Al Rafidain Universiy College of Dentistry

AL RAFIDAIN UNIVERSIY COLLEGE OF DENTISTRY
Pediatric dentistry
Triple antibiotic paste (TAP)
:Presented by
B4
29
‫محمود علي حسين‬
‫يوسف نجيب حسن‬
‫لبنى علي سامي‬
‫نور رعد جاسب‬
‫نور محمد عبد الرزاق‬
‫فاطمة صادق صبيح‬
: Supervised by
Dr. Maha Waleed
.
INTRODUCTION
The success of the endodontic treatment depends on the microbial
suppression in the root canal and periapical region. Endodontic
instrumentation alone cannot achieve a sterile condition. With the advent of
non-instrumentation endodontic treatment and lesion sterilization and tissue
repair, local application of antibiotics has been investigated. Triple antibiotic
paste (TAP) containing metronidazole, ciprofloxacin, and minocycline has
been reported to be a successful regimen in controlling the root canal
pathogen and in managing non-vital young permanent tooth., efficiency,
drawbacks of TAP in endodontic therapy and pulp revascularization.TAP
was proved to be biocompatible. Tetracycline inhibits collagenases and
matrix metalloproteinases , is not cyt otoxic , and increases the level of
interleukin-10, an antiinflammatory .cytokine. In addition, metronidazole
and ciprofloxacin can generate fibroblasts
APPLICATIONS
1. In the regeneration and revascularization protocol of the pulp

2. As an intracanal medicament for the treatment of
a) Periapical lesions
b) External inflammatory root resorption
c) Root fracture
d) Primary teeth
3). As an intracanal agent to control flare-ups
4). As a medicated sealer (to prevent possible re-infection)
5). As an additive to gutta-percha points in root canal obturation (known as
medicated
gutta-percha points)
6). As an intracanal medicament loaded on a scaffold
For the treatment of primary teeth
Previous research in pediatric dentistry has illustrated that TAP can be used in a
very effective way with good clinical success in primary teeth . However,
intracanal medication should not replace the instrumentation phase since the
antibiotic agents alone cannot eradicate canal infection in long term . In these
studies, noninstrumentation endodontic treatment ‘Lesion Sterilization and
Tissue Repair’ and the triple antibiotic the paste were used .
In the study by Takushige et al, triple antibiotic paste was used to treat 87
primary teeth, 81 of which had physiologic root resorption. The treatment was
successful for the majority of patients. Symptoms of gingival swelling, sinus
tracts, induced and spontaneous dull pain, and pain on biting were reduced in all
but a few cases. These few patients resolved after a re-treatment with the same
procedure. In addition, the study noted that all patients later had healthy, normal
successor teeth.
SPECIAL CONSIDERATION
1. Tap and radicular dentine: A number of studies have revealed that the TAP
and the concentration used for regeneration and revascularization protocol
may cause significant loss of dentine and a substantial increase in its
roughness .Several research cases have also demonstrated a greater increase
in the root length in teeth treated with TAP when compared with MTA,
calcium hydroxide, and formocresol . It seems that the TAP is capable of
preparing a matrix for thickening the dentinal walls of the root in
comparison with calcium hydroxide and formocresol ; an effect which could
play a
significant role in shaping of the root canal .
2. Discoloration of the tooth structure:
Teeth treated by the TAP have shown a degree of crown discoloration .likely
that related to the existence of minocycline in the paste. In view of this, great
care and caution should be taken in aesthetic zones. A number of medicinal
replacements, such as amoxicillin , Arestin (OraPharma, Inc., Warminster, PA,
USA), and Cefaclor (a member of the second generation cephalosporins) have
been used to prevent the problem. Recently, the Minocycline-removed
paste or DAP have found its place. ‘European Society of Endodontology’
advocates the use of calcium hydroxide so as to avoid discoloration .
In addition to such modifications in the formula of the paste, several strategies
to make up for the discoloration have been investigated. The most commonly
recommended is internal bleaching to remove cervical discoloration from the
TAP . Another approach is the application of dentine bonding agents or the use
of composite resins as dentinal walls sealants
3. Removal of the paste: Another pitfall to consider during application of TAP
in root canal space is the challenging removal of the paste. Existing irrigation
techniques are not able to effectively remove TAP since it penetrates and binds
into the dentinal structure . Ultrasonic activation of 5.25% sodium
hypochlorite seems to be the most effective method in removing the paste ,
contrary to chlorhexidine which seems to be the least effective intracanal
irrigation solutions.
4. TAP and operative dentistry:The use of TAP as an antibiotic paste is not
limited to endodontics. Investigations have revealed that glass ionomer cement
(GIC) containing TAP is quite effective on Streptococcus mutans and
Lactobacillus casei. Yesilyurt et al. demonstrated that if the concentration of
1.5% TAP is added to GIC, the physical and bonding properties, the
compressive strength, and the bonding strength to dentine are not modified
and stay optimal.
Rationales in combining the antibiotics
Considering the polymicrobial nature of tooth infection, single empirical

antibiotics are not able to provide a bacteria-free zone in the canal. In
addition, using non-specific antibiotic therapy could result in the destruction
of normal bacterial flora which allows residual virulent microorganisms to
repopulate the canal. As a result, it is essential to use a combination of
antibiotics against all endodontic pathogens to prevent microbial resistance
...Tetracycline
Tetracycline, including tetracycline-HCl, minocycline, demeclocycline and

doxycycline are a group of broad-spectrum antibiotics effective against a wide
range of microorganisms. Tetracycline is in the bacteriostatic subgroup of
antibiotics. This could be one of the advantages of this subgroup for its safety,
because when the bacterial cells are not lysed, there will not be any antigenic
byproducts released in the infected area (such as endotoxins) . In addition,
tetracycline possess various unique properties except their antimicrobial
action, including the inhibition of mammalian collagenases, which prevents
tissue degeneration, and the inhibition of clastic cells, which results in anti-
resorptive activities. Naturally, inflammatory diseases such as periodontitis
include numerous tissue collagenases, which could be prevented by the
mentioned tetracycline’s property, thus leading to enhanced formation of
collagen and bone .
In endodontics, tetracycline has been used to erase the smear layer from
instrumented root canal walls, irrigate the retrograde cavities during periapical
surgical procedures and as an intra-canal medicament. It is typically used in
conjunction with corticosteroids and these combinations have antibacterial,
anti-inflammatory, and also anti-resorptive properties, which all can help to
reduce the inflammatory reaction in periapical area including resorption
mediated by some clastic cells .
Metronidazole
Metronidazole is a nitroimidazole compound which exhibits a broad spectrum
of activities against protozoa and anaerobic bacteria. Since it is famous for its
affective antimicrobial activities against anaerobic cocci as well as gram-
negative and gram-positive bacilli, it has been used widely in the
periodontology in both systemic and local forms. Metronidazole
destroys bacteria cells by permeating their membrane and then binding to the
DNA, disrupting the helix structure and causing a very rapid death. It has been
shown that metronidazole is effective against anaerobic bacteria but not in
aerobic bacteria and it prevented the growth of all obligate anaerobes tested
and is more effective against two of the strains in comparison with the calcium
hydroxide . In addition, one study performed by Lima et al. on the
effectiveness of antibiotic-based or chlorhexidine-based medications in
eliminating Enterococcus faecalis biofilms, represented significant differences
between the tested formations. The combination of ciprofloxacin and
metronidazole had a remarkable effect in decreasing the number of 1-day old
bacterial biofilm . However, metronidazole had no effect on improving the
disinfection of biofilms when added to to Kerr Pulp Canal Sealer EWT
to Kerr Pulp Canal Sealer EWT . Another study showed 97% healing when
metronidazolechlorhexidine solution was applied for the treatment of chronic .
apical periodontitis [23] Gao et al. [24]evaluated a sustained release delivery
gutta-percha point containing metronidazole for root canal disinfection and
determined the drug concentration in vitro and the time that the device
maintained an effective drug concentration. The results represent that
a remarkable concentration of metronidazole was released over more than 10
days. On the 10th day, 33.13 microgram/mL of metronidazole was released
which exceeded the minimum .inhibitory concentration of metronidazole
In another evaluation of the disinfection of dentinal tubules using 2%
metronidazole gel, 2% chlorhexidine gel, bioactive glass, and calcium
hydroxide showed that chlorhexidine gel had the best disinfection effect and
after that, metronidazole gel were more efficient than bioactive glass and
calciumhydroxide...
Ciprofloxacin
Ciprofloxacin is a second-generation fluoroquinolone antibiotic . Its range of
effect includes most strains of bacterial pathogens responsible for
gastrointestinal, respiratory, urinary tract, and abdominal infections, including
Escherichia coli, Legionella pneumophila, Haemophilus influenzae,
Klebsiellap neumoniae, Proteus mirabilis, Moraxella catarrhalis, Pseudomonas
aeruginosa, methicillin-sensitive but not methicillin-resistant Staphylococcus
aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Enterococcus
faecalis, and Streptococcus pyogenes. Ciprofloxacin and other
fluoroquinolones are being used for this wide broad spectrum of activities,
their availability in both oral and intravenous formulations and their excellent
tissue penetration.
DOSAGE
TAP should be used in the safest possible concentration (1 mg/mL) since

higher dosages could have undesired results on the stem cells . Even at low
concentrations, TAP has unwanted effects on the proliferative capacity and
mineralized matrix formation of dental pulp cells and apical papilla cells
.According to several studies, a concentration of 0.125 mg/mL of TAP has
no cytotoxic effect on the stem cells; thus, it is expected that a
concentration of the antibiotic combination with the lowest possible side
effects and adequate ability for removing microorganisms, particularly
Enterococcus faecalis (E. faecalis) must be used during endodontic
treatments.
Triple Antibiotic Paste for LSTR – Formulation 1

Metronidazole 33%, Minocycline 34%, Ciprofloxacin 33%
Triple Antibiotic Paste for LSTR – Formulation 2
Metronidazole 30%, Clindamycin 30%, Ciprofloxacin 30%, Iodoform 10%
SIDE EFFECTS
In vitro observations have also indicated that in cases where TAP is used
in regenerative endodontics, higher dentine demineralization and a
reduction in dentine micro-hardness due to changes in the chemical
structure of the superficial dentine can be seen when compared with
calcium hydroxide . Another negative side effect to the conditioning of
the radicular dentine by TAP seems to be the indirect adverse effect on
the stem cells of apical papilla (SCAP) and their survival
Conclusion
The elimination of bacteria from the root canal system

plays a major and critical role in success of the
endodontic treatment. It seems that TAP can be
efficiently used for obtaining this purpose. It may be a
promising medicament in new endodontics; however,
more researches are needed to open new windows to
endodontics.
REFERENCES
1-Prather BT, Ehrlich Y, Spolnik K, Platt JA, Yassen GH. Effects of two combinations of
triple antibiotic paste used in endodontic regeneration on root microhardness and
chemical structure of radicular dentine. J Oral Sci. 2014;56:245–251
2- Namour M, Theys S. Pulp revascularization of immature permanent teeth: a
review of the literature and a proposal of a new clinical protocol. Sci World J.
2014;2014:737503 .
3-Ruparel NB, Teixeira FB, Ferraz CC, Diogenes A. Direct effect of intracanal
medicaments on survival of stem cells of the apical papilla. J Endod. 2012;38:1372–
1375.
4- Sabrah AH, Yassen GH, Liu WC, Goebel WS, Gregory RL, Platt JA. The effect of
diluted triple and double antibiotic pastes on dental pulp stem cells and
established Enterococcus faecalis biofilm. Clin Oral Investig. 2015;19:2059–2066.
5-Krithikadatta J, Indira R, Dorothykalyani AL. Disinfection of dentinal tubules with 2%
chlorhexidine, 2% metronidazole, bioactive glass when compared with calcium
hydroxide as intracanal medicaments. J Endod. 2007;33(12):1473–6.
6-Wang ZP, Wang D, Zhang LJ, Kong L. [The observation of the effect of metronidazole-
chlorhexidine solution on treatment of periapical periodontitis] Shanghai Kou Qiang Yi
Xue. 2003;12(4):244–6.
7-Gao J, Wang ZP, Li XG, Wang D, Zhang L. [The preparation and in vitro release test of
sustained release delivery gutta-percha point containing metronidazole] Shanghai Kou
Qiang Yi Xue. 2004;13(6):557–60.
8-Drusano GL, Standiford HC, Plaisance K, Forrest A, Leslie J, Caldwell J. Absolute oral
bioavailability of ciprofloxacin. Antimicrob Agents Chemother. 1986;30(3):444–6.

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AL RAFIDAIN UNIVERSIY COLLEGE OF DENTISTRY

1. In the regeneration and revascularization protocol of the pulp

Considering the polymicrobial nature of tooth infection, single empirical

Tetracycline, including tetracycline-HCl, minocycline, demeclocycline and

TAP should be used in the safest possible concentration (1 mg/mL) since

Triple Antibiotic Paste for LSTR – Formulation 1

The elimination of bacteria from the root canal system

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