Antimicrobial efficacy of triple antibiotic paste in teeth with primary endodontic infection: A systematic review

INTRODUCTION

Effective decontamination of the infected root canals is essential for achieving predictable treatment outcomes in teeth with apical periodontitis.^[1] Although disinfection is primarily achieved by chemo-mechanical procedures, the role of intracanal medicaments cannot be ignored, especially in cases of refractory lesions.^[2] Evidence suggests that many bacteria remain in the dentinal tubules of the infected root canals even after chemo-mechanical procedures.^[3] Calcium hydroxide (CH) has been the gold standard as an intracanal medicament for many years and is also used with additives such as povidone-iodine and 2% CHX. However, few studies have found bacteria in the canals even after 1 week of placement of CH. Sathorn et al. (2007), in a recent systematic review, concluded that CH had limited effectiveness in eliminating bacteria from human root canal when assessed by culture techniques.^[4]

More recently, the field of endodontics has seen a paradigm shift from repair towards regeneration, especially in immature necrotic teeth. Apexogenesis and thickening of intraradicular dentin are now achievable with the advent of procedures such as revascularization and the use of biological scaffolds such as platelet-rich plasma and platelet-rich fibrin.^[5] Asepsis plays a crucial role in regenerative endodontics. Hoshino’s triple antibiotic paste (TAP), a mixture of three antibiotics, ciprofloxacin, metronidazole, and minocycline has been proved to be most effective for this.^[6] This paste is also useful in lesion sterilization and repair procedures to achieve periradicular healing by non-surgical means.^[7]

Since its introduction by Hoshino et al. in 1996, many in vitro studies have proved its worth as an effective root canal disinfectant.^[8,9] Various authors have used different models such as infecting the extracted teeth with oral microflora, teeth with Enterococcus faecalis biofilm grown in the roots, and animal models for studying and evaluating the antimicrobial potential of TAP.^[10-12] Surprisingly, there have been very few human clinical trials for the same.

Keeping in view the increasing number of clinical cases where this mixture is used and the fact that in vitro studies are performed under a controlled environment, which may differ from clinical situations, it is imperative to base the evidence on human clinical trials. Thus, this systematic review was taken up to study the various human clinical trials which have tested the antimicrobial efficacy of TAP; and to answer the question “is the antimicrobial efficacy of TAP better than the other intracanal medicaments when used clinically inside root canals of teeth with primary root canal infection.”

MATERIAL AND METHODS

This systematic review was reported according to Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines (http://www.prisma-statement.org). The protocol was registered in the PROSPERO database, registration number CRD 42018083806.

RESULTS

Study selection

Two hundred eighty-three studies were obtained for screening from an electronic database and one from the reference list of an article. After screening 234 records by title and abstract, 226 were excluded, and eight were selected for full-text eligibility assessment. From these, two studies were excluded as they used TAP as an irrigant and not intracanal medicament,^[14,15] one excluded because it used a different combination of TAP,^[16] and one study was excluded at it was an animal study.^[12] Finally, four studies were included for this systematic review [Figure 1].

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Figure 1:

PRISMA flow chart showing identification and selection process of articles included.

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DISCUSSION

This study focused on the effect of TAP on bacterial counts in primary root canal infections. Studies done in infected root canals of both primary and permanent teeth were considered as the microbiota of both mature and immature teeth are pretty similar.^[20,21] Studies where a combination of ciprofloxacin, metronidazole, and either tetracycline or minocycline in a ratio of 1:1:1 was used were considered. Minocycline is a semi-synthetic derivative of tetracycline with a similar antibiotic spectrum but has resulted in tooth discoloration.^[22] To overcome this drawback, recently, few studies have substituted minocycline with cefaclor, amoxicillin, or doxycycline.^[23]

Due to variations in the methods of outcome measurement and its evaluation at different points of time, it was not possible to present the results as a meta-analysis. Thus, a narrative synthesis was performed for TAP compared to comparators used. The overall quality of included studies suggested a moderate risk of bias.

Although many in vitro and ex vivo studies have been conducted and proved the antimicrobial efficacy of TAP over other intracanal medicaments in reducing bacterial flora in infected toot canals, few clinical trials have been conducted for the same.^[8,24,25] The clinical studies included in the current review do reiterate the higher efficacy of TAP as an intracanal medicament, but still they were not without limitations. Concentration in which TAP can be used effectively as an intracanal medicament is also essential. It is found to be cytotoxic against stem cells and apical papilla cells at higher concentrations;^[11] however, none of the included studies except Arruda et al. has discussed this fact. Arruda et al. concluded that TAP, when used in a concentration of 1 mg/ml, can also be as effective and less cytotoxic as compared to a higher concentration of 1 g/ml traditionally used. Interestingly, in an in vitro study by Mehta et al.,^[26] where they compared antimicrobial efficacy of TAP and CH, a minimum optical density against E. faecalis could be achieved at a concentration as low as 1.25 μg/ml. Moreover, with these included studies though it was clear that TAP has a higher antimicrobial activity than its comparators, it could not be concluded that what is the optimum duration for its intracanal placement, as all the studies used a different time-period of 7–10 days (Arruda et al.), 21 days (Nagata et al.), 3 days (Ahirwar et al.), and 7 days (Dutta et al.). In an ex vivo study by Ghabraei et al.,^[27] it was found that TAP requires a minimum time of 7 days as intracanal dressing. However, they had tested it specifically against E. faecalis only.

Method of bacterial quantification may also affect the outcome assessment. In the included studies, only in the one by Arruda et al., the reduction of total bacterial levels was evaluated using a culture-independent molecular microbiology assay qPCR. In the other three studies, the colony-forming units cultured on sheep blood agar plates were counted for evaluating the reduction in bacterial colonies after intracanal medication. Kotsilkov et al.^[28] compared the culture method and RTPCR for detection of periodontitis causing bacteria in deep periodontal pockets. In their study, the RT-PCR exhibited a higher sensitivity when compared to the microbiological culture method for detecting periodontal pathogens. This may be because cultivation methods can identify a lesser amount of bacteria because of the problem in keeping the pathogenic bacteria viable, which is essential for standard cultivation. A low sample size (range: 15–48) in all the included studies is also a reason for concern.

CONCLUSION

The results of the present systematic review suggest that there is not enough evidence to suggest a better antimicrobial efficacy of TAP over other intracanal medicaments in clinical studies as there very few randomized clinical studies have assessed antimicrobial efficacy of TAP. Moreover, although several in vitro studies suggest so, there is a need to conduct well reported, correctly designed, high quality, and randomized clinical trials with a large sample size to assess the antimicrobial efficacy of TAP clinically as an intracanal medication in non-vital teeth with apical periodontitis.