classes of antibiotics. Supplies of both vaccines are currently limited. While smallpox vaccination is effective, it elicits dangerous and potentially lethal complications in a number of individuals, and because it is a live-attenuated vaccine, it poses a significant risk for all immunocompromised individuals. The limited antibiotic armamentarium is an even greater concern with respect to future threats, especially in light of an increase in the number of new and reemerging infectious diseases and a marked rise in resistance to existing antibiotics. When the issue of resistance is laid against the dearth of new classes of antibiotics being developed and commercialized today, it becomes clear that no public health response to bioterrorism is likely to prove effective without a wider range of antimicrobials to draw on.

Work must proceed in parallel on nonpathogenic bacteria in the same class as the pathogen. New antibiotic discovery is dependent on an understanding of fundamental cellular mechanisms that are held in common among pathogens and nonpathogens. In most cases, the nonpathogenic cousin has far superior genetics and a deeper database of gene function and regulatory networks allowing discovery and development to proceed at a faster pace. Most antibiotic discovery is, in fact, based on work in nonpathogens that is then directly applicable to the pathogens on the list of biological warfare agents.

An Interagency Task Force on Antimicrobial Resistance has set forth recommendations for judicious use of existing antibiotics; they appeared in the Federal Register almost 2 years ago.4 Although the recommendations were widely endorsed, funds have yet to be appropriated by Congress to implement the plan. Given the long lead time required for development of new antibiotics, we must preserve those we have. Thus it is essential that the recommendations of the task force be implemented without further delay.

Unfortunately, the complacency associated with infectious diseases in the 1960s and the general confidence in existing antibiotics largely arrested the production of new classes of antimicrobials. There has been only one new class in the past three decades, and resistant strains emerged prior to its launch. But the situation may be changing for the better. The public attention to the antibiotic crisis in the early 1990s, coupled with the potential for discovering new antibiotics using genomics, high-throughput screening, microarrays, combinatorial chemistry, and structural biology, has resulted in industry’s reinvestment in antibiotic research.

At first glance, the current antibiotic pipeline looks encouraging. There are more than 18 antibiotics in Phases I through III of clinical development. However, there are no new classes or targets for antibiotics. In particular, there are no new classes of broad-spectrum antibiotics, and the outlook for antivirals, particu-


A Public Health Action Plan to Combat Antimicrobial Resistance appeared in the Federal Register on June 22, 2000 (Volume 65, Number 121). The report is available online at <>.

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