1. ANTIBIOTICS IN ENDODONTICS
PRESENTED BY-
DR. DEBALINA DUTTA
1ST
YEAR PGT
DEPT OF CONSERVATIVE DENTISTRY & ENDODONTICS
HALDIA INSTITUTE OF DENTAL SCIENCES AND RESEARCH
2. CONTENTS
INTRODUCTION
BACTERIAL PATHWAYS INTO THE PULP
ENDODONTIC MICROBES
ANTIMICROBIAL AGENTS
GROSSMAN POLYANTIBIOTIC PASTE
LEDERMIX PASTE
MTAD
TETREACLEAN
ODONTOPASTE
TAP
Conclusion
REFERENCES
3. INTRODUCTION
The bacterial flora of the root canal has been studied over many years. More than 700 species of
bacteria are recognized as normal inhabitants of the oral cavity with 500 species seen in
endodontic infections.
Nagaoka found that rate of bacterial invasion into dentinal tubules increased with the passage of
time, and that it was approximately 1.6 µm/day during the first 25 days and 14 µm/day by 120
days. The deepest bacterial invasion was 3.0 mm after 210 postoperative days.
Antibiotics are the substances produced by microorganisms, which suppress the growth of or kill
other microorganisms at very low concentrations.
They kill or destroy microorganisms, e.g. penicillins, cephalosporins, aminoglycosides,
etc.=Bactericidal agents
They inhibit the growth and multiplication of microorganisms, e.g. sulphonamides, tetracyclines,
chloramphenicol, erythromycin, etc.=Bacteriostatic agents
4. BACTERIAL PATHWAYS INTO THE PULP
Bacteria enter the pulp in various ways:
Dentinal tubules following carious invasion
Crown or root following traumatic exposure of the pulp
Coronal leakage following restorative procedures and restorations
External or internal resorption that can lead to pulp exposures
Periodontal tissue through exposed dentinal tubules, lateral and accessory canals, or apical and lateral foramina
Lymphatic or hematogenous route (anachoresis, defined as the localization of transient bacteria in the blood into an inflamed
area, such as traumatized or inflamed pulp)
5. Schematic diagram showing bacteria in the root canal and the zones of infection, contamination,
irritation, and stimulation
6. Zone of infection Zone of
contamination
Zone of irritation Zone of stimulation
characterized by
polymorphonuclear
leukocytes.
In Fish’s study, infection
was present in the center of
the lesion, and
microorganisms were found
only in that area
characterized by round cell
infiltration. Around the
central zone, Fish observed
cellular destruction, not
from bacteria themselves,
but from toxins discharged
from the central zone
In this area, bone cells had
died and had undergone
autolysis, so the lacunae
appeared empty.
Lymphocytes were prevalent
everywhere.
characterized by
macrophages and
osteoclasts. also
distinguished by small,
round cells.
The collagen frame work
was digested by phagocytic
cells, the macrophages,
while osteoclasts attacked
the bone tissue
the histologic picture is the
one that signifies a body’s
attempt to initiate repair.
characterized by fibroblasts and
osteoblasts.
in response to this stimulation,
collagen fibers were laid down
by the fibroblasts, which acted
both as a wall of defense around
the zone of irritation and as a
scaffolding on which the
osteoblasts built new bone.
10. Enterococcus faecalis
E. faecalis is a gram-positive, facultative anaerobic coccus that is strongly associated with endodontic infections
The prevalence of E. faecalis is 40% in primary endodontic infection and 24%–77% in persistent endodontic infection.
• Endures prolonged periods of nutritional
deprivation [viable but not cultivable (VBNC)
state]
• Binds to dentin and invades dentinal tubules
• Alters host responses
• Suppresses the action of lymphocytes
• Utilizes serum as a nutritional source
• Forms a biofilm
• Possesses lytic enzymes, cytolysin, aggregation
substance, pheromones, and lipoteichoic acid
• Resists intracanal medicaments [i.e., Ca(OH)2]
• Competes with other cells
• Virulence factors—hemolysin, gelatinase,
extracellular super oxide, and aggregation
substance
Survival
and
Virulence
Factors of
E. faecalis
12. Classification of antibacterial agents into
bactericidal and bacteriostatic
Classification of antibacterial agents according
to mechanism of action
15. BETA LACTAM ANTIBIOTICS
−
Penicillin was the first antibiotic developed and used clinically. It was discovered accidentally by Alexander Fleming. The source of
penicillin is the high-yielding Penicillium chrysogenum.
Beta-lactam antibiotics produce bactericidal effect by inhibiting cell wall synthesis in susceptible bacteria.
Bacterial cell wall is composed of peptidoglycan, which has glycan chain cross-linked by peptide chain. The glycan chain is composed of alternating amino sugars, NAM (N-
acetylmuramic acid) and NAG (N-acetylglucosamine).
A pentapeptide (five amino acids), linked to NAM, has a pentaglycine attached to it. This pentaglycine is cross-linked with a pentapeptide of adjacent strand. Transpeptidase
(penicillin binding protein) causes cross-linking between the pentaglycine residue of one strand and fourth aminoacid (D-alanine) of adjacent pentapeptide by cleavage of the terminal
D-alanine (fifth aminoacid residue). This cross-linking makes the cell wall rigid and also gives it stability.
Lactams, structural analogues of D-alanine, inhibit transpeptidase and thus peptidoglycan synthesis.
Cell wall deficient forms are produced, which undergo lysis (bactericidal action). Beta-lactams exert their cidal effect when the bacteria actively multiply and synthesize cell wall.
Penicillin-binding proteins (PBPs), consisting of transpeptidase, other enzymes and related proteins are located in the cell membrane of bacteria.
The cell wall in gram-positive bacteria is composed mainly of highly cross-linked peptidoglycan, which is 50–100-layers thick and is near the cell surface.
In gram-negative bacteria, the peptidoglycan layer is only 1–2 molecules thick. In addition, there is an outer lipopolysaccharide layer. Hence, gram-negative organisms are less
susceptible to penicillins than gram-positive organisms.
17. Therapeutic uses of penicillin in dentistry
In dentistry: Penicillins are used in Vincent’s angina, necrotizing gingivitis, periodontal infections, etc. either alone or with
metronidazole.
Amoxicillin is used alone or with metronidazole in acute necrotizing ulcerative gingivitis, dentoalveolar abscess, osteomyelitis of
mandible, etc. Ampicillin–sulbactam is useful for the treatment of Ludwig’s angina in immunocompetent individuals.
Aminopenicillins in combination with gentamicin have been used for the treatment of subacute bacterial
endocarditis (SABE). To prevent bacterial endocarditis in patients with valvular lesions before undergoing dental
procedures, amoxicillin is the ideal agent—2g given orally, 1 h before the procedure and to prevent bacteraemia.
23. Prophylaxis against specific organisms
The effectiveness of chemoprophylaxis depends on the selection of specific antimicrobial agent, its dosage, time of initiation and
duration of antimicrobial therapy
25. Therapeutic uses of gentamicin
Among aminoglycosides, gentamicin is the most commonly used because it is cheap and effective against most of the aerobic
gram-negative bacilli.
1. In dentistry
Prophylaxis of bacterial endocarditis:
Gentamicin can be used in combination with amoxicillin/ vancomycin for the prophylaxis of endocarditis in high-risk patients
before dental or other surgical procedures.
Combination broadens the spectrum of activity, produces synergistic effect and decreases emergence of resistance.
Penicillin G& gentamicin for S. viridans.
Ampicillin& gentamicin for Enterococcus.
Vancomycin &gentamicin for Enterococcus (patients allergic to -lactam antibiotics).
26. TETRACYCLINES
In dentistry:
Tetracyclines are used as an adjuvant in chronic periodontitis refractory to other antibiotics.
Doxycycline is useful for subgingival plaque as it:
a. gets concentrated in gingival fluid.
b. inhibits collagenase enzyme and prevents destruction of connective tissue in the gum.
c. Tetracyclines may be effective in the treatment of acute necrotizing gingivitis or
periodontitis, either alone or in combination with metronidazole.
28. Active compound is highly effective anti-inflammatory cortisone derivative
(triamcinolone acetonide) combined with a broad-range antibiotic
(demethylchlortetracycline).
29. MTAD
MTAD, introduced by Torabinejad and Johnson at the Loma Linda University in
2003, is an aqueous solution of 3% doxycycline, a broad-spectrum antibiotic;
4.25% citric acid, a demineralizing agent; and 0.5% polysorbate 80
detergent (Tween 80) that lowers the surface tension and increases the
antimicrobial effect of the various irrigation solutions.
It is commercially available as a bi-component product under the name of
BiopureMTAD, In this product, doxycycline hyclate is used instead of its free-
base doxycycline monohydrate, to increase the water solubility.
The pH of BioPureMTAD is 2.It contributes to its role as a calcium chelator,
thereby causing enamel and root surface demineralization. The extent of dentin
surface demineralization is comparable to that of citric acid, and it mainly
removes the inorganic substances.
MTAD in endodontics: an update review,OOOOE Singla et al. e71 Volume 112, Number 3.
30. Antimicrobial efficacy Smear layer removal and tissue-
dissolving action of MTAD
Biocompatibility of MTAD
MTAD must have the capability to
eradicate even the most resistant
microorganisms to be considered
effective
Newberry et al. showed that MTAD in
conjunction with 1.3% NaOCl was
effective in completely eliminating
growth in 7 of 8 strains of E. faecalis.
Use of MTAD has been reported to be
more efficient in removing smear layer
as compared with the use of EDTA
and NaOCl, especially from the
apical third
MTAD has been found to be less
cytotoxic and more biocompatible
than other irrigant solutions. cyto
toxicity of NaOCl/MTAD was found to
be slightly less than NaOCl and
NaOCl/EDTA, indicating that MTAD is
more biocompatible than NaOCl.
31. : Root surface
treated with saline
after root surface
debridement, Viable,
flat, well-attached
cells with elongated
processes attached
to root surface
covered by a heavy
smear layer can be
seen Root surface treated with MTAD
after root surface debridement.
Viable, flat, well-attached cells
with elongated processes
attached to root surface,
following smear layer removal
by MTAD, can be seen
32. As per the manufacturer’s recommendations, MTAD being a 2-part mix needs to be freshly
prepared just before its use. Once mixed, it has a shelf life of about 48 hours, which is
shorter than other irrigants.
ADVANTAGES DISADVANTAGES
• reasonable antimicrobial property
• better smear layer removal
• lesser adverse effects on dentinal structure
• better at promoting adhesion to dentin
• good biocompatibility
• less than optimal antimicrobial activity
• lesser compatibility to dental pulp cells for
• revascularization procedures
• high cost
• reduced shelf life
33. TetraClean
is a mixture of doxycycline hyclate at a lower concentration than MTAD, an acid, and detergents.
It is able to eliminate microorganisms and smear layer in dentinal tubules of infected root canals.
The possible reason for its improved smear layer removal efficacy could be due to its low surface tension, which will
allow better penetration into the dentinal tubules.The basis for reduced efficacy exhibited by TetraClean could be due
to its inability to remove the organic portion of the smear layer.
Haapasalo et al. concluded that TetraClean use should always be preceded by NaOCl irrigation to exert a superior
smear layer removing property.
Mixture tetracycline citric acid and detergent e A root canal irrigant. A review, 3 journal of oral biology and craniofacial research 3 :
www.elsevier.com/locate/jobcr
34. ODONTOPASTE
intracanal medicament consisting of 5% clindamycin hydrochloride, 1% triamcinolone acetonide,
and 0.5% calcium hydroxide.
It is advertised as a dressing for reducing inflammation and postoperative pain and preventing
bacterial growth in root canal systems.
Odontopaste also possesses analgesic effects in endodontic treatment and does not stain teeth, as
demonstrated in other intracanal medications such as Ledermix.
In addition, clindamycin, one of the components of Odontopaste, effectively targets endodontic
pathogens. All these components make Odontopaste an intracanal dressing with potential benefits
in endodontic therapy
Antimicrobial efficacy of Odontopaste in endodontics: a systematic review. Evidence-Based Dentistry (2024) 25,NATURE.
35. TRIPLE ANTIBIOTIC PASTE
TAP is an "intra-canal medicament", which happens to have three antibiotics combined in it, namely metronidazole, ciprofloxacin, and
minocycline, in a definite proportion of 1:1:1 to produce effective results.
TAP has effective antibacterial effects in endodontic regenerative operation.
With the help of its cleansing and sterilizing action, the canal paves the way for the cells carrying the potential to regenerate. The combined
action of the 3 medications in a single mix is extremely effective as the chances of microbial resistance are reduced to a significant percentage.
TAP is not only an effective antimicrobial agent but also possesses a good regeneration-inducing potential. It enables the proliferation of the
stem cells in the apical region, resulting in the obtainment of the apical barrier
Concentration for usage
TAP is prepared in two ways: (i) Mixing ciprofloxacin, metronidazole, and minocycline in a
proportion of 1:1:1, that is ciprofloxacin 33%, metronidazole 33%, and minocycline 34%,
with macrogol and propylene glycol paste concentrated at 0.1-1.0 mg/ml; (ii) Mixing
ciprofloxacin, metronidazole, and minocycline in a proportion of 1:3:3
Triple Antibiotic Paste: A Suitable Medicament for Intracanal Disinfection, 2022 Malu et al. Cureus 14(9): e29186. DOI
10.7759/cureus.29186
36. Minocycline Metronidazole Ciprofloxacin
"broad-spectrum antibiotics", which is
effective against an extensive range of
bacteria.
Being bacteriostatic, it possesses the
advantage of not releasing antigenic
products in the infected region.
Apart from being an excellent
antibacterial substance, it also has a
regeneration-inducing property as it
inhibits the action of clastic cells and stops
the activity of collagenases. Doing this
permits the growth of natural healthy
cells and helps in the regenerative
procedure
a nitroimidazole chemical with a wide
range of anti-anaerobic and anti-
protozoal activity. Because of its
potent activity against a wide range
of bacteria and anaerobic cocci, it has
been widely used in both local and
systemic forms.
It kills the bacteria by perforating and
entering their membranes and
attaching itself to their DNA, causing
the helical structure to be disrupted
and the cell to die quickly.
Metronidazole prevents the
development of all obligatory
anaerobes examined and outperforms
calcium hydroxide against two of the
strains.
Ciprofloxacin belongs to a class of
second-generation fluoroquinolone
antibiotics used to treat bacterial
infections that cause stomach pain,
diarrhoea, and urinary tract infections.
Ciprofloxacin and other
fluoroquinolones are used for various
purposes, in both oral and intravenous
forms, because of their high tissue
penetration.
37. Applications of TAP
TAP, a potent antimicrobial agent, is used in several forms and for several purposes.
is used to preserve the vitality of the pulp by trying to "regenerate and revascularize" the diseased pulp.
TAP is not only a potent disinfecting agent but also plays a vital role in regeneration and revascularization.
The result of increased root length is observed more commonly with the use of TAP and calcium hydroxide than with the use of non-surgical root
canal treatment and mineral trioxide aggregate (MTA) apexification
As it has an antimicrobial effect when used in the root canal, it shows a dual effect - first by acting against Enterococcus faecalis, which is the most
prevailing microbe in the root canal region, and next by bringing in the stem cells, followed by their proliferation, which helps expand the root
length.
An important application of TAP is as an intracanal medicament in the cases of periapical lesions, external inflammatory root resorption, root
fracture, and treatment flareups, which is a common complication of endodontic treatment.
Flare-up is a condition characterized by the onset of severe pain and swelling after an endodontic therapy appointment as a result of an acute
exacerbation of an existing condition demanding an unplanned treatment appointment,TAP can be used as medicaments.
38. Effect on Dentin Effect on Tooth Colour Effect on Stem Cells
Studies have reported that TAP has
a demineralizing effect on dentin,
bringing about specific changes in
its mechanical property leading to
the brittleness of the tooth.
When used at a higher
concentration, 1g/ml, TAP treatment
causes a significant reduction in
microhardness at 500 µm from the
pulp dentin complex compared with
MTA at the same concentration. This
is because of minocycline, which
causes calcium chelation from the
dentin
One of the major drawbacks of
TAP is discolouration of the tooth,
for which minocycline is responsible.
The problem can be resolved by the
use of other medicaments like
amoxicillin and cefaclor. The use of
dentin bonding agents also, to a
great extent, has been proven to
prevent tooth discolouration
TAP is an important material used
for the purpose of regeneration. It
plays a significant role in
preserving the health of the apical
stem cell and, thus, in providing a
microbe-free environment, enabling
the stem cells to proliferate and
help in regeneration. Though
materials like calcium hydroxide can
be used, their toxic effect on the
apical papilla leads to the
avoidance of the use of such
materials. In contrast, TAP has
proven to overcome this drawback,
proving to be the best intracanal
disinfecting material with superior
properties.
Effect of TAP on tooth structure
39. Limitations
of TAP
Tooth discolouration is one of the major
drawbacks of TAP.
Studies have found that TAP was most linked
to discolouration when compared to other
antibiotic pastes like Ledermix, polyantibiotic
paste, and Septomixine Forte. As a result, in
some cases, the use of double antibiotic pate
(DAP) containing only ciprofloxacin and
metronidazole has been suggested. In other
investigations, it was discovered that using
DAP or TAP for a month reduced dentin
microhardness considerably
40. Conclusion
In the last few decades, many reports
have been published on the bacterial
flora of the pulp and periapical and peri
odontal tissues, the pathways of infection,
the immunologic reactions, and the
inflammatory responses.
Although treatment procedures have
changed radically, they reflect a better
understanding of the host–parasite
relationship and of the way in which such
reactions are managed more effectively.
41. REFERENCES
A Textbook of Clinical Pharmacology and Therapeutics, FIFTH EDITION JAMES M RITTER MA DPHIL FRCP FMedSci FBPHARMACOLS Professor of Clinical Pharmacology at King’s
College London School of Medicine, Guy’s, King’s and St Thomas’ Hospitals, London, UK
GROSSMAN’S ENDODONTIC PRACTICE 14TH EDITION
Essentials of Pharmacology for Dentistry 3rd Edition KDTripathiMD
Pharmacological CLASSIFICATION OF DRUGS with Doses and Preparations FIFTH EDITION KD Tripathi
Pharmacology for Dentistry Second Edition Tara V Shanbhag MD
Triple Antibiotic Paste: A Suitable Medicament for Intracanal Disinfection, alu K, Khubchandani M (September 15, 2022) Triple Antibiotic Paste: A Suitable Medicament for
Intracanal Disinfection. Cureus 14(9): e29186. DOI 10.7759/cureus.29186
Mixture tetracycline citric acid and detergent e A root canal irrigant. A review G.P.V. Srikumara,*, K.S. Sekharb, K.G. Nischithc
THE EFFECTS OF MTAD AS ENDODONTIC IRIGANT IN PORPOSE OF INTRAORAL REHABILITATION - a literature review- Liana Aminov1, Mihaela Salceanu1 , Yllka Decolii1*,
Cristina Antohi1*, Antonela Beldiman2, Laura Elisabeta Checherita2 omanian Journal of Medical and Dental Education
Antimicrobial efficacy of Odontopaste in endodontics: a systematic review
MTAD in endodontics: an update review
The effect of MTAD, an endodontic irrigant, on fibroblast attachment to periodontally affected root surfaces: A SEM analysis
Triple antibiotic paste in root canal therapy Rangasamy Vijayaraghavan, Veerabathran Mahesh Mathian, Alagappan Meenakshi Sundaram1, Ramachandran Karunakaran,
Selvaraj Vinodh
![Enterococcus faecalis
E. faecalis is a gram-positive, facultative anaerobic coccus that is strongly associated with endodontic infections
The prevalence of E. faecalis is 40% in primary endodontic infection and 24%–77% in persistent endodontic infection.
• Endures prolonged periods of nutritional
deprivation [viable but not cultivable (VBNC)
state]
• Binds to dentin and invades dentinal tubules
• Alters host responses
• Suppresses the action of lymphocytes
• Utilizes serum as a nutritional source
• Forms a biofilm
• Possesses lytic enzymes, cytolysin, aggregation
substance, pheromones, and lipoteichoic acid
• Resists intracanal medicaments [i.e., Ca(OH)2]
• Competes with other cells
• Virulence factors—hemolysin, gelatinase,
extracellular super oxide, and aggregation
substance
Survival
and
Virulence
Factors of
E. faecalis](https://image.slidesharecdn.com/antibioticsinendodontics-250608123143-6873e6f4/85/Antibiotics-in-endodontics-description-pptx-10-320.jpg)
