Chapter 15. Quinolone Antibacterial Agents

Abstract

This chapter discusses the recent developments on therapeutically useful anti-bacterial quinolone. The biochemical target of quinolones is the procsryotic enzyme DNA gyrase, a type II topoisomerase. In an energy requiring process, bacterial DNA gyrase introduces negative supercoils into circular duplex DNA. Mutants selected in vitro for resistance to one quinolone generally show cross-resistance to other quinolones but not to other classes of antibiotics. Quinolone resistance can also occur from reduced cellular permeability; mutants of this type can show cross-resistance to beta-lactam antibiotics. Norfloxacin (NOR) is less active than other quinolones against ureaplasma and shows only moderate activity against Chlamydia trachomatis . Ciprofloxacin (CIP) shows the same relative spectrum of activity as other fluoroquinolones, but is generally the most potent member of this class. Enoxacin (ENO) shows essentially the same spectrum in vitro as NOR, with NOR being somewhat more potent. The in vitro spectrum and potency of pefloxacin (PEF) is similar to that of NOR, but shows slightly better activity against gram-positive cocci and B. fragilis . The in vitro potency of ofloxacin (OFL) is comparable to NOR against members of the Enterobacteriaceae . Amifloxacin (AMI) has an l-methylamino function reported to be an ethyl equivalent. Rosoxacin (ROS) has good in vitro activity against common urinary pathogens with less activity against the gram-positive cocci . Miloxacin (MIL) is 4- to 8-fold more potent in vitro than NAL AM-833 has in vitro activity similar to NOR except it is more potent vs. S. aureus . CI-934 is generally more potent in vitro than AMI or OFL vs. gram-positive cocci .