Quinolones

The quinolones are a diverse class of antimicrobial agents which target the two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV which inhibit DNA synthesis. The molecular structure of the quinolones has been altered over time with the naphthyridine nucleus being the base for a series of more active compounds, most importantly the fluorination at the 6-position giving the fluoroquinolones. These changes have changed the antibacterial spectrum of activity which was initially predominantly Gram negative bacteria but now includes Gram positive, anaerobes and mycobacteria. This class remain the best oral option for treating infections due to Pseudomonas aeruginosa. There has been a corresponding increase in the list of indications, which now includes urinary tract infections, sexually transmitted infections, ophthalmic infections, gastrointestinal infections, respiratory infections, skin and soft tissue infections, bone and joint infections and tuberculosis. This wider use has led to increasing concerns regarding the emergence of resistance. Resistance can be the result of mutations in chromosomal genes or plasmid-mediated. Important side effects include tendinopathy, aortic dissection, reduced seizure threshold (leading to increased chances of seizures), prolonged QT interval and diarrhea due to C. difficile infection. Care must be exercised to reduce the risk of emerging resistance if they are to remain as useful as they are now.