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INTRODUCTION

This chapter explains how antibacterials work, the ways in which bacteria become resistant, and strategies we can take to minimize that resistance. Specific information about pathogenic bacteria can be found in Chapters 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41; a complete guide to the treatment of infectious diseases is beyond the scope of this book.

Natural materials with some activity against microbes were used in folk medicine in earlier times. Rational approaches to chemotherapy began with Ehrlich’s development of arsenical compounds for the treatment of syphilis early in the 20th century. Years elapsed before the next major development, which was the discovery of the therapeutic effectiveness of a sulfonamide (prontosil rubrum) by Domagk in 1935. Penicillin had been discovered in 1929 by Fleming but could not be adequately purified at that time; this was accomplished later, and penicillin was produced in sufficient quantities so that Florey and colleagues could demonstrate its clinical effectiveness in the early 1940s.

Sulfonamides, penicillin first effective antibacterial agents

Since that time, numerous new antimicrobial agents have been discovered or developed, and many have found their way into clinical practice. Thanks to these medicines, the human experience in industrialized nations is dramatically different today than it was in the pre-antibiotic era. However, this success has come at the cost of rising antimicrobial resistance. In order to be good antimicrobial stewards, all clinicians must understand the ways in which these drugs work, the ways in which bacteria evolve in response to antibiotics, and strategies for their judicious use.

Antimicrobial resistance a critical challenge for modern medicine

ANTIBACTERIAL AGENTS AND THERAPY

ANTIBACTERIAL AGENTS AND THERAPY Overview

Antibacterial medications attack a variety of bacterial targets. In this chapter, we will classify these drugs by their mechanisms of action. In clinical practice, antibacterials may also be grouped by their spectrum of activity, tissue penetration, route of administration, process of metabolism and elimination, toxicity, drug interactions, and cost.

GENERAL CONSIDERATIONS

Clinically effective antimicrobial agents exhibit selective toxicity toward the microbe rather than the host, a characteristic that differentiates them from the disinfectants (see Chapter 3). In most cases, selectivity is explained by action on microbial processes or structures that differ from those of mammalian cells. For example, some agents inhibit the synthesis of the bacterial cell wall (an organelle not present in eukaryotes), and others act on the 70S bacterial ribosome (but not the 80S eukaryotic ribosome). Some antimicrobials, such as penicillin, are usually nontoxic to the host, unless hypersensitivity develops. For others, such as the aminoglycosides, the effective therapeutic dose is relatively close to the toxic dose; as a result, control of dosage ...

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