Effectiveness ofantibiotics used in REPs against bacteria causing infection of the root canalsystemThe use of ciprofloxacin, metronidazole andminocycline in REPs has it experimental support in the researches carried outby Hoshino et al. i in 1988,who studied the bactericidal efficacy of metronidazole against bacteria incarious dentin, concluding that metronidazole effectively disinfected thecarious dentin. Posteriorly, in 1993 Sato etal.
iidemonstrated that different mixture of ciprofloxacin, metronidazole, plus athird antibiotic (amoxicillin, cefaclor, cefroxadine, fosfomycin orrokitamycin) were effective in sterilizing cultured of samples taken fromcarious dentin and infected pulpal tissues. It was found that no bacteria couldbe recovered after treatment with 100 mg/mL of each antibiotic (300 mg/mL ofmixture). Nygaard-Østby et al. iiiassessed the efficacy of ciprofloxacin, metronidazole and minocycline in dentinpenetration and eradication of bacteria from infected dentin. It was found thatthere were no recovered bacteria after 48 h. In 1996, the experiments of Sato et al. iv and Hoshino et al.
v revealed the bactericidal efficacyof a mixture of ciprofloxacin, metronidazole and minocycline to eradicatebacteria from the infected dentine of root canals. Since then, tripleantibiotic paste has been used widely in REPs, becoming the most popularintracanal medicaments in pulp regenerative therapy. Takushige et al. vi used TAP to disinfect 87 infecteddeciduous teeth, resulting in the resolution of symptoms within days, withteeth remaining asymptomatic until exfoliation and eruption of successorpermanent teeth. They found that concentrations of 100 mg/mL of each drugscompletely eradicate cultivable bacteria from infected root canals in clinicalsamples. Ordinola-Zapata et al. viievaluated the antimicrobial activity of calcium hydroxide, 2% chlorhexidinegel, and TAP by using an intraorally infected dentin biofilm model, concludingthat TAP paste was most effective at killing the bacteria in the biofilms onthe intraorally infected dentin model in comparison with 2% chlorhexidine geland calcium hydroxide.Antibiotics used in REPs not only have directantibacterial effects.
DAP (5 mg/mL) exhibited significant residualantibacterial effects against bacterial biofilms from an infected root canal ofan immature tooth viii. Clinical andexperimental studies on efficacy of antibiotics in REPsAfter the experimental confirmation of the highefficacy of the combination of ciprofloxacin, metronidazole and minocycline againstendodontic bacteria, Banchs & Trope 6 used, for the first time, a paste containingthese three antibiotics in a case of regenerative endodontics. The threeantibiotics have been mixed either with water, saline, or propylene glycoluntil a thick creamy mixture was formed and certain physical consistency wasachieved that was deemed ideal by clinicians 2. Windley etal. ixassessed the efficacy of TAP in the disinfection of immature dog teeth withapical periodontitis. The canals were sampled before (S1) and after (S2)irrigation with 1.
25% NaOCl and after dressing with the triple antibiotic paste(S3). Reductions in mean CFU counts between S1 and S2 (p < 0.0001) as wellas between S2 and S3 (p < 0.0001) were statistically significant, indicatingthe effectiveness of a triple antibiotic paste in the disinfection of immatureteeth with apical periodontitis. Recently, a modified triple antibiotic pastedressing (ciprofloxacin, metronidazole and cefixime, a third generation broadspectrum cephalosporin) (mTAP) at concentration of 20 mg of each antibiotic,has been shown to improve the success rate of the revascularization procedurein immature dog teeth with AP x. However, the results of some studies concludedthat the use of intracanal antibiotics might not be necessary in REPs inimmature dogs' teeth with apical periodontitis. A study carried out by Da Silvaet al. xi foundthat teeth treated with sodium hypochlorite irrigation with the EndoVac systemalone, presented more exuberant mineralized formations, more structured apicaland periapical connective tissue, and a more advanced repair process than teethtreated with sodium hypochlorite irrigation with the EndoVac system and TAP.
Similarly, Cohença et al. xiianalyzed samples collected from inmature dog’s teeth root canals with pulpnecrosis and apical periodontitis, seeded in a culture medium for anaerobicbacteria, determining colony-forming unit counts. There was no significantdifference between the groups with or without TAP. Likewise, it has beendemonstrated in REP carried out in immature dog teeth with AP, that TAPdressing during two weeks provides the same level of disinfection thanirrigation with 5.
25% sodium hypochlorite alone in only one session xiii.Recently, the ESE position statement on revitalization procedures advocates theuse of calcium hydroxide instead of antibiotics xiv,considering that there is no strong evidence supporting the use of antibioticsin REPs xv.The ESE position statement on the use of antibiotics in endodontics comes tothe same conclusion xvi. i Hoshino E, Kota K,Sato M et al. Bactericidal efficacy of metronidazole against bacteria of humancarious 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 onbacteria from carious and endodontic lesions of human deciduous teeth. OralMicrobiol Immunol 1993;8:172–76. iii Nygaard-Østby P,Tellefsen G, Sigurdsson TJ et al. Periodontal healing following reconstructivesurgery: 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 bytopical application of a mixture of ciprofloxacin, metronidazole andminocycline in situ. Int Endod J 1996;29:118–24. v HoshinoE, Kurihara-Ando N, Sato I, et al.
In-vitro antibacterial susceptibility ofbacteria taken from infected root dentine to a mixture of ciprofloxacin,metronidazole and minocycline. Int Endod J 1996;29:125–30. vi TakushigeT, Cruz EV, Asgor Moral A et al. Endodontic treatment of primary teeth using acombination of antibacterial drugs. IntEndod J 2004;37:132–8. vii Ordinola-Zapata R,Bramante CM, Minotti PG et al. Antimicrobial activity of triantibiotic paste, 2% chlorhexidine gel, andcalcium hydroxide on an intraoral-infected dentin biofilm model.
J Endod 2013;39:115-8.viiiJacobs JC, Troxel A, Ehrlich Y et al. Antibacterial effects of antimicrobialsused in regenerative endodontics against biofilm bacteria obtained from matureand immature teeth with necrotic pulps.
J Endod 2017;43:575-9. ix Windley W, TeixeiraF, Levin L et al. Disinfection of immature teeth with a triple antibioticpaste. J Endod 2005;31:438-33.x Rodríguez-BenítezS, Stambolsky C, Torres-Lagares D et al. Pulp revascularization ofimmature dog teeth with apical periodontitis using tri-antibiotic paste andplatelet-rich plasma: radiographic study. J Endod 2015;41:1299-1304.
xi da Silva LA, Nelson-FilhoP, da Silva RA et al. Revascularization and periapical repair after endodontic treatment usingapical negative pressure irrigation versus conventional irrigation plustriantibiotic intracanal dressing in dogs’ teeth with apical periodontitis. OralSurg Oral Med Oral Pathol Oral Radiol Endod 2010;109:779-87.xii Cohenca N, HeilbornC, Johnson JD, Flores DS, Ito IY, da Silva LA. Apical negative pressureirrigation versus conventional irrigation plus triantibiotic intracanaldressing on root canal disinfection in dog teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod2010;109:e42-6.xiii Rodríguez-BenítezS, Stambolsky C, Martín-Jiménez M et al.
Root canal disinfection ofimmature dog teeth with apical periodontitis: comparison of three differentprotocols. J Clin Exp Dent 2014;6:e357-e363. xiv European Society of Endodontology. European Societyof Endodontology position statement: revitalization procedures. Int Endod J2016;49:717–23.xvGaller KM. Clinical procedures for revitalization: current knowledge andconsiderations.
Int Endod J 2016;49:926–36.xvi European Society of Endodontology. European Societyof Endodontology position statement: the use of antibiotics in endodontics. IntEndod J 2017; Apr 24. doi: 10.1111/iej.12781.
Epub ahead of printReview.