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Chapter 43 : Implications of Pharmacogenetics for Antimicrobial Prescribing

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Implications of Pharmacogenetics for Antimicrobial Prescribing, Page 1 of 2

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Abstract:

Antimicrobial efficacy and toxicity are influenced by the interplay of factors related to the human host, the microbe, and the drug (1–3). A number of such factors are represented in Fig. 1 (4). Antimicrobials can be described by characteristic pharmacokinetic (PK) and pharmacodynamic (PD) profiles, which in many cases are influenced by absorption, distribution, elimination, and metabolism (ADME) genes. While some antimicrobials are eliminated largely unchanged in urine (e.g., vancomycin) or stool (e.g., atovaquone), many undergo extensive metabolism by phase I enzymes (e.g., cytochrome P450 isoforms) and/or phase II enzymes (e.g., UDP-glucuronosyltransferases). The resultant metabolites may lack antimicrobial activity, or conversely the active moiety may be generated from an inactive parent compound (i.e., prodrug). Toxic and hypersensitivity reactions may be mediated by parent compounds or their metabolites, depending on the particular drug. Antimicrobial disposition is also affected by membrane transporters in various tissues including liver, intestine, kidney, genital tract, and brain (5–7). Genetic polymorphisms that affect ADME gene expression or protein activity may be associated with interindividual differences in exposure to parent compound and/or metabolites. Some of these genotype-phenotype associations have implications for efficacy and toxicity.

Citation: Aung A, Phillips E, Hulgan T, Haas D. 2016. Implications of Pharmacogenetics for Antimicrobial Prescribing, p 613-633. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch43
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FIGURE 1

Relationships among drug, pathogen, and host factors affecting antimicrobial treatment outcome. CCR5, C-C chemokine receptor type 5; HLA, human leukocyte antigen; PD, pharmacodynamics; PK, pharmacokinetics. Modified with permission from Pavlos and Phillips ( ).

Citation: Aung A, Phillips E, Hulgan T, Haas D. 2016. Implications of Pharmacogenetics for Antimicrobial Prescribing, p 613-633. In Persing D, Tenover F, Hayden R, Ieven M, Miller M, Nolte F, Tang Y, van Belkum A (ed), Molecular Microbiology. ASM Press, Washington, DC. doi: 10.1128/9781555819071.ch43
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