[2] The SBLs are similar in structure and mechanistically to the β-lactam target penicillin-binding proteins (PBPs) which are necessary for cell wall building and modifying.

The difference between the PBPs and SBLs is that the latter generates free enzyme and inactive antibiotic by the very quick hydrolysis of the acyl-enzyme intermediate.

[citation needed] The MBLs use the Zn2+ ions to activate a binding site water molecule for the hydrolysis of the β-lactam ring.

It appeared initially in a limited number of bacterial species (E. cloacae, C. freundii, S. marcescens, and P. aeruginosa) that could mutate to hyperproduce their chromosomal class C β-lactamase.

A few years later, resistance appeared in bacterial species not naturally producing AmpC enzymes (K. pneumoniae, Salmonella spp., P. mirabilis) due to the production of TEM- or SHV-type ESBLs (extended spectrum beta lactamases).

Characteristically, such resistance has included oxyimino- (for example ceftizoxime, cefotaxime, ceftriaxone, and ceftazidime, as well as the oxyimino-monobactam aztreonam), but not 7-alpha-methoxy-cephalosporins (cephamycins; in other words, cefoxitin and cefotetan); has been blocked by inhibitors such as clavulanate, sulbactam or tazobactam and did not involve carbapenems and temocillin.

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.

Plasmids responsible for ESBL production frequently carry genes encoding resistance to other drug classes (for example, aminoglycosides).

Carbapenems are the treatment of choice for serious infections due to ESBL-producing organisms, yet carbapenem-resistant (primarily ertapenem-resistant) isolates have recently been reported.

The amino acid substitutions responsible for the extended-spectrum beta lactamase (ESBL) phenotype cluster around the active site of the enzyme and change its configuration, allowing access to oxyimino-beta-lactam substrates.

Opening the active site to beta-lactam substrates also typically enhances the susceptibility of the enzyme to β-lactamase inhibitors, such as clavulanic acid.

Rather than arising by mutation, they represent examples of plasmid acquisition of beta-lactamase genes normally found on the chromosome of Kluyvera species, a group of rarely pathogenic commensal organisms.

The OXA-type beta-lactamases confer resistance to ampicillin and cephalothin and are characterized by their high hydrolytic activity against oxacillin and cloxacillin and the fact that they are poorly inhibited by clavulanic acid.

Other plasmid-mediated ESBLs, such as PER, VEB, GES, and IBC beta-lactamases, have been described but are uncommon and have been found mainly in P. aeruginosa and at a limited number of geographic sites.

CTX-M-15-positive E. coli are a cause of community-acquired urinary infections in the UK,[27] and tend to be resistant to all oral β-lactam antibiotics, as well as quinolones and sulfonamides.

Inhibitor-resistant TEM β-lactamases have been found mainly in clinical isolates of E. coli, but also some strains of K. pneumoniae, Klebsiella oxytoca, P. mirabilis, and Citrobacter freundii.

[28] AmpC-type β-lactamase organisms are often clinically grouped through the acronym, "SPACE": Serratia, Pseudomonas or Proteus, Acinetobacter, Citrobacter, and Enterobacter.

Plasmid-mediated IMP-type carbapenemases (IMP stands for active-on-imipenem), 19 varieties of which are currently known, became established in Japan in the 1990s both in enteric gram-negative organisms and in Pseudomonas and Acinetobacter species.

Biochemical and biophysical studies revealed that VIM variants have only small variations in their kinetic parameters but substantial differences in their thermal stabilities and inhibition profiles.

OXA carbapenemases hydrolyse carbapenems very slowly in vitro, and the high MICs seen for some Acinetobacter hosts (>64 mg/L) may reflect secondary mechanisms.

[citation needed] Originally described from New Delhi in 2009, this gene is now widespread in Escherichia coli and Klebsiella pneumoniae from India and Pakistan.

[29] In general, an isolate is suspected to be an ESBL producer when it shows in vitro susceptibility to the cephamycins (cefoxitin, cefotetan) but resistance to the third-generation cephalosporins and to aztreonam.

Once an ESBL-producing strain is detected, the laboratory should report it as "resistant" to all penicillins, cephalosporins, and aztreonam, even if it is tested (in vitro) as susceptible.

Carbapenems are resistant to ESBL-mediated hydrolysis and exhibit excellent in vitro activity against strains of Enterobacteriaceae expressing ESBLs.

[citation needed] Strains producing only ESBLs are susceptible to cephamycins and carbapenems in vitro and show little if any inoculum effect with these agents.

For infections caused by ESBL-producing Escherichia coli or Klebsiella species, treatment with imipenem or meropenem has been associated with the best outcomes in terms of survival and bacteriologic clearance.

Some patients have responded to aminoglycoside or quinolone therapy, but, in a recent comparison of ciprofloxacin and imipenem for bacteremia involving an ESBL-producing K. pneumoniae, imipenem produced the better outcome There have been few clinical studies to define the optimal therapy for infections caused by ESBL producing Pseudomonas aeruginosa strains.

In 1957, amid concern about allergic reactions to penicillin-containing antibiotics, a beta-lactamase was sold as an antidote under the brand name neutrapen.

[37] While it was not useful in acute anaphylactic shock, it showed positive results in cases of urticaria and joint pain suspected to be caused by penicillin allergy.

[50] Serine beta-lactamases (classes A, C, and D) appear to have evolved from DD-transpeptidases, which are penicillin-binding proteins involved in cell wall biosynthesis, and as such are one of the main targets of beta-lactam antibiotics.