Fluoroquinolones work by binding to DNA gyrase and a related enzyme, topoisomerase IV—both of which are essential for replication of the bacterial DNA. While DNA gyrase tends to be the primary target in gram-negative organisms, topoisomerase is targeted in gram-positive cells. It is not known how these drugs target different enzymes in different cell types, but this mode of action ensures that fluoroquinolones provide broad-spectrum effectiveness. In addition to being broad spectrum and highly potent, the drugs are readily absorbed from the intestine.
Since their introduction, quinolones have gone through four generations of development. There are currently about two dozen different types. Two of the more commonly used quinolones, norfloxacin and ciprofloxacin (Cipro), are prescribed in many cases of urinary tract infections, sexually transmitted diseases, gastrointestinal infections, osteomyelitis, respiratory infections, and soft tissue infections. Newer drugs in this category are sparfloxacin and levofloxacin. Side effects that can limit the use of quinolones include damage to tendons, an increased risk of aortic aneurysm, and brain disturbances. The FDA now requires fluoroquinolones to carry a black box label to warn consumers of these serious side effects.
Another drug that disrupts nucleic acids is rifampin. The primary action of this drug is to block the action of RNA polymerase, thereby preventing transcription. It is somewhat limited in spectrum because the molecule cannot pass through the cell envelope of many gram-negative bacilli. It is mainly used to treat infections by selected gram-positive rods and cocci and a few gram-negative bacteria. Rifampin figures most prominently in treating mycobacterial infections, especially tuberculosis and Hansen’s disease (leprosy), but it is usually given in combination with other drugs to prevent the development of resistance. Rifampin is also recommended for prophylaxis in Neisseria meningitidis carriers and their contacts, and it is occasionally used to treat Legionella, Brucella, and Staphylococcus infections.
