Biocides (antiseptics, disinfectants, preservatives, and sterilants) are critical components of intervention strategies used in clinical medicine for preventing the dissemination of nosocomial diseases. Biocides are also used in community environments for personal hygiene and to prevent cross-contamination with foodborne pathogens. In vitro studies suggest that exposure to biocides results in reduced susceptibility to antibiotics and biocides by intrinsic or acquired mechanisms of resistance. In addition, microorganisms have adapted to biocide exposure by acquiring plasmids and transposons that confer biocide resistance, the same survival strategies to disseminate acquired mechanisms of resistance to biocides as they have for resistance to antibiotics. The scientific community must weigh the risks and benefits of using biocides in clinical and community environments, to determine whether additional precautions are needed to guide biocide development and use. At present, insufficient scientific evidence exists to weigh these risks, and additional research is needed to allow appropriate characterization of risks in clinical and community environments.
N-nitrosodimethylamine (DMN) is not mutagenic in the standard Salmonella plate incorporation assay (Ames test) in the presence of an in vitro metabolic activation system (S-9) derived from rat liver. When the S-9 was derived from Aroclor- or phenobarbital-induced mouse or hamster liver or from uninduced hamster liver, mutagenic activity was observed. Increasing the amount of S-9 above the usual maximum level of 50 microliter per plate increased the mutagenic response. Similarly, the mutagenicity of N-nitrosodiethylamine (DEN) and N-nitrosodi(n-butyl)amine (DBN) was greater in the presence of hamster liver S-9 than when mouse or rat liver was used. Data are also presented indicating that the ability of rat liver S-9 to mediate the mutagenic activity of DMN in the "preincubation" assay is due to the fact that the various components are present in this assay at several times the concentrations attained in the standard plate incorporation assay.
The evolutionary response of bacteria, fungi, viruses, and parasites to the selective pressure exerted by antimicrobial agents is the emergence of populations that resist the action of the antimicrobial. The emergence and dissemination of such resistance in a variety of these pathogens is a growing public health concern. In response, the scientific community developed an action plan to address this public health issue. Antimicrobial, antifungal, and antiviral drug development for the treatment of diseases caused by resistant pathogens is one component of this strategy. In addition, due to the targeting of specific drugs against resistant pathogens, we may more readily accept a given drugs toxicity profile for the added therapeutic benefit. This symposium provides a discussion of the modes of action and mechanisms of resistance to antimicrobial agents, and the use of surveillance systems to help understand the nature and magnitude of resistance. The goal is to help guide antimicrobial drug product development and use. Specific toxicity issues are presented that should be considered in phase 1 development of antimicrobial drug products for use in clinical medicine and veterinary medicine. Finally, the national and global strategies developed by federal agencies in the Public Health Action Plan to Combat Antimicrobial Resistance are outlined.
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