Use of triple antibiotic paste as a disinfectant for a traumatized

immature tooth with a periapical lesion: A case report

Ozlem Marti Akgun, DDS,a Ceyhan Altun, DDS, PhD,b and Gunseli Guven, DDS, PhD,c
Ankara, Turkey
GULHANE MEDICAL ACADEMY

Elimination of microbial contamination from the root canal system is a precondition for successful root canal
treatment. In this regard, mechanical instrumentation, irrigation, and intracanal medication are all important. This case
report assesses the efficacy of a triple antibiotic paste consisting of metronidazole, ciprofloxacin, and minocycline in
the disinfection of immature teeth with apical periodontitis. An 8-year-old girl presented at the Department of Pediatric
Dentistry for the evaluation of right and left maxillary central incisors with crown fractures and luxation. The right
central incisor had a large periapical lesion, which was treated by filling the canal with a ciprofloxacin/metronidazole/
minocycline paste. After 4 months, the patient had no symptoms, and a radiograph showed the radiolucency had
completely resolved. At the 1-year follow-up, a periapical radiograph showed complete root development and apical
closure. These results indicate that triple antibiotic paste is effective in disinfecting immature teeth with periapical
lesions. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;108:e62-e65)

Dental trauma may tear the apical neurovascular bundle
and cause pulp necrosis, resulting in arrested root for-
mation in immature teeth.1 The most important objec-
tive of endodontic treatment of teeth with necrotic pulp
and periapical lesions is the elimination of infection
from the root canal system.2,3 Disinfection is achieved
by irrigation followed by the placement of an intracanal
medicament. A mixture of ciprofloxacin, metronida-
zole, and minocycline has been shown to be very ef-
fective in eliminating endodontic pathogens in vitro and
in vivo.4-6 The mixture has also been demonstrated to
be well tolerated by vital pulp tissue.5
The triple-antibiotic regimen was first tested in vitro
by Sato et al.4,6 and was found to be effective in
treating dentin infected with Escherichia coli.4 Subse-
quent studies by Sato et al.4,6 found various mixtures of
antibacterial drugs, including a mixture of ciprofloxa-
cin/metronidazole/minocycline, to be capable of steril-
izing carious lesions, necrotic pulp, and infected root
dentin of deciduous teeth.5,6 In an animal study, Wind-
ley et al.7 examined the effects of a triple-antibiotic
paste of metronidazole, ciprofloxacin, and minocycline
and found it to be effective in disinfecting immature
dog teeth with apical periodontitis. A wide-spectrum
bactericide, metronidazole has also been shown to be
effective against oral obligate anaerobes, including
those isolated from infected necrotic pulp.8 In selecting
appropriate irrigants and medicaments, regenerative ef-
fects should be taken into consideration along with
antimicrobial properties.9 For example, tetracycline is
known to enhance the growth of host cells on dentin,
not by antimicrobial action, but via the exposure of
embedded collagen fibers or growth factors.10 Triple-
antibiotic paste, on the other hand, contains both bac-
tericidal (metronidazole, ciprofloxacin) and bacteriosta-
tic (minocycline) components, allowing for successful
revascularization and the continued development of the
root to its normal length.11,12
This case report describes the treatment of an imma-
ture maxillary central incisor with apical periodontitis
using a triple-antibiotic (ciprofloxacin/metronidazole/
minocycline) paste. At the 1-year follow-up, root de-
velopment was shown to be complete, and conventional
root canal treatment was performed.

CASE REPORT
a
Research Fellow, Department of Pediatric Dentistry, Dental Sci- An 8-year-old girl presented at the Department of Ped-
ences Centre, Gulhane Medical Academy, Ankara, Turkey. odontics at the Gulhane Medical Academy with a crown
b
Assistant Professor, Department of Pediatric Dentistry, Dental Sci- fracture and luxation of the right maxillary central incisor
ences Centre, Gulhane Medical Academy, Ankara, Turkey.
c resulting from a bicycle accident approximately 1 month
Associate Professor, Department of Pediatric Dentistry, Dental Sci-
ences Centre, Gulhane Medical Academy, Etlik/Ankara, Turkey.
earlier. The patient was asymptomatic, had no known aller-
Received for publication Mar 17, 2009; accepted for publication Apr
gies or systemic problems, and extraoral examination re-
1, 2009. vealed no significant abnormalities. A periapical radiograph
1079-2104/$ - see front matter showed the right maxillary central incisor had an open apex
© 2009 Published by Mosby, Inc. associated with a large radiolucency. Intraoral examination
doi:10.1016/j.tripleo.2009.04.015 revealed fractures of both maxillary central incisors (Fig. 1)

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Volume 108, Number 2 Akgun et al. e63

Fig. 1. A, Preoperative clinical view showing fractures of
both maxillary central incisors and labial sinus tract that
traced to the apex of the right maxillary central incisor. B,
Preoperative radiography of maxillary central incisors. In-
complete apex formation and periapical radiolucency in right
maxillary central incisor were revealed.
Fig. 2. A, Clinical view after 4 months showing no signs of
the sinus tract. B, Radiography of right maxillary central
incisor taken 4 months after the application of triple antibiotic
paste. The radiolucency has completely disappeared, and the
first signs of apical closure and continued root development
can be seen.

and the presence of a labial sinus tract that traced to the apex
of the right maxillary central incisor, which was luxated and
had minor mobility and slight sensitivity to heat. Results of an
electric pulp test (EPT) and vitality test were negative. A
treatment plan was formulated that included endodontic treat-
ment of the right maxillary central incisor. Parents were given
detailed information about the treatment program, and their
informed consent was obtained.
The root canal was irrigated with 2.5% NaOCl and instru-
mented to approximately 1 to 2 mm in apical diameter to
allow for systemic bleeding into the root canal system. The
canal was dried with paper points and filled with a ciprofloxacin/
metronidazole/minocycline paste, as described by Hoshino et
al.5 The access cavity was closed with glass ionomer cement
(Glass Ionomer Luting Cement, S.S. White Manufacturing, Fig. 3. A, Normal clinical appearance at the 2-year follow-
Gloucester, England). The intracanal dressing was changed once up. B, Two-year postoperative radiography of right maxillary
a month for 12 months until a periapical radiograph showed central incisor showing no signs of the periapical radiolu-
complete root development and apical closure. cency and the stage of root development is the same as that of
At the 4-month recall, the patient was asymptomatic, with the contralateral tooth.
no signs of the sinus tract. A radiograph indicated complete
resolution of the radiolucency and continued development of
the tooth apex (Fig. 2). At the 1-year follow-up, the patient
was still asymptomatic, and closure of the apex was observed.
Following treatment, a radiograph was taken to control the
Conventional endodontic treatment was performed using a
periapical area, and the patient was asked to return to the
calcium hydroxide– based sealer (Sealapex, Sybron/Kerr, In-
clinic for follow-up every 3 months. Clinical and radiographic
dústria e Comércia Ltda, Guarulhos, SP, Brazil) and gutta-
follow-up showed no pathological findings. Two years after
percha. The canal was obturated using the vertical condensa-
treatment, the radiographic appearance of the traumatized
tion technique. The coronal fragment was etched with a 37%
right central incisor was similar to that of the left central
phosphoric acid gel for 20 seconds, and the area was rinsed
incisor (Fig. 3), and both clinical and radiographic evidence
for 20 seconds and gently air dried. An adhesive (Excite DSC,
confirmed the efficacy of the triple antibiotic paste.
Ivoclar Vivadent AG, Schaan, Liechtenstein) was applied
according to the manufacturer’s instructions. Finally, to meet
esthetic requirements for anterior teeth, the dental restoration DISCUSSION
(Tetric Ceram, Ivoclar Vivadent AG) was completed with Since its introduction as an intracanal medicament,
composite using the incremental technique, and occlusal ad- the bactericidal effect of calcium hydroxide has made it
justment was performed. the most popular endodontic medicament for use in

e64 Akgun et al.
apexification.13 Although endodontic microorganisms
are unable to survive in the highly alkaline environment
provided by Ca(OH)2,2 the compound may also have a
detrimental effect on vital tissue. Direct contact be-
tween the Ca(OH)2 paste and any vital pulp tissue
remaining in the canal can induce the formation of a
layer of calcified tissue that will prevent the regenera-
tion of pulp tissue into the occupied space within the
canal.12 In contrast, studies have shown that when an
antibiotic paste is used instead of Ca(OH)2, regenerated
pulp tissue is able to occupy the remaining canal
space.11,14
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.11 Not only does the use
of triple-antibiotic paste allow for successful revascu-
larization, the paste has both bactericidal (metronida-
zole and ciprofloxacin) and bacteriostatic (minocy-
cline) properties.11,12
Several case reports have been published on the
revascularization of necrotic root canal systems by
disinfection following bleeding into the canal sys-
tem.6,15,16 In these studies, intracanal irrigants (NaOCl
and chlorhexidine) and antibiotics such as ciprofloxacin/
metronidazole/minocycline paste were used for several
weeks for disinfection.5,14 In theory, if the canal space can
be adequately disinfected and the coronal tooth structure
is sealed to minimize bacterial contamination, regenera-
tion is possible when a suitable matrix for new tissue
growth exists. In fact, case reports have shown that root
development of necrotic immature teeth with apical peri-
odontitis continues following application of an antibiotic
dressing.15 Murray et al.9 have suggested that the revas-
cularization of necrotic pulp in a tooth with a closed apex
may require instrumentation to approximately 1 to 2 mm
in apical diameter to allow systemic bleeding into the root
canal system.
In the present case, the root canal was irrigated with
2.5% NaOCl, instrumented to approximately 1 to 2 mm
in apical diameter, and dried with paper points before
filling with a ciprofloxacin/metronidazole/minocycline
paste. The intracanal dressing was changed every 30 days
for 12 months until tooth symptoms were negative. At the
1-year follow-up, revascularization was achieved, root
development completed, and conventional root canal
treatment applied.
In addition to the ciprofloxacin/metronidazole/minocy-
cline paste, 2 other antibiotic mixtures have been evalu-
ated in earlier studies—a mixture of penicillin, bacitracin,
or chloramphenicol and streptomycin (Grossman’s poly-
antibiotic paste), and a mixture of neomycin, polymyxin,
and nystatin.16 Both of these pastes were found to have
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August 2009
limited efficacy as intracanal medicaments.2 A study by
Molander et al.17 found another antibiotic, clindamycin, to
have no advantage over Ca(OH)2 or other conventional
root canal dressings.
Topical corticosteroids have been used as anti-in-
flammatory agents in endodontics for many years, and
studies have shown that although effective in reducing
pain in teeth with vital pulp, they are ineffective when
the pulp is necrotic.2 The most common corticosteroid
preparations currently available are Ledermix paste
(Lederle Pharmaceuticals, Wolfsratshausen, Germany)
and Septomixine Forte paste (Septodont, Saint-Maur,
France).18 However, in vitro studies have found more
favorable results when antibiotic mixtures such as cip-
rofloxacin/metronidazole/minocycline are used instead
of corticosteroids as topical root canal medicaments.4,5
REFERENCES
1. Soares J, Santos S, César C, Silva P, Sá M, Silveira F, et al.
Calcium hydroxide induced apexification with apical root
development: a clinical case report. Int Endod J 2008;41:
710-9.
2. Elkarim I, Kennedy J, Hussey D. The antimicrobial effects of
root canal irrigation and medication. Oral Surg Oral Med Oral
Pathol 2007;103:560-9.
3. Leonardo MR, Rossi MA, Silva LAB, Ito IY, Bonifacio KC.
Evaluation of bacterial biofilm and microorganisms on the
apical external root surface of human teeth. J Endod 2002;
28:815-8.
4. Sato I, Ando-Kurihara N, Kota K, Iwaku M, Hoshino E. Steril-
ization of infected root-canal dentine by topical application of a
mixture of ciprofloxacin, metronidazole and minocycline in situ.
Int Endod J 1996;29:118-24.
5. Hoshino E, Kurihara-Ando N, Sato I, Uematso H, Sato M,
Kota K, et al. In-vitro antibacterial susceptibility of bacteria
taken from infected root dentine to a mixture of ciprofloxa-
cin, metronidazole and minocycline. Int Endod J 1996;29:
125-30.
6. Sato T, Hoshino E, Uematsu H, Kota K, Iwaku M, Noda T.
Bactericidal efficacy of a mixture of ciprofloxacin, metronida-
zole, minocycline and rifampicin against bacteria of carious and
endodontic lesions of human deciduous teeth in vitro. Microbial
Ecology in Health and Disease 1992;5:171-77.
7. Windley W III, Teixeira F, Levin L, Sigurdsson A, Trope M.
Disinfection of immature teeth with a triple antibiotic paste. J
Endod 2005;31:439-43.
8. Ingham HR, Selkon JB, Hale JH. The antibacterial activity of
metronidazole. J Antimicrob Chemother 1975;1:355-61.
9. Murray PE, Garcia-Godoy F, Hargreaves KM. Regenerative
endodontics: a review of current status and a call for action.
J Endod 2007;33:377-90.
10. Terranova VP, Odziemiec C, Tweden KS, Spadone DP. Repopu-
lation of dentin surfaces by periodontal ligament cells and endo-
thelial cells effect of basic fibroblast growth factor. J Periodontol
1989;60:293-301.
11. Iwaya S, Ikawa M, Kubota M. Revascularization of an immature
permanent tooth with apical periodontitis and sinus tract. Dent
Traumatol 2001;17:185-7.
12. Huang GT. A paradigm shift in endodontic management of
immature teeth: conservation of stem cells for regeneration. J
Dent 2008;36:379-86.
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Volume 108, Number 2 Akgun et al. e65

13. Rafter M. Apexification: a review. Dental Traumatol 2005;21:1-8. 18. Athanassiadis B, Abbott PV, Walsh L. The use of calcium
14. Thibodeau B, Trope M. Pulp revascularization of a necrotic hydroxide, antibiotics and biocides as antimicrobial medica-
infected immature permanent tooth: case report and review of the ments in endodontics. Austral Dent J 2007;52:64-82.
literature. Pediatr Dent 2007;29:47-50.
15. Banchs F, Trope M. Revascularization of immature permanent
teeth with apical periodontitis: new treatment protocol? J Endod Reprint requests:
2004;30:196-200. Gunseli Guven, DDS, PhD
16. Grieve AR, Friend LA, Plant CG. A clinical trial of three root Associate Professor
canal medicaments. Br Dent J 1973;134:188-93. Department of Pediatric Dentistry, Dental Sciences Centre
17. Molander A, Reit C, Dahlen G. Microbiological evaluation of Gulhane Medical Academy
clindamycin as a root canal dressing in teeth with apical peri- Etlik/Ankara, Turkey
odontitis. Int Endod J 1990;23:113-8. guvengunseli@yahoo.com