Treatment of Infections Caused by Extended-Spectrum beta-Lactamase-Producing Enterobacteriaceae

The Enterobacteriaceae, most notably Escherichia coli and Klebsiella pneumoniae, are among the most important causes of serious nosocomial and community-acquired bacterial infections of humans. These organisms may produce extended-spectrum-lactamases (ESBLs) that result in broad spectrum resistance to the-lactam antibiotics, a major class of anti-bacterial agents. The majority of ESBL enzymes in Enterobacteriaceae are encoded on large plasmids typically with other antibiotic resistance genes that are transmissible among different strains and species. Although there is considerable geographic variation, the rate of infections due to ESBL-producing Enterobacteriaceae is rising and these infections have been increasingly recognized to occur in community-based patients. As a result of their broad spectrum resistance profile, empiric treatment failure is common with ESBL-producing Enterobacteriaceae infections. Largely because of their resistance to both hydrolysis and the innoculum effect, the carbapenem class of antibacterials have become widely accepted as the agents of choice for the treatment of serious infections due to ESBL-producing Enterobacteriaceae. However, the superiority of carbapenems over other classes of active agents in the treatment of these infections is inconsistently supported by observational studies and there is a lack of clinical trial data. Future prospective studies are needed to determine the optimal management of these important infections.