The development of vaccines and drugs that prevent and cure bacterial infections was one of the twentieth century's major contributions to human longevity and quality of life. Antibacterial agents are among the most commonly prescribed drugs of any kind worldwide. Used appropriately, these drugs are lifesaving. However, their indiscriminate use drives up the cost of health care, leads to a plethora of side effects and drug interactions, and fosters the emergence of bacterial resistance, rendering previously valuable drugs useless. The rational use of antibacterial agents depends on an understanding of (1) the drugs' mechanisms of action, spectra of activity, pharmacokinetics, pharmacodynamics, toxicities, and interactions; (2) mechanisms underlying bacterial resistance; and (3) strategies that can be used by clinicians to limit resistance. In addition, patient-associated parameters, such as infection site, other drugs being taken, allergies, and immune and excretory status, are critically important to appropriate therapeutic decisions. This chapter provides specific data required for making an informed choice of antibacterial agent.
Antibacterial agents, like all antimicrobial drugs, are directed against unique targets not present in mammalian cells. The goal is to limit toxicity to the host and maximize chemotherapeutic activity affecting invading microbes only. Bactericidal drugs kill the bacteria that are within their spectrum of activity; bacteriostatic drugs only inhibit bacterial growth. While bacteriostatic activity is adequate for the treatment of most infections, bactericidal activity may be necessary for cure in patients with altered immune systems (e.g., neutropenia), protected infectious foci (e.g., endocarditis or meningitis), or specific infections (e.g., complicated Staphylococcus aureus bacteremia). The mechanisms of action of the antibacterial agents to be discussed in this section are summarized in Table 133-1 and are depicted in Fig. 133-1.
Table 133-1 Mechanisms of Action of and Resistance to Major Classes of Antibacterial Agents |Favorite Table|Download (.pdf)
Table 133-1 Mechanisms of Action of and Resistance to Major Classes of Antibacterial Agents
|Letter for Fig. 133-1||Antibacterial Agenta||Major Cellular Target||Mechanism of Action||Major Mechanisms of Resistance|
|A||β-Lactams (penicillins, cephalosporins)||Cell wall||Inhibit cell-wall cross-linking|
1. Drug inactivation (β-lactamase)
2. Insensitivity of target (altered penicillin-binding proteins)
3. Decreased permeability (altered gram-negative outer-membrane porins)
4. Active efflux
|B||Vancomycin||Cell wall||Interferes with addition of new cell-wall subunits (muramyl pentapeptides)||Alteration of target (substitution of terminal amino acid of peptidoglycan subunit)|
|Bacitracin||Cell wall||Prevents addition of cell-wall subunits by inhibiting recycling of membrane lipid carrier||Not defined|
|C||Macrolides (erythromycin)||Protein synthesis||Bind to 50S ribosomal subunit|
1. Alteration of target (ribosomal methylation and mutation of 23S rRNA)
2. Active efflux
|Lincosamides (clindamycin)||Protein synthesis||Bind to 50S ribosomal subunit Block peptide chain elongation|
1. Alteration of target (ribosomal methylation)
2. Active efflux
|D||Chloramphenicol||Protein synthesis||Binds to 50S ribosomal subunit Blocks aminoacyl tRNA attachment|
1. Drug inactivation (chloramphenicol acetyltransferase)
2. Active efflux
|E||Tetracycline||Protein synthesis||Binds to 30S ribosomal subunit Blocks binding of aminoacyl tRNA|
1. Decreased ...
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