scholarly journals New Carbapenemase Inhibitors: Clearing the Way for the β-Lactams

2020 ◽  
Vol 21 (23) ◽  
pp. 9308
Author(s):  
Juan C. Vázquez-Ucha ◽  
Jorge Arca-Suárez ◽  
Germán Bou ◽  
Alejandro Beceiro

Carbapenem resistance is a major global health problem that seriously compromises the treatment of infections caused by nosocomial pathogens. Resistance to carbapenems mainly occurs via the production of carbapenemases, such as VIM, IMP, NDM, KPC and OXA, among others. Preclinical and clinical trials are currently underway to test a new generation of promising inhibitors, together with the recently approved avibactam, relebactam and vaborbactam. This review summarizes the main, most promising carbapenemase inhibitors synthesized to date, as well as their spectrum of activity and current stage of development. We particularly focus on β-lactam/β-lactamase inhibitor combinations that could potentially be used to treat infections caused by carbapenemase-producer pathogens of critical priority. The emergence of these new combinations represents a step forward in the fight against antimicrobial resistance, especially in regard to metallo-β-lactamases and carbapenem-hydrolysing class D β-lactamases, not currently inhibited by any clinically approved inhibitor.

2020 ◽  
Author(s):  
Divyansh Sehgal

As humans are spreading throughout the world, infectious diseases have been a constant companion such as Bubonic Plague (200 Million deaths), 17th Century Great Plague (3 Million deaths), Plague of Justinian (30-50 Million deaths), etc . Coronavirus Disease (COVID-19) which was published on 11th January 2020 showing the intensity of Global research and development activity to develop a drug/vaccine against the disease. COVID-19 is an infectious disease caused by a newly discovered coronavirus. Human to human transmission has created a pandemic situation across the world. Pharmaceutical companies play a crucial role in this scenario to provide Drugs/Vaccines/Therapies to treat and tackle the novel coronavirus disease of 2019. This paper consists of the Drugs and Vaccines which are developed, or in the process of development , their current stage of development (clinical trials) with their patent review.


2019 ◽  
pp. 47-71
Author(s):  
Petr M. Mozias

China’s Belt and Road Initiative could be treated ambiguously. On the one hand, it is intended to transform the newly acquired economic potential of that country into its higher status in the world. China invites a lot of nations to build up gigantic transit corridors by joint efforts, and doing so it applies productively its capital and technologies. International transactions in RMB are also being expanded. But, on the other hand, the Belt and Road Initiative is also a necessity for China to cope with some evident problems of its current stage of development, such as industrial overcapacity, overdependence on imports of raw materials from a narrow circle of countries, and a subordinate status in global value chains. For Russia participation in the Belt and Road Initiative may be fruitful, since the very character of that project provides us with a space to manoeuvre. By now, Russian exports to China consist primarily of fuels and other commodities. More active industrial policy is needed to correct this situation . A flexible framework of the Belt and Road Initiative is more suitable for this objective to be achieved, rather than traditional forms of regional integration, such as a free trade zone.


Author(s):  
Rabia Arshad

Background: Antimicrobial resistance is one of the research priorities of health organizations due to increased risk of morbidity and mortality. Outbreaks of nosocomial infections caused by carbapenem-resistant Acinetobacter Baumannii (CRAB) strains are at rise worldwide. Antimicrobial resistance to carbapenems reduces clinical therapeutic choices and frequently led to treatment failure. The aim of our study was to determine the prevalence of carbapenem resistance in A. baumannii isolated from patients in intensive care units (ICUs). Methods: This cross-sectional study was carried out in the Department of Microbiology, Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, from December 2016 to November 2017. Total 63 non-repetitive A. baumannii were collected from the patients’ specimens, admitted to medical and surgical ICUs and wards of JPMC, Karachi. The bacterial isolates were processed according to standard microbiological procedures to observe for carbapenem resistance. SPSS 21 was used for data analysis. Results: Out of the 63 patients, 40 (63.5%) were male. The age of the patient ranged from 15-85 year, with average of 43 year. 34.9% patients had been hospitalized for 3 days. Chronic obstructive pulmonary disease was present in highest number with average of 58.7% for morbidity. Number of patients on mechanical ventilation was highest (65.1%). All isolates were susceptible to colistin. The resistance to ampicillin-sulbactam, ceftazidime, ciprofloxacin, amikacin, piperacillin- tazobactam and meropenem was 82.5%, 81%, 100%, 87.3%, 82.5% and 82% respectively. Out of 82% CRAB, 77% were obtained from ICUs. Conclusion: This study has revealed the high rate of carbapenem resistance in A. baumannii isolates in ICUs thus leaving behind limited therapeutic options.


2020 ◽  
Vol 22 (5) ◽  
pp. 62-66
Author(s):  
NATALIA S. EPIFANOVA ◽  
◽  
MIKHAIL G. POLOZKOV ◽  

The article studies the necessity and features of transformation of the educational system under conditions of accelerated development in the digital economy. Particular attention in the context of this transformation is given to significance and possibilities of digital literacy, which forms the whole complex of fundamentally new requirements for all participants in the education system. The authors argue that the current stage of development of the digital economy requires the education system not only to digitalize its individual elements and links, but to apply a fundamentally new integrated approach that would transform the education system while taking into account new goals, structure and content of the educational process. The authors define digital literacy as the ability to form and apply educational content through digital technologies. The article gives particular emphasis on the significance and potential of individualizing the educational trajectory and the concept of continuing education. The authors consider the main factors in the development and achievement of the level of digital literacy, considering the requirements that the digital economy is currently imposing on the educational system.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S793
Author(s):  
Lynn-Yao Lin ◽  
Dmitri Debabov ◽  
William Chang ◽  
Urania Rappo

Abstract Background AmpC overproduction is a main mechanism of carbapenem resistance, in the absence of acquired carbapenemases. Ceftazidime-avibactam (CAZ-AVI) has potent in vitro activity against AmpC-producing P. aeruginosa and Enterobacterales that are resistant to carbapenems and other β-lactams. Methods Activity of CAZ-AVI and comparators was evaluated against AmpC-overproducing Enterobacterales (n=77) and P. aeruginosa (n=53) collected from 4 CAZ-AVI clinical trials: RECLAIM (complicated intra-abdominal infection [cIAI]), REPRISE (cIAI/complicated urinary tract infection [cUTI]), RECAPTURE (cUTI) and REPROVE (hospital-acquired pneumonia/ventilator associated pneumonia). In vitro susceptibility of CAZ-AVI and comparators was performed by broth microdilution using ThermoFisher custom panels. CLSI breakpoints were used to determine susceptibility. Quantitative PCR and microarray data were used to characterize presence and expression of AmpC. Clinical response at test of cure was assessed. Results Against 77 AmpC-overproducing Enterobacterales isolates, meropenem-vaborbactam (MVB) (98.7% susceptible [S]), CAZ-AVI (96.1% S), and meropenem (MEM) (96.1% S) had similar in vitro activity (Table), with greater in vitro activity than amikacin (AMK) (84.4% S), gentamicin (61.0% S), and ceftolozane-tazobactam (TZC) (35.1% S). Clinical cures in patients with baseline AmpC-overproducing Enterobacterales were 21/26 (81%) in CAZ-AVI group vs 17/20 (85%) in control groups. Against 53 AmpC-overproducing P. aeruginosa isolates, CAZ-AVI (73.6% S) showed greater in vitro activity than AMK (69.8% S), TZC (58.5% S), and MEM (37.7% S). Clinical cures in patients with baseline AmpC-overproducing P. aeruginosa were 12/14 (86%) in CAZ-AVI group vs 9/12 (75%) in control groups. MIC distributions against the same P aeruginosa isolates were CAZ-AVI (MIC50/90, 4/ >64 µg/mL), MVB (MIC50/90, 8/32 µg/mL), and MEM (MIC50/90, 8/32 µg/mL). Table Conclusion CAZ-AVI was the most active agent against AmpC-overproducing P. aeruginosa with higher proportion of clinical cure than controls. CAZ-AVI was also among the most active agents against AmpC-overproducing Enterobacterales, with >96% isolates susceptible. Disclosures Lynn-Yao Lin, MS, AbbVie (Employee) Dmitri Debabov, PhD, AbbVie (Employee) William Chang, BS, AbbVie (Employee) Urania Rappo, MD, MS, PharmD, Allergan (before its acquisition by AbbVie) (Employee)


Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 744
Author(s):  
Altaf Bandy ◽  
Bilal Tantry

Antimicrobial-resistance in Enterobacterales is a serious concern in Saudi Arabia. The present study retrospectively analyzed the antibiograms of Enterobacterales identified from 1 January 2019 to 31 December 2019 from a referral hospital in the Aljouf region of Saudi Arabia. The revised document of the Centers for Disease Control (CDC) CR-2015 and Magiorakos et al.’s document were used to define carbapenem resistance and classify resistant bacteria, respectively. The association of carbapenem resistance, MDR, and ESBL with various sociodemographic characteristics was assessed by the chi-square test and odds ratios. In total, 617 Enterobacterales were identified. The predominant (n = 533 (86.4%)) isolates consisted of 232 (37.6%), 200 (32.4%), and 101 (16.4%) Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, respectively. In general, 432 (81.0%) and 128 (24.0%) isolates were of MDR and ESBL, respectively. The MDR strains were recovered in higher frequency from intensive care units (OR = 3.24 (1.78–5.91); p < 0.01). E. coli and K. pneumoniae resistance rates to imipenem (2.55 (1.21–5.37); p < 0.01) and meropenem (2.18 (1.01–4.67); p < 0.04), respectively, were significantly higher in winter. The data emphasize that MDR isolates among Enterobacterales are highly prevalent. The studied Enterobacterales exhibited seasonal variation in antimicrobial resistance rates towards carbapenems and ESBL activity.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3193
Author(s):  
Christina Pfab ◽  
Luisa Schnobrich ◽  
Samir Eldnasoury ◽  
André Gessner ◽  
Nahed El-Najjar

The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.


Infolib ◽  
2020 ◽  
Vol 24 (4) ◽  
pp. 2-8
Author(s):  
Umida Teshabaeva ◽  

The article is devoted to the history of the Tashkent Public Library, at the origins of which were prominent scientists of that time, to the present day of the National Library of Uzbekistan. The library fund has more than 7.5 million items in 75 languages of the world. The National Library is the main methodological center of information and library institutions of the Republic. Creation of favorable conditions for readers is one of the priority tasks of the library, which is improved every year by the introduction of new technologies for obtaining information in an operational way. Thanks to membership in the International Consortium «eIFL», users have access to 38 foreign educational databases, 12 of which are licensed. Also, library readers get access to national and world educational collections in different languages of the world.


2021 ◽  
pp. 115-123
Author(s):  
Andrei Nikolaevich Osipov ◽  
Aleksandr Ivanovich Bogachev ◽  
Vadim Rishatovich Gumerov ◽  
Elena Gennadevna Mordovina

2022 ◽  
pp. 15-21
Author(s):  
Oksana Anatolievna Gizinger ◽  
◽  
Irina Yurievna Lepina ◽  
Marina Nikolaevna Bagdasaryan ◽  
◽  
...  

The article presents an analysis of current information on the etiology, pathogenesis, laboratory diagnosis of human papillomavirus. It is shown that at the current stage of development of laboratory diagnostics there is a reliable screening test — cytological examination of smears taken from the ecto- and endocervix. To diagnose HPV, a combination of microscopic (cytological studies) and molecular genetic (PCR) diagnostic methods is used.


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