Development and Implications of Antimicrobial Resistance One of the most ominous trends in the field of antimicrobial chemotherapy over the past decade has been the increasing pace of development of antimicrobial resistance among microbial pathogens. The hypothesis that man can discover a magic bullet to always cure a particular infection has proved false. Physicians are now seeing and treating patients for which there are few therapeutic alternatives, and in some cases, none at all. Until recently there was little concern that physicians might be losing the war in our ability to compete with the evolving resistance patterns of microbial pathogens. Now the general public is very aware of the threat to them if they become infected, thanks to cover story articles in major magazines such as Time, Newsweek, newspapers, and other news sources. Antimicrobial resistance is not a novel problem. Shortly after the widespread introduction of penicillin in the early 1940s, the first strains of penicillin-resistant staphylococci were described. Today it is an uncommon event for a clinical laboratory to isolate an S. aureus that is sensitive to penicillin. Other gram-positive strains of bacteria have become resistant, including the exquisitely sensitive Streptococcus pneumoniae. Sensitivity to vancomycin was once so uniform that it was used in routine clinical laboratories as a surrogate marker for whether an organism should be classified as a gram-positive. That criterion can no longer be relied upon because of emerging resistance among some species. Gram-negative bacteria, viruses, fungi, and parasites all have succeeded in developing resistance.

THE ERA OF ANTIVIRALS Introduction Although there are more than one hundred medically useful antibiotics and fungicides, there are only seven compounds licensed for use as antiviral agents, in the USA. Some of these (acyclovir and ganciclovir) are actually derivatives of each other, making the number of new discoveries even smaller. Moreover, most of these agents are of only limited therapeutic value and have substantial toxicity. It has been more than 100 years ago since Pasteur studied rabies virus (2) and Rous (4) showed that a small filterable agent (not bacteria) caused disease (sarcoma) in chickens. It was nearly 100 years ago that yellow fever virus, the first recognized human pathogenic virus, was unambiguously associated with disease (3). Enteroviruses were cultured for the first time nearly 50 years ago (1). Why then has effective chemotherapy against viruses lagged behind that of other microorganisms? Viruses are often difficult to grow and image. However, with the dynamic advances in molecular biology and increased sophistication in tissue culture, the field of virology has blossomed and resulted in improved methods for detection of virus infection. The use of viruses as models of gene regulation and replication has also resulted in a massive accumulation of information.

THE ERA OF ANTIVIRALS Introduction Although there are more than one hundred medically useful antibiotics and fungicides, there are only seven compounds licensed for use as antiviral agents, in the USA. Some of these (acyclovir and ganciclovir) are actually derivatives of each other, making the number of new discoveries even smaller. Moreover, most of these agents are of only limited therapeutic value and have substantial toxicity. It has been more than 100 years ago since Pasteur studied rabies virus (2) and Rous (4) showed that a small filterable agent (not bacteria) caused disease (sarcoma) in chickens. It was nearly 100 years ago that yellow fever virus, the first recognized human pathogenic virus, was unambiguously associated with disease (3). Enteroviruses were cultured for the first time nearly 50 years ago (1). Why then has effective chemotherapy against viruses lagged behind that of other microorganisms? Viruses are often difficult to grow and image. However, with the dynamic advances in molecular biology and increased sophistication in tissue culture, the field of virology has blossomed and resulted in improved methods for detection of virus infection. The use of viruses as models of gene regulation and replication has also resulted in a massive accumulation of information.

Development and Implications of Antimicrobial Resistance One of the most ominous trends in the field of antimicrobial chemotherapy over the past decade has been the increasing pace of development of antimicrobial resistance among microbial pathogens. The hypothesis that man can discover a magic bullet to always cure a particular infection has proved false. Physicians are now seeing and treating patients for which there are few therapeutic alternatives, and in some cases, none at all. Until recently there was little concern that physicians might be losing the war in our ability to compete with the evolving resistance patterns of microbial pathogens. Now the general public is very aware of the threat to them if they become infected, thanks to cover story articles in major magazines such as Time, Newsweek, newspapers, and other news sources. Antimicrobial resistance is not a novel problem. Shortly after the widespread introduction of penicillin in the early 1940s, the first strains of penicillin-resistant staphylococci were described. Today it is an uncommon event for a clinical laboratory to isolate an S. aureus that is sensitive to penicillin. Other gram-positive strains of bacteria have become resistant, including the exquisitely sensitive Streptococcus pneumoniae. Sensitivity to vancomycin was once so uniform that it was used in routine clinical laboratories as a surrogate marker for whether an organism should be classified as a gram-positive. That criterion can no longer be relied upon because of emerging resistance among some species. Gram-negative bacteria, viruses, fungi, and parasites all have succeeded in developing resistance.

Development and Implications of Antimicrobial Resistance One of the most ominous trends in the field of antimicrobial chemotherapy over the past decade has been the increasing pace of development of antimicrobial resistance among microbial pathogens. The hypothesis that man can discover a magic bullet to always cure a particular infection has proved false. Physicians are now seeing and treating patients for which there are few therapeutic alternatives, and in some cases, none at all. Until recently there was little concern that physicians might be losing the war in our ability to compete with the evolving resistance patterns of microbial pathogens. Now the general public is very aware of the threat to them if they become infected, thanks to cover story articles in major magazines such as Time, Newsweek, newspapers, and other news sources. Antimicrobial resistance is not a novel problem. Shortly after the widespread introduction of penicillin in the early 1940s, the first strains of penicillin-resistant staphylococci were described. Today it is an uncommon event for a clinical laboratory to isolate an S. aureus that is sensitive to penicillin. Other gram-positive strains of bacteria have become resistant, including the exquisitely sensitive Streptococcus pneumoniae. Sensitivity to vancomycin was once so uniform that it was used in routine clinical laboratories as a surrogate marker for whether an organism should be classified as a gram-positive. That criterion can no longer be relied upon because of emerging resistance among some species. Gram-negative bacteria, viruses, fungi, and parasites all have succeeded in developing resistance.

THE ERA OF ANTIVIRALS Introduction Although there are more than one hundred medically useful antibiotics and fungicides, there are only seven compounds licensed for use as antiviral agents, in the USA. Some of these (acyclovir and ganciclovir) are actually derivatives of each other, making the number of new discoveries even smaller. Moreover, most of these agents are of only limited therapeutic value and have substantial toxicity. It has been more than 100 years ago since Pasteur studied rabies virus (2) and Rous (4) showed that a small filterable agent (not bacteria) caused disease (sarcoma) in chickens. It was nearly 100 years ago that yellow fever virus, the first recognized human pathogenic virus, was unambiguously associated with disease (3). Enteroviruses were cultured for the first time nearly 50 years ago (1). Why then has effective chemotherapy against viruses lagged behind that of other microorganisms? Viruses are often difficult to grow and image. However, with the dynamic advances in molecular biology and increased sophistication in tissue culture, the field of virology has blossomed and resulted in improved methods for detection of virus infection. The use of viruses as models of gene regulation and replication has also resulted in a massive accumulation of information.

THE ERA OF ANTIVIRALS Introduction Although there are more than one hundred medically useful antibiotics and fungicides, there are only seven compounds licensed for use as antiviral agents, in the USA. Some of these (acyclovir and ganciclovir) are actually derivatives of each other, making the number of new discoveries even smaller. Moreover, most of these agents are of only limited therapeutic value and have substantial toxicity. It has been more than 100 years ago since Pasteur studied rabies virus (2) and Rous (4) showed that a small filterable agent (not bacteria) caused disease (sarcoma) in chickens. It was nearly 100 years ago that yellow fever virus, the first recognized human pathogenic virus, was unambiguously associated with disease (3). Enteroviruses were cultured for the first time nearly 50 years ago (1). Why then has effective chemotherapy against viruses lagged behind that of other microorganisms? Viruses are often difficult to grow and image. However, with the dynamic advances in molecular biology and increased sophistication in tissue culture, the field of virology has blossomed and resulted in improved methods for detection of virus infection. The use of viruses as models of gene regulation and replication has also resulted in a massive accumulation of information.

Development and Implications of Antimicrobial Resistance One of the most ominous trends in the field of antimicrobial chemotherapy over the past decade has been the increasing pace of development of antimicrobial resistance among microbial pathogens. The hypothesis that man can discover a magic bullet to always cure a particular infection has proved false. Physicians are now seeing and treating patients for which there are few therapeutic alternatives, and in some cases, none at all. Until recently there was little concern that physicians might be losing the war in our ability to compete with the evolving resistance patterns of microbial pathogens. Now the general public is very aware of the threat to them if they become infected, thanks to cover story articles in major magazines such as Time, Newsweek, newspapers, and other news sources. Antimicrobial resistance is not a novel problem. Shortly after the widespread introduction of penicillin in the early 1940s, the first strains of penicillin-resistant staphylococci were described. Today it is an uncommon event for a clinical laboratory to isolate an S. aureus that is sensitive to penicillin. Other gram-positive strains of bacteria have become resistant, including the exquisitely sensitive Streptococcus pneumoniae. Sensitivity to vancomycin was once so uniform that it was used in routine clinical laboratories as a surrogate marker for whether an organism should be classified as a gram-positive. That criterion can no longer be relied upon because of emerging resistance among some species. Gram-negative bacteria, viruses, fungi, and parasites all have succeeded in developing resistance.