The growing problem of antibiotic resistance in clinically relevant Gram-negative bacteria: current situation

Resistance to antimicrobial agents in clinically relevant Gram-negative bacteria is an increasingly important problem, which in the last few years has spread from the hospital setting to the community. In enterobacteria, the main features of this situation include resistance to beta-lactams and quinolones. beta-Lactam resistance is caused by intrinsic beta-lactamases, extended-spectrum beta-lactamases, plasmid-mediated cephamycinases and carbapenemses, particularly when produced in strains with decreased permeability because of altered porin expression. Quinolone resistance is a multifactorial problem in which the importance of plasmid-mediated mechanisms (Qnr proteins, acetylase, active efflux pumps) is being recognized. Several studies in Spain and other countries show that strains with these resistance mechanisms are being isolated with increased frequency. Of particular concern is the spread of Escherichia coli and other species producing extended-spectrum beta-lactamases (most frequently of the CTX-M family), affecting outpatients. Very commonly these mechanisms are simultaneously expressed within the same bacterial host, leading to a multiresistance phenotype. This problem is also of major clinical importance in non-fermenting Gram-negative rods, including Pseudomonas aeruginosa and Acinetobacter baumannii and, to a lesser extent, Stenotrophomonas maltophilia and some other species. Multiresistance in non-fermenting organisms results from the presence of intrinsic mechanisms (production of distinct beta-lactamases, decreased permeability and expression of several active efflux pumps) and from the acquisition of exogenous genes. Therapeutic difficulties reach their maximum when bacteria express resistance to carbapenems (a multifactorial problem) or to polymyxins. New compounds with specific activity against multiresistant Gram-negative rods should be developed, which, together with other measures, would contribute to controlling the current serious situation. (c) 2010 Elsevier Espana, S.L. All rights reserved.