Antimicrobial Efficacies

Caution must be excercised when selecting an antimicrobial agent for clinical use on the basis of tissue or fluid penetration. Body fluids where drug concentration data are clinically relevant include CSF, urine, synovial fluid, and peritoneal fluid. Apart from these areas, more attention should be paid to clinical efficacy, antimicrobial spectrum, toxicity, and cost than to comparative data on penetration into a given body site. 

Abstract Infectious diseases cause severe problems in the aquaculture industry, with viral diseases being responsible for the greatest losses in production. Disease prevention strategies still have some limitations in terms of safety and efficacy. Antimicrobial peptides (AMPs) are molecules of the innate immune system, one of the first lines of defense against pathogens. Usually they not only exhibit antimicrobial activity, but also modulate the immune response. This review focuses on fish AMPs and their antiviral and immunoregulatory activities in order to assess their potential relevance to aquaculture. Since fish depend on their innate immune defenses more than mammals, they could be an alternative source of novel antiviral compounds. 

Cooling water pH affects oxidizing antimicrobial efficacy. The pH determines the relative proportions of hypochlorous acid and hypochlorite ion or, in systems treated with bromine donors, hypobromous acid and hypobromite ion. The acid forms of the halogens are usually more effective antimicrobials than the dissociated forms. Under some conditions, hypochlorous acid is 80 times more effective in controlling bacteria than the hypochlorite ion. Hypochlorous acid predominates below a pH of 7.6. Hypobromous acid predominates below pH 8.7, making bromine donors more effective than chlorine donors in alkaline cooling waters, especially where contact time is limited. 

Antimicrobial efficacy is also affected by demand in the cooling water system, specifically demand exerted by ammonia. Chlorine reacts with ammonia to form chloramines, which are not as efficacious as hypochlorous acid or the hypochlorite ion in microbiological control. Bromine reacts with ammonia to form bromamines. Unlike chloramines, bromamines are unstable and reform hypobromous acid. 

Benzoyl peroxide exercises a potent antimicrobial activity through the release of free oxygen radicals. It suppresses P. acnes in sebaceous follicles much faster than antibiotics, leading to a rapid reduction of the inflammatory lesions number. P. acnes does not develop resistance to benzoyl peroxide, which maintains its efficacy after years of use. Benzoyl peroxide seems to have a mild comedolytic effect while it is not... 

The efficacy of an antimicrobial agent must be investigated by appropriate capacity, challenge and in-use tests to ensure that a standard is obtained which is appropriate to the intended use (Chapter 11). In practice, it is not usually possible to know which organisms are present on the articles being treated. Thus, it is necessary to categorize chemicals according to their antimicrobial capabilities and for the user to have an awareness of what level of antimicrobial action is required in a particular situation (Table 10.1). 

British Pharmacopoeia (1993) Appendix KV C Efficacy of Antimicrobial Preservation, A191-A192, (and BP 1993, 1995 Addendum Appendix XVIIF, A407). London HMSO. (3.2)... 

Monitor for therapeutic response by assessing efficacy and toxicity of the antimicrobial regimen. 

Components of a monitoring plan to assess the efficacy and safety of antimicrobial therapy of CNS infections include clinical signs and symptoms and laboratory data (such as CSF findings, culture, and sensitivity data). 

Monitor chosen antimicrobial therapy for safety and efficacy. ... 

Every patient receiving antimicrobial therapy for skin and soft tissue infections must be monitored for efficacy and safety. Efficacy typically is manifested by reductions in temperature, white blood cell count, erythema, edema, and pain that begin within 48 to 72 hours. To ensure safety, dose antibiotics according to renal and hepatic function as appropriate, and monitor for and minimize adverse drug reactions, allergic reactions, and drug interactions. 

Recommend parameters to monitor antimicrobial therapy for efficacy and toxicity. 

In the CIT/MIT blend the chlorinated species has by far the greater biocidal efficacy but is also the less stable of the two components. Although MIT alone has relatively low antimicrobial performance it has recently been discovered that this compound has truly synergistic activity when combined with BIT and such a blend has several advantages over CIT/MIT products. 

K Peters, S Leitzke, SE Diederichs, K Borner, H Hahn, RE Muller, S Ehlers. Preparation of a clofazimine nanosuspension for intravenous use and evaluation of its therapeutic efficacy in murine Mycobacterium avium infection. J Antimicrobial Chemother 45(l) 77-83,2000. 

The choice of the excipients and their concentration, including their function (e.g., antimicrobial preservatives, antioxidants. ..). In the case of antimicrobial preservatives, data are expected on the preservative efficacy in products on storage, including after reconstitution or dilution and during the period of use. 

Where a large pack size is provided, it might be necessary to undertake more extensive in-use testing and/ or to restrict the in-use shelf life once the container has been opened. In addition to preservative efficacy testing the chemical stability of antimicrobial preservatives should also be investigated over the unopened and in-use shelf lives of the product. 

Where antioxidants or antimicrobial preservatives are used, the finished product release specification will need to include identification tests and assays for these two types of excipient. The shelf life specification should also include a specification for assay for antimicrobial preservatives. Stability data will be required for both antioxidants and antimicrobial preservatives in the finished product, and in addition the preservative efficacy of the formulated product should be examined over its shelf life and by means of appropriate in-use stability tests. Preservative efficacy data should also be presented at the lower limit of the preservative assay. 

Aqueous products that are at greatest risk from microbial spoilage include solutions, suspensions, and emulsions for repeated oral, parenteral, or external use and include critical products such as multidose injections and eye drops. Unpreserved products without adequate antimicrobial efficacy should not be presented in containers intended for use on more than one occasion unless justified. When antimicrobial preservatives are used, their efficacy has to be demonstrated using the Ph Eur test for antimicrobial preservative efficacy. Factors to be taken into account in designing a preserved product include the nature of the preservative, its concentration in the product, the... 

The availability of unpreserved and preserved dosage forms is considered. Mention is made of formulation changes necessitated by multidose products. The need for adequate antimicrobial preservative efficacy can be discussed if this was an issue during product development. 

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