Another research group is taking a radically different approach to drug design. Since most bacteria enter humans at a mucous membrane site, such as the upper and lower respiratory tract or the intestines, these locations act as reservoirs for many pathogens. However, there currently are no drugs that can kill pathogens on mucous membranes without killing surrounding normal bacteria as well, and physicians therefore must wait for infection to occur systemically before treating the patient. If it were possible to safely deplete this disease reservoir on mucous membranes, then it might be possible to markedly lower the incidence of infections. Toward this end, the scientists have developed a new type of reagent, called lytic enzymes, that can prevent infection by specifically destroying pathogenic bacteria on mucous membranes. The enzymes might prove especially useful in hospitals, nursing homes, daycare centers, and other locations where bacterial infections often run rampant.

Participants also examined how the current regulatory approval process for moving new drug candidates to market might be modified to help reduce problems of antimicrobial resistance. Drug developers now must conduct extensive clinical trials to evaluate whether their agent achieves a clinical cure; that is, whether it frees recipients of symptoms. But this marker may not show whether the drug actually killed all of the pathogens—an important requirement for minimizing the emergence of resistance. One suggestion is to examine the pharmacokinetics and pharmacodynamics of new drugs as a complementary part of the approval process. This technical approach, known as PK/PD, is built on taking regular cultures from a person receiving a therapeutic agent and determining when pathogenic microbes are no longer present. In this way, the technology offers a direct measure of the agent’s ability not only to cure the patient but also to completely eliminate the pathogen.

EVOLUTION OF MULTIPLE MECHANISMS OF RESISTANCE TO ß-LACTAM ANTIBIOTICS

Dasantila Golemi-Kotra, Ph.D., Sergei Vakulenko, M.D., Ph.D., and Shahriar Mobashery, Ph.D.

Departments of Chemistry, Pharmacology and Biochemistry and Molecular Biology Institute for Drug Design, Wayne State University, Detroit, MI

Major discoveries in antibiotics were made in succession from the 1950s through the 1970s, an era that has come to be known as the “Golden Age of Antibiotics.” These accomplishments created a sense of euphoria in the medical community as it perceived that bacterial infections were curable.



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