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Senator Frist, Senator Kennedy, thank you for inviting the American Society for Microbiology (ASM) here to participate in your forum. I am Dr. Gail Cassell, chair of the ASM Public and Scientific Affairs Board (PSAB) and a Past President of ASM. I am also Vice President, Infectious Diseases Research of Eli Lilly & Company in Indianapolis, Indiana and a Professor of Microbiology and Pediatrics at the University of Alabama at Birmingham.

The 42,000-plus membership of ASM, which is deeply concerned about the complex issue of antibiotic resistance and emerging infectious diseases, brings many kinds of expertise to this multifaceted public health challenge. Indeed, ASM believes that its membership, representing an unusually broad spectrum of subspecialties, is uniquely suited to provide guidance regarding these complicated issues. Our membership includes research scientists in both the public and private sector, physicians, veterinarians and food microbiologists. These issues touch not only on standard medical practices in the arena of infectious diseases. They also impinge on veterinary medicine, on the agriculture and food sectors, and on important components of the pharmaceutical and biotechnology industries. The impact is not only on public health and safety, but also on national and international trade, the economy, and, in some situations, on political and social stability.

The alarm portending the end of the antibiotic era in the United States sounded in 1989 when the rapid increase of antibiotic resistance to vancomycin in enterococci began. Before that time there were essentially no vancomycin-resistant enterococci. The twenty-fold increase in incidence observed in the brief interval between January 1989 and March of 1993 was especially alarming, because enterococci are the most common cause of hospital-acquired infections in the United States and vancomycin is often the last and only effective antibiotic against these organisms. At the same time, pneumococci, the leading cause of pneumonia, meningitis, and blood stream infections in the elderly and one of the leading causes of middle-ear infections in children in the United States, also were rapidly becoming resistant. Surveillance data from the Centers for Disease Control and Prevention (CDC) indicate that drug resistance in pneumococci was uncommon in the United States through 1987. In 1992, CDC data indicated that 6.6 percent of strains were resistant to penicillin. Now in some parts of the United States resistance rates are as high as 20 to 40 percent.

It is universally accepted that microbial adaptation to change is the primary reason for development of antibiotic resistance, and it is certainly well documented that selective pressure exerted by widespread antimicrobial use is the driving force in antibiotic resistance. Antibiotic resistance has been a problem since the development of the first antibiotics over 50 years ago. So, what changes occurred over the last several years that might have contributed to the sudden surge in antibiotic resistance?

For one thing, there was a substantial increase in antibiotic usage. Sales of antibiotics to drug stores and hospitals in the United States went up from 3.7 billion in 1988 to 5.6 billion in 1993. Moreover, in 1992, an estimated 110 million courses of antimicrobial therapy were prescribed by office-based physicians in the United States. This represents a 28 percent increase over 1980. It is important to emphasize that increased usage of antibiotics has been directly related to a significant increase in infectious diseases during this same time period. From 1980 to 1992, deaths due to infectious diseases in the United States jumped 58 percent. In aggregate infectious diseases are currently the third leading cause of death in the United States. Much of the increase in deaths is due to an increase in pneumonia and bloodstream infections, both of which are most often treatable with antibiotics. In addition, due to increased numbers of children attending daycare facilities, middle ear infections increased in the United States from ~3 million in 1975 to over 9 million in 1997. Middle ear infections are the second leading cause of office visits to physicians and this diagnosis accounts for over 40 percent of all outpatient antimicrobial use. The environmental and socioeconomic factors which are known to have contributed to the increase in the incidence of infectious diseases, have also contributed significantly to development of resistance through genetic mutations and they also have increased the global spread of antibiotic resistant organisms. Increased international travel and commerce, increased numbers of immunocompromised individuals, changes in demographics, and decay of our public health infrastructure over the past decade are perhaps the most important factors.

It is unfortunate that there are many inappropriate prescriptions for antibiotics-inappropriate, either because the optimal antibiotic is not chosen or because the infection being treated is caused by a virus. It is estimated that as many as 50 percent of prescriptions for antibiotics are inappropriate. Inappropriate usage often results from a lack of adequate diagnostic criteria. Upper respiratory infections are particularly problematic, but even in the case of pneumonias, specifically community-acquired pneumonias, the etiology is unknown in at least 50 percent of the cases in all age groups. Moreover, since a large percentage of upper respiratory tract infections in children are viral diseases, not bacterial diseases, diagnostic methods are not readily available in the office environment. Even for those infections that can be diagnosed, like mycoplasma pneumonia, and chlamydia pneumonia, there are no rapid, reliable diagnostic tests suitable for office use. Given this uncertainty, it is not surprising that antibiotics in general and broad-spectrum antibiotics, in particular, are overly prescribed. This is particularly true since recent data indicate that inappropriately treated mycoplasmal respiratory infections can lead to infections of the brain and inappropriately treated chlamydia respiratory diseases can lead to cardiovascular disease.

But there is another more insidious, and perhaps more important factor. Several studies have shown that parental and patient pressure is a common reason given by physicians for prescribing antibiotics even in cases when their usage cannot be justified based on clinical and diagnostic criteria. Americans like quick fixes; patient satisfaction has become a very important financial consideration for physicians.

What should be done to stop the emergence of antibiotic resistant pathogens? First and foremost, both the American Society for Microbiology Task Force on Antibiotic Resistance and the U.S. Office of Technology Assessment Advisory Panel on Antibiotic Resistance in 1994-95 made the plea for establishment of a meaningful national surveillance system for antibiotic resistance. Since the reports have been released, an interagency committee has been formed involving the Food and Drug Administration, the CDC, and the U.S. Department of Agriculture for monitoring of antibiotic resistance in food borne pathogens. However, one only has to look at the rapid spread of drug resistant pneumococci originally detected in Spain, and then rapidly spreading to other parts of the world, to see that a global surveillance system is mandatory.

An urgent need exists to improve selection of antimicrobial drugs in clinical practice. Research is needed to foster development of rapid reliable diagnostic tests for identifying specific infectious causes of illnesses to distinguish between those that are treatable with antimicrobials versus those of viral etiology that are not. More clinical research is needed to clarify the etiology of otitis, chronic sinusitis, and pneumonia, given that in a large percentage of cases the etiology is unknown. Better clinical guidelines are needed, particularly in hospital environments, nursing homes, and day-care facilities.

The time devoted to infectious diseases in the curricula of our medical schools and graduate schools has been reduced dramatically over the past 5-7 years to accommodate the rapid developments in molecular medicine and genetics, and probably also as a consequence of our complacency towards infectious diseases. In many schools specific issues related to antibiotic resistance, including, disinfection and mechanisms of antibiotic resistance, receive less than one hour in the medical school curriculum. This is not adequate. Lastly and perhaps most importantly, one of the strongest recommendations of both advisory groups deals with better education of the general public on the appropriate use of antibiotics.

Both advisory panels emphasized the need for more basic research to better understand the genetic mechanisms underlying antibiotic resistance, particularly in fungi and newly described pathogens. More clinical and epidemiological research are needed to determine the clinical impact of infection with drug resistant pathogens and to identify different therapeutic options when one is confronted with patient management of a drug resistant strain. More basic research is obviously needed to determine mechanisms of spread, particularly in closed populations. Finally, given the wiles of evolution, few would question that microbes will eventually develop resistance to nearly every antibiotic; therefore, we have to continue to focus research leading to better vaccines and other preventive measures.

In summary, the ASM Task Force believes a review of policy options should entail careful consideration of an assessment of programs needed to track this problem through intensive public health surveillance as well as monitoring of antibiotic resistance genetic markers in environmental settings; basic and applied research in both the public and private sectors to understand how antibiotics work, the responses of pathogens to undermine those life-saving activities, and the development of new drugs and other novel strategies to combat those pathogens; and expanded efforts to educate physicians, veterinarians, and other health professionals, as well as patients and their families about the proper use of such drugs and improved strategies for retaining and perhaps extending the useful lifetimes of these valuable pharmaceutical products.

I have copies of the ASM Task Force report which I would like to make available to you and your staff as well as some educational brochures that were developed as a partnership with ASM, CDC and the American Academy of Pediatrics.