metronidazole in combination with amoxicillin or
ciprofloxacin has been successfuly used in the treatment
of advanced periodontitis, especially infections with A.
actinomycetemcomitans .
Metronidazole and amoxicillin in vitro act synergistically
on A. actinomycetemcomitans.
Combination of metronidazole with amoxicillin or
amoxicillin and clavulonic acid can eliminate A.
actinomyctemcomitans and other periodontal pathogens
from the periodontal pockets for at least two years
50
51. Metronidazole and ciprofloxacin can be effective in mixed
periodontal infections, such as the presence of anaerobes,
A. actinomycetemcomitans, enteric bacteria
and pseudomonades.
As this combination is ineffective against most gram-
positive, facultative anaerobic bacteria, it can facilitate
streptococcal colonisation of the pockets which have no
periodontally pathogenic potential
51
52. Serial use of antibiotics is indicated for a combination of antibiotics, in
which one has bactericidal and the other bacteriostatic activity.
Combined administration would lead to antagonistic effects and
therapeutical
failure.
This form of systemic antimicrobial therapy should be used in especially
severe cases of recurrent or refractory periodontitis, where attachment
loss was not arrested despite careful initial therapy, or in cases of
disease reactivation during the supportive phase of therapy, occurring
despite good oral hygiene and repeated mechanical subgingival
instrumentation.
One of the combinations effective in the prevention of recurrent
periodontitis in highrisk individuals is doxycycline and metronidazole
52
53. Local delivery of antibiotics
Advantages
Higher local drug concentrations
Sustained therapeutic drug levels
(independent of patient compliance)
Effective drug levels can be attained at sites
that are difficult to reach
Adverse side effects are minimized
53
54. Tetracycline –containing fibers(Actisite)
An ethylene/ vinyl acetate copolymer fiber
(diameter, 0.5mm) containing tetracycline,
12.7mg per 9 inches.
For 10 days it sustained tetracycline conc.
exceeding 1300 microgram/ml, well beyond
the 32 to 64 microgram/ml required to inhibit
pathogens.
In contrast GCF conc. of only 4-8
microgram/ml were reported after systemic
administration, 250 mg qid for 10 days.
54
56. Subgingival doxycycline(Atridox)
The FDA approved 10% doxycycline in a gel
system using a syringe ( Atridox) .
It is the only local delivery system accepted
by ADA.
56
58. Sub gingival minocycline
The FDA recently approved a new, locally
delivered, sustained release form of
minocycline microspheres ( Arestin)
2% minocycline is encapsulated into
bioresorbable microspheres in a gel carrier.
58
61. Conclusion
Antimicrobial therapy is indicated in cases of disease
where the periodontal
destruction continued, despite thoroughly performed
mechanical therapy. In patients from high-risk groups,
such as aggressive forms of periodontitis or periodontitis
as a manifestation of systemic disease, the use of
antibiotics is indicated as an adjunct to scaling and root
planing. Antibiotics are never indicated in the treatment of
chronic gingivitis.
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