The electronic search identified 186 articles. A
subsequent search at the title and abstract level revealed 107 articles for
full-text reading. After reading them, taking into account the inclusion and
exclusion criteria, 64 articles were discarded, and finally, 43 articles were selected,
being analyzed according to the aims of the review.
Five sections were established in the review: 1)
Scientific evidence about the effectiveness of antibiotics used in REPs against
bacteria implicated in endodontic disease; 2) Scientific evidence supporting
the use of topical antibiotics in REPs; 3) Clinical implications of the use of
antibiotics in REPs; 4) Effect of antibiotics on stem cells; and 5) Ongoing research on the use of antibiotics in REPs.
antibiotics used in REPs against bacteria causing infection of the root canal
The use of ciprofloxacin, metronidazole and
minocycline in REPs has it experimental support in the researches carried out
by Hoshino et al. i in 1988,
who studied the bactericidal efficacy of metronidazole against bacteria in
carious dentin, concluding that metronidazole effectively disinfected the
carious dentin. Posteriorly, in 1993 Sato et
demonstrated that different mixture of ciprofloxacin, metronidazole, plus a
third antibiotic (amoxicillin, cefaclor, cefroxadine, fosfomycin or
rokitamycin) were effective in sterilizing cultured of samples taken from
carious dentin and infected pulpal tissues. It was found that no bacteria could
be recovered after treatment with 100 mg/mL of each antibiotic (300 mg/mL of
mixture). Nygaard-Østby et al. iii
assessed the efficacy of ciprofloxacin, metronidazole and minocycline in dentin
penetration and eradication of bacteria from infected dentin. It was found that
there were no recovered bacteria after 48 h. In 1996, the experiments of Sato et al. iv and Hoshino et al. v revealed the bactericidal efficacy
of a mixture of ciprofloxacin, metronidazole and minocycline to eradicate
bacteria from the infected dentine of root canals. Since then, triple
antibiotic paste has been used widely in REPs, becoming the most popular
intracanal medicaments in pulp regenerative therapy. Takushige et al. vi used TAP to disinfect 87 infected
deciduous teeth, resulting in the resolution of symptoms within days, with
teeth remaining asymptomatic until exfoliation and eruption of successor
permanent teeth. They found that concentrations of 100 mg/mL of each drugs
completely eradicate cultivable bacteria from infected root canals in clinical
samples. Ordinola-Zapata et al. vii
evaluated the antimicrobial activity of calcium hydroxide, 2% chlorhexidine
gel, and TAP by using an intraorally infected dentin biofilm model, concluding
that TAP paste was most effective at killing the bacteria in the biofilms on
the intraorally infected dentin model in comparison with 2% chlorhexidine gel
and calcium hydroxide.
Antibiotics used in REPs not only have direct
antibacterial effects. DAP (5 mg/mL) exhibited significant residual
antibacterial effects against bacterial biofilms from an infected root canal of
an immature tooth viii.
i Hoshino E, Kota K,
Sato M et al. Bactericidal efficacy of metronidazole against bacteria of human
carious dentin in vitro. Caries Res 1988;22:280-2.
ii Sato T, Hoshino E,
Uematsu H et al. In vitro antimicrobial susceptibility to combinations of drugs on
bacteria from carious and endodontic lesions of human deciduous teeth. Oral
Microbiol Immunol 1993;8:172–76.
iii Nygaard-Østby P,
Tellefsen G, Sigurdsson TJ et al. Periodontal healing following reconstructive
surgery: effect of guided tissue regeneration. J Clin Periodontol 1996;23:1073–79.
iv Sato I,
Ando-Kurihara N, Kota K, et al. Sterilization 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.
E, Kurihara-Ando N, Sato I, et al. In-vitro antibacterial susceptibility of
bacteria taken from infected root dentine to a mixture of ciprofloxacin,
metronidazole and minocycline. Int Endod J 1996;29:125–30.
T, Cruz EV, Asgor Moral A et al. Endodontic treatment of primary teeth using a
combination of antibacterial drugs. Int
Endod J 2004;37:132–8.
vii Ordinola-Zapata R,
Bramante CM, Minotti PG et al. Antimicrobial activity of triantibiotic paste, 2% chlorhexidine gel, and
calcium hydroxide on an intraoral-infected dentin biofilm model. J Endod 2013;39:115-8.
Jacobs JC, Troxel A, Ehrlich Y et al. Antibacterial effects of antimicrobials
used in regenerative endodontics against biofilm bacteria obtained from mature
and immature teeth with necrotic pulps. J Endod 2017;43:575-9.