Editing Beta-lactamase (section)

==Carbapenemases==
Carbapenems are famously stable to AmpC β-lactamases and extended-spectrum-β-lactamases. Carbapenemases are a diverse group of β-lactamases that are active not only against the oxyimino-cephalosporins and cephamycins but also against the carbapenems. Aztreonam is stable to the metallo-β-lactamases,
but many IMP and VIM producers are resistant, owing to other mechanisms.   Carbapenemases were formerly believed to derive only from classes A, B, and D, but a class C carbapenemase has been described.

===IMP-type carbapenemases (metallo-β-lactamases) (class B)===
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. IMP enzymes spread slowly to other countries in the Far East, were reported from Europe in 1997, and have been found in Canada and Brazil.

===VIM (Verona integron-encoded metallo-β-lactamase) (Class B)===
A second growing family of carbapenemases, the VIM family, was reported from Italy in 1999 and now includes 10 members, which have a wide geographic distribution in Europe, South America, and the Far East and have been found in the United States. VIM-1 was discovered in ''P. aeruginosa'' in Italy in 1996; since then, VIM-2 - now the predominant variant - was found repeatedly in Europe and the Far East; VIM-3 and -4 are minor variants of VIM-2 and -1, respectively.

Amino acid sequence diversity is up to 10% in the VIM family, 15% in the IMP family, and 70% between VIM and IMP. Enzymes of both the families, nevertheless, are similar. Both are integron-associated, sometimes within plasmids. Both hydrolyse all β-lactams except monobactams, and evade all β-lactam inhibitors. The VIM enzymes are among the most widely distributed MBLs, with >40 VIM variants having been reported. 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.<ref name="Comparison of Verona Integron-Borne">{{cite journal | vauthors = Makena A, Düzgün AÖ, Brem J, McDonough MA, Rydzik AM, Abboud MI, Saral A, Çiçek AÇ, Sandalli C, Schofield CJ | title = Comparison of Verona Integron-Borne Metallo-β-Lactamase (VIM) Variants Reveals Differences in Stability and Inhibition Profiles | journal = Antimicrobial Agents and Chemotherapy | volume = 60 | issue = 3 | pages = 1377–84 | date = December 2015 | pmid = 26666919 | pmc = 4775916 | doi = 10.1128/AAC.01768-15 }}</ref>

=== OXA (oxacillinase) group of β-lactamases (class D) ===
The OXA group of β-lactamases occur mainly in Acinetobacter species and are divided into two clusters. OXA carbapenemases hydrolyse carbapenems very slowly ''in vitro'', and the high MICs seen for some Acinetobacter hosts (>64&nbsp;mg/L) may reflect secondary mechanisms. They are sometimes augmented in clinical isolates by additional resistance mechanisms, such as impermeability or efflux.  OXA carbapenemases also tend to have a reduced hydrolytic efficiency towards penicillins and cephalosporins.<ref name="pmid17374723">{{cite journal | vauthors = Santillana E, Beceiro A, Bou G, Romero A | title = Crystal structure of the carbapenemase OXA-24 reveals insights into the mechanism of carbapenem hydrolysis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 13 | pages = 5354–9 | date = March 2007 | pmid = 17374723 | pmc = 1838445 | doi = 10.1073/pnas.0607557104 | doi-access = free | bibcode = 2007PNAS..104.5354S }}</ref>

===KPC (''K. pneumoniae'' carbapenemase) (class A)===
A few class A enzymes, most noted the plasmid-mediated KPC enzymes, are effective carbapenemases as well. Ten variants, KPC-2 through KPC-11 are known, and they are distinguished by one or two [[amino acid]] substitutions (KPC-1 was re-sequenced in 2008 and found to be 100% homologous to published sequences of KPC-2). KPC-1 was found in North Carolina, KPC-2 in Baltimore and KPC-3 in New York. They have only 45% homology with SME and NMC/IMI enzymes and, unlike them, can be encoded by self-transmissible plasmids.

{{as of |February 2009}}, the class A ''[[Klebsiella pneumoniae]]'' carbapenemase ([[Klebsiella pneumoniae#Resistant strains|KPC]]) globally has been the most common carbapenemase, and was first detected in 1996 in [[North Carolina]], USA.<ref name="pmid19324295">{{cite journal | vauthors = Nordmann P, Cuzon G, Naas T | title = The real threat of Klebsiella pneumoniae carbapenemase-producing bacteria | journal = The Lancet. Infectious Diseases | volume = 9 | issue = 4 | pages = 228–36 | date = April 2009 | pmid = 19324295 | doi = 10.1016/S1473-3099(09)70054-4 }}</ref> A 2010 publication indicated that KPC producing Enterobacteriaceae were becoming common in the United States.<ref name="pmid19854586">{{cite journal | vauthors = Cuzon G, Naas T, Nordmann P | title = [KPC carbapenemases: what is at stake in clinical microbiology?] | language = fr | journal = Pathologie-Biologie | volume = 58 | issue = 1 | pages = 39–45 | date = February 2010 | pmid = 19854586 | doi = 10.1016/j.patbio.2009.07.026 }}</ref>

===CMY (class C)===
The first class C carbapenemase was described in 2006 and was isolated from a virulent strain of ''Enterobacter aerogenes''.<ref name="pmid16677302">{{cite journal | vauthors = Kim JY, Jung HI, An YJ, Lee JH, Kim SJ, Jeong SH, Lee KJ, Suh PG, Lee HS, Lee SH, Cha SS | title = Structural basis for the extended substrate spectrum of CMY-10, a plasmid-encoded class C beta-lactamase | journal = Molecular Microbiology | volume = 60 | issue = 4 | pages = 907–16 | date = May 2006 | pmid = 16677302 | doi = 10.1111/j.1365-2958.2006.05146.x | s2cid = 44982704 | doi-access = free }}</ref> It is carried on a plasmid, pYMG-1, and is therefore transmissible to other bacterial strains.<ref name="pmid15383166">{{cite journal | vauthors = Lee JH, Jung HI, Jung JH, Park JS, Ahn JB, Jeong SH, Jeong BC, Lee JH, Lee SH | title = Dissemination of transferable AmpC-type beta-lactamase (CMY-10) in a Korean hospital | journal = Microbial Drug Resistance | volume = 10 | issue = 3 | pages = 224–30 | year = 2004 | pmid = 15383166 | doi = 10.1089/mdr.2004.10.224 }}</ref>

===SME (Serratia marcescens enzymes), IMI (IMIpenem-hydrolysing β-lactamase), NMC and CcrA ===
In general, these are of little clinical significance.

CcrA (CfiA). Its gene occurs in ca. 1–3% of ''B. fragilis'' isolates, but fewer produce the enzyme since expression demands appropriate migration of an insertion sequence. CcrA was known before imipenem was introduced, and producers have shown little subsequent increase.{{citation needed|date=December 2024}}

===NDM-1 (New Delhi metallo-β-lactamase) (class B)===
{{Main|New Delhi metallo-beta-lactamase}}
Originally described from [[New Delhi]] in 2009, this gene is now widespread in ''[[Escherichia coli]]'' and ''[[Klebsiella pneumoniae]]'' from India and Pakistan. As of mid-2010, NDM-1 carrying bacteria have been introduced to other countries (including the United States and UK), most probably due to the large number of tourists travelling the globe, who may have picked up the strain from the environment, as strains containing the NDM-1 gene have been found in environmental samples in India.<ref name="pmid21478057">{{cite journal | vauthors = Walsh TR, Weeks J, Livermore DM, Toleman MA | title = Dissemination of NDM-1 positive bacteria in the New Delhi environment and its implications for human health: an environmental point prevalence study | journal = The Lancet. Infectious Diseases | volume = 11 | issue = 5 | pages = 355–62 | date = May 2011 | pmid = 21478057 | doi = 10.1016/S1473-3099(11)70059-7 }}</ref> NDM have several variants which share different properties.<ref name="Comparison of Verona Integron-Borne"/>