State‐of‐the‐art therapeutic medical countermeasures for bacterial threat agents

Abstract

AbstractIn the event of another bioterrorism attack with a bacterial agent, antibiotics will be critical medical countermeasures to have in the US Strategic National Stockpile. Conventional antibiotics such as ciprofloxacin, doxycycline, and streptomycin are generally considered a first line of defense against organisms such as Bacillus anthracis and Yersinia pestis. However, antibiotic resistance is a growing public health threat, especially among potentially life‐threatening pathogens; it is possible that threat agent bacteria could naturally evolve, or be engineered to express, antibiotic resistance against commonly used antibiotics. At the same time that the need for novel or improved antibiotics is becoming urgent, the antibiotic development pipeline has slowed, with only two completely new classes of antibiotics having been introduced over the past 40 years. In the present work, we review the current antibiotic pipeline, including novel, innovative approaches being considered to target bacteria or virulence, with a focus on those compounds that have been tested for activity against threat agent bacteria. We opine on the benefits and challenges inherent in certain mechanisms of action and stress that regulatory, policy, and technical strategies need to be revisited in order to incentivize industry to continue antibiotic development. Drug Dev Res 72: 361–378, 2011.© 2011 Wiley‐Liss, Inc.