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Resistance to Quinolones and Fluoroquinolones

  • L. J. V. Piddock
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 91)

Abstract

The quinolone class of oral antimicrobial agents has enjoyed rapid expansion and development over recent years and a revival in interest in the earlier agents nalidixic and oxolinic acid. The quinolone class (which includes 4-pyridone antibacterials) share the 4-quinolone nucleus and also a carboxylic acid substituent at position 3 (Fig. 1). During the last twenty-five years many compounds have been synthesised with additional substituents upon the basic nucleus and have been evaluated for use in antimicrobial chemotherapy. The early agents, nalidixic and oxolinic acid, were only active against gram-negative bacteria and the achievable serum concentrations were below the concentration needed to inhibit most pathogens. Consequently, these agents were limited to the treatment of urinary tract infections. In recent years many compounds have been synthesised with a fluorine substituent at position 6 of the quinolone nucleus (Fig. 1). This was found to enhance the antibacterial activity and enable adequate serum concentrations to be achieved (Hooper and Wolfson 1985). Other substituents in addition to the fluorine have been added to the nucleus with the aim of increasing the anti-gram positive bacterial activity. There are now approximately one dozen significant quinolone and fluoro-quinolone compounds (referred to as “quinolone” for the rest of the chapter) which are active against a broad spectrum of pathogens, including those causing systemic infections. The spectrum of activity for the agents in Fig. 1 has been recently reviewed (Wolfson and Hooper 1985) as has the pharmacology, clinical uses and toxicities in humans (Hooper and Wolfson 1985).

Keywords

Nalidixic Acid Antimicrob Agent Micrococcus Luteus Oxolinic Acid Pipemidic Acid 
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© Springer-Verlag Berlin Heidelberg 1989

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  • L. J. V. Piddock

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