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Accepted Manuscript Title: Bactericidal Efficacy of Photodynamic Therapy Against Enterococcus faecalis in Infected Root Canals: A Systematic Literature Review Author: Shoaib Haider Siddiqui Kamran Habib Awan Fawad Javed PII: S1572-1000(13)00093-8 DOI: http://dx.doi.org/doi:10.1016/j.pdpdt.2013.07.006 Reference: PDPDT 507 To appear in: Photodiagnosis and Photodynamic Therapy Received date: 15-5-2013 Revised date: 27-7-2013 Accepted date: 30-7-2013 Please cite this article as: Siddiqui SH, Awan KH, Javed F, Bactericidal Efficacy of Photodynamic Therapy Against Enterococcus faecalis in Infected Root Canals: A Systematic Literature Review, Photodiagnosis and Photodynamic Therapy (2013), http://dx.doi.org/10.1016/j.pdpdt.2013.07.006 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Page 1: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

Accepted Manuscript

Title: Bactericidal Efficacy of Photodynamic Therapy AgainstEnterococcus faecalis in Infected Root Canals: A SystematicLiterature Review

Author: Shoaib Haider Siddiqui Kamran Habib Awan FawadJaved

PII: S1572-1000(13)00093-8DOI: http://dx.doi.org/doi:10.1016/j.pdpdt.2013.07.006Reference: PDPDT 507

To appear in: Photodiagnosis and Photodynamic Therapy

Received date: 15-5-2013Revised date: 27-7-2013Accepted date: 30-7-2013

Please cite this article as: Siddiqui SH, Awan KH, Javed F, Bactericidal Efficacyof Photodynamic Therapy Against Enterococcus faecalis in Infected Root Canals:A Systematic Literature Review, Photodiagnosis and Photodynamic Therapy (2013),http://dx.doi.org/10.1016/j.pdpdt.2013.07.006

This is a PDF file of an unedited manuscript that has been accepted for publication.As a service to our customers we are providing this early version of the manuscript.The manuscript will undergo copyediting, typesetting, and review of the resulting proofbefore it is published in its final form. Please note that during the production processerrors may be discovered which could affect the content, and all legal disclaimers thatapply to the journal pertain.

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Title: Bactericidal Efficacy of Photodynamic Therapy Against Enterococcus

faecalis in Infected Root Canals: A Systematic Literature Review

Authors: Shoaib Haider Siddiqui,1 Kamran Habib Awan,2 Fawad Javed3

Affiliations:

1. Department of Restorative Dentistry, College of Dentistry, Qaseem University,

Qaseem, Saudi Arabia;

2. Department of Oral Medicine, College of Dentistry, King Saud University,

Riyadh, Saudi Arabia;

3. Engineer Abdullah Bugshan Research Chair for Growth Factors and Bone

Regeneration, 3D Imaging and Biomechanical Laboratory, College of Applied

Medical Sciences, King Saud University, Riyadh, Saudi Arabia;

Running title: PDT and root canal disinfection

Conflict of interest and financial disclosure: The authors declare that they have no

conflict of interest and there was no external source of funding for the present study.

Corresponding author: Dr. Fawad Javed. Engineer Abdullah Bugshan Research

Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical

Laboratory, College of Applied Medical Sciences, King Saud University, Riyadh,

Saudi Arabia. Email: [email protected]

Number of words (Abstract): 242 Number of words (main text): 1959

Number of tables: 3 Number of figures: 0

Number of references: 46 Number of pages: 18

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ABSTRACT

Objective: The aim was to review the bactericidal efficacy of photodynamic therapy

(PDT) against Enterococcus faecalis (E. faecalis) in infected root canals

Methods: To address the focused question “Does PDT exhibit bactericidal effects

against E. faecalis in infected root canals?” PubMed/Medline and Google-Scholar

databases were searched from 1985 up to June 2013 using various combinations of

the following key words: “antibacterial; “bactericidal; “endodontic; “root canal” and

“photodynamic therapy”. Original studies, experimental studies and articles published

only in English language were included. Letters to the editor, historic reviews and

unpublished data were excluded. The pattern of the present review was customized to

primarily summarize the pertinent information.

Results: Seventeen studies (16 ex-vivo and one in-vivo) were included. In these

studies, numbers of teeth used ranged between 30-220 teeth. In these studies,

wavelengths of diode laser used, diameter of fiber and power output ranged between

625-805 nm, 200µm-0.4cm and 40mW-5W respectively. Twelve studies reported

PDT to be effective in eliminating E. faecalis from infected root canals. Four studies

reported conventional irrigation and instrumentation to be more efficient in killing E.

faecalis than PDT. One study reported PDT and conventional endodontic regimes to

be equally effective in eliminating E. faecalis from infected root canals. In most

studies, toluidine blue and/or methylene blue were used as photosensitizers.

Conclusion: Efficacy of PDT in eliminating E. faecalis from infected root canals

remains questionable.

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Key words: antibacterial; endodontic; Enterococcus faecalis; root canal; and

photodynamic therapy.

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INTRODUCTION

Several factors including intraradicular and extraradicular infections, cysts

containing cholesterol crystals and foreign body reactions have been associated with

periradicular infections that may occur after root canal treatment (RCT).[1, 2]

Survival of microorganisms in the apical region of root-filled teeth is believed to play

a role in root canal failure.[1, 2]

Enterococcus faecalis (E. faecalis), a gram-positive facultative anaerobic

coccoid, is one of the primary organisms that play a role in post-treatment endodontic

failure. E. faecalis contributes to endodontic failures by altering host responses,

adhering to host cells, expressing proteins that allow it to compete with other bacterial

cells and suppressing the activity of lymphocytes [3-5]. High percentages (up to 77%)

of E. faecalis have been found in failed RCT cases [3]. Studies [6-10] have reported

that despite mechanical instrumentation and irrigation with antimicrobial irrigants

(such as sodium hypochlorite [NaOCl]), cultivable bacteria persist in nearly 40% to

60% of the canals. Furthermore, E. faecalis has been reported to resist the

bactericidal effects of intracanal calcium hydroxide dressings for at least 10 days by

maintaining pH homeostasis [11, 12].

Photodynamic therapy (PDT) involves vibrant interaction between light and a

photosensitizer (PS) (a chemical compound, usually a dye that can be excited by light

of a particular wavelength) in the presence of oxygen [13-15]. Once the PS

accumulates in the targeted tissues, it is exposed to light of a specific wavelength

(usually red light with wavelength ranging between 630 nm and 700 nm) [16]. This

causes oxidative damage to the target cells (including bacterial and tumor cells) by

inducing the production of reactive oxygen species (ROS) [17]. Studies have reported

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that PDT is effective in the treatment of periodontal diseases and oral premalignant

and malignant lesions such as leukoplakia and oral squamous cell carcinoma

respectively [18-23]. Furthermore, PDT significantly reduces the counts of E. faecalis

in infected root canals compared to traditional endodontic instrumentation/irrigation

treatment protocols [24-36]; however, controversial results have also been reported

[37-40].

Since E. faecalis is a major cause of endodontic failure after RCT and that

PDT exhibits bactericidal efficacy against bacteria (including E. faecalis), the aim of

the present study was to review the bactericidal efficacy of PDT against E. faecalis in

infected root canals.

MATERIALS AND METHODS

Focused question

The addressed focused question was “Does PDT exhibit bactericidal effects

against E. faecalis in infected root canals?”

Eligibility criteria

The following eligibility criteria were imposed: 1) Original articles; 2)

Experimental studies; 3) Clinical studies; 4) Reference list of potentially relevant

original and review studies; 5) Intervention: antibacterial efficacy of PDT against E.

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faecalis in infected root canals; and 6) Articles published only in English-language.

Unpublished data, letters to the editor and historic reviews were excluded.

Search strategy

As a first step, detailed automated searches of MEDLINE/PubMed (National

Library of Medicine, Bethesda, Maryland) and Google-Scholar databases were

performed from 1985 up to and including June 2013 using various combinations of

the following key indexing terms: (a) antibacterial, (b) bactericidal, (c) endodontic,

(d) root canal, and (e) photodynamic therapy.

In the second step, titles and abstracts of studies, which fulfilled the eligibility

criteria were screened by the authors (SHS, KHA and FJ) and checked for agreement.

Hand searching of the reference lists of original and review articles that were found to

be relevant in the first step was also performed. Due to heterogeneity of the studies, a

meta-analysis could not be performed and the pattern of the current review was

customized to mainly summarize the pertinent information (Figure 1).

RESULTS

Characteristics of studies included in the present review

In total, 17 studies [24-40] (16 ex-vivo [25-31, 33-35, 37-39] and one in-vivo

[36]) were included. These studies were performed either at universities or healthcare

centers. The number of teeth used in the 16 ex-vivo studies [23-29, 31-33, 35-37]

ranged between 32 and 220 uniradicular teeth; whereas in the in-vivo study [36] the

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efficacy of PDT in killing E. faecalis strains was assessed in 30 uniradicular teeth

from 21 patients (Table 1). Fifteen studies [24-33, 35, 36, 38-40] experimented on

human teeth whereas Nagayoshi et al. [34] and Hecker et al. [37] used resin blocks

and bovine teeth respectively in their studies. In all studies [24-40], the canals were

initially instrumented using rotary instruments and irrigated with 1% to 6% NaOCl

and 17% ethylenediaminetetraacetic acid (EDTA).

Twelve studies [24-27, 29-36] reported that PDT is effective in eliminating E.

faecalis from infected root canals. Amongst these, three studies [25, 29, 33] reported

that PDT with adjunct NaOCl (2.5%-6%) irrigation is more effecting in killing E.

faecalis compared to when PDT is used alone. In-vivo results by Garcez et al. [36]

reported endodontic bacteria (including E. faecalis ) to significantly reduce following

endodontic therapy with adjunct PDT compared to when endodontic therapy is used

alone for intracanal disinfection.

Four ex-vivo studies [28, 37, 38, 40] reported conventional endodontic

treatment regimes (such as mechanical debridement and copious NaOCl irrigation) to

be significantly more effective in eliminating intracanal bacteria compared to PDT.

One study [39] reported PDT to be as effective as instrumentation/irrigation in

reducing intracanal E. faecalis counts (Table 1).

Characteristics of lasers used for photodynamic therapy

In all studies [24-40] diode lasers with wavelengths ranging between 625-805

nm were used. Wavelengths of diode lasers used in studies [24-27, 29-36] which

reported PDT to be effective in eliminating E. faecalis from infected root canals

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ranged between 625-805 nanometers (nm) whereas wavelengths ranging between

635-660 nm were used in studies [28, 37-40] which reported PDT to be ineffective in

intracanal bacterial disinfection.

Laser parameters of studies that reported photodynamic therapy to be effective

in eliminating Enterococcus faecalis from infected root canals

Twelve studies [24-27, 29-36] reported PDT to be effective in eliminating E.

faecalis from infected root canals. Eleven studies [24-27, 29-35] have an ex-vivo

design and one study [36] was performed in-vivo. In these studies [24-27, 29-36], the

wavelengths of the diode laser used ranged between 600 nm and 805 nm and the

diameter of fiber used for the delivery of light ranged between 200 micrometers (µm)

and 0.4 cm. In these studies [24-27, 29-36], the power output from the laser source

ranged between 40 milliwatts (mW) and 5 watts (W) and the duration of irradiation

ranged between 0.5 minutes and 10 minutes. Methylene blue (MB) (6.25 micrograms

per milliliter [µg/mL]-25µg/mL) and Toluidine blue (TBO) (15µg/mL-12.7

milligrams per milliliter [mg/mL])were used as photosensitizer (PS) in three [26, 27,

30] and seven studies [24-26, 29, 31, 33, 35] respectively. The in-vivo study [36]

used a conjugate between polyethylenimine and chlorine (~19 µg/mL) as PS whereas

phenothiazine chloride (10 mg/mL) and indocyanine green (12.5 mg/mL) were used as

PS in studies by Bago et al. [24] and Nagayoshi et al. [34] respectively (Table 2).

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Laser parameters of studies that reported photodynamic therapy to be

ineffective in eliminating Enterococcus faecalis from infected root canals

Four ex-vivo studies [28, 37, 38, 40] reported PDT to be ineffective in

eliminating E. faecalis from infected root canals. In these studies [28, 37, 38, 40],

wavelengths of the lasers used ranged between 635 nm and 660 and the diameter of

fiber used for light delivery 216 nm and 0.2 cm. the power output ranged between

40mW and 200 mW and the duration of irradiation ranged between one minute and

six minutes. Souza et al. [38] used MB and TBO as PS in the study groups. MB was

used as PS in studies by Nunes et al. [28] and Cheng et al. [40] whereas Hecker et al.

[37] used TBO as PS. In studies by Cheng et al. [40] and Nunes et al. [28]

concentration of MB was 10µg/mL and 100µg/mL (Table 3).

DISCUSSION

The present systematic review was based on the hypothesis that PDT is more

efficient in eliminating E. faecalis from infected root canals compared to traditional

endodontic treatment regimes (instrumentation and irrigation). Results from nearly

70% of the studies [24-27, 29-36] that fulfilled our eligibility criteria showed that

PDT is more efficient in eliminating E. faecalis in infected root canals than

conventional endodontic therapy. It is pertinent to mention that there was an

inconsistency in the methodology and laser parameters used in these studies [24-27,

29-36]. For example, studies by Soukos et al. [27], Nagayoshi et al. [34] and Schlafer

et al. [35] showed that PDT kills significantly more E. faecalis compared to

conventional instrumentation/irrigation. However, in these studies [27, 34, 35] the

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diode laser wavelengths (635nm, 805nm and 628nm respectively), diameter of fiber

used for laser delivery (500µm, 400µm and 0.4 cm respectively), power output (1W,

1W and 5W) and type of PS used (MB, indocyanine green and TBO respectively)

were erratic. Also, the duration of irradiation varied between studies. For example, in

studies by Bago et al. [24] and Rios et al. [29] durations of irradiation were 60

seconds (S) and 30 S respectively; however Foschi et al.[26] and Pagonis et al. [30]

irradiated the root canals for 5 minutes and 10 minutes correspondingly. In this

regard, we find it demanding to precisely contemplate the laser parameters that would

be most effective in eliminating E. fecalis from infected root canals in a clinical

scenario.

Concentration of PS has been reported to influence the overall bactericidal

efficacy of PDT [41]. Nearly 80% of the studies included in this review [24-26, 30-

33, 35] that reported PDT to be effective in killing E. faecalis used either MB and/or

TBO as photosensitizers. Studies have shown that MB (a synthetic non-porphyrin

compound [phenothiazine]) is compatible with wavelengths of visible light (up to 685

nm) and has a high rate of generation of reactive species [42, 43]. In addition, studies

[44, 45] have reported that MB when used in concentrations of 100µg/mL minimizes

the chances of dental discoloration, while safeguarding its photo-bactericidal

properties studies. TBO is structurally similar to MB and exhibits bactericidal effects

similar to those of MB. From the literature reviewed, we observed an inconsistency in

the concentration of the photosensitizers used. In these studies, concentrations of MB

concentrations ranged from 6.25µg/mL to 25µg/mL whereas TBO concentrations

ranged from 15µg/mL to 12.5mg/mL. However, it has also been reported that PDT

with either MB or TBO does not have a significant additional effect to the chemo-

mechanical preparation using 2.5% NaOCl as an irrigant in the reduction of E.

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faecalis counts [38]. An explanation in this regard may be the presence of low

concentration of available oxygen in the canals, particularly in irregularities and in

dentinal tubules. Under such circumstances, formation of cytotoxic oxygen

derivatives may be either be blocked or minimized. In clinical scenarios, the PS may

be unable to diffuse well into irregular canals and dentinal tubules or even through

possible bacterial biofilms persisting on untouched canal walls. These factors may

compromise the outcome of PDT in infected root canals. Further studies using

standardized laser parameters and PS concentration/s are warranted to assess the

efficacy of PDT in eliminating E. faecalis from infected root canals.

Sassone et al. [46] reported that 1.0–5.0% NaOCl is most effective in an in

vitro test on agar plates and presence of residual NaOCl inside the dentinal tubules is

critical for effective disinfection. It is pertinent to mention that in all studies, included

in the present review, initial instrumentation and irrigation with 1-6% NaOCl and

17% EDTA was performed prior to PDT. Therefore, it is tempting to speculate that

residual NaOCl in the dentinal tubules played a role in the overall canal disinfection

process.

CONCLUSION

Within the limits of the present review, it is concluded that the efficacy of

PDT in eliminating E. fecalis from infected root canals remains questionable. Further

well-designed studies are needed to examine the role of PDT as a bactericidal agent in

infected root canals.

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Acknowledgements

The authors would like to thank the College of Dentistry Research Center and

Deanship of Scientific Research at King Saud University, Saudi Arabia for funding

this research project (Project # FR 0058).

The authors report no conflicts of interest related to this study.

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Figure legend

Figure 1. Study selection protocol.

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References

[1] Evans M, Davies JK, Sundqvist G, Figdor D. Mechanisms Involved in the

resistance of enterococcus faecalis to calcium hydroxide. International Endodontic

Journal 2002;35:221-8.

[2] Stuart CH, Schwartz SA, Beeson TJ, Owatz CB. Enterococcus faecalis: Its role in

root canal treatment failure and current concepts in retreatment. Journal of

Endodontics 2006;32:93-8.

[3] Rocas IN, Siqueira JF, Jr., Santos KR. Association of enterococcus faecalis with

different forms of periradicular diseases. Journal of Endodontics 2004;30:315-20.

[4] Love RM. Enterococcus faecalis--A mechanism for its role in endodontic failure.

International Endodontic Journal 2001;34:399-405.

[5] Lee W, Lim S, Son HH, Bae KS. Sonicated extract of enterococcus faecalis

induces irreversible cell cycle arrest in phytohemagglutinin-activated human

lymphocytes. Journal of Endodontics 2004;30:209-12.

[6] Mcgurkin-Smith R, Trope M, Caplan D, Sigurdsson A. Reduction Of intracanal

bacteria using gt rotary instrumentation, 5.25% naocl, edta, and Ca(OH)2. Journal Of

Endodontics 2005;31:359-63.

[7] Bystrom A, Sundqvist G. The antibacterial action of sodium hypochlorite and

EDTA in 60 cases of endodontic therapy. International Endodontic Journal

1985;18:35-40.

[8] Shuping GB, Orstavik D, Sigurdsson A, Trope M. Reduction of intracanal bacteria

using nickel-titanium rotary instrumentation and various medications. Journal of

Endodontics 2000;26:751-5.

Page 16: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

Page 15 of 29

Accep

ted

Man

uscr

ipt

16

[9] Kvist T, Molander A, Dahlen G, Reit C. Microbiological evaluation of one- and

two-visit endodontic treatment of teeth with apical periodontitis: A randomized,

clinical trial. Journal of Endodontics 2004;30:572-6.

[10] Siqueira JF, Jr., Rocas IN, Paiva SS, Guimaraes-Pinto T, Magalhaes KM, Lima

KC. Bacteriologic investigation of the effects of sodium hypochlorite and

chlorhexidine during the endodontic treatment of teeth with apical periodontitis. Oral

Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontics

2007;104:122-30.

[11] Orstavik D, Haapasalo M. Disinfection by endodontic irrigants and dressings of

experimentally infected dentinal tubules. Endodontics & Dental Traumatology

1990;6:142-9.

[12] Haapasalo M, Orstavik D. In vitro infection and disinfection of dentinal tubules.

Journal of Dental Research 1987;66:1375-9.

[13] Mang TS, Tayal DP, Baier R. Photodynamic therapy as an alternative treatment

for disinfection of bacteria in oral biofilms. Lasers in Surgery and Medicine

2012;44:588-96.

[14] Marotti J, Tortamano P, Cai S, Ribeiro MS, Franco JE, De Campos TT.

Decontamination of dental implant surfaces by means of photodynamic therapy.

Lasers in Medical Science 2013;28:303-9.

[15] Schar D, Ramseier CA, Eick S, Arweiler NB, Sculean A, Salvi GE. Anti-

infective therapy of peri-implantitis with adjunctive local drug delivery or

photodynamic therapy: Six-month outcomes of a prospective randomized clinical

trial. Clinical Oral Implants Research 2013;24:104-10.

Page 17: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

Page 16 of 29

Accep

ted

Man

uscr

ipt

17

[16] Eichler M, Lavi R, Shainberg A, Lubart R. Flavins are source of visible-light-

induced free radical formation in cells. Lasers in Surgery and Medicine 2005;37:314-

9.

[17] Sperandio FF, Huang YY, Hamblin MR. Antimicrobial photodynamic therapy to

kill gram-negative bacteria. Recent Patents On Anti-Infective Drug Discovery 2013;

Apr 1. Doi: 10.2174/1574891X113089990012 [Epub Ahead Of Print]

[18] Giannelli M, Formigli L, Lorenzini L, Bani D. Combined photoablative and

photodynamic diode laser therapy as an adjunct to non-surgical periodontal treatment:

A randomized split-mouth clinical trial. Journal of Clinical Periodontology

2012;39:962-70.

[19] Novaes AB, Jr., Schwartz-Filho HO, De Oliveira RR, Feres M, Sato S,

Figueiredo LC. Antimicrobial Photodynamic Therapy In The Non-Surgical Treatment

Of Aggressive Periodontitis: Microbiological Profile. Lasers in Medical Science

2012;27:389-95.

[20] De Oliveira RR, Schwartz-Filho HO, Novaes AB, et al. Antimicrobial

photodynamic therapy in the non-surgical treatment of aggressive periodontitis:

cytokine profile in gingival crevicular fluid, preliminary results. Journal of

Periodontology 2009;80:98-105.

[21] Romanos Ge, Brink B. Photodynamic therapy in periodontal therapy:

microbiological observations from a private practice. General Dentistry 2010;58:E68-

73.

[22] Kawczyk-Krupka A, Waskowska J, Raczkowska-Siostrzonek A, et al.

Comparison of cryotherapy and photodynamic therapy in treatment of oral

leukoplakia. Photodiagnosis and Photodynamic Therapy 2012;9:148-55.

Page 18: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

Page 17 of 29

Accep

ted

Man

uscr

ipt

18

[23] Milstein Dm, Van Kuijen Am, Copper MP, et al. Monitoring microcirculatory

alterations in oral squamous cell carcinoma following photodynamic therapy.

Photodiagnosis and Photodynamic Therapy 2012;9:69-75.

[24] Bago I, Plecko V, Gabric Panduric D, Schauperl Z, Baraba A, Anic I.

Antimicrobial efficacy of a high-power diode laser, photo-activated disinfection,

conventional and sonic activated irrigation during root canal treatment. International

Endodontic Joural 2013;46:339-47.

[25] Vaziri S, Kangarlou A, Shahbazi R, Nazari Nasab A, Naseri M. Comparison of

the bactericidal efficacy of photodynamic therapy, 2.5% sodium hypochlorite, and 2%

chlorhexidine against enterococcous faecalis in root canals; An in vitro study. Dental

Research Journal 2012;9:613-8.

[26] Foschi F, Fontana CR, Ruggiero K, et al. Photodynamic inactivation of

enterococcus faecalis in dental root canals in vitro. Lasers in Surgery and Medicine

2007;39:782-7.

[27] Soukos NS, Chen PS, Morris JT, et al. Photodynamic therapy for endodontic

disinfection. Journal of Endodontics 2006;32:979-84.

[28] Nunes MR, Mello I, Franco GC, et al. Effectiveness of photodynamic therapy

against enterococcus faecalis, with and without the use of an intracanal optical fiber:

an in vitro study. Photomedicine and Laser Surgery 2011;29:803-8.

[29] Rios A, He J, Glickman GN, et al. Evaluation of photodynamic therapy using a

light-emitting diode lamp against enterococcus faecalis in extracted human teeth.

Journal of Endodontics 2011;37:856-9.

[30] Pagonis TC, Chen J, Fontana CR, et al. Nanoparticle-based endodontic

antimicrobial photodynamic therapy. Journal of Endodontics 2010;36:322-8.

Page 19: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

Page 18 of 29

Accep

ted

Man

uscr

ipt

19

[31] Fonseca MB, Junior PO, Pallota RC, et al. Photodynamic Therapy for root canals

infected with enterococcus faecalis. photomedicine and laser surgery 2008;26:209-13.

[32] Bergmans L, Moisiadis P, Huybrechts B, Van Meerbeek B, Quirynen M,

Lambrechts P. Effect of photo-activated disinfection on endodontic pathogens ex

vivo. International Endodontic Journal 2008;41:227-39.

[33] Poggio C, Arciola CR, Dagna A, et al. Photoactivated disinfection (PAD) in

endodontics: An in vitro microbiological evaluation. The International Journal of

Artificial Organs 2011;34:889-97.

[34] Nagayoshi M, Nishihara T, Nakashima K, et al. Bactericidal effects of diode

laser irradiation on enterococcus faecalis using periapical lesion defect model. ISRN

Dentistry 2011;2011:870364.

[35] Schlafer S, Vaeth M, Horsted-Bindslev P, Frandsen EV. Endodontic

photoactivated disinfection using a conventional light source: an in vitro and ex vivo

study. Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and

Endodontics 2010;109:634-41.

[36] Garcez AS, Nunez SC, Hamblim MR, Suzuki H, Ribeiro MS. Photodynamic

therapy associated with conventional endodontic treatment in patients with antibiotic-

resistant microflora: A preliminary report. Journal of Endodontics 2010;36:1463-6.

[37] Hecker S, Hiller KA, Galler KM, Erb S, Mader T, Schmalz G. Establishment of

an optimized ex vivo system for artificial root canal infection evaluated by use of

sodium hypochlorite and the photodynamic therapy. International Endodontic Journal

2013;46:449-57.

[38] Souza LC, Brito PR, De Oliveira JC, et al. Photodynamic therapy with two

different photosensitizers as a supplement to instrumentation/irrigation procedures in

Page 20: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

Page 19 of 29

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promoting intracanal reduction of enterococcus faecalis. Journal of Endodontics

2010;36:292-6.

[39] Miranda RG, Santos EB, Souto RM, Gusman H, Colombo AP. Ex vivo

antimicrobial efficacy of the endovac((r)) system plus photodynamic therapy

associated with calcium hydroxide against intracanal enterococcus faecalis.

International Endodontic Journal 2013;46:499-505.

[40] Cheng X, Guan S, Lu H, et al. Evaluation of the bactericidal effect of Nd:Yag,

Er:Yag, Er,Cr:YSGG laser radiation, and antimicrobial photodynamic therapy

(APDT) in experimentally infected root canals. Lasers In Surgery And Medicine

2012;44:824-31.

[41] Konopka K, Goslinski T. Photodynamic therapy in dentistry. Journal of Dental

Research 2007;86:694-707.

[42] Ball DJ, Luo Y, Kessel D, Griffiths J, Brown SB, Vernon Di. The induction of

apoptosis by a positively charged methylene blue derivative. Journal of

Photochemistry and Photobiology B, Biology 1998;42:159-63.

[43] Severino D, Junqueira HC, Gugliotti M, Gabrielli DS, Baptista MS. Influence of

negatively charged interfaces on the ground and excited state properties of methylene

blue. Photochemistry and Photobiology 2003;77:459-68.

[44] George S, Kishen A. Photophysical, photochemical, and photobiological

characterization of methylene blue formulations for light-activated root canal

disinfection. Journal of Biomedical Optics 2007;12:034029.

[45] Zanin IC, Goncalves RB, Junior AB, Hope CK, Pratten J. Susceptibility of

streptococcus mutans biofilms to photodynamic therapy: An in vitro study. The

Journal of Antimicrobial Chemotherapy 2005;56:324-30.

Page 21: Bactericidal efficacy of photodynamic therapy against Enterococcus faecalis in infected root canals: A systematic literature review

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21

[46] Sassone LM, Fidel RA, Fidel SR, Dias M, Hirata RJ. Antimicrobial activity of

different concentrations of naocl and chlorhexidine using a contact test. Brazilian

Dental Journal 2003;14:99-102.

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Table 1. Characteristics of studies that fulfilled our eligibility criteria

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Authors et

al.

Study

Design

Methodology

Results

Conclusion Number of

teeth used

Treatment groups

Bago et

al.[24]

Ex-vivo 120

uniradicular

human teeth

Group-1: LED irradiation

Group-2: PDT

Group-3: PDT using 3D Endoprobe

Group-4: Irrigation with NaOCl

Group-5: sonic agitation of NaOCl

Group-6: Irrigation with NaCl

PDT was significantly more

effective than LED

irradiation and single NaOCl

irrigation in reducing E.

faecalis in root canals.

PDT significantly

reduces E. faecalis

counts in infected

root canals.

Vaziri et

al.[25]

Ex-vivo 90

uniradicular

human teeth

Group-1: Irrigation with 2% CHX

Group-2: Irrigation with 2.5% NaOCl

Group-3: PDT

Group-4: PDT + 2.5% NaOCl

Positive control: Bacterium inoculation

but no treatment

Negative control: No bacterium

inoculation and no treatment

Group-4 showed significant

reduction in E. faecalis

compared to other groups.

PDT + 2.5% NaOCl

significantly reduced

E. faecalis counts in

infected root canals.

Table 1. Characteristics of studies that fulfilled our eligibility criteria

Table 1

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Foschi et

al.[26]

Ex-vivo 64

uniradicular

human teeth

Group-1: MB placed in canal

Group-2: Irradiation with LED.

Group-3: PDT

Canals in Group-3 achieved

77.5% reduction of E.

faecalis viability whereas

those in groups 1 and 2

reduced bacterial viability by

19.5% and 40.5%

respectively.

PDT significantly

reduces E. faecalis

counts in infected

root canals.

Soukos et

al.[27]

Ex-vivo 60

uniradicular

human teeth

Group-1: MB placed in canal

Group-2: Irradiation with LED

Group-3: No LED and no MB

Group-4: PDT

Canals in Group-4 achieved

up to 97% reduction of E.

faecalis. Specimens in

groups 1, 2 and 3 eliminated

all bacteria except E.

faecalis.

PDT significantly

reduces E. faecalis

counts in infected

root canals.

Nunes et

al.[28]

Ex-vivo 60

uniradicular

human teeth

Group-1/Control: No treatment

Group-2: Irrigation with 1% NaOCl

Group-3: PDT

Specimens in Groups 2 and 3

showed significant reduction

in E. faecalis compared to

Group-1. Greatest reduction

was observed among

specimens in Group-2

(99.99%) than those in

Group-3.

NaOCl caused

significantly more

disinfection

compared to PDT.

Rios et

al.[29]

Ex-vivo uniradicular

human teeth

(no. of teeth

unknown)

Group-1: Irrigation with 6% NaOCl

Group-2: TBO placed in canal

Group-3: Irradiation with LED

Group-4: PDT

Group-5: Canals irrigated with 6%

NaOCl followed by PDT

E. faecalis survival rate was

significantly lower in Group-

5 as compared to other

groups.

PDT + 6% NaOCl

significantly reduce

E. faecalis counts in

infected root canals.

Pagonis et Ex-vivo 32 Group-1/Control: No treatment E. faecalis colonization was PDT significantly

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al.[30] uniradicular

human teeth

Group-2: PDT. significantly reduced in

Group-2 compared to Group-

1.

reduces E. faecalis

counts in infected

root canals.

Fonseca et

al.[31]

Ex-vivo 46

uniradicular

human teeth

Group-1/Control: No treatment

Group-2: PDT using laser and TBO.

In Group-2, E. faecalis

colonies were reduced by

99.9% compared to Group-1

(2.6%).

PDT significantly

reduces E. faecalis

counts in infected

root canals.

Bergmans

et al.[32]

Ex-vivo 38

uniradicular

human teeth

Group-1: PDT

Group-2: LED irradiation plus EDTA

Group-3: TBO placed in canals

Group-4: EDTA placed in canals

There was a significant

reduction in E. faecalis

colonization in Group-1

(~88% reduction) compared

to other groups.

PDT significantly

reduces E. faecalis

counts in infected

root canals.

Poggio et

al.[33]

Ex-vivo 100

uniradicular

human teeth

Group-1: PDT

Group-2: PDT + 5% NaOCl irrigation

Group-3:Irrigation with TBO

Group-4: PDT for a longer duration

Group-5: 5% NaOCl irrigation

Antibacterial effects were

significantly higher in

Groups 2 and 4 compared to

other groups

PDT + 5% NaOCl

significantly reduce

E. faecalis counts in

infected root canals.

Nagayoshi

et al.[34]

Ex-vivo Model of a

periapical

lesion in

resin blocks

Group-1: PDT using LED and

Indocyanine green.

Positive control: Irrigation with 2.5%

NaOCl

Negative control: Irrigation with saline.

Viability of E. faecalis was

significantly reduced in

Group-1 compared to other

groups.

PDT significantly

reduces E. faecalis

counts in infected

root canals.

Schlafer et

al.[35]

Ex-vivo 80 human

molar teeth

Group-1: PDT using Red LED and TBO

Group-2: Bacteria suspension mixed

with 0.85% NaCl but no irradiation.

Nearly 99% of all bacteria

(including E. faecalis) were

eradicated following PDT.

PDT significantly

reduces E. faecalis

counts in infected

root canals.

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Garcez et

al.[36]

In-vivo 30

uniradicular

teeth from

21 patients

Microbiological samples were taken:

Group-1: after assessing the root canal

Group-2: after endodontic treatment

Group-3: endodontic treatment and PDT

In Group-3, all bacteria

including E. faecalis were

eliminated compared to other

groups.

PDT when used as

an adjunct to

endodontic therapy

effectively reduces

intracanal bacteria

than when

endodontic treatment

is done alone.

Hecker et

al.[37]

Ex-vivo Bovine

lower

incisors (no.

of teeth

unknown)

Group-1: coronal section treated with

NaOCl

Group-2: coronal section treated with

PDT

Control: Apical section containing

culture medium.

Group-1 showed significant

reduction in E. faecalis

colonization compared to

Group-2 and 3.

NaOCl caused

significantly more

disinfection

compared to PDT.

Souza et

al.[38]

Ex-vivo 70

uniradicular

human teeth

Phase A: Mechanical instrumentation and

bacterial count

Phase B: Bacterial count in each group

Group-1: PDT + 2.5% NaOCl

Group-2: PDT + 2.5% NaOCl

Group-3: PDT + 0.85% NaCl

Group-4: PDT + 0.85%

In Phase A,

mechanical debridement

significantly reduced

bacterial counts compared to

PDT compared to baseline.

In Phase B, PDT

failed to enhance

disinfection even after

instrumentation and NaOCl

irrigation.

Irrigation with

NaOCl was significantly

more effective than NaCl.

PDT does not

augment the

supplemental effect

of instrumentation/

irrigation procedures

with reference to

root canal

disinfection.

Miranda et Ex-vivo 125 Group-1/Control: Instrumentation + A significant reduction of E. Conventional

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CHX: Chlorhexidine DW: Distilled water E. faecalis : Enterococcus faecalis Er,Cr:YSGG: Erbium, chromium: yttrium, scandium,

gallium, garnet Er:YAG: Erbium-doped yttrium aluminium garnet MB: Methylene Blue NaCl: Sodium chloride NaOCl: Sodium

hypochlorite NS: Normal saline LED: Light emitting diode PDT: Photodynamic therapy PS: Photosensitizer TBO: Toludine Blue

* Endovac® system: an effective irrigation system that delivers irrigant to the entire working length of the canal.[39]

al.[39]* uniradicular

human teeth

irrigation with 5.25% NaOCl.

Group-2: Instrumentation + irrigation

with Endovac®* system.

Group-3: Instrumentation + irrigation

with 5.25% NaOCl + PDT

Group-4: Instrumentation + irrigation

with Endovac®* system + PDT

faecalis mean counts was

observed in all groups with

no differences between the

groups.

instrumentation and

irrigation and PDT

are equally effective

in reducing

intracanal E. faecalis

counts.

Cheng et

al.[40]

Ex-vivo 220

uniradicular

human teeth

Group-1:Nd:YAG laser alone

Group-2: Canals filled with 5.25%

NaOCl, NS and DW successively and

radiated with Er:YAG laser

Group-3: Canals were filled with NS and

DW successively and irradiated with

Er:YAG laser

Group-4: Er,Cr:YSGG laser alone

Group-5: PDT

Treatment protocol in

Group-2 showed the highest

antibacterial effect compared

to other groups.

Bactericidal efficacy

of

Er:YAG/NaClO/NS/

DW was higher than

that of other

treatment protocols.

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Table 2. Laser parameters of studies showing positive outcomes of photodynamic therapy towards elimination of Enterococcus faecalis from

infected root canals.

MB: Methylene Blue TBO: Toluidine Blue

Authors et al. Laser

Wavelength

(in nm)

Diameter

of fiber

(in µm)

Power

Output

(in mW)

Power

Density

( mW/cm2)

Energy

fluence

(in J/cm2)

Duration of

irradiation

(in minutes)

Photosensitizer

(concentration in µg/mL)

Bago et al.[24] 660 320 100 — — 1 a) Phenothiazine Chloride (103 µg/mL)

b) TBO (155 µg/mL)

Vaziri et al.[25] 625 — — 200 12 1 TBO (15 µg/mL)

Foschi et al.[26] 665 500 — 100 60 5 MB (6.25 µg/mL)

Soukos et al.[27] 665 500 1000 100 30 5 MB (25 µg/mL)

Rios et al.[29] 628 — — — — 0.5 TBO (—)

Pagonis et al.[30] 665 250 1000 100 60 10 MB (6.25 µg/mL)

Fonseca et al.[31] 660 600 50 — 400 5 TBO (—)

Bergmans et

al.[32]

635 300 100 — — 1.5 TBO (12.5x103 µg/mL)

Poggio et al.[33] 628 — 1000 — — 0.5

1.5

a) TBO (100 µg/mL)

b) TBO (100 µg/mL)

Nagayoshi et

al.[34]

805 400 5000 — — 2 Indocyanine green (12.5x103

µg/mL)

Schlafer et al.[35] 628 4x103 1000 — — 0.5 TBO (100 µg/mL)

Garcez et al.[36] 660 200 40 — — 4 conjugate between polyethylenimine and

chlorine (~19 µg/mL)

Table 2

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Table 3. Laser parameters of studies that reported photodynamic therapy to be ineffective towards elimination of Enterococcus faecalis from

infected root canals.

MB: Methylene Blue TBO: Toluidine Blue

Authors et al. Laser

Wavelength

(in nm)

Diameter

of fiber

(in µm)

Power

Output

(in mW)

Power

Density

( mW/cm2)

Energy

fluence

(in J/cm2)

Duration of

irradiation

(in minutes)

Photosensitizer

(concentration in µg/mL)

Nunes et al.[28] 660 216 90 — — 5 MB (100 µg/mL)

Hecker et al.[37] 635 — 200 — — 6 TBO (—)

Souza et al.[38] 660 300 40 — — 4 a) MB (—)

b) TBO (—)

Cheng et al.[40] 660 2000 200 — — 1 MB (10 µg/ml)

Table 3