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Essential Metabolic Routes as a Way to ESKAPE From Antibiotic Resistance.

ABSTRACT: Antibiotic resistance is a worldwide concern that requires a concerted action from physicians, patients, governmental agencies, and academia to prevent infections and the spread of resistance, track resistant bacteria, improve the use of current antibiotics, and develop new antibiotics. Despite the efforts spent so far, the current antibiotics in the market are restricted to only five general targets/pathways highlighting the need for basic research focusing on the discovery and evaluation of new potential targets. Here we interrogate two biosynthetic pathways as potentially druggable pathways in bacteria. The biosynthesis pathway for thiamine (vitamin B1), absent in humans, but found in many bacteria, including organisms in the group of the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter sp.) and the biosynthesis pathway for pyridoxal 5'-phosphate and its vitamers (vitamin B6), found in S. aureus. Using current genomic data, we discuss the possibilities of inhibition of enzymes in the pathway and review the current state of the art in the scientific literature.

SUBMITTER: Barra ALC

PROVIDER: S-EPMC7093009 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Essential Metabolic Routes as a Way to ESKAPE From Antibiotic Resistance.

Barra Angélica Luana C ALC Dantas Lívia de Oliveira C LOC Morão Luana Galvão LG Gutierrez Raíssa F RF Polikarpov Igor I Wrenger Carsten C Nascimento Alessandro S AS

Frontiers in public health 20200228

Antibiotic resistance is a worldwide concern that requires a concerted action from physicians, patients, governmental agencies, and academia to prevent infections and the spread of resistance, track resistant bacteria, improve the use of current antibiotics, and develop new antibiotics. Despite the efforts spent so far, the current antibiotics in the market are restricted to only five general targets/pathways highlighting the need for basic research focusing on the discovery and evaluation of ne ...[more]

PMID: 32257985

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Project description:BackgroundAntibiotic resistance (ABR) is one of the biggest threats to global health. Infections by ESKAPE (Enterococcus, S. aureus, K. pneumoniae, A. baumannii, P. aeruginosa, and E. coli) organisms are the leading cause of healthcare-acquired infections worldwide. ABR in ESKAPE organisms is usually associated with significant higher morbidity, mortality, as well as economic burden. Directing attention towards the ESKAPE organisms can help us to better combat the wide challenge of ABR, especially multi-drug resistance (MDR).ObjectiveThis study aims to systematically review and evaluate the evidence of the economic consequences of ABR or MDR ESKAPE organisms compared with susceptible cases or control patients without infection/colonization in order to determine the impact of ABR on economic burden.MethodsBoth English-language databases and Chinese-language databases up to 16 January, 2019 were searched to identify relevant studies assessing the economic burden of ABR. Studies reported hospital costs (charges) or antibiotic cost during the entire hospitalization and during the period before/after culture among patients with ABR or MDR ESKAPE organisms were included. The costs were converted into 2015 United States Dollars. Disagreements were resolved by a third reviewer.ResultsOf 13,693 studies identified, 83 eligible studies were included in our review. The most studied organism was S. aureus, followed by Enterococcus, A. baumannii, E. coli, E. coli or/and K. pneumoniae, P. aeruginosa, and K. pneumoniae. There were 71 studies on total hospital cost or charge, 12 on antibiotic cost, 11 on hospital cost or charge after culture, 4 on ICU cost, 2 on hospital cost or charge before culture, and 2 on total direct and indirect cost. In general, ABR or MDR ESKAPE organisms are significantly associated with higher economic burden than those with susceptible organisms or those without infection or colonization. Nonetheless, there were no differences in a few studies between the two groups on total hospital cost or charge (16 studies), antibiotic cost (one study), hospital cost before culture (one study), hospital cost after culture (one study). Even, one reported that costs associated with MSSA infection were higher than the costs for similar MRSA cases.ConclusionsABR in ESKAPE organisms is not always, but usually, associated with significantly higher economic burden. The results without significant differences may lack statistical power to detect a significant association. In addition, study design which controls for severity of illness and same empirical antibiotic therapy in the two groups would be expected to bias the study towards a similar, even negative result. The review also highlights key areas where further research is needed.

Dataset Information

Essential Metabolic Routes as a Way to ESKAPE From Antibiotic Resistance.

Publications

Essential Metabolic Routes as a Way to ESKAPE From Antibiotic Resistance.

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