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115103-85-0 Sequence between the fabI alleles of Staphylococci is in the order of 82?4 (published sequences at NCBI) and we expect that our hybridization probe used in the mRNA expression assay would bind equally well to the fabI alleles of S. epidermidis and eg S. haemolyticus. Therefore yet other mechanisms seem to be involved. One isolate had a predicted change at amino acid residue 204. An alteration of fabI in this position is well known from clinical as well as in vitro triclosan selected mutants of S. aureus with triclosan tolerance [24,26]. The mutation has been shown, in S. aureus fabI, to correlate with elevated triclosan MIC through the formation of a stable triclosan 2NAD+2FabI complex not seen in the wildtype fabI [24]. The amino acid residue at position 95 has, just as that at position 204, been thought to lie in the cofactor binding region of S. aureus fabI [27]. It is interesting though that the most frequently in vitro selected mutation, A95V, that is also identified as the mutation with the greatest impact on inhibition of S. aureus fabI [27] has never, as far as we are aware, been detected in clinical staphylococci isolates. An explanation could be that this mutation has a relatively larger fitness cost than the other mutations. As other in situ studies [7?0] we did not find a significant correlation between triclosan tolerant isolates and antibiotic resistance in staphylococci. Only the previous discussed study [16] has found such an association, where triclosan tolerance was associated to 1662274 methicillin resistance in S. epidermidis. Importantly we did not see increased antibiotic resistance in our laboratory adapted isolates either. It seems at least that in S. epidermidis there is no crossresistance to antibiotics but the possibility of co-selection in vivo with for example methicillin and maybe other, not yet identified traits is still not fully elucidated. We believe, based on others and our findings, that the targeted use of triclosan is safe in regard to development of antibiotic cross-resistance and in working 23727046 concentrations should be effective against S. epidermidis. A claim has been made for using triclosan in medical devices such as sutures with the aim to lower rates of nosocomial infections. Recently a multicenter,prospective, double-blinded, parallel group study was conducted in Finland [41] comparing triclosan-coated suture material with noncoated sutures in the control group. Among the 276 patients undergoing lower limb revascularization surgery, similar surgical wound infection rates of 21.9 to 22.3 were found. The widespread (and often Ergocalciferol web unregulated) use of triclosan in textiles, chopping boards and in antibacterial soaps in the domestic setting might need to be reconsidered. Aiello et al. [42] reviewed the literature on commonly used soaps containing triclosan in the community setting. In working concentrations 0.1 ?.45 wt/vol (1000?500 mg/l) triclosan containing soaps were no more effective than plain soap in preventing infectious illness symptoms and reducing bacterial levels on the hands. Finally, taking the environmental concerns about aquatic organisms and toxic by-products into consideration together with the still not fully understood consequences of an increased tolerance in some bacterial species, we think the use of triclosan should be more regulated and restricted for purposes that have been proven beneficial.Supporting InformationTable S1 Multilocus sequence typing (MLST) was performed for 15 S. epide.Sequence between the fabI alleles of Staphylococci is in the order of 82?4 (published sequences at NCBI) and we expect that our hybridization probe used in the mRNA expression assay would bind equally well to the fabI alleles of S. epidermidis and eg S. haemolyticus. Therefore yet other mechanisms seem to be involved. One isolate had a predicted change at amino acid residue 204. An alteration of fabI in this position is well known from clinical as well as in vitro triclosan selected mutants of S. aureus with triclosan tolerance [24,26]. The mutation has been shown, in S. aureus fabI, to correlate with elevated triclosan MIC through the formation of a stable triclosan 2NAD+2FabI complex not seen in the wildtype fabI [24]. The amino acid residue at position 95 has, just as that at position 204, been thought to lie in the cofactor binding region of S. aureus fabI [27]. It is interesting though that the most frequently in vitro selected mutation, A95V, that is also identified as the mutation with the greatest impact on inhibition of S. aureus fabI [27] has never, as far as we are aware, been detected in clinical staphylococci isolates. An explanation could be that this mutation has a relatively larger fitness cost than the other mutations. As other in situ studies [7?0] we did not find a significant correlation between triclosan tolerant isolates and antibiotic resistance in staphylococci. Only the previous discussed study [16] has found such an association, where triclosan tolerance was associated to 1662274 methicillin resistance in S. epidermidis. Importantly we did not see increased antibiotic resistance in our laboratory adapted isolates either. It seems at least that in S. epidermidis there is no crossresistance to antibiotics but the possibility of co-selection in vivo with for example methicillin and maybe other, not yet identified traits is still not fully elucidated. We believe, based on others and our findings, that the targeted use of triclosan is safe in regard to development of antibiotic cross-resistance and in working 23727046 concentrations should be effective against S. epidermidis. A claim has been made for using triclosan in medical devices such as sutures with the aim to lower rates of nosocomial infections. Recently a multicenter,prospective, double-blinded, parallel group study was conducted in Finland [41] comparing triclosan-coated suture material with noncoated sutures in the control group. Among the 276 patients undergoing lower limb revascularization surgery, similar surgical wound infection rates of 21.9 to 22.3 were found. The widespread (and often unregulated) use of triclosan in textiles, chopping boards and in antibacterial soaps in the domestic setting might need to be reconsidered. Aiello et al. [42] reviewed the literature on commonly used soaps containing triclosan in the community setting. In working concentrations 0.1 ?.45 wt/vol (1000?500 mg/l) triclosan containing soaps were no more effective than plain soap in preventing infectious illness symptoms and reducing bacterial levels on the hands. Finally, taking the environmental concerns about aquatic organisms and toxic by-products into consideration together with the still not fully understood consequences of an increased tolerance in some bacterial species, we think the use of triclosan should be more regulated and restricted for purposes that have been proven beneficial.Supporting InformationTable S1 Multilocus sequence typing (MLST) was performed for 15 S. epide.

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