Beta-lactamase: Difference between revisions

Members of this family commonly express β-lactamases (e.g., TEM-3, TEM-4,<ref>{{cite web | title = Ambler class A beta-lactamases: TEM | url = http://bldb.eu/BLDB.php?prot=A#TEM | work = Beta-Lactamase DataBase (BLDB }}</ref> and SHV-2 <ref>{{cite web | title = Ambler class A beta-lactamases: SHV | url = http://bldb.eu/BLDB.php?prot=A#SHV | work = Beta-Lactamase DataBase (BLDB) }} </ref>) which confer resistance to expanded-spectrum (extended-spectrum) cephalosporins. In the mid-1980s, this new group of enzymes, the extended-spectrum β-lactamases (ESBLs), was detected (first detected in 1979).<ref name="pmid314270">{{cite journal | vauthors = Sanders CC, Sanders WE | title = Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases | journal = Antimicrobial Agents and Chemotherapy | volume = 15 | issue = 6 | pages = 792–797 | date = June 1979 | pmid = 314270 | pmc = 352760 | doi = 10.1128/AAC.15.6.792 }}</ref> The prevalence of ESBL-producing bacteria have been gradually increasing in acute care hospitals.<ref>{{cite journal | vauthors = Spadafino JT, Cohen B, Liu J, Larson E | title = Temporal trends and risk factors for extended-spectrum beta-lactamase-producing Escherichia coli in adults with catheter-associated urinary tract infections | journal = Antimicrobial Resistance and Infection Control | volume = 3 | issue = 1 | pages = 39 | year = 2014 | pmid = 25625011 | pmc = 4306238 | doi = 10.1186/s13756-014-0039-y }}</ref> The prevalence in the general population varies between countries, e.g. approximately 6% in Germany<ref>{{cite journal | vauthors = Symanzik C, Hillenbrand J, Stasielowicz L, Greie JC, Friedrich AW, Pulz M, John SM, Esser J | display-authors = 6 | title = Novel insights into pivotal risk factors for rectal carriage of extended-spectrum-β-lactamase-producing enterobacterales within the general population in Lower Saxony, Germany | journal = Journal of Applied Microbiology | date = December 2021 | pmid = 34856042 | doi = 10.1111/jam.15399 | s2cid = 244854840 }}</ref> and France,<ref>{{cite journal | vauthors = Nicolas-Chanoine MH, Gruson C, Bialek-Davenet S, Bertrand X, Thomas-Jean F, Bert F, Moyat M, Meiller E, Marcon E, Danchin N, Noussair L, Moreau R, Leflon-Guibout V | display-authors = 6 | title = 10-Fold increase (2006-11) in the rate of healthy subjects with extended-spectrum β-lactamase-producing Escherichia coli faecal carriage in a Parisian check-up centre | journal = The Journal of Antimicrobial Chemotherapy | volume = 68 | issue = 3 | pages = 562–568 | date = March 2013 | pmid = 23143897 | doi = 10.1093/jac/dks429 }}</ref> 13% in Saudi Arabia,<ref>{{cite journal | vauthors = Kader AA, Kamath KA | title = Faecal carriage of extended-spectrum beta-lactamase-producing bacteria in the community | journal = Eastern Mediterranean Health Journal| volume = 15 | issue = 6 | pages = 1365–1370 | date = 2009 | pmid = 20218126 }}</ref> and 63% in Egypt.<ref>{{cite journal | vauthors = Valverde A, Grill F, Coque TM, Pintado V, Baquero F, Cantón R, Cobo J | title = High rate of intestinal colonization with extended-spectrum-beta-lactamase-producing organisms in household contacts of infected community patients | journal = Journal of Clinical Microbiology | volume = 46 | issue = 8 | pages = 2796–2799 | date = August 2008 | pmid = 18562591 | pmc=2519510 | doi = 10.1128/JCM.01008-08 }}</ref> ESBLs are beta-lactamases that hydrolyze extended-spectrum cephalosporins with an oxyimino side chain. These cephalosporins include [[cefotaxime]], [[ceftriaxone]], and [[ceftazidime]], as well as the oxyimino-monobactam [[aztreonam]]. Thus ESBLs confer [[Multiple drug resistance|multi-resistance]] to these antibiotics and related oxyimino-beta lactams. In typical circumstances, 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. A broader set of β-lactam antibiotics are susceptible to hydrolysis by these enzymes. An increasing number of ESBLs not of TEM or SHV lineage have recently been described.<ref name="pmid9230382">{{cite journal | vauthors = Emery CL, Weymouth LA | title = Detection and clinical significance of extended-spectrum beta-lactamases in a tertiary-care medical center | journal = Journal of Clinical Microbiology | volume = 35 | issue = 8 | pages = 2061–2067 | date = August 1997 | pmid = 9230382 | pmc = 229903 | doi = 10.1128/JCM.35.8.2061-2067.1997 }}</ref> 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. [[Carbapenem]]s are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant (primarily [[ertapenem]]-resistant) isolates have recently been reported.<ref name="Grundmann_2010">{{cite journal | vauthors = Grundmann H, Livermore DM, Giske CG, Canton R, Rossolini GM, Campos J, Vatopoulos A, Gniadkowski M, Toth A, Pfeifer Y, Jarlier V, Carmeli Y | display-authors = 6 | title = Carbapenem-non-susceptible Enterobacteriaceae in Europe: conclusions from a meeting of national experts | journal = Euro Surveillance | volume = 15 | issue = 46 | date = November 2010 | pmid = 21144429 | doi = 10.2807/ese.15.46.19711-en }}</ref> ESBL-producing organisms may appear susceptible to some extended-spectrum [[cephalosporin]]s. However, treatment with such antibiotics has been associated with high failure rates.{{Citation needed|date=December 2015}}

 

 

==== TEM beta-lactamases (class A) ====