scholarly journals Pyridine-2,6-Dithiocarboxylic Acid and Its Metal Complexes: New Inhibitors of New Delhi Metallo -Lactamase-1

Marine Drugs ◽  
2020 ◽  
Vol 18 (6) ◽  
pp. 295
Author(s):  
Chris S. Thomas ◽  
Doug R. Braun ◽  
Jose Luis Olmos ◽  
Scott R. Rajski ◽  
George N. Phillips ◽  
...  

Carbapenem-resistant Enterobacteriaceae continue to threaten human health worldwide with few effective treatment options. New Delhi metallo--lactamase (NDM) enzymes are a contributing element that drive resistance to many -lactam- and carbapenem-based antimicrobials. Many NDM inhibitors are known, yet none are clinically viable. In this study, we present and characterize a new class of NDM-1 inhibitors based on a pyridine-2,6-dithiocarboxylic acid metal complex scaffold. These complexes display varied and unique activity profiles against NDM-1 in kinetic assays and serve to increase the effectiveness of meropenem, an established antibacterial, in assays using clinical Enterobacteriaceae isolates.

2020 ◽  
Vol 41 (S1) ◽  
pp. s305-s305
Author(s):  
Karoline Sperling ◽  
Amy Priddy ◽  
Nila Suntharam ◽  
Adam Karlen

Background: With increasing medical tourism and international healthcare, emerging multidrug resistant organisms (MDROs) or “superbugs” are becoming more prevalent. These MDROs are unique because they are resistant to antibiotics and can carry special resistance mechanisms. In April 2019, our hospital was notified that a superbug, New Delhi Metallo-β-lactamase(NDM)–producing carbapenem-resistant Enterobacteriaceae (CRE), was identified in a patient who had been transferred to another hospital after being at our hospital for 3 weeks. Our facility had a CRE admission screening protocol in place since 2013, but this patient did not meet the criteria to be screened on admission. Methods: The infection prevention (IP) team consulted with the Minnesota Department of Health (MDH) and gathered stakeholders to discuss containment strategies using the updated 2019 CDC Interim Guidance for Public Health Response to Contain Novel or Targeted Multidrug-resistant Organisms (MDROs) to determine whether transmission to other patients had occurred. NDM CRE was classified under tier 2 organisms, meaning those primarily associated with healthcare settings and not commonly identified in the region, and we used this framework to conduct an investigation. A point-prevalence study was done in an intensive care unit that consisted of rectal screening of 7 patients for both CRE and Candida auris, another emerging MDRO. These swabs were sent to the Antibiotic Resistance Laboratory Network (ARLN) Central Regional Lab at MDH for testing. An on-site infection control risk assessment was done by the MDH Infection Control Assessment and Response (ICAR) team. Results: All 7 patients were negative for both CRE and C. auris, and no further screening was done. During the investigation, it was discovered that the patient had had elective ambulatory surgery outside the United States in March 2019. The ICAR team assessment provided overall positive feedback to the nursing unit about isolation procedures, cleaning products, and hand hygiene product accessibility. Opportunities included set-up of soiled utility room and updating our process to the 2019 MDH recommendation to screen patients for CRE and C. auris on admission who have been hospitalized, had outpatient surgery, or hemodialysis outside the United States in the previous year. Conclusions: Point-prevalence study results showed no transmission of CRE and highlighted the importance of standard precautions. This event supports the MDH recommendation to screen for CRE any patients who have been hospitalized, had outpatient surgery, or had hemodialysis outside the United States in the previous year.Funding: NoneDisclosures: None


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S792-S792
Author(s):  
Alfredo Traversa ◽  
Linda Poggensee ◽  
Geneva M Wilson ◽  
Katie J Suda ◽  
Charlesnika T Evans ◽  
...  

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) are classified as an “urgent threat” to public health. Historically, colistin and tigecycline had been considered the drugs of choice for CRE infections, while other agents such as aminoglycosides and carbapenems had been used as adjunctive therapy. However, the FDA approval of ceftazidime-avibactam in 2015, meropenem-vaborbactam in 2017, and plazomicin in 2018 has expanded treatment options. Our purpose was to assess trends in CRE treatment for “new” antibiotics (ceftazidime-avibactam, meropenem-vaborbactam, plazomicin) as compared with other antibiotics with CRE activity. Methods This was a retrospective cohort study describing treatment of CRE blood stream infections (BSI) across 134 VA facilities from 2012-2018. Patients were censored at their first positive blood culture with CRE. Categorical data was assessed with a Fisher’s exact test or chi-square test. Trends test and logistic regression were used to describe changes in CRE treatment over time. Results 724 patients with positive blood cultures for CRE were identified during the study period. Most patients were male (94%), white (32%) or Hispanic (38%), and the mean age was 71.5+11.9. Of those patients that received antibiotics (N=697), 53.4% carbapenems, 40.3% received aminoglycosides, 39.3% received polymyxins, 32.9% penicillins, 32.6% extended spectrum cephalosporins, 26.1% fluoroquinolones, 11.6% ceftazidime/avibactam, and 0.4% ceftolazone/tazobactam. Over the study period, there was decreased utilization of aminoglycosides (P < 0.0026) and colistin (P< 0.002) and increases in extended spectrum cephalosporins (P < 0.001) and ceftazidime/avibactam (P < 0.001). Conclusion Utilization of “older” agents such as aminoglycosides and polymyxins for the treatment of CRE blood stream infections is decreasing in the VA. Treating CRE with ceftazidime/avibactam, a newly approved antibiotic, and extended spectrum cephalosporins are increasing. Disclosures All Authors: No reported disclosures


2014 ◽  
Vol 35 (4) ◽  
pp. 434-436 ◽  
Author(s):  
Larissa M. Pisney ◽  
M. A. Barron ◽  
E. Kassner ◽  
D. Havens ◽  
N. E. Madinger

We describe the results of carbapenem-resistant Enterobacteriaceae (CRE) screening as part of an outbreak investigation of New Delhi metallo-β-lactamase–producing CRE at a tertiary care university teaching hospital. The manual method for CRE screening was useful for detecting patients with asymptomatic CRE carriage but was time-consuming and costly.


Author(s):  
Chirag Manojkumar Modi ◽  
Suman Praveen Singh ◽  
Yagnesh Gajanand Pandya ◽  
Chirag Premjibhai Patel ◽  
Rupal Minesh Patel

Introduction: Carbapenem Resistant Enterobacteriaceae (CRE) are major cause of community as well as healthcare associated infections and have limited treatment options. Measuring the magnitude of the problem of CRE, it is important for making strategies to lower its spread. Aim: To assess the incidence and prevalence rate of CRE in a tertiary care hospital of Gujarat, India. Materials and Methods: Retrospective data was collected for a period from 2014 to 2018 using Laboratory Information System (LIS). Prevalence of CRE was determined as number of CRE isolated per 100 Enterobacteriaceae isolated during the study period whereas incidence rate was determined as number of CRE cases per 1000 patient-days. Consumption of Carbapenems was calculated as Defined Daily Dose (DDD) per 1000 patient-days. Demographic data including age, gender, location in the hospital and sample type from which CRE was isolated was also analysed using Microsoft Excel. Results: The incidence of CRE cases per 1000 patient-days in 2014 to 2018 was 1.66, 2.11, 1.90, 2.26 and 1.91, respectively with an overall incidence of 1.99 per 1000 patient-days. The overall prevalence of CRE over a period of five years was found to be 29.07%. Klebsiellasp. was the most common CRE and had the highest percentage of Carbapenem resistance among all Enterobacteriaceae. Conclusion: The rate of CRE in present study was high and worrisome. Screening of the patient for CRE, source isolation and stringent implementation of infection control practices is required to confine the spread of CRE in this institute.


2015 ◽  
Vol 87 (15) ◽  
pp. 7738-7745 ◽  
Author(s):  
Jimmy Ming-Yuan Huang ◽  
Grace Henihan ◽  
Daniel Macdonald ◽  
Annette Michalowski ◽  
Kate Templeton ◽  
...  

2012 ◽  
Vol 6 (05) ◽  
pp. 457-461 ◽  
Author(s):  
Rima I El-Herte ◽  
George F Araj ◽  
Ghassan M Matar ◽  
Maysa Baroud ◽  
Zeina A Kanafani ◽  
...  

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48   and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.


2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab

Carbapenems are a class of antimicrobial agents reserved for infections caused by multidrug-resistant microorganisms. The emergence of carbapenem resistance has become a serious public health threat. This type of antimicrobial resistance is spreading at an alarming rate, resulting in major outbreaks and treatment failure of community-acquired and nosocomial infections caused by the clinically relevant carbapenem-producing Enterobacteriaceae or carbapenem-resistant Enterobacteriaceae. This review is focused on carbapenem resistance, including mechanisms of resistance, history and epidemiology, phenotypic and genotypic detection in the clinically relevant bacterial pathogens and the possible treatment options available.


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