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Past, present, and future of antimicrobial agents
68
AJIC February 1997
Reviews
largely responsible for changing the direction of nursing care with respect to the ritual of doublebagging. These articles are examples of the kinds of studies needed in infection prevention and control to challenge costly rituals without scientific bases, and we hope that more research in this area will be done in the future. Marguerite McMillan Jackson, RN, PhD Associate Clinical Professor of Family and Preventive Medicine University of California San Diego
Pneumocystis pneumonia--Los Angeles Centers for Disease Control. MMWR 1981;30:250-2.
Little did we suspect that this ll/2-page report would identify a new syndrome with such profound medical and social implications. The article began with the description of five homosexual men at three different hospitals in Los Angeles who had Pneumocystis carinii pneumonia during a 7-month period. Before this report, infection with P. carinii was almost exclusively described in severely immunosuppressed patients. The authors of this report noted this unusual occurrence and suggested "the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections such as pneumocystosis and candidiasis." Although it took another 2 years for this "common exposure," HIV, to be discovered in 1983, a sensitive serologic test for antibodies to HIV became available in 1985. This test enabled us to diagnose infection even in the absence of symptoms. The impact that HIV infection would ultimately have on infection prevention and control was not realized until after the discovery of the etiologic virus. Although an infectious agent was suspected early in the pandemic, early reports of transfusion-associated AIDS were highly suggestive of a blood-borne pathogen, in this case, a previously undescribed retrovirus. Other blood-borne pathogens (hepatitis B and C viruses) attracted increased attention, and national standards were developed to deal with these agents. Stimulated by the discovery of these bloodborne pathogens, the development of sensitive and specific serologic tests became paramount. On the basis of unprecedented discoveries in molecular biology, both diagnosis and treatment of these blood-borne pathogens evolved. The synthesis and clinical utility of reverse-transcriptase inhibitors such as zidovudine and the subsequent development of the protease inhibitors have evolved from our intimate understanding of the
basic molecular biology of HIV. The treatment of opportunistic infections seen in patients with HIV has also seen great strides. Our knowledge of the medical implications of HIV infection has progressed steadily during the past 15 years. Transmission of HIV continues to occur. Our ability to prevent perinatal transmission of HIV has been demonstrated in a rigorous clinical trial; however, many women with HIV infection do not realize that they are infected. Although educational efforts have succeeded in preventing the transmission of HIV in other high risk groups, there remains a disenfranchised portion of our population among whom these efforts remain suboptimal. In 1997, we possess several promising active antiretroviral agents, some with the possible potential to transform HIV infection into a chronic infection. Our ability to prevent opportunistic infections continues to grow. We recognize effective means of preventing transmission of HIV infection. Only through continued patient education and research will we be able to use those tools that have been developed since that report in June 1981, when astute clinicians first recognized a new syndrome. Leland S. Rickman, MD Associate Clinical Professor of Medicine University of California San Diego
Past, present, and future of antimicrobial agents Moellering RC. Am J Med 1995;99(Suppl 6A):11S-25S. Reprint requests: Robert C. Moellering, Jr., MD, Department of Medicine, Deaconess Hospital, One Deaconess Rd., Boston, MA 02215.
Bacteria have been on earth for billions of years. For clinical use, antibiotics have only been available for a little longer than 50 years. Incredible progress toward rational antimicrobial design and understanding has been made in this relatively short period, but we are still threatened by the fact that bacteria and other microorganisms are remarkably resourceful and have shown a surprising ability to survive in the modern antibiotic era. Moellering's article is a well-written and concise overview of past, present, and anticipated future developments of antimicrobial agents. Moellering initially describes past achievements with treatment of wounds and other types of therapy extending back thousands of years before the modern antibiotic era. He then brings us to the dawn of the antibiotic era by presenting many
AJIC Volume 25, Number 1
Reviews 6 9
accomplishments and achievements from various prominent pioneering researchers, including many who received Nobel Prizes for their vital contributions. A review of the antimicrobial chemical modification advancements that have yielded many new and improved therapeutic agents brings us to the present antibiotic era. Moellering also examines the hurdles encountered along the way--most notably the problems associated with antibacterial resistance. The remainder of the article is devoted to the future of antimicrobial development. A number of major areas of current investigation are examined and include development of (1) novel "classic" antimicrobials, (2) potentiators of known antimicrobials, (3) inhibitors of new targets in bacterial cellular functions, (4) inhibitors of genes relating to pathogenesis, (5) deployment of antisense nucleotides, and (6) chemical modification of currently known agents to overcome resistance. Moellering concludes by stating, "If we are able to carry out all of these [developmental] tasks efficiently, there is no question that we will bring with us into the 21 st century the control of infec-
tious diseases that started with such great promise in the 20th." This will help to fulfill the infectious disease clinician's dream, namely, the use of truly narrow-spectrum "magic bullet" antibiotics to treat infections. To accomplish this, however, tremendous resources and crucial research are still needed. Fortunately, the pharmaceutical industry is now turning its attention posthaste to this seriously neglected developmental area. This article is most suitable for infection control professionals with a strong interest in the future of antimicrobial drug development. This synopsis visits where we have been, where we are currently, and where we are headed in the area of antimicrobial research currently under investigation to assist in the fight against infectious diseases. For further in-depth reading on antimicrobial history and development, the reader is referred to The Antibiotic Paradox (Levy SB. New York: Plenum, 1992.) and The Miracle Cure (Wainwright M, Cambridge [MA]: Basil Blackwell, 1990.). Charles L. James, PharmD
Infectious Diseases PharmacistSpecialist University of CaliforniaSan Diego Medical Center
The Reviews and Comments at a Glance section is edited by Leland S. Rickman, MD, and Marguerite McMillan Jackson, RN, PhD. Books and monographs may be submitted for review and should be sent to Leland S. Rickman, MD, and Marguerite McMillan Jackson, RN, PhD, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8951. Individual reprints of articles reviewed must be obtained from the designated author.
AJIC February 1997
Reviews
largely responsible for changing the direction of nursing care with respect to the ritual of doublebagging. These articles are examples of the kinds of studies needed in infection prevention and control to challenge costly rituals without scientific bases, and we hope that more research in this area will be done in the future. Marguerite McMillan Jackson, RN, PhD Associate Clinical Professor of Family and Preventive Medicine University of California San Diego
Pneumocystis pneumonia--Los Angeles Centers for Disease Control. MMWR 1981;30:250-2.
Little did we suspect that this ll/2-page report would identify a new syndrome with such profound medical and social implications. The article began with the description of five homosexual men at three different hospitals in Los Angeles who had Pneumocystis carinii pneumonia during a 7-month period. Before this report, infection with P. carinii was almost exclusively described in severely immunosuppressed patients. The authors of this report noted this unusual occurrence and suggested "the possibility of a cellular-immune dysfunction related to a common exposure that predisposes individuals to opportunistic infections such as pneumocystosis and candidiasis." Although it took another 2 years for this "common exposure," HIV, to be discovered in 1983, a sensitive serologic test for antibodies to HIV became available in 1985. This test enabled us to diagnose infection even in the absence of symptoms. The impact that HIV infection would ultimately have on infection prevention and control was not realized until after the discovery of the etiologic virus. Although an infectious agent was suspected early in the pandemic, early reports of transfusion-associated AIDS were highly suggestive of a blood-borne pathogen, in this case, a previously undescribed retrovirus. Other blood-borne pathogens (hepatitis B and C viruses) attracted increased attention, and national standards were developed to deal with these agents. Stimulated by the discovery of these bloodborne pathogens, the development of sensitive and specific serologic tests became paramount. On the basis of unprecedented discoveries in molecular biology, both diagnosis and treatment of these blood-borne pathogens evolved. The synthesis and clinical utility of reverse-transcriptase inhibitors such as zidovudine and the subsequent development of the protease inhibitors have evolved from our intimate understanding of the
basic molecular biology of HIV. The treatment of opportunistic infections seen in patients with HIV has also seen great strides. Our knowledge of the medical implications of HIV infection has progressed steadily during the past 15 years. Transmission of HIV continues to occur. Our ability to prevent perinatal transmission of HIV has been demonstrated in a rigorous clinical trial; however, many women with HIV infection do not realize that they are infected. Although educational efforts have succeeded in preventing the transmission of HIV in other high risk groups, there remains a disenfranchised portion of our population among whom these efforts remain suboptimal. In 1997, we possess several promising active antiretroviral agents, some with the possible potential to transform HIV infection into a chronic infection. Our ability to prevent opportunistic infections continues to grow. We recognize effective means of preventing transmission of HIV infection. Only through continued patient education and research will we be able to use those tools that have been developed since that report in June 1981, when astute clinicians first recognized a new syndrome. Leland S. Rickman, MD Associate Clinical Professor of Medicine University of California San Diego
Past, present, and future of antimicrobial agents Moellering RC. Am J Med 1995;99(Suppl 6A):11S-25S. Reprint requests: Robert C. Moellering, Jr., MD, Department of Medicine, Deaconess Hospital, One Deaconess Rd., Boston, MA 02215.
Bacteria have been on earth for billions of years. For clinical use, antibiotics have only been available for a little longer than 50 years. Incredible progress toward rational antimicrobial design and understanding has been made in this relatively short period, but we are still threatened by the fact that bacteria and other microorganisms are remarkably resourceful and have shown a surprising ability to survive in the modern antibiotic era. Moellering's article is a well-written and concise overview of past, present, and anticipated future developments of antimicrobial agents. Moellering initially describes past achievements with treatment of wounds and other types of therapy extending back thousands of years before the modern antibiotic era. He then brings us to the dawn of the antibiotic era by presenting many
AJIC Volume 25, Number 1
Reviews 6 9
accomplishments and achievements from various prominent pioneering researchers, including many who received Nobel Prizes for their vital contributions. A review of the antimicrobial chemical modification advancements that have yielded many new and improved therapeutic agents brings us to the present antibiotic era. Moellering also examines the hurdles encountered along the way--most notably the problems associated with antibacterial resistance. The remainder of the article is devoted to the future of antimicrobial development. A number of major areas of current investigation are examined and include development of (1) novel "classic" antimicrobials, (2) potentiators of known antimicrobials, (3) inhibitors of new targets in bacterial cellular functions, (4) inhibitors of genes relating to pathogenesis, (5) deployment of antisense nucleotides, and (6) chemical modification of currently known agents to overcome resistance. Moellering concludes by stating, "If we are able to carry out all of these [developmental] tasks efficiently, there is no question that we will bring with us into the 21 st century the control of infec-
tious diseases that started with such great promise in the 20th." This will help to fulfill the infectious disease clinician's dream, namely, the use of truly narrow-spectrum "magic bullet" antibiotics to treat infections. To accomplish this, however, tremendous resources and crucial research are still needed. Fortunately, the pharmaceutical industry is now turning its attention posthaste to this seriously neglected developmental area. This article is most suitable for infection control professionals with a strong interest in the future of antimicrobial drug development. This synopsis visits where we have been, where we are currently, and where we are headed in the area of antimicrobial research currently under investigation to assist in the fight against infectious diseases. For further in-depth reading on antimicrobial history and development, the reader is referred to The Antibiotic Paradox (Levy SB. New York: Plenum, 1992.) and The Miracle Cure (Wainwright M, Cambridge [MA]: Basil Blackwell, 1990.). Charles L. James, PharmD
Infectious Diseases PharmacistSpecialist University of CaliforniaSan Diego Medical Center
The Reviews and Comments at a Glance section is edited by Leland S. Rickman, MD, and Marguerite McMillan Jackson, RN, PhD. Books and monographs may be submitted for review and should be sent to Leland S. Rickman, MD, and Marguerite McMillan Jackson, RN, PhD, UCSD Medical Center, 200 W. Arbor Dr., San Diego, CA 92103-8951. Individual reprints of articles reviewed must be obtained from the designated author.