Multiple resistance in Gram-negative bacteria

When extended spectrum cephalosporins were introduced into clinical practice some 20 years ago it was widely predicted that these agents would effectively remove the problem of infections caused by resistant Enterobacteriaceae. It very rapidly became clear that the rapid evolution of antibiotic resistance genes in Gram-negative bacteria, particularly with their fluid gene pool, could circumvent the pharmaceutical industry's efforts. In the last 10 years, extended-spectrum beta-lactamases have become the major mechanism of resistance in Enterobacteriaceae to these valuable antimicrobials. In many parts of the world resistance levels have reached the point where these agents can no longer be used, this has resulted in greatly increased usage of fluoroquinolones and carbepenem antibiotics and, once again, a variety of mechanisms of resistance have been recognized which are becoming increasingly common. The review discusses various aspects of the molecular evolution of resistance to these three major groups of antibiotics and reviews the role of mobile elements in Gram-negative bacteria in the dissemination of genes encoding resistance to these classes of antimicrobial. It is concluded that there is already a growing problem of potentially untreatable infections caused by Enterobacteriaceae and Pseudomonas aeruginosa which, unless novel agents are introduced, could pose a major threat to the health of both hospitalized patients and, with the movement of these genes into faecally carried community Gram-negative bacteria, patients with infections in the community. (C) 2004 Lippincott Williams Wilkins.