المؤلفون: Livesey, T.C., Mahmoud, L.A.M., Katsikogianni, Maria G., Nayak, Sanjit

مصطلحات موضوعية: MOFs, Antimicrobial resistance (AMR), Polymers, Drug delivery, Composite, Biodegradable

الوصف: Yes ; Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition to ongoing efforts on preventive strategies and infection control, there is ongoing research towards the development of novel vaccines, antimicrobial agents, and optimised diagnostic practices to address AMR. However, developing new therapeutic agents and medicines can be a lengthy process. Therefore, there is a parallel ongoing worldwide effort to develop materials for optimised drug delivery to improve efficacy and minimise AMR. Examples of such materials include functionalisation of surfaces so that they can become self-disinfecting or non-fouling, and the development of nanoparticles with promising antimicrobial properties attributed to their ability to damage numerous essential components of pathogens. A relatively new class of materials, metal-organic frameworks (MOFs), is also being investigated for their ability to act as carriers of antimicrobial agents, because of their ultrahigh porosity and modular structures, which can be engineered to control the delivery mechanism of loaded drugs. Biodegradable polymers have also been found to show promising applications as antimicrobial carriers; and, recently, several studies have been reported on delivery of antimicrobial drugs using composites of MOF and biodegradable polymers. This review article reflects on MOFs and polymer-MOF composites, as carriers and delivery agents of antimicrobial drugs, that have been studied recently, and provides an overview of the state of the art in this highly topical area of research.

العلاقة: Livesey TC, Mahmoud LAM, Katiskogianni MG et al (2023) Metal-organic frameworks and their biodegradable composites for controlled delivery of antimicrobial drugs. Pharmaceutics. 15(1): 274.; http://hdl.handle.net/10454/19321Test; https://doi.org/10.3390/pharmaceutics15010274Test

الإتاحة: https://doi.org/10.3390/pharmaceutics15010274Test
http://hdl.handle.net/10454/19321Test

المؤلفون: Farhat, M.R., Freschi, L., Calderon, R., Ioerger, T., Snyder, M., Meehan, Conor J., de Jong, B.C., Rigouts, L., Sloutsky, A., Kaur, D., Sunyaev, S., van Soolingen, D., Shendure, J., Sacchettini, J., Murray, M.

مصطلحات موضوعية: Antimicrobial resistance, Bacterial genetics, Genome-wide association studies, Tuberculosis

الوصف: Yes ; Drug resistance diagnostics that rely on the detection of resistance-related mutations could expedite patient care and TB eradication. We perform minimum inhibitory concentration testing for 12 anti-TB drugs together with Illumina whole-genome sequencing on 1452 clinical Mycobacterium tuberculosis (MTB) isolates. We evaluate genome-wide associations between mutations in MTB genes or non-coding regions and resistance, followed by validation in an independent data set of 792 patient isolates. We confirm associations at 13 non-canonical loci, with two involving non-coding regions. Promoter mutations are measured to have smaller average effects on resistance than gene body mutations. We estimate the heritability of the resistance phenotype to 11 anti-TB drugs and identify a lower than expected contribution from known resistance genes. This study highlights the complexity of the genomic mechanisms associated with the MTB resistance phenotype, including the relatively large number of potentially causal loci, and emphasizes the contribution of the non-coding portion of the genome. ; Biomedical research grant from the American Lung Association (PI MF, RG-270912-N), a K01 award from the BD2K initiative (PI MF, ES026835), and an NIAID U19 CETR grant (P.I. M.M., AI109755), the Belgian Science Policy (Belspo) (L.R., C.J.M.).

العلاقة: Farhat MR, Freschi L, Calderon R et al (2019) GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions. Nature Communications. 10(1): article 2128.; http://hdl.handle.net/10454/17274Test; https://doi.org/10.1038/s41467-019-10110-6Test

الإتاحة: https://doi.org/10.1038/s41467-019-10110-6Test
http://hdl.handle.net/10454/17274Test

المؤلفون: Lempens, P., Meehan, Conor J., Vandelannoote, K., Fissette, K., de Rijk, P., Van Deun, A., Rigouts, L., de Jong, B.C.

مصطلحات موضوعية: Antimicrobial resistance, Bacterial genomics, Genetic association study, Infectious-disease diagnostics, Pathogens

الوصف: Yes ; The majority of Mycobacterium tuberculosis isolates resistant to isoniazid harbour a mutation in katG. Since these mutations cause a wide range of minimum inhibitory concentrations (MICs), largely below the serum level reached with higher dosing (15 mg/L upon 15–20 mg/kg), the drug might still remain partly active in presence of a katG mutation. We therefore investigated which genetic mutations predict the level of phenotypic isoniazid resistance in clinical M. tuberculosis isolates. To this end, the association between known and unknown isoniazid resistance-conferring mutations in whole genome sequences, and the isoniazid MICs of 176 isolates was examined. We found mostly moderate-level resistance characterized by a mode of 6.4 mg/L for the very common katG Ser315Thr mutation, and always very high MICs (≥19.2 mg/L) for the combination of katG Ser315Thr and inhA c-15t. Contrary to common belief, isolates harbouring inhA c-15t alone, partly also showed moderate-level resistance, particularly when combined with inhA Ser94Ala. No overt association between low-confidence or unknown mutations, except in katG, and isoniazid resistance (level) was found. Except for the rare katG deletion, line probe assay is thus not sufficiently accurate to predict the level of isoniazid resistance for a single mutation in katG or inhA. ; European Research Council (Starting Grant INTERRUPTB 311725 to CM, LR and BdJ), The Damien Foundation

العلاقة: Lempens P, Meehan CJ, Vandelannoote K et al (2018) Isoniazid resistance levels of Mycobacterium tuberculosis can largely be predicted by high-confidence resistance-conferring mutations. Scientific Reports. 8(1): article 3246.; http://hdl.handle.net/10454/17278Test; https://doi.org/10.1038/s41598-018-21378-xTest

الإتاحة: https://doi.org/10.1038/s41598-018-21378-xTest
http://hdl.handle.net/10454/17278Test

المؤلفون: Guan, X., Mu, X., Ji, W., Yuan, C., He, P., Zhang, L., Huang, Y., Li, J., Chen, J., Zhong, H., Pang, S., Tan, N., Deng, Q., Gao, K., Chang, Chien-Yi, Liu, H.

مصطلحات موضوعية: Infants, Group B Streptococcus, Neonatal infections, Serotype, Multilocus sequence type (MLST), Antimicrobial resistance

الوصف: Yes ; Background: Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in infants in both developed and developing countries. To our knowledge, only a few studies have been reported the clinical features, treatment and outcomes of the GBS disease in China. The severity of neonatal GBS disease in China remains unclear. Population-based surveillance in China is therefore required. Methods: We retrospectively collected data of <3 months old infants with culture-positive GBS in sterile samples from three large urban tertiary hospitals in South China from Jan 2011 to Dec 2014. The GBS isolates and their antibiotic susceptibility were routinely identified in clinical laboratories in participating hospitals. Serotyping and multi-locus sequence typing (MLST) were also conducted for further analysis of the neonatal GBS disease. Results: Total 70 cases of culture-confirmed invasive GBS infection were identified from 127,206 live births born in studying hospitals, giving an overall incidence of 0.55 per 1000 live births (95% confidence interval [CI] 0.44–0.69). They consisted of 49 with early-onset disease (EOD, 0.39 per 1000 live births (95% CI 0.29–0.51)) and 21 with late-onset disease (LOD, 0.17 per 1000 live births (95% CI 0.11–0.25)). The incidence of EOD increased significantly over the studying period. Five infants (4 EOD and 1 LOD) died before discharge giving a mortality rate of 7.1% and five infants (7.1%, 2 EOD and 3 LOD) had neurological sequelae. Within 68 GBS isolates from GBS cases who born in the studying hospitals or elsewhere, serotype III accounted for 77.9%, followed by Ib (14.7%), V (4.4%), and Ia (2.9%). MLST analysis revealed the presence of 13 different sequence types among the 68 GBS isolates and ST-17 was the most frequent sequence type (63.2%). All isolates were susceptible to penicillin, ceftriaxone, vancomycin and linezolid, while 57.4% and 51.5% were resistant to erythromycin and clindamycin, respectively. Conclusions: This study gains the insight into the spectrum of ...

العلاقة: http://hdl.handle.net/10454/15101Test; https://doi.org/10.1186/s12879-017-2811-0Test

الإتاحة: https://doi.org/10.1186/s12879-017-2811-0Test
http://hdl.handle.net/10454/15101Test

المؤلفون: Meehan, Conor J., Goig, G.A., Kohl, T.A., Verboven, L., Dippenaar, A., Ezewudo, M., Farhat, M.R., Guthrie, J.L., Laukens, K., Miotto, P., Ofori-Anyinam, B., Dreyer, V., Supply, P., Suresh, A., Utpatel, C., van Soolingen, D., Zhou, Y., Ashton, P.M., Brites, D., Cabibbe, A.M., de Jong, B.C., de Vos, M., Menardo, F., Gagneux, S., Gao, Q., Heupink, T.H., Liu, Q., Loiseau, C., Rigouts, L., Rodwell, T.C., Tagliani, E., Walker, T.M., Warren, R.M., Zhao, Y., Zignol, M., Schito, M., Gardy, J., Cirillo, D.M., Niemann, S., Comas, I., Van Rie, A.

مصطلحات موضوعية: Antimicrobial resistance, Bacteria, Bacterial genetics, Clinical microbiology, Communication and replication, Infectious-disease diagnostics, Pathogens, Policy and public health in microbiology, Standards, Tuberculosis, Whole genome amplification

الوصف: No ; Whole genome sequencing (WGS) of Mycobacterium tuberculosis has rapidly progressed from a research tool to a clinical application for the diagnosis and management of tuberculosis and in public health surveillance. This development has been facilitated by drastic drops in cost, advances in technology and concerted efforts to translate sequencing data into actionable information. There is, however, a risk that, in the absence of a consensus and international standards, the widespread use of WGS technology may result in data and processes that lack harmonization, comparability and validation. In this Review, we outline the current landscape of WGS pipelines and applications, and set out best practices for M. tuberculosis WGS, including standards for bioinformatics pipelines, curated repositories of resistance-causing variants, phylogenetic analyses, quality control and standardized reporting. ; European Research Council grant (INTERRUPTB; no. 311725), European Research Council grant (TB-ACCELERATE; no. 638553), Foundation for Innovative New Diagnostics, German Center for Infection Research (DZIF), Deutsche Forschungsgemeinschaft (German Research Foundation) under Germany’s Excellence Strategy (EXC 22167–390884018), FWO Odysseus G0F8316N, US National Institutes of Health BD2K K01 (MRF ES026835), Agence Nationale de la Recherche (ANR-16-CD35-0009)

العلاقة: Meehan CJ, Goig GA, Kohl TA et al (2019) Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nature Reviews Microbiology. 17(9): 533-545.; http://hdl.handle.net/10454/17276Test; https://doi.org/10.1038/s41579-019-0214-5Test

الإتاحة: https://doi.org/10.1038/s41579-019-0214-5Test
http://hdl.handle.net/10454/17276Test

المؤلفون: Rimmer, Stephen, Venuganti, V., MacNeil, S., Garg, P., Douglas, I., Foster, S.

مصطلحات موضوعية: Antimicrobial resistance, Biomaterials, Eye infections, Diagnostics, Drug delivery

الوصف: yes ; On 14/15th March 2016 we held a MRC/DBT funded workshop on the theme of Materials to Combat Antibiotic Resistance. The workshop was part of a continuing series of events that are part of the work of UK-India Centre for Advanced Technologies-Minimising the indiscriminate use of Antibiotics (UKICAT–MA). The following is the collection of presentations and the results of discussions highlighting key themes for future work by this group. Combating antibiotic resistance is perhaps the biggest issue facing the global community in the 21st century and no other area, with the exception perhaps of nuclear conflict, has the capacity to significantly reduce living standards and mortality rates. Key objectives identified by WHO1 in this area among five key aspects, include: Objective 4-to optimize the use of antimicrobial agents Objective 5-new medicines, diagnostic tools, vaccines and other interventions Our aims in this series of workshops are to provide an Indo-UK forum for: discussions of our advances in providing technologies to address these objectives; facilitate the interface between UK and Indian clinicians, materials and biological scientists and to identify key areas for new projects. An important aspect of the work in a global context is that by combining the UK and Indian community and clinical experiences we cover most of the scenarios that the global population might expect to encounter

العلاقة: Rimmer S, Venuganti V, MacNeil S, Garg P, Douglas I, Foster S (2016) MRC/DBT Workshop UK-India Centre for Advanced Technologies-Minimising the indiscriminate use of Antibiotics (UKICAT–MA) 14th/15th March 2016, Hyderabad, India.; http://hdl.handle.net/10454/8622Test

الإتاحة: http://hdl.handle.net/10454/8622Test

المؤلفون: Rimmer, Stephen

مصطلحات موضوعية: Antimicrobial resistance, Wounds

الوصف: Yes ; The purpose of this workshop was to promote interdisciplinary learning and collaborations between UK and India in the area of bacteria and wounds, particularly when bacteria are increasingly antibiotic resistant. To this end we invited colleagues from India with clinical experience ofmanaging bacterially infected wounds in patients, particularly when antibiotic resistant (Dr Prashant Garg) and colleagues from India with expertise in developing new drug delivery systems (Prof Nikhil Singh and Dr Vamsi Venuganti) and together with UK delegates, spanning those with international experience in investigating bacterial infections (Prof Simon Foster), investigating how biofilms communicate (Prof Paul Williams), international expertise in discovering materials for antimicrobial resistance and for instruction of macrophages (Prof Morgan Alexander), expertise in developing responsive films for detecting infection in wounds using a visible signal (Prof Toby Jenkins) and other scientists working on the axis of detecting and treating infection in wounds. ; MRC/DBT

العلاقة: http://hdl.handle.net/10454/8770Test

الإتاحة: http://hdl.handle.net/10454/8770Test

المؤلفون: Wright, Claire Louise, Snelling, Anna M., Newton, L., Kerr, Kevin G.

مصطلحات موضوعية: Resistance, bacterial, Intensive care unit (ICU), Hospital water sources, Microbiology, Hospital-acquired infections, Water, Antimicrobial resistance, Nosocomial infections

الوصف: yes ; It is estimated that 5-10% of hospitalised patients in developed countries contract hospital acquired infections (HAI). Increasing levels of antimicrobial resistance manifested by many HAI-causing pathogens such as Acinetobacter spp in the intensive care unit (ICU) setting present a significant challenge to those managing these infections. Consequently, much attention has been focused on the prevention of HAIs. Particular emphasis has been placed on interventions intended to interrupt patient-to-patient transmission of pathogens, such as enhanced hand hygiene and identification of patients colonised with methicillin-resistant Staphylococcus aureus (MRSA) using rapid DNA-based screening techniques. However, comparatively little attention has been given to the hospital environment, including water supplies, as a source of nosocomial pathogens of importance for patients on the critical care unit. This article reviews the role of hospital water sources in the epidemiology of HAI and new technologies which can be employed in the prevention and control of such infections.

العلاقة: http://www.greycoatpublishing.co.uk/content/Journals/BJIC.aspTest; Wright, C. L., Snelling, A. M., Newton, L. and Kerr, K. G. (2008). Water-associated nosocomial infections. British Journal of Intensive Care. Summer, pp. 64-67.; http://hdl.handle.net/10454/4882Test

الإتاحة: http://hdl.handle.net/10454/4882Test