Norfloxacin, a Fluoroquinolone Antibacterial Agent. Classification, Mechanism of Action, and in Vitro Activity

Norfloxacin is an orally absorbed fluoroquinolone antibacterial with a fluorine at position 6 and a piperazine ring at position 7. These changes have resulted in a marked enhancement (compared with that of the older quinolones) of in vitro antibacterial activity. Specifically, the antibacterial spectrum of norfloxacin includes Pseudomonas aeruginosa, as well as enteric pathogens. Norfloxacin is also active against both penicillin-susceptible and penicillin-resistant strains of Neisseria gonorrhoeae. Relative to its activity against gram-negative bacteria, norfloxacin is somewhat less active against gram-positive cocci. In general, the staphylococci are more susceptible to the drug than are the streptococci. As with all fluoroquinolones, norfloxacin's activity against anaerobic bacteria is poor. For urinary tract bacterial isolates, the following Bauer-Kirby disk diffusion zone-size breakpoints have been proposed: greater than or equal to 17 mm, susceptible; 13 to 16 mm, intermediate; less than or equal to 12 mm, resistant. Bacteria with minimal inhibitory concentrations (MICs) less than or equal to 16 micrograms/ml are considered susceptible; those with MICs greater than or equal to 32 micrograms/ml are considered resistant to norfloxacin. The mechanism of action of norfloxacin involves inhibition of the A subunit of the important bacterial enzyme DNA gyrase, which is essential for DNA replication. Plasmid-mediated resistance to the fluoroquinolones is not encountered. Further, although some cross-resistance within the fluoroquinolone class has occurred, there is little cross-resistance between norfloxacin and antibiotics of other classes.