Antiseptics and Antibiotic Resistance
Antiseptics and Antibiotic Resistance
abstract & commentary
Synopsis: The commonly used antiseptic, triclosan, may select for antibiotic resistance in P aeruginosa.
Source: Chuanchuen R, et al. Antimicrob Agents Chemother. 2001;45:428-432.
Chuanchuen and colleagues, using a series of defined Pseudomonas aeruginosa mutants, evaluated the possibility that triclosan, a widely used antiseptic, may select for resistance to clinically useful antibiotics. A major mechanism of antibiotic resistance in this organism is the result of overexpression of efflux pumps. In vitro studies demonstrated that triclosan was a substrate for all 3 tripartite efflux pumps studied—MexAB-OprM, MexCD-OprJ, and MexEF-OprN. Triclosan resistance, which was selected at a frequency of 10-6, was associated with a multidrug resistant phenotype and with a 94-fold increase in ciprofloxacin MIC. This resistance was associated with overexpression of the MexCD-OprJ efflux system resulting from a mutation in the nfxB regulatory gene.
Comment by Stan Deresinski, MD, FACP
Triclosan is a 2-hydroxyphenylether antiseptic that is present in a wide variety of lotions, hand soaps, oral rinses, and toothpastes. It has even been incorporated into plastics and fabrics. Triclosan is more effective than chlorhexidine in reducing MRSA hand colonization, although the latter is more effective with regard to Gram-negative colonization.1 The antibacterial activity of triclosan is the consequence of inhibition of a key enzyme in bacterial fatty acid synthesis, enoyl-acyl carrier protein (ACP) reductase (FabI). Resistance to triclosan has been associated with mutations in the gene encoding this enzyme.
Among the homologs of FabI normally susceptible to inhibition by triclosan is the enoyl-ACP reductase of Plasmodium falciparum, as well as mycobacterial InhA.2 Mutations affecting this latter enzyme are associated with resistance to isoniazid in mycobacterial species.3 This and other observations raised the possibility that triclosan may select for bacteria resistant to clinically useful antibiotics, a concern that was amplified by the finding that triclosan is a substrate of E coli multidrug efflux pumps.
Four multidrug resistance efflux systems (MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY) have been characterized in P aeruginosa, and these account for most intrinsic antibiotic resistance in this organism. Chuanchuen et al have now demonstrated that triclosan is a substrate for at least 3 P aeruginosa efflux pumps and that triclosan resistance associated with overexpression of the MexCD-OprJ efflux system is selected in vitro at the very high rate of 10-6. These triclosan-selected strains exhibit a multidrug resistant phenotype, including a 94-fold increase in MIC to ciprofloxacin. Overexpression of this efflux system was also associated with mutations in the nfxB regulatory gene.
In addition to its use in hospitals, triclosan has been incorporated into innumerable household and personal hygiene products. This has raised concern that the widespread use of this and other antiseptics in everyday life may lead to acceleration of the development of resistance to clinically useful antibiotics. As an example, Chlorhexidine resistance in S aureus has been reported to be related to selection of staphylococci containing qacA genes, which encodes an efflux system, in multiresistance plasmids.4
Chuanchuen et al have demonstrated that antibiotic resistance may occur as the result of exposure to an antiseptic. This finding has real and urgent public health and policy implications.
References
1. Faoagali JL, et al. Am J Infect Control. 1999;27: 320-326.
2. Surolia N, Surolia A. Nat Med. 2001;7:167-173.
3. Parikh SL, et al. Biochemistry. 2000;39:7645-7650.
4. Russell AD. J Pharm Pharmacol. 2000;52:167-173.
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