The quinolones: future prospects

Abstract

It has been a remarkable journey. Nalidixic acid was first synthesized in 1961 as a 1,8 naphthyridine by-product of chloroquine production and found to have a limited Gram-negative antibacterial spectrum sufficient only for patients with urinary infection [1]. Now, four decades later, we have an array of agents which appear to be remarkably safe and well tolerated, readily administered through both oral and parenteral routes with wide distribution throughout the body, with surprising effectiveness for a wide range of bacterial infections. No one would have predicted this outcome during the first two decades of quinolone history. For those of us who have lived with these molecules through their therapeutic evolution, we continue to be surprised and delighted with the ability of the pharmaceutical industry to modify the basic molecule and manipulate it to achieve major changes in antibacterial activity and improve pharmacokinetics. With regard to changing structure and ensuing activity and adverse reactions, the basic molecule has proved to be very amenable in a way reminiscent of the beta-lactam molecule.