2. CONTENTS
Introduction
Rationale for use of antibiotics in periodontal therapy
Commonly prescribed antibiotics in periodontal therapy
Penicillins (Amoxicillin)
Nitroimadazole (Metronidazole)
Tetracyclines
Macrolides (Azithromycin,Clarithromycin)
Lincomycin derivatives(Clindamycin)
Fluoroquinolones (Ciprofloxacin)
Antibiotic resistance
Conclusion
References
3. INTRODUCTION
Definition :
Antibiotics may be defined as the substances produced by
the microorganisms, which suppresses the growth of or
kill other microorganisms at very low concentrations.
4. CLASSIFICATION
A) Mechanism of action :
1. Inhibit cell wall synthesis
• Penicillins
• Cephalosporins
• Vancomycin
• Bacitracin
2. Cause leakage from cell membranes
• Polypeptides – Polymycins, colistin, Bacitracin
• Polyenes – Amphotericin B, Nystatin
5. 5. Inhibit DNA gyrase
• Fluoroquinolones – Ciprofloxacin
6. Interfere with DNA function
• Rifampacin
• Metronidozole
7. Interfere with DNA synthesis
• Idoxuridine
• Acyclovir
• Zidovudine
6. 8) Interfere with intermediary metabolism
Sulfonamides
Pyrimethamine
Ethambutol
7. B) Chemical structure
1. Sulfonamides and related drugs
• Sulfadiazine and others
• Sulfones – Dapsone (DDS), Paraaminosalicylic acid
(PAS).
2. Diaminopyrimidines
• Trimethoprim
• Pyrimethamine
3. Quinolones
• Nalidixic acid
• Ciprofloxacin
• Norfloxacin
12. C) Type of organisms against which primarily active
1. Antibacterial
• Penicillins
• Aminoglycosides
• Erythromycin
2. Antifungal
• Griseofulvin
• Amphotericin B
• Ketoconazole
3. Antiviral
• Idoxuridine
• Acyclovir
• Zidovudine
17. RATIONALE
Bacterial deposits periodontal infections
Mechanical treatment
Inability to eliminate pathogens like A. actinomycetemcomitans
Recolonization by pathogens residing in non – dental sites (Dorsum of
Tongue, Tonsils)
Adjunctive systemic antibiotics
(Van winkelhoff AJ,Rams TE, Slots J.Periodontol 2000 1996;10:45-78)
18. Acute periodontal infections associated with systemic
manifestations
Prophylaxis in medically compromised patients
Recurrent periodontitis
19. Ideal antibiotic for use in periodontal disease should be:
1. Specific for periodontal pathogen
2. Non-toxic
3. Substantive
4. Not in general use for treatment of other diseases
5. Inexpensive
(Gibson W,1982)
20. GUIDELINES
1. Clinical diagnosis—patients diagnosis can change over time
2. Continuing disease activity
3. Selection based on patients medical, dental status, current
medications and microbial analysis
4. Microbiologic plaque sampling
--method
--indications: aggressive forms of disease, disease refractory to
standard mechanical therapy, periodontitis with systemic condition
21. 5. Reduce need for periodontal surgery in chronic
periodontitis patients
(Loesche 1992)
6. Antibiotics as monotherapy not recommended
--disruption of biofilm physically
(Greenstein 2005)
7. Slots et al 2000-- regenerative healing
--start antibiotics 1-2 days prior to surgery continue for 8
days
--not well documented
22. 8. Meta-analysis( Haffajee and Socransky 2003)
--similar effects for all antibiotics
--aggressive periodontitis patients benefited more
--overall factors
25. Tetracyclines
widely used in the treatment of periodontal diseases.
--used in treating refractory periodontitis; including localized aggressive
periodontitis.
ability to concentrate in the periodontal tissues and inhibit the growth of
A. actinomycetemcomitans.
---anticollagenase effect that can inhibit tissue destruction and may aid bone
regeneration.
26. Pharmacology: produced naturally from certain species of Streptomyces or
derived semisynthetically.
--bacteriostatic and are effective against rapidly multiplying bacteria.
--more effective against gram-positive bacteria than gram-negative bacteria.
insoluble complexes by chelation
27. concentration in the gingival crevice is 2 to 10 times that in serum
(Bader and Goldhaber 1968.)
low gingival crevicular fluid concentration (2 to 4 µg/ml) are very
effective against many periodontal pathogens.
(Gordon et al and Pascale et al)
28. Side effects
contraindicated during pregnancy
cross the placenta and form a stable calcium complex in bone forming
tissue which can result in retardation of skeletal development
not given to nursing mothers
29. Clinical Use:
localized aggressive periodontitis (LAP).
Systemic tetracycline can eliminate tissue bacteria and has been shown to
arrest bone loss and suppress A. actinomycetemcomitans levels in
conjunction with scaling and root planing (Slots et al 1983)
Increased post treatment bone levels
30. Specific agents
Tetracyclines:
--administration of 250 mg qid.
Minocycline:
-- suppresses spirochetes and motile rods as effectively as scaling and root
planing, up to 3 months after therapy.
-- twice a day
--less photo and renal toxicity
-may cause reversible vertigo.
31. Minocycline --200 mg per day for I week
•reduction in total bacterial counts,
•complete elimination of spirochetes for periods of up to 2 months
•improvement in all clinical parameters.
(Ciancio 2000)
32. Doxycycline
-- same spectrum of activity as minocycline
-once daily,
Compliance --its absorption from the gastrointestinal tract is not
altered by calcium, metal ions, or antacids, as is absorption of other
tetracyclines.
--100 mg twice daily the first day, then 100 mg once daily
--subantimicrobial dose to inhibit collagenase, it is recommended in a
20mg dose twice daily.
33. Penicillins
Pharmacology : natural and semi-synthetic derivatives of broth cultures
of penicillium mold
basic structure-- thiazolidine ring fused with a beta lactam ring
inhibit bacterial cell wall production-- bactericidal.
Substitutions and modifications on the acyl side chain ---semi synthetic
penicillins-- enhanced antimicrobial properties such stability to gastric
acids, resistance to hydrolytic enzymes
The side chain also determines the stability of the penicillin against
degradation by gastric acid and by enzyme penicillinase (beta
lactamase)
34. Amoxicillin: semisynthetic penicillin
extended antimicrobial spectrum --gram-positive and gram-negative
bacteria.
excellent absorption after oral administration
susceptible to penicillinase,.
Amoxicillin may be useful in the management of patients with
aggressive periodontitis, both in the localized and generalized forms.
Jorgensen slots (2000) Recommended dosage is 500 mg tid for 8 days.
35. Amoxicillin-Clavulanate :
management of patients with refractory or localized aggressive periodontitis.
Bueno and co-workers arrested alveolar bone loss in patients with
periodontal disease that was refractory to treatment with other antibiotics
including tetracycline, metronidazole, and clindamycin.
Side effects
Allergic reactions(10%)
36. Metronidazole
Pharmacology: Metronidazole is a Nitroimidazole compound developed
in France to treat protozoal infections
bactericidal to obligate anaerobic organisms
disrupt bacterial DNA synthesis in conditions in which a low reduction
potential is present.
37. Absorption, fate and excretion:
•rapidly and almost completely (80%) absorbed from the small bowel
•Food does not affect its bioavailability.
•The drug is metabolized mainly in liver
•The drug crosses the placental barrier and is present in the milk.
38. Metronidazole is not the drug of choice for treating A.
actinomycetemcotnitans infections
Rams and Slots 1992 showed, it is effective against A.
actinomycetemcomitans when used in combination with other
antibiotics.
Greenstein in 1993 showed that Metronidazole is also effective against
anaerobes such as P. gingivalis and P. intermedia.
39. Clinical Usage: Metronidazole has been used clinically to treat, acute
necrotizing ulcerative gingivitis, chronic periodontitis, and aggressive
periodontitis.
Studies have suggested that when combined with amoxicillin or
amoxicillin -clavulanate potassium ---localized aggressive or refractory
periodontitis.
40. Dosage :500mg tds for 8 days
Loesche 1992---> 20% spirochetes anaerobic infection
reduced need for surgery
Side Effects:
antabuse effect when alcohol is ingested
inhibits warfarin metabolism---inc prothrombin time
41. Cephalosporins:
Pharmacology:
similar in action and structure to penicillins. They are frequently used in
medicine and are resistant to a number of beta-lactamases
Clinical Usage: not generally used to treat dental-related infections
penicillins are superior to Cephalosporins in their range of action
against periodontopathic bacteria.
42. Side Effects: Patients allergic to penicillins must be considered allergic to all
beta-lactam products
Rashes, urticaria, fever, and gastrointestinal upset
43. Clindamycin
Pharmacology: effective against anaerobic bacteria.
--patient is allergic to penicillin.
Clinical Usage: Clindamycin has shown efficacy in patients with
periodontitis refractory to tetracycline therapy. Walker and co-workers
have shown aid in stabilizing refractory patients.(150 mg qid for 10 days.)
Jorgensen and Slots have recommended a regimen of 300 mg twice daily
for 8 days.
44. Side Effects:
pseudomembranous colitis
Diarrhea or cramping that develops during the use of clindamycin may
be indicative of colitis --should be discontinued.
45. Ciprofloxacin
Pharmacology: Ciprofloxacin is a quinolone active against gram-
negative rods, including all facultative and some anaerobic putative
periodontal pathogens.
Chelation –cations --Decreased absorption
Clinical Usage:
minimal effect on Streptococcus species---facilitate the establishment
of a microflora associated with periodontal health.
only antibiotic in periodontal therapy to which all strains of A.
actinomycetemcomitans are susceptible.
used in combination with metronidazole. (Slots et al 1992)
46. Side Effects: Nausea, headache, and abdominal discomfort have been associated
with ciprofloxacin.
-inhibit the metabolism of theophylline, and caffeine and concurrent
administration can produce toxicity.
---enhance the effect of warfarin
---NSAIDS--- Increased risk of central nervous system stimulation
47. Macrolides
Pharmacology: Macrolide antibiotics contain a many-membered
lactone ring to which one or more deoxy sugars are attached.
inhibit protein synthesis
bacteriostatic or bactericidal, depending on the concentration of the
drug and the nature of the microorganism.
Clinical Usage:
Erythromycin does not concentrate in gingival crevicular fluid, and it
is not effective against most putative periodontal pathogens. For these
reasons, it is not recommended as an adjunct to periodontal therapy
48. Azithromycin
member of the azalide class of macrolides.
effective against anaerobes and gram-negative bacilli
500 mg once daily for three consecutive days.
Concentration in tissue specimens from periodontal lesions is
significantly higher than that of normal gingiva
49. --penetrates fibroblasts and phagocytes in concentrations 100 to 200
times greater than that of the extracellular compartment.
actively transported to sites of inflammation by phagocytes and then
released directly into the sites of inflammation as the phagocytes
rupture during phagocytosis.
50. Drug interactions
Methylprednisolone ---Increased steroid concentration
Nonsedating antihistamines (terfenadine, astemizole)
Increased antihistamine concentration--with the risk of life-threatening
arrhythmia
Theophylline---- Increased serum levels
56. SERIAL AND COMBINATION
ANTIBIOTIC THERAPY
why combination?
1)Synergism
2)Reduction in severity/incidence of adverse effects
3) Prevent emergence of resistance
4)Broaden spectrum of activity
57. Rams and Slots metronidazole along with amoxicillin and
ciprofloxacin.
metronidazole-amoxicillin combinations provided excellent elimination
of many organisms in adult and localized aggressive periodontitis that
had been treated unsuccessfully with tetracyclines and mechanical
debridement.
58. Metronidazole-ciprofloxacin
effective against A. actinomycetemcomitans. Metronidazole targets
obligate anaerobes, and ciprofloxacin targets facultative anaerobes.
This is a powerful combination against mixed infections. Studies of this
drug combination in the treatment of refractory periodontitis have
documented marked clinical improvement.
therapeutic benefit --reducing or eliminating pathogenic organisms
prophylactic benefit --predominantly streptococcal microflora.
59. Metronidazole + amoxicillin 250 mg/t.i.d./8 days of each drug
Metronidazole + ciprofloxacin 500 mg/b.i.d./8 days of each drug
60. Antibiotic resistance
indiscriminate use
Cross Resistance: Microorganism are resistance to particular drug frequently are
resistance to other chemically related antimicrobial agent
organisms growing in biofilms are more resistant to antibiotics than the
same species growing in a planktonic (unattached) state
slower rate of growth of bacterial species in biofilms
(Ashby et al 1994)
61. The growth rates of these deeper cells decreased allowing them to
survive better
the slower-growing bacteria often over express ‘‘nonspecific
defense mechanisms’’
62. ion-exchange resin
extracellular enzymes such as b-lactamases, formaldehyde lyase and
formaldehyde dehydrogenase may become trapped and concentrated in
the extracellular matrix, thus inactivating susceptible, typically
positively charged-- hydrophilic antibiotics.
Super-resistant bacteria
Quorum sensing
with calcium, magnesium, aluminium and. iron interferes with absorption. 2hr gap of mealshence substances like milk that contains calcium and antacids reduce their absorptionFood also interferes with the bioavailability
). This allows a high drug concentration to be delivered into periodontal pockets
since they are excreted in milk.
A. actinomycetemcomitans is a frequent causative microorganism in LAP and is tissue invasive.
, . It is inexpensive; but compliance may be reduced by having to take four capsules per day thus facilitating compliance when compared with tetracycline
patients may be more compliant. . To reduce gastrointestinal upset, 50 mg can be taken twice daily.
The 2 rings constitute the fundamental nucleus of all the penicillins. essential for antibacterial activity.
Tetra metro n clindaa /3-lactamase produced by certain bacteria that breaks the penicillin ring structure and thereby renders penicillins ineffective
Tetra metro n clinda
. The metabolites are excreted mainly in the urine, imparting a deep red-brown color to it.
. The response is generally proportional to the amount ingested and can result in severe cramps, nausea, and vomiting. Products containing alcohol should be avoided during therapy and for at least 1 day after therapy is discontinued.
(ciprofloxacin) Mg¹¹, Zn¹¹) in antacids, due to chelationvitamins and dairy products
, which are associated with periodontal health
by binding to the 50 S ribosomal subunits of sensitive microorganisms.
Amox and clavulanic…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, not in combination……..possible inly if sunergistic so dose can b reduced
reviewed combination therapy using systemic …. periodontal infections contain a wide diversity of bacteria,
no single antibiotic is effective against all putative pathogens.
"mixed" infections can include a variety of aerobic, microaerophilic, and anaerobic bacteria, both gram negative and gram positive
May be necessary to use more than one antibiotic, either serially or in combination (Slots et al 1992).
However, before combinations of antibiotics are used, the periodontal pathogen(s) being treated must be identified and antibiotic susceptibility testing performed.
This combination may provide a
A paper by Timothy Walsh from Cardiff University and colleagues, published in the Lancet Infectious Diseases journal, reveals that the gene, known as NDM-1, is widespread in the water used for cooking, washing and drinking in Delhi. Called New Delhi metallobeta-lactamase, or NDM-1 for short, the enzyme destroys carbapenems, an important group of antibiotics used for difficult infections in hospitals, and has been found in a wide variety of bacterial types. (7 April 2011)1000 to 1500 times gr8erThe mechanisms
of increased resistance in biofilms differ from
species to species, from antibiotic to antibiotic and
for biofilms growing in different habitats
than faster-growing cells at the peripheryshock proteins
multi-drug efflux pumps
strongly charged or chemically
highly reactive agents can fail to reach the…Erythromycin not affected…broon 2000 multi drug effector pumps
deeper zones of the biofilm because
