INTRODUCTION TO ANTIMICROBIAL AGENTS
Antimicrobial agents provide some of the most dramatic examples of the advances of modern medicine. Many infectious diseases once considered incurable and lethal are now amenable to treatment with a few doses of antibiotics. The remarkably powerful and specific activity of antimicrobial drugs is due to their selectivity for targets that are either unique to prokaryote and fungal microorganisms or much more important in these organisms than in humans. Among these targets are bacterial and fungal cell wall-synthesizing enzymes (Chapters 43 and 48), the bacterial ribosome (Chapters 44 and 45), the enzymes required for nucleotide synthesis and DNA replication (Chapter 46), and the machinery of viral replication (Chapter 49). The special group of drugs used in mycobacterial infections is discussed in Chapter 47. The cytotoxic antiseptics and disinfectants are discussed in Chapter 50. The clinical uses of many antimicrobial agents are reviewed in Chapter 51.
The major problem threatening the continued success of antimicrobial drugs is the development of resistant organisms. Bacteria “invented” antibiotics billions of years ago, and resistance is primarily the result of bacterial adaptation to antibiotic exposure over millennia. Antibiotic resistance mechanisms existed before the clinical use of antibiotics, even to synthetic drugs that were created in the 20th century. Since resistance mechanisms are already present in nature, an inevitable consequence of antimicrobial use is the selection of resistant microorganisms, one of the clearest examples of evolution in action. Over the last 70 years, antibiotic use in patients and animals has fueled a major increase in the prevalence of drug-resistant pathogens. In recent years, highly resistant gram-negative organisms with novel mechanisms of resistance have been increasingly reported. Some of these strains have spread over vast geographic areas as a result of patients seeking medical care in different countries.
Much attention has been focused on eliminating the misuse of antibiotics to slow the tide of resistance. Antibiotics are misused in a variety of ways, including use in patients who are unlikely to have bacterial infections, use over unnecessarily prolonged periods, and use of multiple agents or broad-spectrum agents when not needed. Large quantities of antibiotics have been used in agriculture to stimulate growth and prevent infection in livestock, and this has added to the selection pressure that results in resistant organisms. In December 2013, the FDA announced a program to phase out the nontherapeutic use of antibiotics in livestock. However, even if this program is successful, it will take years before the benefits are apparent.
Antibiotic resistance has many negative consequences. The prevalence of resistant organisms drives the use of broader-spectrum, less efficacious, or more toxic antibiotics. Not surprisingly, infections caused by antibiotic-resistant pathogens are associated with increased costs, morbidity, and mortality. Each year in the United States, at least 2 million people acquire serious infections with resistant bacteria. At least 23,000 people die each year ...