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ABBREVIATIONS

Abbreviations

ABC: ATP binding cassette

AUC: area under the Cp-time curve

CCR5: chemokine receptor type 5

CD4: T-helper cells

CMV: cytomegalovirus

Cp: plasma concentration

CPmax: peak plasma concentration

CYP: cytochrome P450

DHFR: dihydrofolate reductase

DHPS: dihydropteroate synthase

E: effect

EC: effective concentration

ELF: epithelial lining fluid

Emax: maximal effect

HIV: human immunodeficiency virus

IC: inhibitory concentration

MALDI-TOF MS: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

MEC: minimum effective concentration

MIC: minimum inhibitory concentration

PAE: postantibiotic effect

PCR: polymerase chain reaction

PK/PD: pharmacokinetics-pharmacodynamics

PrEP: preexposure prophylaxis

rpoB: RNA polymerase

ANTIMICROBIAL CHEMOTHERAPY: CLASSES AND ACTIONS

This chapter reviews the general classes of antimicrobial drugs, their mechanisms of action and mechanisms of resistance, and principles of drug selection. Chapters 57 through 68 present the pharmacological properties and uses of individual classes of antimicrobials.

Microorganisms of medical importance fall into four categories: bacteria, viruses, fungi, and parasites. The broad classification of antibiotics—a term we will use colloquially to encompass all manner of antimicrobial agents—follows this classification closely, so that we have antibacterial, antiviral, antifungal, and antiparasitic agents. However, there are many antibiotics that work against more than one category of microbes, especially those that target evolutionarily conserved pathways. Classification of an antibiotic can be performed along several dimensions, including the class and spectrum of microorganisms it kills, the biochemical pathway it interferes with, and the chemical structure of its pharmacophore.

Antimicrobial molecules should be viewed as ligands whose receptors are typically microbial proteins. The term pharmacophore, introduced by Ehrlich, defines that active chemical moiety of the drug that binds to the microbial receptor. The microbial proteins targeted by the antibiotic are essential components of biochemical reactions in the microbes, and interference with these physiological pathways inhibits the replication of or directly kills the microorganisms. The biochemical processes commonly inhibited include cell wall synthesis, cell membrane synthesis and function, ribosomal translation, nucleic acid metabolism, topoisomerase-mediated chromosomal conformational changes, viral proteases, viral integrases, viral envelope entry/fusion proteins, folate synthesis, and parasitic chemical detoxification processes. Recently, antisense antibiotics have been developed; these work by inhibiting gene expression in bacteria in a sequence-specific manner. Furthermore, interferon-based products work by inducing specific antiviral activities of the infected human cells.

TYPES AND GOALS OF ANTIMICROBIAL THERAPY

A useful way to organize the types and goals of antimicrobial therapy is to consider where antibiotics are initiated with respect to the disease progression timeline (Figure 56–1); therapy can be classified as primary prophylaxis, preemptive, empirical, definitive, or suppressive/secondary prophylaxis.

Figure 56–1

Categories of antimicrobial therapy in relation to disease progression.

Primary Prophylaxis

Prophylaxis involves administering antibiotics to patients who are not yet infected or have not yet ...

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