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Chapter 22 : Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in

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Abstract:

The emergence of resistance to penicillin and other beta-lactam antibiotics in pneumococci in the 1980s and 1990s led to the increased use of macrolides, fluoroquinolones, and other nonbetalactam antibiotics for pneumococcal infections. This chapter focuses on the molecular mechanisms of non-beta-lactam resistance in . Resistance to macrolides can occur by enzymatic inactivation, modification of the target by methylation or mutation, and active efflux. Proteins of the ABC transporter superfamily are organized such that two ATP-binding domains located cytoplasmically interact with two hydrophobic domains consisting of six to eight transmembrane domains. The esterase activity identified in hydrolyzed 14- and 16-membered macrolides. The primary targets of other quinolones have been determined; trovafloxacin, levofloxacin, and norfloxacin target topoisomerase IV (ParC), whereas the primary target of gatifloxacin is DNA gyrase (GyrA). The use of fluoroquinolones to treat pneumococcal infections is the most important factor in the emergence of fluoroquinolone resistance in . Inducible expression allows the mRNA to be made in an inactive conformation that becomes active by the presence of an inducing macrolide. In the United States, population-based surveillance for invasive disease showed that the rapid increase in macrolide resistance was correlated with the spread of mega in pneumococci. Exciting, recent data indicate that the total burden of antimicrobial resistance can be reduced by the use of pneumococcal conjugate vaccines that reduce colonization and transmission of the vaccine serotypes.

Citation: Ambrose K, Stephens D. 2004. Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in , p 350-366. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch22

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Mobile Genetic Elements
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Major Facilitator Superfamily
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Upper Respiratory Tract Infections
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Tables

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TABLE 1

Molecular mechanisms of antibiotic resistance in

Citation: Ambrose K, Stephens D. 2004. Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in , p 350-366. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch22
Generic image for table
TABLE 2

Genetic bases for antibiotic resistance in pneumococci

Citation: Ambrose K, Stephens D. 2004. Macrolide, Quinolone, and Other Non-β-Lactam Antibiotic Resistance in , p 350-366. In Tuomanen E, Mitchell T, Morrison D, Spratt B (ed), The Pneumococcus. ASM Press, Washington, DC. doi: 10.1128/9781555816537.ch22

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