Original Title: Triklosanbelagte suturer til forebygging av infeksjoner i operasjonsområde: en fullstendig metodevurdering

Authors' objectives: One of the most common complications after surgery is surgical site infections. To prevent infections, absorbable sutures coated with the antimicrobial agent triclosan have been used. An antimicrobial agent inhibits the growth or kills microorganisms such as bacteria, fungi, and viruses. The term is often used interchangeably with antibiotics. However, triclosan can lead to environmental pollution and is associated with antibiotic resistance. Due to these undesirable properties, bans on triclosan have been implemented in many areas. Chlorhexidine is another antimicrobial agent used to prevent infections, but it is not used on sutures to the same extent as triclosan. Moreover, chlorhexidine is not listed by Miljødirektoratet, the environmental directorate in Norway, as environmentally harmful substance that meet the PBT criteria (substances that are persistent, bioaccumulative, and toxic). A multidisciplinary team of experts from the fields of surgery, infectious diseases, antibiotic resistance, transplant medicine, infection control and environmental pollution have participated in the work of this report. The research questions we aimed to address were: 1. What is the efficacy and safety of triclosan-coated sutures compared to standard (uncoated) sutures in order to prevent surgical site infections? 2. What studies can be found relating to the efficacy and safety of chlorhexidinecoated sutures compared to standard sutures in order to prevent surgical site infections? 3. What are the economic consequences of using triclosan-coated sutures compared to standard sutures in order to prevent surgical site infections? 4. Assess whether the use of triclosan-coated sutures can lead to the development of resistance, thereby reducing the effectiveness of clinically important antimicrobial agents. 5. Evaluate whether the use of triclosan-coated sutures can impact the environment

Authors' results and conclusions: We have summarized the efficacy and safety and assessed the health economic consequences of the use of triclosan-coated sutures compared to standard sutures for the prevention of surgical site infections. Triclosan is an antimicrobial agent associated with antibiotic resistance and environmental pollution. Therefore, we have also evaluated the potential impact of triclosancoated sutures on antibiotic resistance and the environment. The certainty to the estimates of effect were assessed using the GRADE tool (high, moderate, low, or very low). In the meta-analyses of the studies with low and moderate risk of bias, we found that the use of triclosan-coated sutures compared to standard sutures resulted in: • no difference or possibly a small reduction in the risk of infections after gastrointestinal/abdominal surgeries. (GRADE: low). • little or no difference after cardiovascular surgeries. (GRADE: low) • uncertain results for orthopaedic surgeries, and both fewer and more infections may occur. The confidence interval was wide. (GRADE: very low). • no difference or possibly a small reduction in the risk of infections after clean (non-infected) surgeries. Cardiovascular and orthopaedic surgeries are classified as clean. (GRADE: low) For subgroup analyses of superficial infections, studies with low risk of bias, and studies with participant numbers over 1000, the confidence intervals crossed the line of no effect. We assessed the certainty of the evidence as moderate for studies with low risk of bias and low in the others. In these analyses, we did not differentiate between different surgical procedures. In the health economic assessment, subgroup analyses within gastrointestinal and abdominal surgeries of laparoscopic colon surgery, open colon surgery, and laparoscopic gallbladder removal suggested that triclosan-coated sutures may provide both cost savings and additional costs. The results for all three analyses indicated a tendency that the use of triclosan-coated sutures potentially would lead to less cost savings the lower the infection incidence. Triclosan can be linked to antibiotic resistance in several important pathogenic bacteria as well as environmental bacteria, and it can lead to increased transfer of antibiotic resistance genes between bacteria. One question is whether any benefit from the use of triclosan outweighs the risk of developing antibiotic resistance. The amounts of triclosan expected to be released into the environment after use in sutures are low. Although the emission is undesirable, the impact on the environment is likely to be minimal. If the use of triclosan-coated sutures is a valuable, environmental considerations will probably not be an obstacle to their use. If new studies are to be conducted, our experts from the field have proposed studies with a cluster-randomized design where infections after caesarean sections, gallbladder surgeries, and colon surgeries are registered.

Authors' methods: We used the recently published report (2022) from the National Institute for Health and Care Excellence (NICE), hereafter referred to as the NICE report, as a basis for our search and presentation of results. We assessed the NICE report to have high methodological quality. We updated the search from the NICE report and included relevant randomized controlled trials (RCTs) using the machine learning tool EPPI-reviewer. We assessed the risk of bias in the included RCTs for research question 1. The primary outcomes were the incidence of surgical site infections in different subgroup analyses. In addition, we investigated the incidence of wound dehiscence. According to our experts, it is unlikely that any potential effect of triclosan in one type of surgery can be extrapolated to others. Therefore, we performed (as described in the NICE report) subgroup analyses of the occurrence of infections categorized by surgical sites and for clean surgeries. Surgeries can be classified into different degrees of contamination. Other subgroup analyses included studies with low, moderate, and high risk of bias, studies with more than 1000 and more than 500 participants, studies conducted in countries with similar levels of antibiotic resistance to Norway, studies funded by companies and non-company-funded studies, as well as studies that exclusively included children. We calculated relative risks (RR) with 95% confidence intervals (CI). We assessed the certainty of the evidence, i.e. the extent to which we have confidence that the effect estimate is close to the true underlying effect, using the GRADE tool. The assessments are graded to high, moderate, low, or very low confidence. For research question 2 regarding chlorhexidine-coated sutures, we included studies with a control group and presented the results from the articles in a table. We did not assess the certainty of the evidence of the studies or perform any analyses. We conducted cost-consequence analyses of triclosan-coated sutures compared to standard sutures for the prevention of surgical site infections. We developed a decision tree model that included the probability of developing a deep or superficial infection, the costs associated with treating the infection, and the relative risk of using triclosancoated sutures versus standard sutures. We performed an analysis of all surgeries in Norway (approximately 413,000 surgical procedures based on figures from the Directorate of Health for 2021), using the effect estimate from the meta-analysis across all studies with different types of surgery (N = 17). We also conducted three subgroup analyses specifically for laparoscopic colon surgery, open colon surgery, and laparoscopic gallbladder removal. For these analyses, we used the effect estimate from the meta-analysis of gastrointestinal/abdominal surgeries (N = 8). A project member, Kristin Hegstad, formulated the chapter and conducted a literature search in PubMed using the keywords a) triclosan, antibiotic, and cross-resistance, b) triclosan, antibiotic, and co-resistance, c) triclosan, antibiotic, and horizontal gene transfer, and d) triclosan, antibiotic, and spread. The review articles identified in these searches were used to find original articles that did not appear in the searches. The main research question was whether the effect of clinically important antimicrobial agents is reduced due to development of resistance when triclosan-coated sutures are used. The sub-questions were: • Is triclosan resistance linked to antibiotic resistance? Describe any known concurrent resistance to triclosan and antibiotics in pathogenic bacteria (diseasecausing bacteria) and environmental bacteria, and their occurrence. • Does the use of triclosan contribute to increased horizontal gene transfer and thus the spread of antibiotic resistance? (The spread of resistance through horizontal gene transfer can occur when bacteria acquire resistance genes from other bacteria that are already resistant to antimicrobial agents). • What concentrations of triclosan are expected locally in the patient, and is this sufficient to affect the development of antibiotic resistance? A project collaborator, Marius Gudbrandsen, formulated this chapter. Risk assessments from the European Chemicals Agency were used as a starting point, with supporting literature searches on specific topics, and the documentation was reviewed to find information on whether the use of triclosan-coated sutures could impact the environment. The questions related to the topic were as follows: • What amounts of triclosan can be expected to be released into the environment if triclosan-coated sutures are used? • Can these amounts contribute to risks of adverse effects in the environment? • Can metabolites of triclosan pose a risk?

Project Status: Completed

URL for project: https://www.fhi.no/en/cristin-projects/ongoing/triclosan-coated-sutures-for-prevention-of-surgical-site-infection---protoc/

Year Published: 2023

URL for published report: https://www.fhi.no/en/publ/2023/Triclosan-coated-sutures-for-prevention-of-surgical-site-infection/

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: Norway

Organisation Name: Norwegian Institute of Public Health

Contact Address: P.O. Box 222 Skoyen, N-0123, Oslo