Extended-spectrum beta-lactamases

INTRODUCTION

Extended-spectrum beta-lactamases (ESBL) are enzymes that confer resistance to most beta-lactam antibiotics, including penicillins, cephalosporins, and the monobactam aztreonam. Infections with ESBL-producing organisms have been associated with poor outcomes.

Community and hospital-acquired ESBL-producing Enterobacteriaceae are prevalent worldwide [1]. Reliable identification of ESBL-producing organisms in clinical laboratories can be challenging, so their prevalence is likely underestimated. Carbapenems are the best antimicrobial agent for infections caused by such organisms.

The types and detection of extended-spectrum beta-lactamases as well as the epidemiology and treatment of organisms that produce them are discussed in this topic. The clinical features and diagnosis of the infections that ESBL-producing organisms often cause are discussed elsewhere. (See "Gram-negative bacillary bacteremia in adults" and "Acute complicated cystitis and pyelonephritis" and "Epidemiology, pathogenesis, microbiology, and diagnosis of hospital-acquired, ventilator-associated, and healthcare-associated pneumonia in adults" and "Clinical features, diagnosis, and treatment of Klebsiella pneumoniae infection".)

BETA-LACTAMASES

Beta-lactamases are enzymes that open the beta-lactam ring, inactivating the antibiotic. The first plasmid-mediated beta lactamase in gram-negative bacteria was discovered in Greece in the 1960s. It was named TEM after the patient from whom it was isolated (Temoniera) [2]. Subsequently, a closely related enzyme was discovered and named TEM-2. It was identical in biochemical properties to the more common TEM-1 but differed by a single amino acid with a resulting change in the isoelectric point of the enzyme.

These two enzymes are the most common plasmid-mediated beta-lactamases in gram-negative bacteria, including Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, and Neisseria gonorrhoeae. TEM-1 and TEM-2 hydrolyze penicillins and narrow spectrum cephalosporins, such as cephalothin or cefazolin. However, they are not effective against higher generation cephalosporins with an oxyimino side chain, such as cefotaxime, ceftazidime, ceftriaxone, or cefepime. Consequently, when these antibiotics were first introduced, they were effective against a broad group of otherwise resistant bacteria. A related but less common enzyme was termed SHV, because sulfhydryl reagents had a variable effect on substrate specificity. (See "Beta-lactam antibiotics: Mechanisms of action and resistance and adverse effects" and "Cephalosporins".)