The Widely Used Antimicrobial Triclosan Induces High Levels of Antibiotic Tolerance In Vitro and Reduces Antibiotic Efficacy up to 100-Fold In Vivo.

The antimicrobial triclosan is used in a wide range of consumer products ranging from toothpaste, cleansers, socks, and baby toys. A bacteriostatic inhibitor of fatty acid synthesis, triclosan is extremely stable and accumulates in the environment. Approximately 75% of adults in the United States have detectable levels of the compound in their urine, with a sizeable fraction of individuals (>10%) having urine concentrations equal to or greater than the minimal inhibitory concentration for Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Previous work has identified connections between defects in fatty acid synthesis and accumulation of the alarmone guanosine tetraphosphate (ppGpp), which has been repeatedly associated with antibiotic tolerance and persistence. Based on these data, we hypothesized that triclosan exposure may inadvertently drive bacteria into a state in which they are able to tolerate normally lethal concentrations of antibiotics. Here we report that clinically relevant concentrations of triclosan increased E. coli and MRSA tolerance to bactericidal antibiotics as much as 10,000-fold in vitro and reduced antibiotic efficacy up to 100-fold in a mouse urinary tract infection model. Genetic analysis indicated that triclosan-mediated antibiotic tolerance requires ppGpp synthesis but is independent of growth. These data highlight an unexpected and certainly unintended consequence of adding high concentrations of antimicrobials in consumer products, supporting an urgent need to reevaluate the costs and benefits of the prophylactic use of triclosan and other bacteriostatic compounds.

Comparison of methods for calculating the health costs of endocrine disrupters: a case study on triclosan.

BACKGROUND: Socioeconomic analysis is currently used in the Europe Union as part of the regulatory process in Regulation Registration, Evaluation and Authorisation of Chemicals (REACH), with the aim of assessing and managing risks from dangerous chemicals. The political impact of the socio-economic analysis is potentially high in the authorisation and restriction procedures, however, current socio-economic analysis dossiers submitted under REACH are very heterogeneous in terms of methodology used and quality. Furthermore, the economic literature is not very helpful for regulatory purposes, as most published calculations of health costs associated with chemical exposures use epidemiological studies as input data, but such studies are rarely available for most substances. The quasi-totality of the data used in the REACH dossiers comes from toxicological studies. METHODS: This paper assesses the use of the integrated probabilistic risk assessment, based on toxicological data, for the calculation of health costs associated with endocrine disrupting effects of triclosan. The results are compared with those obtained using the population attributable fraction, based on epidemiological data. RESULTS: The results based on the integrated probabilistic risk assessment indicated that 4894 men could have reproductive deficits based on the decreased vas deferens weights observed in rats, 0 cases of changed T3 levels, and 0 cases of girls with early pubertal development. The results obtained with the Population Attributable Fraction method showed 7,199,228 cases of obesity per year, 281,923 girls per year with early pubertal development and 88,957 to 303,759 cases per year with increased total T3 hormone levels. The economic costs associated with increased BMI due to TCS exposure could be calculated. Direct health costs were estimated at €5.8 billion per year. CONCLUSIONS: The two methods give very different results for the same effects. The choice of a toxicological-based or an epidemiological-based method in the socio-economic analysis will therefore significantly impact the estimated health costs and consequently the political risk management decision. Additional work should be done for understanding the reasons of these significant differences.

The effect of triclosan coated sutures on rate of surgical site infection after hip and knee replacement: a protocol for a double-blind randomised controlled trial.

BACKGROUND: 187,000 hip and knee joint replacements are performed every year in the National Health Service (NHS). One of the commonest complications is surgical site infection (SSI), and this represents a significant burden in terms of patient morbidity, mortality and cost to health services around the world. The aim of this randomised controlled trial (RCT) is to determine if the addition of triclosan coated sutures to a standard regimen can reduce the rate of SSI after total knee replacement (TKR) and total hip replacement (THR). METHODS: 2400 patients due to undergo a total hip or knee replacement are being recruited into this two-centre RCT. Participants are recruited before surgery and randomised to either standard care or intervention group. Participants, outcome assessors and statistician are blind to treatment allocation throughout the study. The intervention consists of triclosan coated sutures vs. standard non-coated sutures. The primary outcome is the Health protection Agency (HPA) defined superficial surgical site infection at 30 days. Secondary outcomes include HPA defined deep surgical site infection at 12 months, length of hospital stay, critical care stay, and payer costs. DISCUSSION: To date there are no orthopaedic randomised controlled trials on this scale assessing the effectiveness of a surgical intervention, particularly those that can be translated across the surgical specialities. The results from this trial will inform evidence-based recommendations for suture selection in the management of patients undergoing total hip or knee replacement. If triclosan coated sutures are found to be an effective intervention, implementation into clinical practice could improve long-term outcomes for patients undergoing hip and knee replacement. TRIAL REGISTRATION: Current Controlled Trials ISRCTN 17807356.

An economic model: value of antimicrobial-coated sutures to society, hospitals, and third-party payers in preventing abdominal surgical site infections.

BACKGROUND: While the persistence of high surgical site infection (SSI) rates has prompted the advent of more expensive sutures that are coated with antimicrobial agents to prevent SSIs, the economic value of such sutures has yet to be determined. METHODS: Using TreeAge Pro, we developed a decision analytic model to determine the cost-effectiveness of using antimicrobial sutures in abdominal incisions from the hospital, third-party payer, and societal perspectives. Sensitivity analyses systematically varied the risk of developing an SSI (range, 5%-20%), the cost of triclosan-coated sutures (range, $5-$25/inch), and triclosan-coated suture efficacy in preventing infection (range, 5%-50%) to highlight the range of costs associated with using such sutures. RESULTS: Triclosan-coated sutures saved $4,109-$13,975 (hospital perspective), $4,133-$14,297 (third-party payer perspective), and $40,127-$53,244 (societal perspective) per SSI prevented, when a surgery had a 15% SSI risk, depending on their efficacy. If the SSI risk was no more than 5% and the efficacy in preventing SSIs was no more than 10%, triclosan-coated sutures resulted in extra expenditure for hospitals and third-party payers (resulting in extra costs of $1,626 and $1,071 per SSI prevented for hospitals and third-party payers, respectively; SSI risk, 5%; efficacy, 10%). CONCLUSIONS: Our results suggest that switching to triclosan-coated sutures from the uncoated sutures can both prevent SSIs and save substantial costs for hospitals, third-party payers, and society, as long as efficacy in preventing SSIs is at least 10% and SSI risk is at least 10%.

Triclosan-coated sutures reduce the incidence of wound infections and the costs after colorectal surgery: a randomized controlled trial.

BACKGROUND: In colorectal surgeries, surgical site infections (SSIs) frequently cause morbidity; an incidence of up to 20% has been shown in previous studies. Recently, to prevent microbial colonization of suture material in operative wounds, triclosan-coated polyglactin suture materials with antimicrobial activity have been developed; however, their significance in colorectal surgery remains unclear. This randomized controlled trial was conducted to assess the value of triclosan-coated polyglactin sutures in colorectal surgery. METHODS: A total of 410 consecutive patients who had undergone elective colorectal operations were enrolled in this trial. Of those patients, the 206 in the study group underwent wound closure with triclosan-coated polyglactin 910 antimicrobial sutures, and the 204 patients in the control group received conventional wound closures with polyglactin 910 sutures. RESULTS: The study group and the control group were comparable regarding risk factors for SSIs. The incidence of wound infection in the study group was 9 of 206 patients (4.3%), and that in the control group was 19 of 204 patients (9.3%). The difference is statistically significant in the 2 groups (P = .047). The median additional cost of wound infection management was $2,310. The actual entire additional cost, therefore, of 9 patients in the study group was $18,370, and that of 19 patients in the control group was $60,814. CONCLUSION: Triclosan-coated sutures can reduce the incidence of wound infections and the costs in colorectal surgery.