Extended-Spectrum β-Lactamases: a Clinical Update

Abstract

SUMMARY Extended-spectrum β-lactamases (ESBLs) are a rapidly evolving group of β-lactamases which share the ability to hydrolyze third-generation cephalosporins and aztreonam yet are inhibited by clavulanic acid. Typically, they derive from genes for TEM-1, TEM-2, or SHV-1 by mutations that alter the amino acid configuration around the active site of these β-lactamases. This extends the spectrum of β-lactam antibiotics susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described. The presence of ESBLs carries tremendous clinical significance. The ESBLs are frequently plasmid encoded. Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides). Therefore, antibiotic options in the treatment of ESBL-producing organisms are extremely limited. Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant isolates have recently been reported. ESBL-producing organisms may appear susceptible to some extended-spectrum cephalosporins. However, treatment with such antibiotics has been associated with high failure rates. There is substantial debate as to the optimal method to prevent this occurrence. It has been proposed that cephalosporin breakpoints for the Enterobacteriaceae should be altered so that the need for ESBL detection would be obviated. At present, however, organizations such as the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) provide guidelines for the detection of ESBLs in klebsiellae and Escherichia coli. In common to all ESBL detection methods is the general principle that the activity of extended-spectrum cephalosporins against ESBL-producing organisms will be enhanced by the presence of clavulanic acid. ESBLs represent an impressive example of the ability of gram-negative bacteria to develop new antibiotic resistance mechanisms in the face of the introduction of new antimicrobial agents.

High Prevalence and Significant Association of ESBL and QNR Genes in Pathogenic Klebsiella pneumoniae Isolates of Patients from Kolkata, India

“…Significant association between the presence of bla and QNR genes (as observed in the study) is of serious concern since quinolone resistant ESBL bacteria has limited treatment options. Higher resistance against Ciprofloxacin in ESBL Klebsiella has been previously reported by Paterson et al and Lautenbach et al [17,24].…”

Development of a multiplex PCR system and its application in detection of blaSHV, blaTEM, blaCTX-M-1, blaCTX-M-9 and blaOXA-1 group genes in clinical Klebsiella pneumoniae and Escherichia coli strains

“…However, there exists some reports that tend to suggest that TEM-1 may also contribute to the ESBL trait in concert with other β-lactamases. 7,40 Upon DNA sequencing of PCR products from all strains with bla group genes, the distribution of the β-lactamase subtypes corresponded with the M-PCR results. CTX-M-14 and CTX-M-3 were the most prevalent among the ESBL-producing clinical K. pneumoniae and E. coli strains.…”

“…16 The phenotypic screening and detection of β-lactamase (bla) genes are routinely carried out through tedious culture-based methods, whereas their definitive confirmation in Enterobacteriaceae and other bacteria is achieved largely by molecular methods. 17 As the current subtypes and variants are continuously evolving and disseminating both geographically and among the various bacterial species, 7 growing numbers of Enterobacteriaceae, especially K. pneumoniae and E. coli from clinical sources tend to harbor multiple β-lactamases and exhibit multiresistance to the various β-lactams. Consequently, existing efforts geared toward sustained and continuous development of new accurate and rapid molecular methods with the ability to simultaneously detect multiple bla genes in single and/or mixed bacterial strains must be sustained.…”

Role of EDTA and CSE1034 in curli formation and biofilm eradication of Klebsiella pneumoniae: a comparison with other drugs

“…4 It has been observed that the extended spectrum b-lactamases producing K. pneumoniae strain is not susceptible to third-generation cephalosporins viz., ceftizoxime, cefotaxime, ceftriaxone and ceftazidime etc. 5 Analysis performed in Europe with 5000 Enterobacteriaceae isolates showed a high degree of resistance to many antibiotics 6 due to bacterial biofilm formation. 7 It has earlier been reported that curli fibers are a major factor in adhesion to surfaces and biofilm formation in many enterobacteria.…”