Ann. N.Y. Acad. Sci. ISSN 0077-8923

A N N A L S O F T H E N E W Y O R K A C A D E M Y O F SC I E N C E S Issue: Antimicrobial Therapeutics Reviews

Introduction to Antimicrobial Therapeutics Reviews: Infectious Diseases of Current and Emerging Concern

Infectious diseases know no boundaries. Antibiotic-resistant infectious diseases are especially promiscuous and increasingly cause critical global problems. As the U.S. Centers for Disease Control and Prevention Web site states, “Resistance anywhere is resistance everywhere” http://www.cdc.gov/getsmart/ healthcare/factsheets/resistance.html. In this volume of reviews, selected infectious diseases with origins in diverse geographical areas have been examined and the need for new approaches to treat resistant strains of the causative pathogens especially noted. In the initial review by Fowler et al.,1 campaigns to raise public awareness of antimicrobial resistance are highlighted, including warnings about the possibility of a post-antibiotic era. As a result of these dire predictions, recent changes in public policy, especially in Europe, offer glimmers of hope that new therapies may be developed to treat these diseases. Among the positive policy changes that have been recently implemented are new guidance documents for the approval of antibacterial agents to treat resistant infections. The evolution of these revised regulatory pathways is outlined in the review by Rex et al.,2 demonstrating a commitment by North American and European agencies to encourage the more rapid development of novel therapies to treat antibiotic-resistant pathogens. Resistant pathogens continue to pose increasing therapeutic challenges. A most worrisome development has been the relatively rapid increase in carbapenem-resistant Enterobacteriaceae (CRE) that has challenged the infectious disease community. These organisms are generally multidrug resistant, with few, if any, treatment options. Temkin et al.3 provide a short history of carbapenemase-mediated resistance, together with a discussion of the epidemiology and possible medical approaches to CRE-infected patients, who ideally should be housed in isolation facilities to avoid pathogen transmission. Additional factors contributing to antibacterial resistance are described from sub-Saharan Africa, as discussed by Kariuki and Dougan,4 where conditions such as poor sanitation, variable water supplies, high proportions of immunocompromised patients, and political disruptions may result in suboptimal medical treatment. Emergence of drug-resistant tuberculosis (TB) in Africa, as well as other parts of the world, is another challenge that requires creative thinking. Mdluli and coworkers5 describe the need for new treatment paradigms for TB and suggest that novel drug targets may be exploitable for the development of new anti-TB agents in the future. Multidrug resistance in typhoid fever is another concern that affects global health. Tatavarthy et al.6 address some of the epidemiological and genetic aspects of drug-resistant Salmonella enterica serotype Typhi in their review of possible treatment options available for infections caused by these pathogens. Alternatives to antibiotics are discussed by Allen et al.,7 who suggest that drug resistance has limited the utility of classical antibiotic classes in human and veterinary medicine. A number of nonantibiotic approaches include both prophylactic and treatment therapies that avoid traditional drug targets and may thus reduce resistance selection. Following this review is a discussion of sepsis, a clinical syndrome with high mortality and poor response to antibiotic therapy. Lyle et al.8 provide possible explanations for the low success rates for clinical trials for the treatment of sepsis and propose that further studies on the human immune response may provide new understanding of this syndrome. doi: 10.1111/nyas.12541 C 2014 New York Academy of Sciences. Ann. N.Y. Acad. Sci. 1323 (2014) v–vi 

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Viral diseases with global impact are also included in this volume. Influenza with its highly mutable genome remains a zoonotic disease that requires continuous surveillance. Webster and Govorkova review the epidemiology of influenza viruses in relation to antigenic drift of new and emerging strains.9 They recognize the need for therapeutic approaches other than neuraminidase inhibitors, including the development of novel vaccines that may minimize the effect of rapid strain mutations. Dengue is another viral disease that affects tens of millions of people a year with debilitating consequences. Thomas10 describes the lack of prophylactic or therapeutic dengue drugs, and the potential utility of a dengue vaccine, a goal that requires commitment to increased research capabilities in this area. Together, these articles emphasize the impact of infectious diseases on the health of both human and animal populations worldwide. The need for new agents to counteract the causative agents will continue, with the hope that new approaches to antimicrobial therapy will be a major focus of diverse research groups in the future.

Karen Bush Department of Molecular and Cellular Biochemistry Indiana University Bloomington, Indiana References 1. Fowler, T., D. Walker & S.C. Davies. 2014. The risk/benefit of predicting a post-antibiotic era: Is the alarm working? Ann. N.Y. Acad. Sci. 1323: 1–10. 2. Rex, J.H., M. Goldberger, B.I. Eisenstein & C. Harney. 2014. The evolution of the regulatory framework for antibacterial agents. Ann. N.Y. Acad. Sci. 1323: 11–21. 3. Temkin, E., A. Adler, A. Lerner & Y. Carmeli. 2014. Carbapenem-resistant Enterobacteriaceae: biology, epidemiology, and management. Ann. N.Y. Acad. Sci. 1323: 22–42. 4. Kariuki, S. & G. Dougan. 2014. Antibacterial resistance in sub-Saharan Africa: an underestimated emergency. Ann. N.Y. Acad. Sci. 1323: 43–55. 5. Mdluli, K., T. Kaneko & A. Upton. 2014. Tuberculosis drug discovery and emerging targets. Ann. N.Y. Acad. Sci. 1323: 56–75. 6. Tatavarthy, A., V.A. Luna & P.T. Amuso. 2014. How multidrug resistance in typhoid fever affects treatment options. Ann. N.Y. Acad. Sci. 1323: 76–90. 7. Allen, H.K., J. Trachsel, T. Looft & T.A. Casey. 2014. Finding alternatives to antibiotics. Ann. N.Y. Acad. Sci. 1323: 91–100. 8. Lyle, N.H., O.M. Pena, J.H. Boyd & R.E.W. Hancock. 2014. Barriers to the effective treatment of sepsis: antimicrobial agents, sepsis definitions, and host-directed therapies. Ann. N.Y. Acad. Sci. 1323: 101–114. 9. Webster, R.G. & E.A. Govorkova. 2014. Continuing challenges in influenza. Ann. N.Y. Acad. Sci. 1323: 115–139. 10. Thomas, S.J. 2014. Developing a dengue vaccine: progress and future challenges. Ann. N.Y. Acad. Sci. 1323: 140–159.

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C 2014 New York Academy of Sciences. Ann. N.Y. Acad. Sci. 1323 (2014) v–vi 

Introduction to Antimicrobial therapeutics reviews: infectious diseases of current and emerging concern.

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