Test methods antimicrobial efficacy

In 1998, a CEFIC working group composed of industry experts from EPAS (European Producers of Antimicrobial Substances) and EPFP (European Producers of Formulated Preservatives) compiled a listing of over 200 relevant efficacy testing methods and around 100 of these were critically analysed in... 

The purpose of this example is to demonstrate the efficacy of a silver composition of the present invention against the bacteria that cause tuberculosis. This example describes the procedures for evaluation of the present invention for tuberculocidal efficacy. The methodology is based on the Tuberculocidal Activity Test Method as accepted by the EPAon Dec. 11, 1985. [Refer to United States Environmental Protection Agency, 1986. Office of Pesticides and Toxic Substances. Data Call-In Notice for Tubercuolocidal Effectiveness Data for All Antimicrobial Pesticides with Tuberculocidal Claims. (Received Jun. 13, 1986). 

Test methods to demonstrate the efficacy of additives, such as antimicrobial agents, should be used to determine whether such additives remain effective and unchanged throughout the projected shelf-life. 

The purpose of surrogate endpoint test methods within this public health framework is to demonstrate that a product is efficacious in reducing risks of infection or acquisition of disease within a given situation. As such, the methods must address the key performance criteria for the product under conditions that simulate use situation(s). The key performance parameter for topical antimicrobial products is effectiveness against a spectrum of bacteria representative of those encountered in the targeted situations. Depending on the situation and task, speed of action and residual activity may also be key parameters. 

Many antimicrobial efficacy evaluations of topical antimicrobial products involve measurements of microbial population reductions at a specific time point after exposure to the product. To determine this accurately, the antimicrobial action of the product must be stopped at the time specified for sample, and it is for this action that neutralizer systems are employed. The validity of the neutralizer system must be established prior to performing the antimicrobial efficacy test. This concern for neutralizer validity has long been known, and a number of methods have been proposed for validating neutralizer systems [1-5]. Each of the methods focuses on two major concerns (1) the neutralizer system must demonstrably neutralize the antimicrobial properties of the product, and (2) the neutralizer system must be proven nontoxic to the test microorganism(s). Few validation methods apply techniques of statistical analysis to the determination of their validity... 

Topical antimicrobial efficacy tests comprise test methods similar to those outlined in the Food and Drug Administration s Tentative Final Monograph for Healthcare Antiseptic Drug Products time-kill kinetic studies effectiveness testing of a surgical hand scrub effectiveness testing of an antiseptic handwash or... 

In many advanced countries there are legal restrictions on the claims that can be made about antimicrobials, because they are not all completely effective in killing all microorganisms. So expressions like self-sterilising , hygienic and germ-ifee are associated with specific levels of performance and not automatically acceptable just because a biocide is used. As a result, there has been considerable interest in the development of appropriate test methods for measuring antimicrobial efficacy. 

The ZOI test, also widely known as the Kirby-Bauer disk diffusion test, is a fast in vitro but semiquantitative test [169], The original purpose of this test was to replace the MIC test for small molecule antibiotic efficacy [169], Soon, this method was adopted and modified to evaluate antimicrobial efficacy of silver and polymeric devices with eluting antimicrobial agents [170], Conunonly used eluting antimicrobial agents are zinc salt/particles [171-173], silver salt/particles [173-177], and chlorhexi-dine [178,179], These antimicrobial agents can be compounded/blended into polyurethanes or coated/adsorbed on polyurethanes. 

The library of silver-NHC compounds has been greatly expanded due to the contributions of Tacke and coworkers (13a-21) [13-17] and Roland et al. (22a-25b) [18]. Compounds 13a-21 (Figure 6.1), all bearing the acetate ligand, were evaluated for their antimicrobial efficacy against S. aureus and . coli using a qualitative Kirby-Bauer disk-diffusion method. The imidazolium salt precursors, silver acetate, and the vehicle (dimethylsulfoxide) served as controls. The results of the tests were mixed, with a number of compounds having a weak... 

Many articles are treated with antimicrobials to kill or inhibit the growth of bacteria and/or mold. Treated articles are subject to a variety of test methods used to confirm antimicrobial activity. Some of these articles come in contact with the human body and therefore must be tested in order to assess their biocompatibility under conditions of intended use. Determining the efficacy and biocompatibility of these treated articles is crucial. 

There are a number of test methods that can be used to determine antimicrobial efficacy as well as biocompatibility of treated articles. Standards setting organizations such as the American Society for Testing and Materials (ASTM) and American Association of Textile Chemist and Colorist (AATCC) provide standard test methods that can be used to show antimicrobial efficacy of treated articles. There are also other efficacy test methods that fall outside the purview of these two organizations that are very effective. The ISO Technical Committee 194 has developed the ISO 10993 biocompatibility series which address the biological evaluation of medical devices including standards for those treated with antimicrobials. 

Because the halogenated hydantoins are anchored and do not readily release fi ee chlorine, conventional methods for demonstrating antimicrobial efficacy based on the diffusive release of fi ee biocide into the local microenvironment— the so-called zone of microbial inhibition— cannot be applied. Inhibitory zones are minimal under circumstances where the challenge method depends on the slow release of biocides into an area populated by growing organisms, the net effect of which is to kill those which fall within a range of concentrations that is lethal. Retention of Cl on the grafted hydantoin demands that a test method be... 

Preservatives should not usually be included in parenteral formulations except where a multidose product is being developed. The Committee for Proprietary Medicinal Products (CPMP) Notes for Guidance on Inclusion of Antioxidants and Antimicrobial Preservatives in Medicinal Products states that the physical and chemical compatibility of the preservative (or antioxidant) with the other constituents of the formulation, the container and closure must be demonstrated during the development process. The minimum concentration of preservative should be used, which gives the required level of efficacy, as tested using pharmacopoeial methods. Certain preservatives should be avoided under certain circumstances, and preservatives should be avoided entirely for some specialised routes. The guidelines also require that both the concentration and efficacy of the preservative are monitored over the shelf life of the product. In multidose injectable products, the efficacy of the preservative must be established under simulated in-use conditions. Table 9.2 shows some of the most commonly encountered preservatives in licensed products and their typical concentrations. 

---