Bacterial Resistance to Antimicrobials PDF

Preface

On June 9, 1999, the New York Times published a lengthy obituary for Anne Miller. Ms. Miller, who was 90 when she died, was not a celebrity or a high-profi le politician. Her claim to fame was that, at the age of 33, she had been one of the fi rst people to be given the new and largely untested antibiotic penicillin. The transformation in her condition, which occurred within days, from a young woman slipping into death to a woman who could sit up in bed, eat meals, and chat with visitors was a stunning demonstration of what was to become commonplace in a new era of medicine. Such seemingly miraculous cures soon led physicians and the public to call antibiotics "miracle drugs."

Since then, antibiotics have not only saved people with pneumonia and other dreaded diseases, such as tuberculosis, but also have become the foundation on which much of modern medicine rests. Antibiotics make routine surgery feasible. They protect cancer patients whose chemotherapy had rendered them temporarily susceptible to a variety of infections. They even cure diseases like ulcers that had been considered uncurable chronic conditions. In recent years, antibiotic use has been extended to agriculture, where it plays an important role in preventing infections and in promoting animal growth.

The success of antibiotics in so many areas has, ironically, led antibiotics to become an endangered category of drugs. Bacteria have once again demonstrated their enormous genetic fl exibility by becoming resistant to one antibiotic after another. At fi rst, bacterial resistance to antibiotics, such as penicillin, did not seem very alarming because new antibiotics were regularly being discovered and introduced into clinical use. In the 1970s, however, a scant two decades after the introduction of the fi rst antibiotics, the number of new antibiotics entering the pipeline from laboratory to clinic began to decrease. Antibiotic discovery and development are expensive, especially considering the speed with which bacterial resistance can arise. And they are becoming more and more diffi cult to discover and develop. These factors have led pharmaceutical companies to be less and less interested in antibiotic production. One company after another has shut down or cut back on its antibiotic discovery program.

Finally, the medical community has begun to take antibiotic-resistant bacteria seriously. The public has also become alarmed. This alarm is refl ected in the number of articles in the popular press anguishing about the new "superbugs." Agricultural use of antibiotics has been called into question as a possible threat to human health. There is also the potential fallout if antibiotics were to be "lost." Medical researchers have failed to cure many diseases, and the public accepts these failures with grumbling stoicism. But what if overuse of antibiotics caused physicians to lose a cure, an event that would be a fi rst in history? How would this affect public confi dence in the medical community?

This book explores many of the aspects of the growing problem posed by antibiotic-resistant bacteria. What is unique about this book is that it is a blend of the purely scientifi c and the practical, an approach that is essential because antibiotic resistance is a social and economic problem as well as a scientifi c problem. Chapter 1 explores the history of antibiotics and how bacteria became resistant to them. Understanding the forces leading to the overuse and abuse of antibiotics that have sped the appearance of ever more resistant bacteria is important because it impresses on people the need for rapid and effective future action. The speed with which resistance has arisen is something that everyone needs to appreciate.

Chapter 2 discusses the ecology of antibiotic resistance genes. In recent years, scientists have realized that there is more to the epidemiology of resistance than the transmission of resistant strains of bacteria. Resistance genes are also moving from one bacterium to another, across species and genus lines. Bacteria do not have to spend years mutating their way to resistance; they can become resistant within hours by obtaining genes from other bacteria. Also clear from this chapter, however, is how primitive and inadequate our understanding of resistance ecology still is.

Chapters 3 through 14 describe the means by which bacteria become resistant to antibiotics, methods of detecting resistance genes, and the latest fi ndings on resistance or susceptibility specifi c to particular groups of bacteria. The bacteria that cause human and animal disease exhibit a staggering diversity. There is no one answer to the question of how bacteria become resistant to antibiotics. Understanding resistance mechanisms is the foundation for more rational design of new antibiotics that are themselves resistant to resistance mechanisms.

A complementary approach, exemplifi ed by combination of a compound that inhibits bacterial β-lactamases with a β-lactam antibiotic, offers great promise. More such successes are needed. To take such an approach, however, is necessary to understand the mechanisms of resistance at a very basic level. Even in the case of the β-lactamase inhibitors, variations in the mechanisms of resistance have foiled this approach in some bacteria that do not use β-lactamases as a resistance mechanism. These chapters pull together all of the information on resistance mechanisms in different groups of bacteria in a way that should help future efforts to develop such combination therapies.

Chapters 15 and 16 examine the public health aspects of the resistance problem. Science alone is not going to solve the resistance problem. Communicating scientifi c advances and new understandings of forces that promote the rapid development of resistance is essential if the public is to join in the effort to slow the increase in bacterial resistance to antibiotics. Taking antibiotics is a personal matter for most people, a decision made by them and their physicians. As long as antibiotic use remains a personal matter and is not put in the context of public welfare, it is unlikely that progress will be made toward saving antibiotics.

Chapter 17 addresses the problem of fi nding and developing new antibiotics. This chapter is written by an "insider," a scientist who runs an antibiotic discovery program and thus knows the industry side of the problem. Since the resistance genie is out of the bottle and it will not be easy to put him back in, the continued discovery of new antibiotics is going to be a critical part of the effort to combat resistant bacterial strains. This effort is a critical legacy that we owe our children, who are the ones most likely to bear the consequences of the crisis we have precipitated.

This book is one-stop shopping for anyone interested in all of the facets of bacterial resistance to antibiotics. The breadth of the topics covered refl ects the input of a diversity of editors, some of whom have spent their careers in the ivory tower of academic research, some who have had an interest in the public health issues involving the resistance problem, and some who have had direct experience with antibiotic discovery and development. The book represents a unique contribution to the continuing discussion of the best ways to respond to the challenge posed by resistant bacteria. Victory in this battle is not going to be easy. After all, our bacterial adversaries have had a 3-billion-year evolutionary head start. Their diversity and ability to respond to adversity are amazing and frightening. Disseminating information and thus stimulating more scientists to become part of the solution to the problem of resistant bacteria is our best strategy for victory.