Carbapenemases in Enterobacteriaceae – overview and importance
Carbapenem-resistant Enterobacteriaceae infections are an increasingly global threat, especially because carbapenemase production is more frequent than other resistance mechanisms and is encoded by genes located on transferable genetic structures. This review tries to show the diversity of carbapenemases and to underline their importance.
Pentru a eluda acţiunea antibioticelor, enterobacteriile şi-au dezvoltat diferite mecanisme de protecţie, cum ar fi creşterea impermeabilităţii membranare sau producţia de enzime capabile să hidrolizeze antibioticele. Infecţiile cu Enterobacteriaceae rezistente la carbapeneme reprezintă o ameninţare anthelmintic de în continuă creştere, îndeosebi deoarece producţia de carbapenemaze este mai frecventă comparativ cu alte mecanisme de rezistenţă şi este codificată de către gene localizate pe structuri genetice transferabile.
Acest review încearcă să arate pe scurt bacterie oxa 48 carbapenemazelor şi să atragă atenţia asupra importanţei acestora.
The critical list includes Enterobacteriaceae that are carbapenem-resistant or producers of extended-spectrum beta-lactamases ESBL. Carbapenems are frequently the last antimicrobials that can be used in multidrug-resistant infections, especially in invasive ones or those associated with immunosuppression.
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Carbapenem-resistant Enterobacteriaceae infections occur mainly in the hospital setting, but there have been reports of community spreading as well The purpose of this short review is to highlight the carbapenemase diversity and have a close-up at the most frequently and clinically important sub-types of carbapenemases. Carbapenemase classification Carbapenem resistance may be caused by multiple mechanisms.
The most frequent mechanism, that bacterie oxa 48 also the most important both clinically and epidemiologically, is the production of one or multiple enzymes that have the ability of degrading carbapenems.
These enzymes are called carbapenemases and they belong to the large group of beta-lactamases. There are different classifications of beta-lactamases based on their structure or function, but one of the most widely used is the revised Ambler classification 8.
Genes encoding these different types bacterie oxa 48 carbapenemases are located either chromosomally, plasmidic or both. Others mechanisms include the association of impermeability and another type of enzyme usually an ESBL or a cephalosporinase and they may be the subject bacterie oxa 48 a future article.
Class A Chemically speaking, this class hydrolyses molecules using an active site serine at position 70 3. Along with classes C and D that have similar active-site serine β-lactamases, they form intermediates of acyl-enzyme, thus differentiating them from class B carbapenemases 3.
Bacterie oxa 48, Masader – Oman Virtual Science Library
This property allows them to degrade beta-lactams at various degrees, from penicillins for which they have a high affinity as substrate to carbapenems. Their activity is inhibited by beta-lactamase inhibitors clavulanate, sulbactam, tazobactam, avibactam and in the case of Klebsiella pneumoniae Carbapenemase KPCby boronic acid and EDTA 4.
The carbapenemase gene blaKPC is located on a Tn3 transposon Tn and is associated with high dissemination in the environment. The worldwide spread of KPC in Klebsiella pneumoniae is currently connected to a single clone called ST although within a certain location, the clones may present bacterie oxa 48 characteristics bacterie oxa 48, for instance, the Multi Locus Sequence Typing MLST type or the structure of plasmids 3.
A recent study based on literature bacterie oxa 48 showed Bacterie oxa 48 as KPC-endemic 10although smaller studies in our country did not show similar results 11, GES-type carbapenemases are enzymes that bacterie oxa 48 have an ESBL-like spectrum of activity, but changes in the active site confers them the ability to hydrolyze carbapenems substitution of Glycine at position by an Asparagine or a 37 Serine 12, There are 31 GES enzymes described to date out of which 10 are carbapenemases GES-2, -4, -5, -6, and - The blaGES genes have been described as gene cassettes associated with class 1 or class 3 integrons on plasmids with different types of replicases 3, IMI carbapenemases may be either chromosomally, or plasmid-encoded.
Bacterie oxa 48. 5_D_Timofte_Screening_implementation.pdf
There are 9 variants described to date 3. IMI-2 was firstly found in E. A strain of E. Class B This class possesses the highest carbapenemase activity Their spectrum of activity includes all beta-lactams penicillins, cephalosporins, carbapenemssparing the monobactam aztreonam.
Chromosomal genes coding them were first described in environmental bacteria such as Bacillus cereus, Aeromonas spp. IMP and VIM are most frequently transmitted by class 1 integrons through cassettes which allows them to integrate resistance genes that encode for other classes of antimicrobials as well 4.
A study showed that all-cause day mortality in VIM-1 K. There have also been described pandrug-resistant VIM strains, bacterie oxa 48 concerns regarding future spreading of this type of strains Since they were first discovered inNDM-1 producing bacteria have been mostly associated with the Indian subcontinent as it is considered the main reservoir for blaNDM-1 genes 4.
Bacterie oxa 48
However, there have been reports worldwide From the 16 currently described variants in bacterie oxa 48 or colonized patients, most are somehow linked to India, Pakistan, Sri Lanka or Bangladesh by travel, hospitalization, colonization due to contaminated water etc.
The blaNDM-1 gene is associated with different plasmid types that vary in size and associated resistance genes 4.
These associated resistance genes give a large number of resistance patterns as they might encode other carbapenemases, AmpC cephalosporinases, ESBLs along with aminoglycoside armA, rmtA and rmtCmacrolide ereCrifampicin arr-2sulfamethoxazole sul2quinolones qnrA6 and qnrB1 and chloramphenicol cmlA resistance 4, Class D Carbapenemases in this class are called oxacillinases with over variants described to date Their enzymatic activity is inhibited in vitro by NaCl.
Oxacillinase OXA and its variants were identified only in Enterobacteriaceae, not in Acinetobacter spp. OXA producers hydrolyze penicillins at a high level but may hydrolyze carbapenems poorly, thus presenting high bacterie oxa 48 diameters on the antibiogram resulting in errors of interpretation and, therefore, in treatment They resist the action of beta-lactamase inhibitors, but they remain susceptible to third generation cephalosporins in the absence of other associated resistance mechanisms which results in the probable underestimation of OXA-type producers 4.
However, its plasmidic location makes it easy to spread in the hospital settings and in community. Also, the association of different resistance mechanisms is increasing, a multiyear, multicenter study describing 3 strains of K. It is believed that OXA-type precursors belong to Shewanella species Discussions and importance Bacterie oxa 48 infections are a growing problem worldwide.
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The rapid dissemination in the hospital settings and in the community along with the limited therapeutic options are causes of great concern and call for immediate measures. Regarding carbapenem-resistance through production of carbapenemases, it is important to know that not all carbapenemases are necessarily worrisome.
If the genes carrying the carbapenemases production are encoded chromosomally, they will not spread horizontally; they will only carry on the gene to the next generation of bacteria.
Also, it is very important to differentiate between cases of infection and carriage. CPE carriers excrete bacteria inconstantly for a long period of time and treatment is need only in selected cases. In cases of CPE infections, the specter of in bacterie oxa 48 antibiotic hydrolysis has a great variability therefore every antibiogram must be carefully interpreted by the clinical bacterie oxa 48 who must efficiently communicate with the clinician in order of taking the best therapeutic decision for the patient.
What will the future bring? The high bacterie oxa 48 continuingly increasing incidence of ESBLs will bacterie oxa 48 likely make carbapenems consumption high as well.
High utilization of carbapenems will force bacteria to find ways of survival thus giving rise to pan-drug resistance. Because antibiotic development is a long process, the first thing to do is limiting the spread of these bacteria which can be done by taking rigorous hygiene measures.
Regarding the treatment, there are articles recommending certain molecules or antibiotic associations, depending on the carbapenemase class, but further in vivo studies are necessary in order to make specific treatment protocols for CPE infections. For class A carbapenemases, it appears that the last remaining treatment options are polymyxins, tigecycline and, if susceptible, aminoglycosides ST clones usually remain susceptible to gentamicin However, not all infections may be treated with these molecules.
As class B carbapenemases are not able of hydrolyzing aztreonam, there have been studies bacterie oxa 48 its activity, both alone and in combination with beta-lactamase inhibitors.
A study comparing in vitro activity of aztreonam versus aztreonam-avibactam combination 31 showed increased activity of the combination against isolates producing class A, B or D carbapenemaes.
Fecal transplant is another promising method of intestinal decolonization In the mean time, the development of new antibiotics should be a priority for the pharmaceutical companies, universities and other research groups.
Faced with a post-antibiotic era, there is an bacterie oxa 48 need for action. Educating doctors regarding good antibiotic prescription, as well as educating the population concerning the existence of CPE and what they can do about it good hygiene, use of antibiotics only when necessary etc. Articole din ediţiile anterioare Rezistenţa la antibiotice a Cutibacterium anterior Propionibacterium acnes. În fiziopatologie sunt implicaţi o serie de