Gram Negative Bacteria
| Autor: | Oliveira J; Fundação Universidade do Estado de Mato Grosso, Reygaert WC; Oakland Un William Beaumont Sch of Med |
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| Jazyk: | angličtina |
| Zdroj: | 2021 Jan. |
| Abstrakt: | Gram-negative bacteria (GNB) are among the most significant public health problems in the world due to the high resistance to antibiotics. These microorganisms have great clinical importance in hospitals because they put patients in the intensive care unit (ICU) at high risk and lead to high morbidity and mortality.[1][2] Two large groups, Enterobacteriaceae and the non-fermenters, are responsible for most clinical isolates; nevertheless, other clinically concerning gram-negative organisms exist, including Neisseria , Haemophilus spp ., Helicobacter pylori , and Chlamydia trachomatis . Antibiotic Resistance These organisms have a range of mechanisms to prevent the action of many antimicrobials used in clinical medicine. Some of the mechanisms of resistance include efflux pumps,[3] alteration of the drug binding site and membrane permeability,[4] degradation enzymes, and the conformational change of the drug culminating in its inactivation.[5] GNB has two membranes, an external and an internal. The external membrane expresses a potent immune response inducer, lipopolysaccharide (LPS), which is composed of three units: a hydrophilic polysaccharide, O antigen, and a hydrophobic domain is known as lipid A. Lipid A are responsible for the higher endotoxic activity of these bacteria.[6][7] However, the LPS is heterogeneous in the various bacterial groups, and some bacteria manifest this antigen weakly due to genetic changes and are not recognized by Toll-like receptors. In contrast, there are BGN groups that can trigger such a response in large proportions. Thus, LPS can trigger the innate immune response through Toll-like receptors 4 (TLR4), which occurs in many immune cells such as monocytes, macrophages, dendritic cells, and neutrophils. The resulting activation of the innate immune response mediated by LPS together with TLR4 receptors culminates in an exacerbated response with the production of cytokines, chemokines, and interferons and its suppression. The response of the immune system depends on both the severity of the infectious process and the structure of the LPS in the aggressive bacteria, which imbricates to the virulence of the BGN and, as a consequence, while some bacteria like Escherichia coli potential induce the immune system, other bacteria like Helicobacter pylori are weakly antigenic.[8] Enterobacteriaceae Enterobacteriaceae are a heterogeneous group widely dispersed in nature. They account for about 80% of gram-negative isolates with a myriad of disease-causing general/species in humans, including urinary tract infections, pneumonia, diarrhea, meningitis, sepsis, endotoxic shock, and many others. The general/species that frequently affect humans are Escherichia , Proteus , Enterobacter , Klebsiella , Citrobacter , Yersinia , S higella , and Salmonella, among others. The laboratory characterization is an essential component when it comes to microorganisms; therefore, it is imperative to expose characteristics of Enterobacteriaceae , which are bacilli, non-sporulated, have variable motility, grow in the presence and absence of oxygen, ferment organisms of glucose, are cytochrome oxidase negative, and have the ability to reduce nitrate to nitrite.[9] Antimicrobial Resistance These organisms diffuse their plasmids by conjugation, which gives rise to resistance to almost all existing antibiotics. The family of enzymes carbapenemase – KPC, NDM-1, IMP, VIM, OXA-48 – is undoubtedly one of the most significant health challenges of the century, given the potential for dissemination between species and mortality rates due to infections caused by bacteria with such plasmids.[10] Colistin, one of the few antibiotics that still treat multiresistant infections, already has a mobile resistance gene, mcr-1, and Enterobacteriaceae has a crucial role in the spread of this gene, with worldwide reports.[11] Moreover, a further concern is that they usually associate these genes with other resistance genes ( CTX-M, NDM, IMP ), producing resistance to cephalosporins and carbapenems, enhancing the deleterious effects caused by these microorganisms.[6] Non-Fermenters The non-fermenter, gram-negative bacilli (BNF) have a lower frequency of isolation when compared to Enterobacteriac eae; however, they are a relevant group since they cause severe, fatal infections, especially in the hospital environment. They also cause opportunistic diseases in ICU patients who undergo invasive procedures. The main BNF microorganisms that cause disease in humans are Pseudomonas aeruginosa , Acinetobacter baumannii , Burkholderia cepacia , Stenotrophomonas ., Alcaligenes , Moraxella. These stand out for being aerobic, non-sporulated; they are incapable of fermenting sugars, using them through the oxidative route.[12] The critical issue regarding BNF, when it comes to the antimicrobial sensitivity profile, is undoubtedly their intrinsic resistance since they produce a variety of genes with multiple mechanisms capable of mitigating the microbicidal action. Thus, it stands out in P. aeruginosa , cephalosporinase of type AmpC, and efflux systems that confer resistance to b-lactams. The most frequent are MexAB-OprM[13]; and loss of OprD (which gives impermeability to the bacterial cell due to the loss of porin)[14]. Acinetobacter baumannii naturally produces AmpC cephalosporinase and oxacillinase (OXA), leaving it spontaneously immune to many drugs. The genetic ingenuity of this microorganism goes further, and it combines high impermeability with genetic plasticity, combining with the resistance of mechanisms such as extended-spectrum b-lactamases (ESBL).[15] The Stenotrophomonas exhibit a pattern of intrinsic multi-resistance, especially in patients who have had contact with carbapenems. Thus, Stenotrophomonas present several efflux pumps and produce two carbapenemases – L1 (resistance to all carbapenems) and L2 (cephalosporinase),[16] in synthesis. These mechanisms, associated or separate, restrict the treatment options to an alarming level. Although it is sensitive to sulfamethoxazole-trimethoprim and has an increased resistance mediated by plasmids.[17] (Copyright © 2021, StatPearls Publishing LLC.) |
| Databáze: | MEDLINE |
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