Antimicrobials multiple

Single-dose preparations intended for use in eye surgery do not contain excipient ingredients, in order to avoid tissue irritation. However, multiple-dose containers may require antioxidants (qv), antimicrobial preservatives, or buffers to maintain stabiHty and stefiHty. Such solutions are packaged in polyethylene flexible dropper units called droptainers or in glass dropper botdes. 

Russell D, Bakhtyari A, Jazrawi RP, Whitlock L, Ridgway C, McHale M, Abel S (2003) Multiple dose study to investigate the safety of UK-427,857 (100 mg or 300mg) BID for 28 days in healthy males and females. In 43rd interscience conference on antimicrobial agents and chemotherapy, Chicago, IL, USA... 

Large-volume parenterals (LVPs) and small-volume parenterals (SVPs) containing no antimicrobial agent should be terminally sterilized. It is common practice to include an antimicrobial agent in SVPs that cannot be terminally sterilized or are intended for multiple-dose use. The general exceptions are products that pass the USP Antimicrobial Preservative Effectiveness Test [1] because of the antimicrobial activity of the active... 

The purpose of in-use stability studies is to establish the period for which a product intended to be used on more than one occasion may be used after reconstitution or dilution or the withdrawal of the first dose from the container without adversely affecting the integrity of the product and with the product retaining acceptable quality characteristics. This type of test can be applied to any multiple use product (e.g., sterile products in multiple-use containers, powders or granules including those used to produce oral solutions or suspensions) but is likely to be of particular importance in the case of products that are manufactured with an inert headspace gas, for products containing antioxidants to protect an active ingredient that is liable to oxidative decomposition, and for products that contain a volatile antimicrobial preservative. 

To select rational antimicrobial therapy for a given infection, a variety of factors must be considered, including the severity and acuity of the disease, host factors, factors related to the drugs used, and the necessity for use of multiple agents. 

Increasing the coverage of antimicrobial therapy is generally necessary in mixed infections where multiple organisms are likely to be present, such as intraabdominal and female pelvic infections in which a variety of aerobic and anaerobic bacteria may produce disease. Another clinical situation in which increased spectrum of activity is desirable is with nosocomial infection. 

The effectiveness of various PS proposed for antimicrobial PDT can be judged on several criteria. These PS should be able to kill multiple classes of microbes at relatively low concentrations and low fluences of hght. PS should be reasonably nontoxic in the dark and should demonstrate selectivity for microbial cells over mammalian cells. PS should ideally have large extinction coefficients in the red part of the spectrum and demonstrate high triplet and singlet oxygen quantum yields. 

In contrast, Snyder has demonstrated that an RI derivative ofp53 can restore endogenous p53 activity the RI derivative induced apoptosis by activation of endogenous p53 and by restoration of function to several p53 DNA contact mutants. Rl-modified peptides have also been investigated as potential alternatives for bost defense peptides. Indeed, a RI derivative of indolicidin retained tbe antimicrobial and antiendotoxic acitivities of the natural peptide. As the antiendotoxin activities of the Rl-derivative were conserved these results might indicate the conservation of multiple immunomodulatory activities upon retro-inversion, highlighting the potential of this modification for therapeutic applications. 

Although it has become obvious that a fluorine atom in position 6 is the best substituent for antimicrobial activity, the reasons for this effect remain unclear. A comparative study of numerous quinolones seems to indicate that this F-substitution in position 6 affords both a better affinity with gyrase (2-17 times) and the best cell penetration (1-70 times).The presence of this fluorine lowers the basicity of the nitrogen-containing substituent in position 7, and this fact could play a role. However, there are multiple factors to take into account and interpretations must be carefully considered. Thus, replacing the fluorine atom by a chlorine in pefloxacin does not affect the activity on the enzyme, but a decrease of the bacterial activity is observed. This shows the importance of the pharmacokinetic factors. ... 

Mecfianism of Action A cyclic polypeptide antimicrobial but the mechanism of action is not well understood. Therapeutic Effect Suppresses mycobacterial multiplication. Pharmacokinetics Not well absorbed from the GI tract. Undergoes little metabolism. Primarily excreted unchanged in urine. Haif-iife 4-6 hr (half-life is increased with impaired renal function). 

In this chapter, it is emphasized that antimicrobial preservatives should not be used as a substitute to GMPs or solely to reduce the viable microbial population of a nonsterile product. It is recommended that antimicrobial effectiveness of preservatives must be demonstrated for dosage forms such as multiple-dose topical and... 

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