Optimizing therapy for infections caused by Enterobacteriaceae producing extended-spectrum β-lactamases

The spread of multidrug-resistant Enterobacteriaceae is complicating the treatment of nosocomial infections. In many parts of the world, resistance to third-generation cephalosporins exceeds 10% of total nosocomial isolates and 30% of isolates detected in the intensive care unit. This resistance is frequently due to the acquisition of plasmids containing genes encoding for extended-spectrum beta-lactamases (ESBLs). Furthermore, these mobile elements often carry genes encoding resistance to other drugs such as aminoglycosides. A high risk of poor clinical outcome has been observed in patients infected with ESBL producers receiving third-generation cephalosporins, even if the organism appears susceptible to the antibiotic. For this reason, clinical microbiology laboratories are advised to incorporate specific ESBL detection methodology into routine clinical practice. This should prevent erroneous use of cephalosporins for these infections. Most ESBL producers remain susceptible to carbapenems, and these agents are considered the drugs of choice against ESBL-producing organisms. Unfortunately, there is now an increasing occurrence of carbapenem resistance in the Enterobacteriaceae. In this context, clinical response to new antibiotics (e.g., tigecycline) and old antibiotics (e.g., colistin) with good in vitro activity against ESBL producers needs to be evaluated.