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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 wide spread 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 encode 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.
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.
Source: D’Agata EMC, Wise S, Stewart A. Nosocomial transmission of Mycobacterium tuberculosis from an extrapulmonary site. Infect Control Hosp Epidemiol 2001; 22:10-12.
In a cautionary tale that shows how insidiously tuberculosis can spread from an undiagnosed patient, the authors report TB infection in 12 health care workers.
Their findings suggest there was minimal, if any, aerosolization of tubercle bacilli from the patient’s lungs. Instead, transmission of TB occurred through aerosolization of tubercle bacilli from manipulation of the genitourinary wounds. The study underscores the extent of transmission among health care workers as a result of unrecognized genitourinary tract TB, the second most common site of extrapulmonary TB after lymphadenitis. As a result of the case, the authors recommend airborne precautions for patients with open wounds of the genitourinary tract in whom bacterial cultures are negative, until a TB diagnosis has been excluded.
The case occurred in Tennessee, where a patient was admitted for drainage of a prostatic abscess and a bilateral orchiectomy. He died after 27 days of hospitalization, and disseminated TB was then diagnosed at autopsy.
There was no evidence of active pulmonary tuberculosis throughout the patient’s hospitalization. TB skin test conversions occurred only among workers who were exposed to the patient during or after his surgical procedures. A total of 12 (13%)
of 95 exposed health care workers who were previously nonreactive had newly positive tests.
The workers were all treated and cleared of infection. By logistic regression, irrigation or packing of the surgical site was the only independent risk factor associated with TB conversion among nurses. Manipulation of infected tissues of the genitourinary tract can result in nosocomial transmission of tuberculosis, the authors concluded.
Although the patient had microscopic evidence of pulmonary TB at autopsy, several factors argue against airborne transmission of TB from the respiratory tract. A chest radiograph on admission revealed no abnormalities, and there were no TB conversions among the 23 workers exposed to the patient prior to surgery.