REVIEW ARTICLE |
https://doi.org/10.5005/jp-journals-10015-2350 |
Success Rate of Triple Antibiotic Paste for Lesion Sterilization and Tissue Repair Therapy in Primary Molars: A Systematic Review
1–5Department of Pediatric and Preventive Dentistry, Terna Dental College and Hospital, Navi Mumbai, Maharashtra, India
6Department of Public Health Dentistry, Terna Dental College and Hospital, Navi Mumbai, Maharashtra, India
Corresponding Author: Farhin A Katge, Department of Pediatric and Preventive Dentistry, Terna Dental College and Hospital, Navi Mumbai, Maharashtra, India, Phone: +91 022-27721839, e-mail: pedotdc@gmail.com
Received: 09 November 2023; Accepted: 10 December 2023; Published on: 31 January 2024
ABSTRACT
Aim: To elucidate the clinical and radiographical success rate of triple antibiotic paste (TAP) using lesion sterilization and tissue repair (LSTR) therapy in primary molars.
Materials and methods: Electronic databases and gray literature were screened from 1st January 2004 to 30th September 2020 for randomized controlled trials (RCTs), and clinical trials that assessed the success of LSTR therapy in primary molars were chosen for the review. Two independent reviewers were involved in the selection of studies, extraction of data, assessment of bias using Cochrane Collaboration’s tool in accordance with Review Manager software, and revised, validated version of methodological index for nonrandomized studies (MINORS) criteria, clinical and radiographic success of TAP.
Results: Eight studies were selected for qualitative analysis where the risk of bias varied from low to unclear according to the Cochrane tool’s domains. Overall, studies showed a high risk of bias and a low level of evidence. Included studies demonstrated clinical success rate ranged from 83.3 to 100% at 12 months, 82.3 to 84.2% at 18–21 months, and 82.7% at 24–27 months, while radiographic success rate ranged from 45.8 to 90% at 12 months, 40.7 to 76.4% at 18–21 months, and 36.7% at 24–27 months recall visits.
Conclusion: Lesion sterilization and tissue repair (LSTR) therapy using TAP showed favorable clinical success but a low radiographic success rate in primary molars.
Clinical significance: Lesion sterilization and tissue repair (LSTR) therapy can be a suitable alternative treatment option to salvage a tooth with a poor prognosis. Literature supports the rationale of employing LSTR therapy in such situations, thereby restricting the need for the premature extraction of a primary tooth.
How to cite this article: Ghorpade TM, Katge FA, Poojari MS, et al. Success Rate of Triple Antibiotic Paste for Lesion Sterilization and Tissue Repair Therapy in Primary Molars: A Systematic Review. World J Dent 2023;14(12):1112–1118.
Source of support: Nil
Conflict of interest: None
Keywords: 3 Mix, Lesion sterilization and tissue repair therapy, Noninstrumentation endodontic treatment, Primary teeth, Triple antibiotic paste
INTRODUCTION
Pediatric dentistry aims to maintain primary dentition until normal exfoliation.1 Early loss of primary dentition can cause space loss, disturbance in eruption sequence, and ectopic eruption, resulting in functional disability.2,3 Therefore, it is important to salvage the primary teeth for the proper skeletal, dental, and psychological development of the child.4
Root canal treatment is aimed at the removal of bacteria from an infected root canal and periapical region, preventing reinfection. Root canals of primary teeth at the stage of physiologic root resorption are not feasible for biomechanical preparation and obturation.2 Hence, chemomechanical means of preparation are being followed to establish complete sterilization of canals and to improve the prognosis of treatment. As indicated by Grossman in 1972, the utilization of antibacterial medications in endodontic lesions can be one of the clinical methods that might be attempted to sterilize lesions.5
Takushige et al.,2 in the Cariology Research Unit of Niigata University School of Dentistry, Japan, treated necrosed primary molars with the concept of lesion sterilization and tissue repair (LSTR) therapy. It was popularized by Takushige, who used propylene glycol as a vehicle mixed with antibacterial drugs to disinfect root canals and periapical infections.2 LSTR therapy is a ”new biologic approach in the treatment of carious lesions with periapical involvement using a mixture of triple antibiotic paste (TAP).”
Lesion sterilization and tissue repair (LSTR) therapy is a single-visit, conservative approach that reduces the need for extraction of teeth with poor prognosis. It involves the application of three broad-spectrum antibiotics: ciprofloxacin, metronidazole, and minocycline in a ratio of 1:3:3 (one part of ciprofloxacin, and three parts of metronidazole and minocycline)2 or 1:1:1 (equal parts of ciprofloxacin, metronidazole, and minocycline) ratio.6 Macrogol and propylene glycol or saline are used as a vehicle to increase penetration of antibiotic paste in deep dentinal tubules. This mixture is known as TAP or 3 Mix or 3 Mix MP.2
Considering the current importance of chemical disinfection for necrosed primary teeth and its maintenance until normal exfoliation, the aim of this systematic review was to elucidate the clinical and radiographic success rate of TAP as LSTR therapy for primary molars.
MATERIALS AND METHODS
The present systematic review was recorded in the PROSPERO database under protocol CRD42020189501 on 31st May 2020. Guidelines pertaining to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed to carry out the review.7
The research question was formulated in population, interventions, comparisons, and outcomes (PICO) format based on PRISMA guidelines. What is the clinical and radiographic success rate of TAP for LSTR therapy in primary molars?
The terms used were according to the eligibility criteria to identify clinical trials based on elements of the PICO format as follows:
- Population: Primary molars are indicated for pulpectomy or with poor prognosis.
- Interventions: TAP is composed of ciprofloxacin, metronidazole, and minocycline mixed with MP or saline.
- Comparison: It is not applicable to this systematic review as there were multiple variations in the comparison group. Randomized controlled trials (RCT) conducted with pulpectomy as a control group have used different obturating materials, thus making it difficult to standardize the control group. LSTR has been performed using TAP with different combinations and modifications of antibacterial drugs, making the comparison with the available data impossible.
- Outcomes: Clinical and radiographic success rates were categorized separately and combined if given for the overall success after a minimum of 12 months.
Randomized controlled trials (RCTs) and clinical trials reporting both clinical and radiographic success rates of TAP for LSTR therapy were considered for inclusion; however, studies in which the outcome was microbial evaluation or only clinical success of LSTR therapy, case reports, case series, observational studies, review of literature, cohorts reviews, historical reviews, in vitro studies, animal studies, editorials letters, only abstracts were excluded.
Search Strategy
The following databases were searched from 1st January 2004 to 30 September 2020: The National Library of Medicine (MEDLINE PubMed); Cochrane Library; EBSCOhost-Dentistry and Oral Sciences Source; Google Scholar; open gray literature. Search terms used for the search strategy included key concepts, controlled vocabulary terms (MeSH terms), and free text terms (Table 1). The terms were combined using suitable Boolean operators (AND, OR). A similar search strategy was implemented in all electronic searches. English language and time limit filters were used at the end as search limits.
| Population | Intervention | Outcome | Others | |
|---|---|---|---|---|
| Key concept | Primary molars | TAP | Success rate | LSTR therapy |
| Free terms/text words/TIAB terms | Deciduous molars Deciduous dentition Primary dentition Primary teeth Baby teeth Milk teeth |
3 Mix 3 Mix MP Antibiotic paste Antibiotic mix Antibacterial drugs Antibacterial paste Triantibacterial paste Triantibacterial drugs Antibacterial mix 3 Mix ointment Three antibiotics combination |
Efficacy | LSTR treatment LSTR Noninstrumentation endodontic treatment Noninstrumentation endodontic therapy Noninstrumental endodontic treatment Needleless endodontic treatment |
| MeSH terms | Posterior teeth |
Additionally, relevant journals were individually hand-searched. All cross-reference lists of selected studies were screened for additional articles that could meet the eligibility criteria of the study.
Selection of Studies
Based on the eligibility criteria, two review authors (TG and SD) selected articles independently based on keywords, titles, and abstracts. In order to fulfill the inclusion criteria, the full text of every study was obtained. If the full text was not available, the authors of the relevant abstracts were contacted to reduce the risk of publication bias.
Data Extraction
A specially formulated data extraction sheet was used by two review authors (TG and SD) to collect data independently. The data extracted was presented in graphs and figures only if both authors had the same result independently. Disagreement was resolved during consensus meetings with the third reviewer (FK).
The extracted data items were as follows: authors and year of publication; country where study was performed; number of teeth included; demographic details of the patients; intervention; outcomes; study design; period of follow-up; results; postoperative clinical and radiographic evaluation. All outcomes were tabulated at 12, 18, 24, and 27 months.
Quality Appraisal
Included RCTs were evaluated for methodological quality and risk of bias using ”Cochrane Collaboration’s tool for assessing the risk of bias” in accordance with Review Manager (RevMan) [Computer program Version 5.4].8,9 The included studies were evaluated independently by two review authors (TG and SD) for the assessment of the risk of bias. A revised, validated version of the methodological index for nonrandomized studies (MINORS) criteria was utilized for noncomparative trials.10
DATA ANALYSIS AND RESULT
Study Selection
The database search showed seven articles on PubMed, 10 on the Cochrane database, 44 on EBSCOhost, and 199 on Google Scholar. Results obtained through database searches were systematically managed using Mendeley software (version 1803). In the first phase of the screening process, duplicates were removed to determine inclusion. After removing duplicates, 217 articles were finally evaluated according to PRISMA.11 In the second phase, titles and abstracts were screened independently by authors (TG, SD) to identify studies for inclusion. A total of 194 articles were determined to be irrelevant based on titles and abstracts; hence, they were excluded. In the third phase of the screening process, 15 articles were eliminated as they did not meet inclusion criteria. Any incongruity over the final inclusion was discussed among the authors; if required, the third author (FK) acted as an arbiter. Hence, eight full-text articles were selected.12–19 Flowchart 1 depicts the PRISMA flow diagram. A detailed full-text evaluation of the included studies was carried out and summarized systematically in Table 2.
Flowchart 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram showing the process from identification to inclusion of the studies
| Study ID | Author | Study design | Participants and age-group | Intervention | Period of follow-up (months) | Results | Postoperative clinical evaluation | Postoperative radiographic evaluation Test | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical success rate | Radiographic success rate | Pain and tenderness | Abscess (I/O or E/O) | Fistula or sinus tract | Abnormal mobility | Decrease in radiolucency | Static radiolucency | Increase in radiolucency/bone loss | Bone regeneration | ||||||
| 1 | Prabhakar et al.,12 India | RCT | 60 primary molars from 41 children aged 4–10 years | LSTR therapy, including coronal and radicular pulp removal using 3 Mix in 1:3:3 ratio (n = 30) | 12 | 93.3% | 76.7% | 6.6% | 6.6% | – | – | – | 40% | 16.7% | 36.7% |
| 2 | Nakornchai et al.,13 Thailand | RCT | 50 primary molars from 37 children aged 4–8 years | LSTR therapy with 3 Mix MP in a 1:1:1 ratio (n = 25) | 12 | 96% | 76% | – | 4% | 4% | – | – | Bifurcation radiolucency = 16%; periapical radiolucency = 20% | – | – |
| 3 | Pinky et al.,14 India | RCT | 40 primary molars from 28 children aged 4–10 years | LSTR with other antibacterial paste (ciprofloxacin + ornidazole + minocycline) (n = 20) | 12 | 90% | 90% | 10% | – | – | – | – | 35% | – | 55% |
| 4 | Trairatvorakul et al.,15 Thailand | Clinical trial | 80 primary molars from 58 children aged 3–8 years | 3 Mix MP in the ratio of 1:1:1 (n = 80) | 12 | 95.8% | 45.8% | – | – | – | 4.2% | – | – | – | – |
| 18–21 | 81.4% | 40.7% | – | 1.8% | 1.8% | 14% | – | – | – | – | |||||
| 24–27 | 75% | 36.7% | – | 3.8% | 3.8% | 13.5% | – | 15.8% | 68.4% | – | |||||
| 5 | Nanda et al.,16 India | RCT | 40 primary molars from 38 children aged 4–10 years | LSTR with other antibacterial paste (ciprofloxacin + ornidazole + minocycline) (n = 20) | 12 | 100% | 81% | 0% | 0% | 0% | 0% | – | 35% | 15% | 30% |
| 6 | Raslan et al.,17 Syria | RCT | 42 mandibular primary molars | LSTR with other antibacterial paste (ciprofloxacin + ornidazole + minocycline) (n = 21) | 12 | 100% | 94.44% | 0% | 0% | 0% | 0% | 61.11% | 16.67% | 5.56% | – |
| 7 | Zacharczuk et al.,18 Argentina | RCT | 46 primary molars from children aged 6.3 ± 1.49 years | LSTR therapy with 3 MIX MP in a 1:1:1 ratio (n = 23) | 12 | 83.3% | 77.7% | – | – | – | – | – | – | – | – |
| 18 | 82.3% | 76.4% | – | – | – | – | – | – | – | – | |||||
| 8 | Divya et al.,19 India | RCT | 30 primary molars from 17 children aged 4–9 years | LSTR with 3 Mix in a 1:3:3 ratio (n = 15) | 12 | 93% | 60% | 7.6% | 7.6% | 0% | 7.6% | 86.6% | 0% | 6.6% | – |
Study Characteristics
The characteristics of the eight selected studies are listed in Table 2. Studies were published from 2008 to 2019. Four studies were conducted in India,12,14,16,19 two were performed in Thailand,13,15 one was carried out in Syria,17 and one was done in Argentina.18 Seven studies were RCTs,12–14,16–19 and one study was a noncomparative clinical trial.15 A total number of 224 primary molars were treated with LSTR therapy. The age of participants in the studies varied from 3 to 11 years, with a mean age of 7 years.
Among the included studies, three studies have used TAP in the ratio of 1:3:3,12,14,16 while five studies have reported the use of TAP in a 1:1:1 ratio13,15,17–19 for LSTR therapy in primary molars. Five studies have used MP,12,13,15,17,18 two studies have used only propylene glycol,14,15 and one study has used normal saline as a carrier.19 The final restoration placed was stainless steel crowns (1) used in seven studies13–19 and composite resin used in one.12
Evaluation of Clinical Outcome
In most studies, teeth were clinically asymptomatic at 12 months;12–14,16,17,19 18 months18 and 27 months.15 Two studies16,17 have shown that all patients were asymptomatic, had no sensitivity to percussion, no abnormal mobility, and had complete resolution of swelling and sinus. Results of data extracted showed clinical success rate of TAP for LSTR therapy ranged from 83.3 to 100% at 12 months, 82.3 to 84.2% at 18–21 months, 82.7% at 24–27 months recall (Table 2).12–19
Evaluation of Radiographic Outcome
After LSTR therapy, the radiographic signs noticed were static or reduced size of bifurcation, periapical radiolucency, no continuation of external root resorption, no progression of internal root resorption, and bone regeneration at 12, 18, and 27 months.
The radiographic success rate of TAP for LSTR therapy in primary molars ranged from 45.8 to 90% at 12 months, 40.7 to 76.4% at 18–21 months, and 36.7% at 24–27 months recall (Table 2).12,19
Assessment of Risk of Bias
Collaboration’s risk of bias tool (RevMan) was used to assess the methodological quality of individual studies for RCTs (seven studies) (Table 2). Five studies by Prabhakar et al.,12 Pinky et al.,14 Nanda et al.,16 Zacharczuk et al.,18 and Divya et al.19 showed a high risk of bias as they contain more than one high-risk domain with respect to blinding of clinical and radiographic outcome assessment, random sequence generation, blinding of study participants and personnel. Two studies by Nakornchai et al.13 and Raslan et al.17 showed unclear risk of bias as they contain one or more unclear risks with respect to allocation concealment and blinding of radiological outcome assessment.20,21 Attrition bias and reporting bias were not considered/reported in this review (Figs 1 and 2).
Fig. 1: Risk of bias summary: review authors’ judgments about each risk of bias item for each included study
Fig. 2: Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies
The quality assessment of Trairatvorakul et al.15 was done using the revised and validated version of the MINORS criteria. It showed a low risk of bias (Table 3).10
| MINORS tool adapted as per this systematic review | Score |
|---|---|
| A clearly stated aim | 2 |
| Inclusion of consecutive patients | 2 |
| Prospective collection of data | 1 |
| Endpoints appropriate to the aim of the study | 2 |
| Unbiased assessment of the study endpoint (blinding of participants, personnel, clinical and radiographic outcomes) | 1 |
| Follow-up period appropriate to the aim of the study endpoint | 2 |
| Loss to follow-up <5% | 2 |
| Prospective calculation of study size | 0 |
| Total score | 12/16 |
| 0 = not reported, 1 = reported but inadequate, 2 = reported and adequate | |
| High risk: score ≤12; low risk: score greater than 12 and ≤16 | |
Overall, low quality of evidence was observed in the eight included studies.
DISCUSSION
The success of conventional pulpectomy depends upon mechanical debridement and removal of microbes. However, because of the presence of multiple tortuous and accessory canals, some residual microbes are left in deeper layers of dentin. Hence, sterilization of root canals is important for the successful outcome of pediatric endodontics.22,25 LSTR therapy can help us to overcome all the above problems. As it is a noninstrumentation procedure, it prevents excessive instrumentation of root canals and irritation of periapical tissues, thus averting further damage to permanent teeth.
The reasons for the success of TAP as an endodontic treatment are its biocompatibility and components, which are both bactericidal (metronidazole and ciprofloxacin) and bacteriostatic (minocycline). It can easily distribute through dentin and dentinal tubules, creating a sterile zone, which can also lead to tissue repair.
The differences in study designs, sample sizes, proportions of antibiotics in TAP, carrier, and treatment procedures are some of the factors that may influence clinical and radiographic success.
Isolation is essential during endodontic therapy to avoid bacterial contamination of pulp tissue.26 American Academy of Pediatric Dentistry recommends rubber dam isolation or other methods of effective isolation techniques to minimize microbial contamination at the area of treatment. All the studies except two studies by Pinky et al.14 and Trairatvorakul et al.15 haven’t mentioned isolation, which may interfere with the success rate of TAP for LSTR therapy.
In order to achieve better penetration of antimicrobial drugs, they were mixed with carriers, which helped in killing bacteria deep in dentinal tubules. Prabhakar et al.,12 Nakornchai et al.,13 Trairatvorakul et al.,15 Raslan et al.,17 and Zacharczuk et al.18 have used a mixture of propylene glycol and macrogol; Pinky et al.14 and Nanda et al.16 used only propylene glycol and Divya et al.19 used normal saline as carrier. According to Cruz et al., the most favorable compound to carry TAP into the entire dentin and through dentinal tubules was propylene glycol, thus aiding in the effective eradication of bacteria.27 The results of all included studies have shown that the clinical and radiographic success rate of LSTR therapy is not influenced by the diversity of TAP in proportions or the carrier used.
Previous authors, such as Takushige et al.,2 stated that intracanal instrumentation was avoided and only extirpation of coronal necrotic pulp tissue was performed using a sharp spoon excavator or diamond bur. But Jaya et al.,28 Reddy et al.,5 and Arangnnal et al.29 have reported mechanical removal of radicular pulp tissue during LSTR therapy. Prabhakar et al. demonstrated a statistically significant difference in the success rate of LSTR therapy when comparing the use of nonmechanical instrumentation and TAP in primary teeth with and without radicular pulp extirpation, favoring the group in whom radicular pulp tissue was extirpated.12 Therefore, in this systematic review, such studies in which TAP was used when radicular pulp was mechanically manipulated during LSTR therapy were excluded as differences in LSTR procedure may influence the outcome of this systematic review.
During the LSTR procedure, cavities were chemically irrigated with 2.5% sodium hypochlorite by Nakornchai et al.,13 and Zacharczuk et al.,18 normal saline (0.9% w/v) by Pinky et al.14 and Nanda et al.16 and ethylenediamine tetraacetic acid by Trairatvorakul et al.,15 35% phosphoric acid was used as irrigant by Raslan et al.17 Primary teeth tend to show worst prognosis in cases of pulp necrosis associated with periapical lesions posttreatment. Hence, an irrigating solution was used to achieve disinfection and removal of the smear layer. Daher et al. suggested that irrespective of the choice of treatment modality being pulpectomy or LSTR; there is a need for smear layer removal as survival rates were lower in cases of initial pulp necrosis as compared to irreversible pulp inflammation.30
After pulp extirpation, root canal orifices were enlarged by 1 mm in diameter and 2 mm in depth, called medication cavities, to receive medicament. This was done by Prabhakar et al.,12 Pinky et al.,14 Trairatvorakul et al.,15 Nanda et al.,16 and Raslan et al.17 in the LSTR procedure. However, Kayalvizhi et al.25 and Moss et al.25 found it unnecessary to enlarge the canal orifices, which act as receptacles for the medication. According to other studies, enhanced dispersion of TAP occurs due to the porosity and permeability of the pulpal floor. Moreover, the carrier in the paste assists in further rapid penetration of the paste into dentinal tubules.27
After pulp extirpation, hemostasis was achieved using a cotton pellet saturated with 10% sodium hypochlorite in the included studies by Nakornchai et al.,13 Trairatvorakul et al.15 and Raslan et al.17 The 10% sodium hypochlorite is nontoxic to pulp tissues and does not interfere with pulp healing. It minimizes chances for chronic inflammation and internal resorption, which may be attributed to a higher radiographic success rate.
A previous study by Duanduan et al.,30 reported that the type of material, time between intermediate restoration, and permanent restoration influence the outcome of LSTR therapy. The final restoration was stainless steel crowns (SSC) in all included studies13,19 except one study by Prabhakar et al.,12 which used composite resin as final restorative material. In the study by Pinky et al.,14 permanent restorations with glass ionomer cement were done 15 days after the procedure, and at 30 days, preformed SSC was placed. The clinical success of LSTR among the ones who received SSC as final restoration was similar to the patients who got final restoration at the same appointment.
Trairatvorakul et al.,15 Detsomboonrat and Duanduan et al.30 achieved lower success rates of 75 and 84.62%, respectively, with long-term follow-up in clinical procedures. Hence, clinically, the success rate of TAP in LSTR therapy reduces as posttreatment duration increases, while radiographically, the outcomes are heterogeneous.
Considering clinical and radiographic success results in the current systematic review, lower radiographic success was seen in comparison to clinical success using TAP for LSTR therapy in primary molars. This is caused by differences in study designs, sample sizes, various carriers used in the preparation of TAP, and different evaluation criteria used in the included studies.
Limitations
The studies included here consisted only of RCTs and clinical trials. While formulating the results of this systematic review, literature available in other study designs like case studies, case reports, case series, and in vitro studies were not taken into consideration. Out of all the search forums used, many articles were excluded due to the unavailability of full text, even after trying other sources like hand searching or mailing to the authors. Articles published in any language other than English were not considered for the review.
Author Contributions
- TG and FK: Conception and design.
- TG and SD: Drafting the manuscript.
- TG, SD, and SS: Revising it critically for important intellectual content.
- TG, SD, FK, RJ: Acquisition of data, analysis, interpretation of data, and writing of the scientific text.
All authors read and approved the final manuscript.
CONCLUSION
After analyzing eight included studies, it was found that LSTR therapy using a TAP in primary molars has shown favorable clinical success and a low radiographic success rate. In the present review, we found low-quality evidence suggesting the success rate of TAP for LSTR therapy in primary molars. There is a paucity of studies regarding long-term follow-up of LSTR therapy; hence, more good quality studies of longer follow-up are required to determine the success rate of TAP for LSTR therapy in primary molars. Future studies should report characteristics of study populations, blinding of study participants and personnel, adequate documentation, and follow-up of dropouts.
REFERENCES
1. Cohen S, Burns RC. Pathways of the pulp. 6th edition. St. Louis: Mosby Inc 1994;633–671.
2. Takushige T, Cruz EV, Asgor Moral A, Hoshino E. Endodontic treatment of primary teeth using a combination of antibacterial drugs. Int Endod J 2004;37(1):132–138.10.1111/j.0143-2885.2004.00771.x
3. Cohen M, Burns RC. Pathways of pulp. 8th edition. St. Louis: Mosby Inc 2002;797–844.
4. Finn SB. Clinical pedodontics. 4th edition. Philadelphia: WB Saunders Company 2004;71–91.
5. Reddy S, Ramakrishna Y. Evaluation of antimicrobial efficacy of various root canal filling materials used in primary teeth: a microbiological study. J Clin Pediatr Dent 2007;31(3):193–198. DOI: 10.17796/jcpd.31.3.t73r4061424j2578
6. Ingle JI, Bakland LK. Endodontics. 5th edition. Hamilton, Ontario, Canada: Elsevier 2002.
7. Ghorpade T, Katge F, Poojari M, et al. Success rate of TAP for Lesion Sterilization and Tissue Repair. Therapy in primary molars: A systematic review. PROSPERO 2020 CRD42020189501 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020189501
8. Moher D, Shamseer L, Clarke M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015;4(1):1. DOI: 10.1186/2046-4053-4-1
9. Higgins JPT, Altman DG, Steme JAC. Chapter 8: Assessing risk of bias in included studies. In:Higgins J, Green S (eds) Cochrane Handbook for Systematic Reviews of Interventions version 5.0. Chichester, UK: John Wiley & Sons, Ltd., 2008.
10. Slim K, Nini E, Forestier D, et al. Methodological index for non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg 2003;73(9):712–716. DOI: 10.1046/j.1445-2197.2003.02748.x
11. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 2009;339:b2535. DOI: 10.1136/bmj.b2535
12. Prabhakar AR, Sridevi E, Raju OS, et al. Endodontic treatment of primary teeth using combination of antibacterial drugs: an in vivo study. J Indian Soc Pedod Prev Dent 2008;26(1):5–10.
13. Nakornchai S, Banditsing P, Visetratana N. Clinical evaluation of 3Mix and Vitapex as treatment options for pulpally involved primary molars. Int J Paediatr Dent 2010;20(3):214–221. DOI: 10.1111/j.1365-263X.2010.01044.x
14. Pinky C, Shashibhushan KK, Subbareddy VV. Endodontic treatment of necrosed primary teeth using two different combinations of antibacterial drugs: an in vivo study. J Indian Soc Pedod Prev Dent 2011;29(2):121–127. DOI: 10.4103/0970-4388.84684
15. Trairatvorakul C, Detsomboonrat P. Success rates of a mixture of ciprofloxacin, metronidazole, and minocycline antibiotics used in the non-instrumentation endodontic treatment of mandibular primary molars with carious pulpal involvement. Int J Paediatr Dent 2012;22(3):217–227. DOI: 10.1111/j.1365-263X.2011.01181.x
16. Nanda R, Koul M, Srivastava S, et al. Clinical evaluation of 3 Mix and other mix in non-instrumental endodontic treatment of necrosed primary teeth. J Oral Biol Craniofac Res 2014;4(2):114–119. DOI: 10.1016/j.jobcr.2014.08.003
17. Raslan N, Mansour O, Assfoura L. Evaluation of antibiotic mix in non-instrumentation endodontic treatment of necrotic primary molars. Eur J Paediatr Dent 2017;18(4):285–290. DOI: 10.23804/ejpd.2017.18.04.04
18. Zacharczuk GA, Toscano MA, López GE, et al. Evaluation of 3Mix-MP and pulpectomies in non-vital primary molars. Acta Odontol Latinoam 2019;32(1):22–28.
19. Divya DV, Prasad MG, Radhakrishna AN, et al. Triple antibiotic paste versus propolis: a clinical quest for the reliable treatment of periapical lesions in primary molars. Saudi Endod J 2019;9(1):34–39. DOI: 10.4103/sej.sej_42_18
20. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. DOI: 10.1136/bmj.d5928
21. Furlan AD, Malmivaara A, Chou R, et al. 2015 Updated method guideline for systematic reviews in the Cochrane back and neck group. Spine (Phila Pa 1976) 2015;40(21):1660–1673. DOI: 10.1097/BRS.0000000000001061
22. Hibbard ED, Ireland RL. Morphology of root canals of the primary teeth. J Dent Child 1957;24(1):250–257.
23. 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(2):118–124. DOI: 10.1111/j.1365-2591.1996.tb01172.x
24. Kayalvizhi G, Subramaniyan B, Suganya G. Topical application of antibiotics in primary teeth: an overview. J Dent Child 2013;80(2):71–79.
25. American Academy on Pediatric Dentistry Clinical Affairs Committee-Pulp Therapy Subcommittee, American Academy on Pediatric Dentistry Council on Clinical Affairs. Guideline on pulp therapy for primary and young permanent teeth. Pediatr Dent 2009;30:170–174.
26. Cruz EV, Kota K, Huque J, et al. Penetration of propylene glycol into dentine. Int Endod J 2002;35(4):330–336. DOI: 10.1046/j.1365-2591.2002.00482.x
27. Jaya AR, Praveen P, Anantharaj A, et al. In vivo evaluation of lesion sterilization and tissue repair in primary teeth pulp therapy using two antibiotic drug combinations. J Clin Pediatr Dent 2012;37(2):189–191. DOI: 10.17796/jcpd.37.2.e5131jp6m1w33v66
28. Arangannal P, Muthiah G, Jeevarathan J, et al. Lesion sterilization and tissue repair in nonvital primary teeth: an in vivo study. Contemp Clin Dent 2019;10(1):31–35. DOI: 10.4103/ccd.ccd_124_18
29. Doneria D, Thakur S, Singhal P, et al. In search of a novel substitute: clinical and radiological success of lesion sterilization and tissue repair with modified 3mix-mp antibiotic paste and conventional pulpectomy for primary molars with pulp involvement with 18 months follow-up. Contemp Clin Dent 2017;8(4):514–521. DOI: 10.4103/ccd.ccd_47_17
30. Duanduan A, Sirimaharaj V, Chompu-inwai P. Retrospective study of pulpectomy with Vitapex® and LSTR with three antibiotics combination (3Mix) for non-vital pulp treatment in primary teeth. CMU J Nat Sci 2013;12(2):131–139. DOI: 10.12982/CMUJNS.2013.0012
________________________
© The Author(s). 2023 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.