β-Lactamases continue to be the leading cause of resistance to β-lactam antibiotics among gram-negative bacteria. In recent years there has been an increased incidence and prevalence of extended-spectrum β-lactamases (ESBLs), enzymes that hydrolyze and cause resistance to oxyimino-cephalosporins and aztreonam. The majority of ESBLs are derived from the widespread broad-spectrum β-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including the CTX-M and OXA-type enzymes as well as novel, unrelated β-lactamases. Several different methods for the detection of ESBLs in clinical isolates have been suggested. While each of the tests has merit, none of the tests is able to detect all of the ESBLs encountered. ESBLs have become widespread throughout the world and are now found in a significant percentage of Escherichia coli and Klebsiella pneumoniae strains in certain countries. They have also been found in other Enterobacteriaceae strains and Pseudomonas aeruginosa. Strains expressing these β-lactamases will present a host of therapeutic challenges as we head into the 21st century.

Extended-Spectrum β-Lactamases in the 21st Century: Characterization, Epidemiology, and Detection of This Important Resistance Threat

An Italian nationwide survey was carried out to assess the prevalences and the antimicrobial susceptibilities of members of the family Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs). Over a 6-month period, 8,015 isolates were obtained from hospitalized patients and screened for resistance to extended-spectrum cephalosporins and monobactams. On the basis of a synergistic effect between clavulanate and selected beta-lactams (ceftazidime, aztreonam, cefotaxime, cefepime, and ceftriaxone), 509 isolates were found to be ESBL positive (6.3%). Colony blot hybridization with bla(TEM) and bla(SHV) DNA probes allowed one to distinguish four different genotypes: TEM-positive, SHV-positive, TEM- and SHV-positive, and non-TEM, non-SHV ESBL types. MICs for each isolate (E-test) were obtained for widely used beta-lactams, combinations of beta-lactams with beta-lactamase inhibitors, aminoglycosides, and fluoroquinolones. Among ESBL-positive strains, Klebsiella pneumoniae, Proteus mirabilis, and Escherichia coli accounted for 73.6% of isolates. Overall, TEM-type ESBLs were more prevalent than SHV-type enzymes (234 versus 173), whereas the prevalence of strains producing both TEM- and SHV-type ESBLs was similar to that of isolates producing non-TEM, non-SHV enzymes (55 and 38, respectively). In vitro, all but one of the ESBL-producing isolates remained susceptible to imipenem. Susceptibility to other drugs varied: piperacillin-tazobactam, 91%; amoxicillin-clavulanic acid, 85%; cefoxitin, 78%; amikacin, 76%; ampicillin-sulbactam, 61%; ciprofloxacin, 58%; and gentamicin, 56%. Associated resistance to aminoglycosides and ciprofloxacin was observed most frequently among TEM-positive strains. Since therapeutic options for multiresistant Enterobacteriaceae are limited, combinations of beta-lactams and beta-lactamase inhibitors appear to represent an important alternative for treating infections caused by ESBL-producing ENTEROBACTERIACEAE:

Occurrence of Extended-Spectrum β-Lactamases in Members of the Family Enterobacteriaceae in Italy: Implications for Resistance to β-Lactams and Other Antimicrobial Drugs

Characteristics, epidemiology and clinical importance of emerging strains of Gram-negative bacilli producing extended-spectrum beta-lactamases.

β-Lactamase production was detected in 147 (52%) of 282 consecutive nonduplicate Proteus mirabilis isolates obtained over a 1-year period from the S. Matteo Hospital of Pavia (northern Italy). Seventy isolates (48% of the β-lactamase producers) were found to produce extended-spectrum β-lactamases (ESBLs), identified as PER-1 (first report in this species) and TEM-52 in 52 and 18 isolates, respectively. Analysis of clonal diversity of the ESBL producers suggested different spreading patterns for the two ESBL determinants.

Emerging Extended-Spectrum β-Lactamases in Proteus mirabilis

https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(15)30037-9/pdf

Multidrug resistance in Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs).

A new natural TEM-2 derivative, named TEM-72, was identified in a Proteus mirabilis strain and in a Morganella morganii strain isolated in Italy in 1999. Compared to TEM-1, TEM-72 contains the following amino acid substitutions: Q39K, M182T, G238S, and E240K. Kinetic analysis showed that TEM-72 exhibits an extended-spectrum activity, including activity against oxyimino-cephalosporins and aztreonam. Expression of bla(TEM-72) in Escherichia coli was capable of decreasing the host susceptibility to the above drugs.

TEM-72, a New Extended-Spectrum β-Lactamase Detected in Proteus mirabilis and Morganella morganii in Italy

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TEM-72, a New Extended-Spectrum β-Lactamase Detected in Proteus mirabilis and Morganella morganii in Italy