Upload
fawad
View
217
Download
2
Embed Size (px)
Citation preview
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.
Page 1 of 29
Accep
ted
Man
uscr
ipt
1
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
Page 2 of 29
Accep
ted
Man
uscr
ipt
3
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.
Page 3 of 29
Accep
ted
Man
uscr
ipt
4
Key words: antibacterial; endodontic; Enterococcus faecalis; root canal; and
photodynamic therapy.
Page 4 of 29
Accep
ted
Man
uscr
ipt
5
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
Page 5 of 29
Accep
ted
Man
uscr
ipt
6
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.
Page 6 of 29
Accep
ted
Man
uscr
ipt
7
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
Page 7 of 29
Accep
ted
Man
uscr
ipt
8
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
Page 8 of 29
Accep
ted
Man
uscr
ipt
9
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).
Page 9 of 29
Accep
ted
Man
uscr
ipt
10
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
Page 10 of 29
Accep
ted
Man
uscr
ipt
11
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.
Page 11 of 29
Accep
ted
Man
uscr
ipt
12
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.
Page 12 of 29
Accep
ted
Man
uscr
ipt
13
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.
Page 13 of 29
Accep
ted
Man
uscr
ipt
14
Figure legend
Figure 1. Study selection protocol.
Page 14 of 29
Accep
ted
Man
uscr
ipt
15
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 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 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 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 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 19 of 29
Accep
ted
Man
uscr
ipt
20
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 20 of 29
Accep
ted
Man
uscr
ipt
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.
Page 21 of 29
Accep
ted
Man
uscr
ipt
22
Table 1. Characteristics of studies that fulfilled our eligibility criteria
Page 22 of 29
Accep
ted
Man
uscr
ipt
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
Page 23 of 29
Accep
ted
Man
uscr
ipt
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
Page 24 of 29
Accep
ted
Man
uscr
ipt
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.
Page 25 of 29
Accep
ted
Man
uscr
ipt
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
Page 26 of 29
Accep
ted
Man
uscr
ipt
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.
Page 27 of 29
Accep
ted
Man
uscr
ipt
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
Page 28 of 29
Accep
ted
Man
uscr
ipt
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
Page 29 of 29
Accep
ted
Man
uscr
ipt
Figure