J Pharm Bioallied Sci. 2012 Aug; 4(Suppl 2): S230S233.

doi: 10.4103/0975-7406.100214
PMCID: PMC3467921

Triple antibiotic paste in root canal therapy

Rangasamy Vijayaraghavan, Veerabathran Mahesh Mathian, Alagappan Meenakshi

Sundaram,1 Ramachandran Karunakaran, and Selvaraj Vinodh

Address for correspondence: Dr. Rangasamy Vijayaraghavan E-

mail: moc.liamg@navagar.yajivrd

Received 2011 Dec 1; Revised 2012 Jan 2; Accepted 2012 Jan 26.

Copyright : Journal of Pharmacy and Bioallied Sciences

This is an open-access article distributed under the terms of the Creative Commons
Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract
The role of microorganisms in the development and perpetuation of pulp and periapical
diseases has clearly been demonstrated in animal models and human studies.[1] The
development and progression of endodontically induced periapical lesion is clearly associated
with the presence of microorganisms in the root canal system.[2] Bacteria in infected root
canals and periradicular tissues are capable of invading and residing deeply within dentin and
in cementum around the periapex. Endodontic therapy is aimed at elimination of bacteria
from the infected root canal and at the prevention of infection.[3] The infection of the root
canal system is considered to be a polymicrobial infection, consisting of both aerobic and
anaerobic bacteria. Because of the complexity of the root canal infection, it is unlikely that
any single antibiotic could result in effective sterilization of the canal. More likely, a
combination would be needed to address the diverse flora encountered. The combination that
appears to be most promising consists of metronidazole, ciprofloxacin, and minocycline.[4]
Majority of bacteria in the infected root canal dentin are obligate anaerobes. Hence,
metronidazole was selected as the first choice among antibacterial drugs. Even at a high
concentration, it cannot kill all the bacteria, indicating the necessity for combination of other
drugs. Propylene glycol can be used as a vehicle for the delivery of this paste.[3] The triple-
antibiotics regimen was first tested by Sato et al.[5] Teeth with immature root development,
necrotic pulps, and apical periodontitis present multiple challenges for successful treatment.[6]

Recently, the concept of revascularization of necrotic pulps regained interest and became an
alternative conservative treatment option for young permanent teeth with immature roots.[7]
Lesion sterilization and tissue repair (LSTR) therapy employs the use of a combination of
antibacterial drugs (metronidazole, ciprofloxacin, and minocycline) for the disinfection of
oral infectious lesions, including dentinal, pulpal, and periradicular lesions.[8] Traditionally,
the treatment of immature permanent teeth with necrotic pulps involves long-term application
of calcium hydroxide to induce apexification at the root apex. Recently, mineral trioxide
aggregate (MTA) has been used in one-step apexification procedures to create an artificial
apical barrier on which the obturation material can be compacted. Although clinically
successful for treatment of apical periodontitis, these techniques do not help strengthen the
root, and in the absence of continued development of the root, the roots remain thin and
fragile.[9] Hoshino et al. performed an in vitro study testing the antibacterial efficacy of these
drugs alone and in combination against the bacteria of infected dentin, infected pulps, and
periapical lesions. Alone, none of the drugs resulted in complete elimination of bacteria.
However, in combination, these drugs were able to consistently sterilize all samples.[10]
Metronidazole is a nitroimidazole compound that exhibits a broad spectrum of activity
against protozoa and anaerobic bacteria. Minocycline is a semisynthetic derivative of
tetracycline with a similar spectrum of activity. Ciprofloxacin, a synthetic fluoroquinolone,
has a bactericidal mode of action.[4]

The endodontic regenerative procedure (ERP), an alternative clinical approach to

apexification, has received great attention in recent years. This treatment protocol involves
the use of a triple antibiotic paste (TAP) consisting of metronidazole, minocycline, and
ciprofloxacin as a dressing and the induction of bleeding to create a matrix for the ingrowth
of new vital tissue in the pulp canal space.[10]

A gentle treatment regimen (minimal or no instrumentation and an intracanal medication with

TAP) before ERP may conserve any viable tissue that may remain in the canal (stem cells in
the apical papilla (SCAP) and dental pulp stem cells in the pulp).[10] Many clinical
investigations have reported an increase in root thickness and length, resembling normal
maturation of the root after TAP therapy.[1113]

With the increase in non-surgical approach, the goal of this study is to perform a literature
search on TAP in endodontics No attempt is made to undertake additional statistical analysis.

Materials and Methods

A PubMed, Medine search was carried out with the key words: non-vital, young
permanent tooth, and triple antibiotic paste. Articles were selected after reading the title
and abstract. References from the selected articles were also considered for review. Case
reports, and in vitro, in vivo animal studies and investigations on TAP were included for
review.

Discussion

Modern concept of medicine emphasizes prevention and reversal of the diseases. Only when
these attempts fail, we would take on the unfavorable approaches, i.e., surgical intervention
and restoration with artificial prostheses.[14] The success of non-surgical endodontic
treatment method is based on appropriate cleaning, shaping, asepsis, and filling of the root
canal.[2] Several case reports have been published on non-surgical management of tooth with
a non-vital pulp and persisting sinus tract using TAP. TAP was successful in promoting the
healing and repair of the periapical tissue.[2,15] The systemic administration of antibiotics
relies on patient compliance with the dosing regimens followed by absorption through the
gastrointestinal tract and distribution via the circulatory system to bring the drug to the
infected site. Hence, the infected area requires a normal blood supply which is no longer the
case for teeth with necrotic pulps and for teeth without pulp tissue. Therefore, local
application of antibiotics within the root canal system may be a more effective mode for
delivering the drug.[15]

Microorganisms in dentinal tubules may constitute a reservoir from which root canal and
surrounding tissue infection and re-infection may occur.[16] Portenier et al. demonstrated
that dentin itself can have an inhibitory effect on the bactericidal activity of intracanal
medicaments like calcium hydroxide.[17]

William Windley observed a statistically significant reduction in bacteria, following the

irrigation and antibiotic paste protocol. 90% of the bacteria remained positive following
irrigation with 10 ml 1.25% sodium hypochlorite. However, this dropped to 30% following
the application of the TAP for 2 weeks.[4]

Dental trauma may tear the apical neurovascular bundle and cause pulp necrosis, resulting in
arrested root formation in immature teeth.[18] The traditional approach for treating cases of a
necrotic immature permanent tooth was apexification with calcium hydroxide or MTA, but it
does not lead to a further thickening of dentinal walls or an increased root length.[19] It is
difficult to get an appropriate apical seal in teeth with open apices by using the conventional
endodontic treatment methods. Long-term use of calcium hydroxide has several
disadvantages such as multiple treatment appointments, probable recontamination of the root
canal system during treatment period, and increased brittleness of root dentin which increases
the risk of future cervical root fractures.[20] An alternative material of choice for
apexification is MTA[21] and it has shown high success rates.[2224] Regenerative
endodontics is an emerging field focusing on replacing traumatized and diseased pulp tissue
in these teeth.[25] Utilization of stem cells to regenerate the lost tissues may reverse tissues to
their normal state. Regenerative endodontics deals with the healing of impaired dental tissues,
including dentin, pulp, cementum, and periodontal tissues.[14]

Regeneration can occur from vital pulp cells remaining at the apical end of the root canal,[19]
the multipotent dental pulp stem cells,[26] the stem cells in the periodontal ligament,[27] and
stem cells from apical papilla or in bone marrow. The blood clot itself is a rich source of
growth factors.[27] Revascularization of the pulp space in a tooth with necrotic infected pulp
tissue and apical periodontitis has been thought to be impossible.[4] Nygaard-Ostby and
Hjortdal successfully regenerated pulps after vital pulp removal in immature teeth, but were
unsuccessful when the pulp space was infected. Thus, if the canal is effectively disinfected,
revascularization should occur similar to that in an avulsed immature tooth.[4] Once the canal
infection is controlled, it resembles the avulsed tooth that has a necrotic but sterile pulp space.
The blood clot is then introduced so as to mimic the scaffold that is in place with the ischemic
necrotic pulp in the avulsed tooth.[7] In this situation, the necrotic uninfected pulp acts as a
scaffold for the ingrowth of new tissue from the periapical area. The absence of bacteria is
critical for successful revascularization because the new tissue will stop at the level at which
it meets bacteria in the canal space. The clinical effectiveness of the TAP in the disinfection
of immature teeth with apical periodontitis has been reported.[7] Calcium hydroxide can
cause necrosis of the surrounding tissue, destroying remnant vital tissues that have the
potential to differentiate into new pulp.[28]
When the canal is properly disinfected, the inflammatory process reverses and the tissues
may proliferate. Revascularization of immature teeth with apical periodontitis depends
mainly on: (a) disinfection of the canal; (b) placement of a matrix in the canal for tissue
ingrowth; and (c) a bacterial tight seal of the access opening. Since the infection of the root
canal system is considered to be polymicrobial, a combination of drugs would be needed to
treat the diverse flora. Thus, the recommended protocol combines the use of metronidazole,
ciprofloxacin, and minocycline.[7]

Raison Bose compared TAP, calcium hydroxide, and formocresol as intracanal medicaments
in non-vital young permanent tooth. The triple antibiotic group showed the highest
percentage increase in the dentin wall thickness compared with the other two groups. TAP
can help promote functional development of the pulpdentin complex.[9] Reynolds et al.
achieved revascularization of a necrotic bicuspid using TAP.[7] TAP contains both
bactericidal (metronidazole, ciprofloxacin) and bacteriostatic (minocycline) agents to allow
for successful revascularization.[29]

In apexification, the canal is temporarily filled until a hard tissue barrier forms at the apex.
Because the canal space is filled, there is no space available for vital tissue to proliferate into
the root canal and the possibility of revascularization is eliminated.[30] Investigations have
proved that topical doxycycline and minocycline can improve radiographic and histological
evidence of revascularization in immature avulsed permanent teeth.[31,32] Several reports
have recently demonstrated the potential for revascularization after infection if a sterile
environment is created.[29,33] After disinfection, the canal should be filled with a resorbable
matrix to encourage the ingrowth of new tissue. Finally, the coronal access must be sealed to
prevent re-infection.[4]

TAP was proved to be biocompatible.[28] Tetracycline inhibits collagenases and matrix

metalloproteinases,[34] is not cyt otoxic,[35] and increases the level of interleukin-10, an
anti-inflammatory cytokine.[36] In addition, metronidazole and ciprofloxacin can generate
fibroblasts.[37]

The concern of the antibiotic paste is that it may cause bacterial resistance.[14,38]
Additionally, minocycline may cause tooth discoloration.[14] Thibodeau and Trope
suggested cefaclor instead of minocycline in TAP.[39] Reynolds et al. used dentin bonding
agent and composite resin before placement of the triple antibiotic dressing to prevent
discoloration, but the discoloration was only reduced.[7] The discoloration by the tetracycline
family is thought to be a photo-initiated reaction.[40] Minocycline binds to calcium ions via
chelation to form an insoluble complex.[41] It should be limited to the root canal because of
the potential risk of tooth discoloration.[40]

Conclusion

Success of the endodontic treatment relies upon the elimination of bacteria from the root
canal. Microorganisms in the periapical region can cause re-infection and failure. From the
existing literature, it is clear that TAP can be effectively used for sterilization of canals and
healing of periapical pathology. The effectiveness of TAP in managing non-vital young
permanent tooth is based on the availability of viable stem cells. Development of resistant
bacterial strains and tooth discoloration are the possible drawbacks of this technique. TAP
seems to be promising medicament in the sterilization and revascularization.

Footnotes
Source of Support: Nil

Conflict of Interest: None declared.

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