The Changing Epidemiology of Extended Spectrum Beta-Lactamases (ESBL) Infections of the Urinary Tract Focusing on Clinical Resistance and Therapeutic Options

The first betalactamases were identified in a species of E.coli in 1940 (1). However, the ability of bacteria to produce enzymes that destroy the b-lactam ring was noted even before penicillin was developed. In fact, many of the gram-negative bacteria possess chromosomally mediated blactamases, which help the bacteria find a niche when faced with competition from other bacteria that naturally produce b-lactams. In 1965, the first plasmid mediated betalactamases was discovered. This occurred in a strain of E.coli isolated from the blood culture of a patient from Greece whose name was Temoniera. The beta -lactamases was named TEM-1 after the patient’s name from whom it was isolated. (2) This strain soon spread to other members of the Enterobacteriaceae species, Hemophilus influenza, Neisseria gonorrhoeae and Pseudomonas aeruginosa due to the plasmid mediated transfer. Around the same time a second plasmid mediated beta-lactamases was found in Klebsiella pneumonaie and E.coli. This was called SHV-1 (sulfhydryl variable) (3). The advent of the blactam class of antibiotics was influenced largely by the discovery of these enzymes. An example of this was the development of oxyimino-cephalosporin, which showed good stability against the TEM-1 and SHV-1 b-lactamases (4). This class of antibiotics soon became the workhorse for these types of serious infections. Unfortunately, resistance to this class soon became evident in 1985 with beta-lactamases showing the ability to hydrolyze these compounds in K.pneumoniae (5). Because this enzyme was noted to be active against expanded spectrum b-lactams these enzymes were labeled as “extended spectrum beta-lactamases” –ESBL. Several b-lactamases have continued to be with over 130 TEMS types and over 50 SHV types known to date. These are mainly found in E.coli, K.pneumoniae and P.mirabilis, but have also been found in other species of the Enterobacteriacae family and even in some nonenteric bacteria such as Acinetobacter species. Shortly after the introduction of new broad-spectrum cephalosporins such as cefotaxime and ceftazidime, non-TEM and non SHV ESBL’s were discovered. This new class of ESBL’s