JAC Advance Access originally published online on May 4, 2007
Journal of Antimicrobial Chemotherapy 2007 60(1):176-177; doi:10.1093/jac/dkm132
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Correspondence |
Triclosan resistance in methicillin-resistant Staphylococcus aureus expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics—authors' response
Biomaterials-Related Infection Group, Division of Orthopaedic and Accident Surgery, School of Medical and Surgical Sciences, C Floor West Block, Queens Medical Centre, University Hospitals Nottingham, Nottingham NG7 2UH, UK
* Corresponding author. Tel: +44-115-82-31115; Fax: +44-115-82-31118; E-mail: roger.bayston{at}nottingham.ac.uk
Keywords: SCVs , S. aureus , MRSA , antimicrobial biomaterials
We welcome the opportunity to reply to the comments by Seaman et al.1 on our recent article.2 First, they say that we recognize, ‘as others have done, ... the potential role of triclosan in [small colony variant (SCV)] generation’. In fact, apart from the parallel publication by Seaman et al.,3 we know of no other which points out the association between triclosan exposure and SCV generation.
Secondly, Seaman et al. state that SCVs are unlikely to initiate infections. Several studies have found persisting serious infections from which only SCVs have been isolated.4,5 Of course, these could be the result of antimicrobial chemotherapy as Seaman et al. recognize, but SCVs have also been found in chronic infection without antibiotic exposure and they can be induced experimentally by the intracellular milieu alone. In addition, there is some evidence that Staphylococcus aureus SCVs are at least as virulent as their wild-types6,7 and have successfully initiated infections in animal models.7–9 This assertion by Seaman et al. is therefore unfounded. Similarly, they state that as the SCVs would be on the skin surface, it is questionable whether they would be able to initiate an infection in healthy individuals. Even healthy people undergo surgery, and most surgical site infection is caused by staphylococci from the skin. Their comments regarding skin to skin transmission being prevented by alcohol hand washes and gloves fail to recognize that, although these are important, they are not perfect.
We agree with their comment that triclosan-impregnated polymers such as those used in sutures might constitute a risk of SCV generation; indeed, this was the implication of our paper. A range of items impregnated with triclosan are available, and several authors have pointed this out in recent papers.3,10,11
Seaman et al. ask what the triclosan concentration in the discs was. This was 0.3% (w/w), but the most important concentration in respect of attached bacteria is that in the Nernst layer, and this cannot be measured directly. Seaman et al. studied their SCVs in the planktonic mode, in which very different physiological conditions apply. This could account for some of the differences between the two sets of SCVs, such as susceptibility to gentamicin, although considerable variation within SCVs is widely accepted. Our isolates were identified phenotypically (API) as S. aureus and shown to be indistinguishable from the wild-type by PFGE. Furthermore, they were generated anew on several separate exposures. As experienced clinical microbiologists we are very familiar with microbial identification and the possibility of contamination, and we can assure Seaman et al. that we were not reporting contaminants. The mechanism of triclosan resistance in SCVs was not the subject of our paper, but the suggestion that triclosan might have multiple targets is controversial and either mutation or multicopy of FabI or overexpression of efflux pumps is generally accepted as the cause.
Although triclosan is important in infection control, we consider that exposure to the antiseptic in the way described in our paper is clinically relevant, and reporting the generation of SCVs in this way is not ‘a danger of too much speculation’ as Seaman et al. suggest.
None of the authors has received financial or other support in connection with this research. All are employed by the University of Nottingham and/or the National Health Service, UK.
References
1 Seaman PF, Ochs D, Day MJ. Comment on: Triclosan resistance in methicillin-resistant Staphylococcus aureus expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics. J Antimicrob Chemother (2007) doi:10.1093/jac/dkm118.
2
Bayston R, Ashraf W, Smith T. Triclosan resistance in methicillin-resistant Staphylococcus aureus expressed as small colony variants: a novel mode of evasion of susceptibility to antiseptics. J Antimicrob Chemother (2007) 59:848–53.
3
Seaman PF, Ochs D, Day MJ. Small-colony variants: a novel mechanism for triclosan resistance in methicillin-resistant Staphylococcus aureus. J Antimicrob Chemother (2007) 59:43–50.
4 Spanu T, Romano L, D'Inzeo T, et al. Recurrent ventriculoperitoneal shunt infection caused by small-colony variants of Staphylococcus aureus. Clin Infect Dis (2005) 41:48–52.[CrossRef]
5 Seifert H, Wisplinghoff H, Schnabel P, et al. Small colony variants of Staphylococcus aureus and pacemaker infection. Emerg Infect Dis (2003) 9:1316–8.[Web of Science][Medline]
6
Vaudaux P, Francois P, Bisognano CM, et al. Increased expression of clumping factor and fibronectin-binding proteins by hemB mutants of Staphylococcus aureus expressing small colony variant phenotypes. Infect Immun (2002) 70:5428–37.
7 Jonsson I-M, von Eiff C, Proctor RA, et al. Virulence of hemB mutant displaying the phenotype of Staphylococcus aureus small colony variant in a murine model of septic arthritis. Microb Pathog (2003) 34:73–9.[CrossRef][Web of Science][Medline]
8 Bates DM, von Eiff C, McNamara PJ, et al. Staphylococcus aureus menD and hemB mutants are as infective as the parent strains, but the menadione biosynthetic mutant persists within the kidney. J Infect Dis (2003) 187:1654–61.[CrossRef][Web of Science][Medline]
9
Musher DM, Baughn RE, Young EJ. Two forms of Staphylococcus aureus in blood of patients with staphylococcal sepsis. J Clin Microbiol (1979) 9:23–7.
10 Levy SB. Antibacterial household products: cause for concern. Emerg Infect Dis (2001) 7:512–5.[Web of Science][Medline]
11 Edmiston CE, Seabrook GR, Goheen MP, et al. Bacterial adherence to surgical sutures: can antibacterial-coated sutures reduce the risk of microbial contamination? J Am Coll Surg (2006) 203:481–9.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  B. T. Tsuji, C. von Eiff, P. A. Kelchlin, A. Forrest, and P. F. Smith Attenuated Vancomycin Bactericidal Activity against Staphylococcus aureus hemB Mutants Expressing the Small-Colony-Variant Phenotype Antimicrob. Agents Chemother., April 1, 2008; 52(4): 1533 - 1537. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||