Overview

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 pills. 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 much older and less selective cytotoxic antiseptics and disinfectants are discussed in Chapter 50. The clinical uses of all these agents are summarized in Chapter 51.

The major problem threatening the continued success of antimicrobial drugs is the development of resistant organisms. Microorganisms can adapt to environmental pressures in a variety of effective ways, and their response to antibiotic pressure is no exception. An inevitable consequence of antimicrobial usage is the selection of resistant microorganisms, perhaps the most obvious example of evolution in action. Overuse and inappropriate use of antibiotics in patients has fueled a major increase in prevalence of multidrug-resistant pathogens. Antibacterial antibiotics are misused by providers 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.

As a result of antibiotic pressure, highly resistant gram-negative organisms with novel mechanisms of resistance are increasingly reported. Some of these strains have spread over vast geographic areas as a result of patients seeking medical care in different countries. Much larger quantities of antibiotics have been used in agriculture to stimulate growth and prevent infection in farm animals and this has added to the selection pressure that results in resistant organisms.

Unfortunately, as the need has grown in recent years, development of novel drugs has slowed. The most vulnerable molecular targets of antimicrobial drugs have been identified and, in many cases, crystallized and characterized. Pending the identification of new targets and compounds, it seems likely that over the next decade we will have to rely on currently available families of drugs. In the face of continuing development of resistance, considerable effort will be required to maintain the effectiveness of these drug groups.

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