Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study

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Most resistant micro-organisms, such as E.faecalis survive in chronic infection of the root canal at the periapical area and are difficult to remove by various root canal irrigants. C.albicans has been found in chronic infections of root canals of primary teeth due to its ability to invade dentinal tubules. The multiple bacteria strains which cause endodontic infections, make it difficult to clean root canals with a single effective antibiotic. Hence Triple Antibiotic Paste (TAP) has been previously introduced, consisting of ciprofloxacin, metronidazole, and minocycline. Although this mixture aids in pulp regeneration and has been used to disinfect root canal systems, it is linked to tooth discolouration. The aim of this study is to evaluate and compare the antimicrobial efficacy of a newly formulated 3C antibiotic paste (consisting of Ciprofloxacin, Clindamycin, and Cefaclor) with conventional TAP against E. faecalis and C. albicans. In this in-vitro laboratory study, pure culture of C. albicans and E. faecalis will be grown on Sabouraud’s dextrose agar (SD) agar and Brain heart infusion agar (BHI) agar respectively and will be suspended for 24 hours at 37°C. For comparison of antimicrobial efficacy, the zone of inhibition will be for the 3C antibiotic paste against conventional TAP (control) for E. faecalis and C. albicans, and will be determined using digital calliper in millimetre after every 24 and 72 hours. We hypothesise that the newly formulated 3C paste will have better antimicrobial efficacy when compared with conventional TAP. It is expected that a newly formulated 3C paste will prove to be the successful as root canal filling material for primary teeth." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/12-754", "name": "Comparative evaluation of antimicrobial efficacy of 3C antibiotic..." } } ] } Home Browse Comparative evaluation of antimicrobial efficacy of 3C antibiotic... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Chandra A and Thosar N. Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.12688/f1000research.133458.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Study Protocol Revised Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] Aakriti Chandra https://orcid.org/0009-0003-0650-0719 1 , Nilima Thosar 1 Aakriti Chandra https://orcid.org/0009-0003-0650-0719 1 , Nilima Thosar 1 PUBLISHED 11 Jan 2024 Author details Author details 1 Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Sawangi Meghe, Wardha, Maharastra, 442001, India Aakriti Chandra Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation Nilima Thosar Roles: Conceptualization, Funding Acquisition, Project Administration, Resources, Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Datta Meghe Institute of Higher Education and Research collection. This article is included in the Antimicrobial Resistance collection. Abstract Root canal infection in primary teeth is polymicrobial in nature. Most resistant micro-organisms, such as E.faecalis survive in chronic infection of the root canal at the periapical area and are difficult to remove by various root canal irrigants. C.albicans has been found in chronic infections of root canals of primary teeth due to its ability to invade dentinal tubules. The multiple bacteria strains which cause endodontic infections, make it difficult to clean root canals with a single effective antibiotic. Hence Triple Antibiotic Paste (TAP) has been previously introduced, consisting of ciprofloxacin, metronidazole, and minocycline. Although this mixture aids in pulp regeneration and has been used to disinfect root canal systems, it is linked to tooth discolouration. The aim of this study is to evaluate and compare the antimicrobial efficacy of a newly formulated 3C antibiotic paste (consisting of Ciprofloxacin, Clindamycin, and Cefaclor) with conventional TAP against E. faecalis and C. albicans. In this in-vitro laboratory study, pure culture of C. albicans and E. faecalis will be grown on Sabouraud’s dextrose agar (SD) agar and Brain heart infusion agar (BHI) agar respectively and will be suspended for 24 hours at 37°C. For comparison of antimicrobial efficacy, the zone of inhibition will be for the 3C antibiotic paste against conventional TAP (control) for E. faecalis and C. albicans , and will be determined using digital calliper in millimetre after every 24 and 72 hours. We hypothesise that the newly formulated 3C paste will have better antimicrobial efficacy when compared with conventional TAP. It is expected that a newly formulated 3C paste will prove to be the successful as root canal filling material for primary teeth. READ ALL READ LESS Keywords Triple Antibiotic Paste, Clindamycin, Cefaclor, root canal filling material Corresponding Author(s) Aakriti Chandra ( [email protected] ) Close Corresponding author: Aakriti Chandra Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2024 Chandra A and Thosar N. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Chandra A and Thosar N. Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.12688/f1000research.133458.2 ) First published: 27 Jun 2023, 12 :754 ( https://doi.org/10.12688/f1000research.133458.1 ) Latest published: 11 Jan 2024, 12 :754 ( https://doi.org/10.12688/f1000research.133458.2 ) Revised Amendments from Version 1 As per reviewer comment, the methods of antibiotic preparation was elaborated thoroughly including drug specifications, concentration along with referencing done, the limitation of the studywas added i.e. that it is an in vitro microbiological study so the study of cultivating the microbial biofilms in root canal will be considered in future studies. In addition, reference no 13 was also added. As per reviewer comment, the methods of antibiotic preparation was elaborated thoroughly including drug specifications, concentration along with referencing done, the limitation of the studywas added i.e. that it is an in vitro microbiological study so the study of cultivating the microbial biofilms in root canal will be considered in future studies. In addition, reference no 13 was also added. See the authors' detailed response to the review by Shiva Shojaeian READ REVIEWER RESPONSES Introduction Background and rationale Microorganisms are crucial in the development of pulpal and periapical diseases. The polymicrobial character of the infection in the root canal system is primarily dominated by anaerobes. 1 One of the frequently isolated among them is E. faecalis. E. faecalis is one of the most resistant micro-organisms and is most difficult to remove from the periapical areas of the tooth through conventional methods. 2 About 23–70% E. faecalis can be isolated from infected root canals with symptoms of chronic apical periodontitis. 3 Among Fungi, Candida species are found in about 3–18% of infected root canals. 4 According to earlier research, C. albicans and E. faecalis can infiltrate the dentinal tubules to varying depths, hence removal of these bacteria is facilitated by the use of an efficient antimicrobial agent in the root canal. 5 Over the years, several materials were tested in an effort to find an ideal obturating material for a primary tooth, such as zinc oxide eugenol, Maisto paste, Triple Antibiotic Paste etc. 6 The antimicrobial efficacy of Triple Antibiotic Paste was evaluated for its use as root canal filling material with different modifications by various authors. 7 , 8 In Triple Antibiotic Paste, the antibiotics used are: Ciprofloxacin, metronidazole, and minocycline in 1:1:1 concentration. 9 Ciprofloxacin is a second-generation fluoroquinolone antibiotics active against a broad range of bacteria, especially Enterobacteriaceae and Neisseria. 10 Metronidazole is a nitro imidazole compound having a broad spectrum of anti-anaerobic and anti-protozoal activity. 9 Minocycline is a member of the Tetracycline class of broad-spectrum antibiotics, which work by exerting bacteriostatic action on a wide variety of microorganisms. 8 , 9 But, Minocycline causes discoloration of tooth as stated by various authors. 11 , 12 For the same reason, Sara Alsubait et al (2020) in their study had replaced minocycline with Cefaclor. Cefaclor is a second generation cephalosporin antibiotic which is mostly effective against most strains of Gram positive aerobes as well as gram negative aerobes. 10 A broad-spectrum antibiotic called Clindamycin is effective against infections that produce beta-lactamases as well as against aerobic and anaerobic microorganisms. 10 Prasanna et al (2020) in their study concluded that Clindamycin could inhibit the levels of C albicans by 90% but Metronidazole could not inhibit the C. albicans. 8 With respect to above literature, considering the disadvantage associated with Minocycline and reduced antimicrobial efficacy of Metronidazole, the present study has planned to use the 3C paste consisting of Ciprofloxacin, Clindamycin, and Cefaclor as a root canal filling material for primary teeth. The aim of the present study will be to evaluate and compare the antimicrobial efficacy of 3C paste with conventional Triple Antibiotic Paste against E. faecalis and C. albicans. Objectives The objectives of the study will be to evaluate the antimicrobial efficacy of 3C paste and triple antibiotic paste against E. faecalis and C. albicans ; and also to compare the antimicrobial efficacy of 3C paste with Triple Antibiotic Paste against E. Faecalis and C. albicans. Protocol Study design This in vitro study will be conducted at Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research, Sawangi Meghe, Wardha in collaboration with the Institution of Pharmaceutical Education and Research, Borgaon (Meghe), Wardha. The present study will be an in vitro experimental microbiological study. Ethics statement Although no human or animal participants will be involved in this research, as per institutional guidelines, ethical approval for the study was obtained from the institutional ethics committee of Datta Meghe Institute of Higher Education and Research, Wardha (Ref. No. DMIHER (DU)/IEC/2023/564 approved on 02/02/2023). Methods For the antimicrobial analysis brain heart infusion agar (BHI), Sabouraud’s dextrose agar (SD), Agar plates, Petri dishes , E. faecalis strain , C.albicans strain will be used. For preparation of paste, Ciprofloxacin, Clindamycin, Cefaclor, Metronidazole, Minocycline, Propylene glycol/macrogol will be required. These steps are outlined in full in the sections below. E. faecalis strain and C.albicans strain and the powder form of antibiotics will be included for the study. However other bacterial strains will be excluded from the study. Preparation of Triple Antibiotic Paste (control group) Triple Antibiotic Paste will be prepared by mixing equal proportion of Ciprofloxacin (200 mg), Metronidazole (400 mg), and Minocycline (100 mg) in 1:1:1. Then a part of the solvent (propylene glycol-macrogol) in 1:1 ratio will be dispensed to obtain soft, uniform consistency. 13 The resultant paste will be stored in an airtight container. Preparation of 3C antibiotic paste (experimental group) 3C paste will be prepared in the same manner as Triple Antibiotic Paste. In 3C paste, the antibiotics Ciprofloxacin (200 mg), Cefaclor (100 mg), and Clindamycin (400 mg) (1:1:1) will be mixed with one part of Propylene Glycol-one part of Macrogol in 5:1 (powder: liquid) ratio to get desired consistency as required for the paste. Procedure Pure colonies of C. albicans ( ATCC 2091 ) and E. faecalis ( ATCC 35550 ) will be grown on Sabouraud’s dextrose (SD) agar and Brain heart infusion (BHI) agar respectively and will be suspended in 5 ml of SD broth and BHI broth for 24 hours at 37°C. The actively growing microorganisms in broth cultures will have turbidity adjusted to the 0.5 McFarland standard. 3 , 5 The agar well diffusion method will then be followed. Wells of 3-4 mm will be prepared in the respective agar and then all the wells will be loaded with test material. The agar plates will be incubated at 37°C for 24 and 72 hours to achieve good bacterial growth before analysis. The inhibition zones of microbes will be evaluated using digital calliper in millimetre after every 24 and 72 hours. All the procedures will be repeated in triplicates to minimize errors. Primary outcomes to be measured The antimicrobial efficacy of newly formulated 3C antibiotic paste will be measured by bacterial growth and will be compared with the Triple Antibiotic Paste. Data analysis and statistical plan Statistical analysis will be done using software SPSS Version 23.0. P value will be considered significant for <0.05. Descriptive analysis, i.e., mean distribution of inhibition zones will be recorded. A repeated measures ANOVA for intragroup comparison will be done on application of triplicate test of every group. Independent sample t test will be done for intergroup comparison. Expected outcome It is expected that a newly formulated 3C paste will be able to show antimicrobial efficacy and will prove to be the successful as root canal filling material for primary teeth. Dissemination This study will be published in an indexed journal. Study status Not yet started. Discussion Complete eradication of micro-organism from root canal space is a challenging task in primary teeth due to morphology of the root canal. The multiple bacteria strains which cause endodontic infections, make it impossible to clean root canals with a single effective antimicrobial agent. 9 Hence, a combination of drugs commonly known as Triple Antibiotic Paste (TAP) was introduced as treatment modality by Hoshino et al (1996) to eliminate the micro-organisms from infected root canal of primary teeth. It is usually composed of Ciprofloxacin, metronidazole, and minocycline (1:1:1). This mixture aids in pulp regeneration as well as the disinfection of the root canal system. 14 An in vivo study conducted by Pinky C et al (2011) using two different combination of antibiotics in deciduous teeth consisting of ciprofloxacin, metronidazole, and minocycline i.e., TAP in group A and modified combinations consisting of ciprofloxacin, ornidazole, and minocycline in group B. Where they found both the groups showed significant results. However, group B had better result than group A clinically and radiographically. 15 A similar study was conducted in year 2013 by Sabrah et al. comparing the antibacterial activity of Triple Antibiotic Paste (TAP) and Double Antibiotic Paste (DAP) against Enterococcus faecalis and Porphyromonas gingivalis in comparison to calcium hydroxide. They found that both TAP and DAP were significantly more efficient in the reduction of bacterial biofilms in comparison to calcium hydroxide. 16 Similarly a study conducted by Dahake P et al . (2020) on Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of Clindamycin (C), Metronidazole (M), Doxycycline (D) as well as their combination CMD that clindamycin could inhibit the levels of C albicans by 90% but Metronidazole could not inhibit the C. albicans and also concluded that combination CMD can be used to achieve predictable better results. 17 Govindaraju et al. (2021) had evaluated Antibiotic sensitivity of the following intracanal medicaments grouped into 4 groups consisting of TAP (Ciprofloxacin, metronidazole, and doxycycline); Calcium hydroxide paste; Odontopaste and Sterile saline (0.9%) as a negative control against E. Faecalis, S. mutants, and S. aureus. In which they found that TAP showed the highest inhibition zone to conclude that TAP had better antibacterial activity than other groups. 18 However, Minocycline causes discoloration of tooth as stated by various authors. 11 , 12 For the same reason, Sara Alsubait et al. (2020) in their study had replaced minocycline with Cefaclor. 11 The limitation of this study is that it is an in-vitro microbiological study hence further study are required to remove microbial biofilms from the root canal, as they penetrate into the dentinal tubules which are more challenging to eradicate. Considering the disadvantages associated with conventional Triple Antibiotic Paste and reduced antimicrobial efficacy of Metronidazole, a new formulation in the form of 3C paste consisting of Ciprofloxacin, Clindamycin and Cefaclor will be prepared for its use as a root canal filling material for primary teeth. Data availability No data are associated with this article. References 1. Paul P, Chandru TP, Peedikayil FC, et al. : Effectiveness of various intracanal medicaments on Candida albicans. SRM J. Res. Dent. Sci. 2020 Apr 1; 11 (2): 82. Publisher Full Text 2. Alghamdi F, Shakir M: The influence of Enterococcus faecalis as a dental root canal pathogen on endodontic treatment. Cureus. 2020 Mar 13; 12 (3). Publisher Full Text 3. Dumani A, Yoldas O, Yilmaz S, et al. : In vitro susceptibility of E. faecalis and C. albicans isolates from apical periodontitis to common antimicrobial agents, antibiotics and antifungal medicaments. J. Clin. Exp. Dent. 2012 Feb; 4 (1): e1–e7. PubMed Abstract | Publisher Full Text 4. Yoo YJ, Kim AR, Perinpanayagam H, et al. : Candida albicans virulence factors and pathogenicity for endodontic infections. Microorganisms. 2020 Aug 26; 8 (9): 1300. 5. Shaik J, Garlapati R, Nagesh B, et al. : Comparative evaluation of antimicrobial efficacy of triple antibiotic paste and calcium hydroxide using chitosan as carrier against Candida albicans and Enterococcus faecalis. J. Conserv. Dent. 2014 Jul; 17 (4): 335–339. PubMed Abstract | Publisher Full Text | Free Full Text 6. Rajsheker S, Mallineni SK, Nuvvula S: Obturating Materials Used for Pulpectomy in Primary Teeth-A Mini Review. J. Dent. Craniofac. Res. 2018; 03 (1): 3. Publisher Full Text 7. Sijini OT, Sabbagh HJ, Baghlaf KK, et al. : Clinical and radiographic evaluation of triple antibiotic paste pulp therapy compared to Vitapex pulpectomy in non-vital primary molars. Clin. Exp. Dent. Res. 2021 Oct; 7 (5): 819–828. 8. Dahake PT, Jha RK, Baliga SM: Evaluation of combination of three antimicrobial agents against common endodontic pathogens. Int. J. Sci. Res. 2019; 8 (11): 63–64. 9. Malu K, Khubchandani M: Triple Antibiotic Paste: A Suitable Medicament for Intracanal Disinfection. Cureus. 2022 Sep 15; 14 (9). Publisher Full Text 10. Tripathi KD: Essentials of medical pharmacology. JP Medical Ltd; 2013 Sep 30. 11. Alsubait S, Alsaad N, Alahmari S, et al. : The effect of intracanal medicaments used in Endodontics on the dislocation of two calcium silicate-based filling materials. BMC Oral Health. 2020 Dec; 20 (1): 1–7. Publisher Full Text 12. Thomas MS: Crown discoloration due to the use of triple antibiotic paste as an endodontic intra-canal medicament. Saudi Endod. J. 2014 Jan 1; 4 (1): 32. Publisher Full Text 13. Makandar S, Noorani T: Triple Antibiotic Paste—Challenging Intracanal Medicament: A Systematic Review. J. Int. Oral Health. 2020; 12 : 189–196. Publisher Full Text 14. Hoshino E, Kurihara-Ando N, Sato I, et al. : In-vitro antibacterial susceptibility of bacteria taken from infected root dentine to a mixture of ciprofloxacin, metronidazole and minocycline. Int. Endod. J. 1996 Mar; 29 (2): 125–130. PubMed Abstract | Publisher Full Text 15. 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 Apr 1; 29 (2): 121–127. PubMed Abstract | Publisher Full Text 16. Sabrah AH, Yassen GH, Gregory RL: Effectiveness of antibiotic medicaments against biofilm formation of Enterococcus faecalis and Porphyromonas gingivalis. J. Endod. 2013 Nov 1; 39 (11): 1385–1389. Publisher Full Text 17. Dahake PT, Baliga SM: Antimicrobial efficacy of a new tri-antibiotic combination against resistant endodontic pathogens: an in-vitro study. Braz. Dent. Sci. 2020 Sep 30; 23 (4): 8. Publisher Full Text 18. Govindaraju L, Jenarthanan S, Subramanyam D, et al. : Antibacterial activity of various intracanal medicament against enterococcus faecalis, streptococcus mutans and staphylococcus aureus: an in vitro study. J. Pharm. Bioallied Sci. 2021 Jun; 13 (Suppl 1): 157. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 27 Jun 2023 ADD YOUR COMMENT Comment Author details Author details 1 Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Sawangi Meghe, Wardha, Maharastra, 442001, India Aakriti Chandra Roles: Conceptualization, Data Curation, Methodology, Writing – Original Draft Preparation Nilima Thosar Roles: Conceptualization, Funding Acquisition, Project Administration, Resources, Supervision, Validation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 11 Jan 2024, 12:754 https://doi.org/10.12688/f1000research.133458.2 version 1 Published: 27 Jun 2023, 12:754 https://doi.org/10.12688/f1000research.133458.1 Copyright © 2024 Chandra A and Thosar N. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Chandra A and Thosar N. Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.12688/f1000research.133458.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 11 Jan 2024 Revised Views 0 Cite How to cite this report: Latief MA. Reviewer Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.161170.r249916 ) The direct URL for this report is: https://f1000research.com/articles/12-754/v2#referee-response-249916 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 01 Apr 2025 Mohammad Adhitya Latief , University of Indonesia, Depok, West Java, Indonesia Approved VIEWS 0 https://doi.org/10.5256/f1000research.161170.r249916 Strong point and advantage of this research are : 1. Novel Formulation: The study introduces a new antibiotic paste (3C paste) consisting of Ciprofloxacin, Clindamycin, and Cefaclor, which aims to improve antimicrobial efficacy against resistant microorganisms like ... Continue reading READ ALL Strong point and advantage of this research are : 1. Novel Formulation: The study introduces a new antibiotic paste (3C paste) consisting of Ciprofloxacin, Clindamycin, and Cefaclor, which aims to improve antimicrobial efficacy against resistant microorganisms like E. faecalis and C. albicans in primary teeth. ​ This formulation potentially reducing aesthetic concerns associated with root canal treatments. ​ It has broad-spectrum efficacy which potentially offering a more effective solution for polymicrobial infections in root canals. ​ 2. Potential Clinical Application: If successful, the 3C paste could become a preferred root canal filling material for primary teeth, improving treatment outcomes and patient satisfaction. ​ Room for Improvement 1. Detailed Methodology, regarding the preparation methods for the antibiotic pastes should be elaborated further, including drug specifications, concentrations, and milligram/milliliter details to ensure reproducibility. ​ 2. Long-Term Outcomes, this research should also investigate the long-term outcomes of using the 3C paste, including its impact on tooth integrity, patient comfort, and recurrence of infections especially if this could be done in in vitro studies. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Dentoalveolar Surgery, oral and maxillofacial trauma, dental and maxillofacial implants I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Latief MA. Reviewer Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.161170.r249916 ) The direct URL for this report is: https://f1000research.com/articles/12-754/v2#referee-response-249916 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: S R S. Reviewer Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.161170.r249912 ) The direct URL for this report is: https://f1000research.com/articles/12-754/v2#referee-response-249912 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 19 Jun 2024 Srinidhi S R , Dr. D. Y. Patil Dental College & Hospital, Pune, India Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.161170.r249912 Introduction - The study synopsis gives a background about the type of microbes and their persistence in root canals of deciduous teeth. The common microbes which are present even after routine canal cleaning and disinfection methods have been mentioned. ... Continue reading READ ALL Introduction - The study synopsis gives a background about the type of microbes and their persistence in root canals of deciduous teeth. The common microbes which are present even after routine canal cleaning and disinfection methods have been mentioned. However, I would like to put a few additions the authors can add which will help the readers in better understanding the rationale for the use of antibiotic pastes. Both of these suggestions are minor revisions . The results of this study will give a better idea for the clinician as to the protocol to be applied in such recalcitrant cases. 1. The authors have mentioned about the persistence of C albicans and E faecalis . It can also be added that in spite of various irrigants and activation methods (give examples), these microbes resist removal. 2. Mention any study which has used Clindamycin as one of the medicaments. The reference given is of the textbook only. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Endodontic microbiology, irrigants and techniques I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT S R S. Reviewer Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.161170.r249912 ) The direct URL for this report is: https://f1000research.com/articles/12-754/v2#referee-response-249912 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 27 Jun 2023 Views 0 Cite How to cite this report: Shojaeian S. Reviewer Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.146449.r184034 ) The direct URL for this report is: https://f1000research.com/articles/12-754/v1#referee-response-184034 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 22 Aug 2023 Shiva Shojaeian , Department of Endodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.146449.r184034 The study would be improved if it is conducted to evaluate the antimicrobial efficacy of 3C paste and triple antibiotic on E. faecalis and C. albicans biofilm. Microbial biofilms in the root canal, penetrate into the dentinal tubules which are more challenging to eradicate ... Continue reading READ ALL The study would be improved if it is conducted to evaluate the antimicrobial efficacy of 3C paste and triple antibiotic on E. faecalis and C. albicans biofilm. Microbial biofilms in the root canal, penetrate into the dentinal tubules which are more challenging to eradicate compared with microorganisms growing in the cultivation media. E. faecalis and C. albicans can cultivate in root canal specimens to form microbial biofilm on dentin therefore the condition is more similar to the clinical situation The methods of antibiotic preparation should be elaborated thoroughly including Drug specifications, concentration, and milligram/milliliter. The specimens should be assigned to the experimental and negative and positive control groups. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Endodontic regenersation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Shojaeian S. Reviewer Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.146449.r184034 ) The direct URL for this report is: https://f1000research.com/articles/12-754/v1#referee-response-184034 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 06 Oct 2023 Aakriti Chandra , Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Sawangi Meghe, Wardha, 442001, India 06 Oct 2023 Author Response The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs ... Continue reading The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs has been established. The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs has been established. Competing Interests: no competing interests Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 06 Oct 2023 Aakriti Chandra , Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Sawangi Meghe, Wardha, 442001, India 06 Oct 2023 Author Response The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs ... Continue reading The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs has been established. The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs has been established. Competing Interests: no competing interests Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 27 Jun 2023 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 11 Jan 24 read read Version 1 27 Jun 23 read Shiva Shojaeian , Shahid Beheshti University of Medical Sciences, Tehran, Iran Srinidhi S R , Dr. D. Y. Patil Dental College & Hospital, Pune, India Mohammad Adhitya Latief , University of Indonesia, Depok, Indonesia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Latief M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 01 Apr 2025 | for Version 2 Mohammad Adhitya Latief , University of Indonesia, Depok, West Java, Indonesia 0 Views copyright © 2025 Latief M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Strong point and advantage of this research are : 1. Novel Formulation: The study introduces a new antibiotic paste (3C paste) consisting of Ciprofloxacin, Clindamycin, and Cefaclor, which aims to improve antimicrobial efficacy against resistant microorganisms like E. faecalis and C. albicans in primary teeth. ​ This formulation potentially reducing aesthetic concerns associated with root canal treatments. ​ It has broad-spectrum efficacy which potentially offering a more effective solution for polymicrobial infections in root canals. ​ 2. Potential Clinical Application: If successful, the 3C paste could become a preferred root canal filling material for primary teeth, improving treatment outcomes and patient satisfaction. ​ Room for Improvement 1. Detailed Methodology, regarding the preparation methods for the antibiotic pastes should be elaborated further, including drug specifications, concentrations, and milligram/milliliter details to ensure reproducibility. ​ 2. Long-Term Outcomes, this research should also investigate the long-term outcomes of using the 3C paste, including its impact on tooth integrity, patient comfort, and recurrence of infections especially if this could be done in in vitro studies. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Dentoalveolar Surgery, oral and maxillofacial trauma, dental and maxillofacial implants I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Latief MA. Peer Review Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.161170.r249916) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-754/v2#referee-response-249916 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 S R S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 19 Jun 2024 | for Version 2 Srinidhi S R , Dr. D. Y. Patil Dental College & Hospital, Pune, India 0 Views copyright © 2024 S R S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Introduction - The study synopsis gives a background about the type of microbes and their persistence in root canals of deciduous teeth. The common microbes which are present even after routine canal cleaning and disinfection methods have been mentioned. However, I would like to put a few additions the authors can add which will help the readers in better understanding the rationale for the use of antibiotic pastes. Both of these suggestions are minor revisions . The results of this study will give a better idea for the clinician as to the protocol to be applied in such recalcitrant cases. 1. The authors have mentioned about the persistence of C albicans and E faecalis . It can also be added that in spite of various irrigants and activation methods (give examples), these microbes resist removal. 2. Mention any study which has used Clindamycin as one of the medicaments. The reference given is of the textbook only. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Yes Are sufficient details of the methods provided to allow replication by others? Yes Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests No competing interests were disclosed. Reviewer Expertise Endodontic microbiology, irrigants and techniques I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) S R S. Peer Review Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.161170.r249912) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-754/v2#referee-response-249912 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Shojaeian S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 22 Aug 2023 | for Version 1 Shiva Shojaeian , Department of Endodontics, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran 0 Views copyright © 2023 Shojaeian S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions The study would be improved if it is conducted to evaluate the antimicrobial efficacy of 3C paste and triple antibiotic on E. faecalis and C. albicans biofilm. Microbial biofilms in the root canal, penetrate into the dentinal tubules which are more challenging to eradicate compared with microorganisms growing in the cultivation media. E. faecalis and C. albicans can cultivate in root canal specimens to form microbial biofilm on dentin therefore the condition is more similar to the clinical situation The methods of antibiotic preparation should be elaborated thoroughly including Drug specifications, concentration, and milligram/milliliter. The specimens should be assigned to the experimental and negative and positive control groups. Is the rationale for, and objectives of, the study clearly described? Yes Is the study design appropriate for the research question? Partly Are sufficient details of the methods provided to allow replication by others? No Are the datasets clearly presented in a useable and accessible format? No Competing Interests No competing interests were disclosed. Reviewer Expertise Endodontic regenersation I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 06 Oct 2023 Aakriti Chandra, Department of Pediatric and Preventive Dentistry, Sharad Pawar Dental College and Hospital, Datta Meghe Institute of Higher Education and Research (Deemed to be University), Sawangi Meghe, Wardha, 442001, India The study of cultivating the microbial biofilms in root canal will be considered in future studies. the drug specifications will be given in final study once MIC of the dugs has been established. View more View less Competing Interests no competing interests reply Respond Report a concern Shojaeian S. Peer Review Report For: Comparative evaluation of antimicrobial efficacy of 3C antibiotic paste with triple antibiotic paste as root canal filling material for primary teeth: An in-vitro study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2024, 12 :754 ( https://doi.org/10.5256/f1000research.146449.r184034) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/12-754/v1#referee-response-184034 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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