Emerione A, a novel fungal metabolite as an inhibitor of New Delhi metallo-β-lactamase-1, restores carbapenem susceptibility in carbapenem-resistant isolates

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

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Carbapenem-Resistant Enterobacteriaceae Rectal Screening during an Outbreak of New Delhi Metallo-β-Lactamase–Producing Klebsiella pneumoniae at an Acute Care Hospital

Infection Control and Hospital Epidemiology ◽

10.1086/675597 ◽

2014 ◽

Vol 35 (4) ◽

pp. 434-436 ◽

Cited By ~ 14

Author(s):

Larissa M. Pisney ◽

M. A. Barron ◽

E. Kassner ◽

D. Havens ◽

N. E. Madinger

Keyword(s):

Klebsiella Pneumoniae ◽

Acute Care ◽

Teaching Hospital ◽

Tertiary Care ◽

Acute Care Hospital ◽

University Teaching ◽

New Delhi ◽

Care Hospital ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

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.

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Enterobacteriaceae isolates carrying the New Delhi metallo-β-lactamase gene in Yemen

Journal of Medical Microbiology ◽

10.1099/jmm.0.073767-0 ◽

2014 ◽

Vol 63 (10) ◽

pp. 1316-1323 ◽

Cited By ~ 24

Author(s):

Alima Gharout-Sait ◽

Samer-Ahmed Alsharapy ◽

Lucien Brasme ◽

Abdelaziz Touati ◽

Rachida Kermas ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Susceptibility Testing ◽

Enterobacter Cloacae ◽

New Delhi ◽

Carbapenem Resistant ◽

Genes Encoding ◽

Phenotypic Tests ◽

Lactamase Gene ◽

Sequence Types

Ten carbapenem-resistant Enterobacteriaceae (eight Klebsiella pneumoniae isolates and two Enterobacter cloacae) isolates from Yemen were investigated using in vitro antimicrobial susceptibility testing, phenotypic carbapenemase detection, multilocus sequence typing (MLST) and replicon typing. Carbapenemase, extended-spectrum β-lactamase (ESBL) and plasmid-mediated quinolone resistance determinant genes were identified using PCR and sequencing. All of the 10 carbapenem-resistant Enterobacteriaceae were resistant to β-lactams, tobramycin, ciprofloxacin and cotrimoxazole. Imipenem, doripenem and meropenem MICs ranged from 2 to >32 mg l−1 and ertapenem MICs ranged from 6 to >32 mg l−1. All of the K. pneumoniae isolates showed ESBL activity in phenotypic tests. Genes encoding bla NDM were detected in all strains. All K. pneumoniae strains produced CTX-M-15 ESBL and SHV β-lactamases. TEM-1 β-lactamase was detected in seven isolates. Nine isolates were qnr positive including QnrB1, QnrA1 and QnrS1, and six isolates produced AAC-6′-Ib-cr. MLST identified five different sequence types (STs): ST1399, ST147, ST29, ST405 and ST340. Replicon typing showed the presence of IncFII1K plasmids in four transformants. To the best of our knowledge, this is the first report of NDM-1-producing Enterobacteriaceae isolates in Yemen.

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Systematic surveillance and meta-analysis on the prevalence of Metallo-β-Lactamase producers among carbapenem resistant clinical isolates in Pakistan

10.21203/rs.2.23189/v1 ◽

2020 ◽

Author(s):

Noor ul Ain ◽

Samyyia Abrar ◽

Rehan Ahmad Khan ◽

Abdul Hannan ◽

Namrah Imran ◽

...

Keyword(s):

Infection Control ◽

Meta Analysis ◽

Carbapenem Resistance ◽

Epidemiological Surveillance ◽

Health Concern ◽

New Delhi ◽

Significant Heterogeneity ◽

Carbapenem Resistant ◽

Geographical Regions ◽

Clinically Significant

Abstract Background: Rapid emergence of carbapenem resistance (CR) is a health concern of pertinent importance. Epidemiological surveillance of CR at global and indigenous level (Pakistan) can help to improve infection control strategy and establish pharmacovigilance programs. This study evaluate the prevalence of clinically significant CR isolates, and its genetic variant distribution among different geographical regions of Pakistan. Methods: A meta-analysis was conducted to present the current rate of CR infections and prevalence of Metallo-β-lactamases (MBLs). The proposed subject was researched using robustic electronic databases a) PubMed b) PubMed Central® (PMC), and c) Google Scholar to identify the available literature. Thereafter, relevant data was extracted and statistical analysis was performed using STATA version 14. Result: A total of 110 relevant studies were identified with 19 meeting the inclusion criteria for the meta-analysis of CR, while 22 for MBLs. Pooled rate for carbapenem resistance was determined to be 0.28 (95% CI: 0.26-0.31) with overall significant heterogeneity (I 2 =99.61%, p<0.001) and significant estimated score ES=0 (Z=22.65, p<0.001). In case of Pakistan, the overall pooled proportion of MBL producers was 0.34 (95% CI: 0.29-0.39) with overall heterogeneity significance (I 2 =99.62%, p<0.001) and respective significant ES=0 (Z=13.17, p<0.001). Conclusively, diverse variants of carbapenemases (VIM, IMP, NDM, KPC, GIM, SIM) along with other co-existing β-lactamase variants (OXA, TEM, SHV, CTX-M) have been reported across the country. However, New Delhi Metallo-β-lactamase (NDM)-variants were reported in predominant literature. Conclusion: The prevalence of CR isolates in Pakistan is alarming, associated with MBL production primarily evident from the studies. The study emphasizes the need for regular surveillance, pharmacovigilance and antibiotic stewardship programs to ensure the availability of data to the authorities for preemptive measures of infection control.

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

Marine Drugs ◽

10.3390/md18060295 ◽

2020 ◽

Vol 18 (6) ◽

pp. 295

Author(s):

Chris S. Thomas ◽

Doug R. Braun ◽

Jose Luis Olmos ◽

Scott R. Rajski ◽

George N. Phillips ◽

...

Keyword(s):

Metal Complex ◽

Metal Complexes ◽

Effective Treatment ◽

Human Health ◽

Treatment Options ◽

New Delhi ◽

New Class ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

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.

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Spread of ST348 Klebsiella pneumoniae Producing NDM-1 in a Peruvian Hospital

Microorganisms ◽

10.3390/microorganisms8091392 ◽

2020 ◽

Vol 8 (9) ◽

pp. 1392 ◽

Cited By ~ 1

Author(s):

Maria J. Pons ◽

Marta Marí-Almirall ◽

Barbara Ymaña ◽

Jeel Moya-Salazar ◽

Laura Muñoz ◽

...

Keyword(s):

Klebsiella Pneumoniae ◽

Molecular Data ◽

Resistance Mechanisms ◽

Conjugative Plasmid ◽

New Delhi ◽

Carbapenem Resistant ◽

Gradient Diffusion ◽

Adults And Children ◽

First Time ◽

Esbl Producers

The aim of this study was to characterize carbapenem-resistant Klebsiella pneumoniae (CR-Kp) isolates recovered from adults and children with severe bacteremia in a Peruvian Hospital in June 2018. Antimicrobial susceptibility was determined by disc/gradient diffusion and broth microdilution when necessary. Antibiotic resistance mechanisms were evaluated by PCR and DNA sequencing. Clonal relatedness was assessed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Plasmid typing was performed with a PCR-based method. Thirty CR-Kp isolates were recovered in June 2018. All isolates were non-susceptible to all β-lactams, ciprofloxacin, gentamicin and trimethoprim-sulfamethoxazole, while mostly remaining susceptible to colistin, tigecycline, levofloxacin and amikacin. All isolates carried the blaNDM-1 gene and were extended spectrum β-lactamase (ESBL) producers. PFGE showed four different pulsotypes although all isolates but two belonged to the ST348 sequence type, previously reported in Portugal. blaNDM-1 was located in an IncFIB-M conjugative plasmid. To our knowledge, this is the first report of an New Delhi metallo-β-lactamase (NDM)-producing K. pneumoniae recovered from both children and adults in Lima, Peru, as well as the first time that the outbreak strain ST348 is reported in Peru and is associated with NDM. Studies providing epidemiological and molecular data on CR-Kp in Peru are essential to monitor their dissemination and prevent further spread.

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Rapid Electrochemical Detection of New Delhi Metallo-beta-lactamase Genes To Enable Point-of-Care Testing of Carbapenem-Resistant Enterobacteriaceae

Analytical Chemistry ◽

10.1021/acs.analchem.5b01270 ◽

2015 ◽

Vol 87 (15) ◽

pp. 7738-7745 ◽

Cited By ~ 23

Author(s):

Jimmy Ming-Yuan Huang ◽

Grace Henihan ◽

Daniel Macdonald ◽

Annette Michalowski ◽

Kate Templeton ◽

...

Keyword(s):

Electrochemical Detection ◽

Point Of Care ◽

New Delhi ◽

Beta Lactamase ◽

Point Of Care Testing ◽

Carbapenem Resistant ◽

Carbapenem Resistant Enterobacteriaceae

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Evaluation of High-level Disinfection Processes for Linear Endoscopic Ultrasound Scopes Following New Delhi Metallo-beta-lactamase Carbapenem-resistant Enterobacteriaceae bacteremia

American Journal of Infection Control ◽

10.1016/j.ajic.2019.04.136 ◽

2019 ◽

Vol 47 (6) ◽

pp. S4-S5

Author(s):

Emily Moulton ◽

Regan Trappler ◽

Lucy He ◽

Holly Taylor ◽

Deeb Oweis

Keyword(s):

Endoscopic Ultrasound ◽

New Delhi ◽

Beta Lactamase ◽

Carbapenem Resistant ◽

High Level ◽

Carbapenem Resistant Enterobacteriaceae

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Evaluation of the EDTA-Modified Carbapenem Inactivation Method for Detecting Metallo-β-Lactamase-Producing Pseudomonas aeruginosa

Journal of Clinical Microbiology ◽

10.1128/jcm.02015-19 ◽

2020 ◽

Vol 58 (6) ◽

Cited By ~ 8

Author(s):

Christian M. Gill ◽

Maxwell J. Lasko ◽

Tomefa E. Asempa ◽

David P. Nicolau

Keyword(s):

Pseudomonas Aeruginosa ◽

Klebsiella Pneumoniae ◽

Test Performance ◽

New Delhi ◽

Large Collection ◽

Testing Methods ◽

Prolonged Incubation ◽

Content Type ◽

Carbapenem Resistant ◽

Genotypic Profile

ABSTRACT The prevalence of carbapenem-resistant Pseudomonas aeruginosa is increasing. Identification of carbapenemase-producing P. aeruginosa will have therapeutic, epidemiological, and infection control implications. This study evaluated the performance of the EDTA-modified carbapenem inactivation method (eCIM) in tandem with the modified carbapenem inactivation method (mCIM) against a large collection of clinical P. aeruginosa isolates (n = 103) to provide clinicians a phenotypic test that not only identifies carbapenemase production but also distinguishes between metallo-β-lactamase and serine-carbapenemase production in P. aeruginosa. The mCIM test was performed according to Clinical and Laboratory Standards Institute guidelines, while the eCIM was conducted as previously described for Enterobacteriaceae. Test performance was compared to the genotypic profile as the reference. mCIM testing successfully categorized 91% (112/123) of P. aeruginosa isolates as carbapenemases or non-carbapenemase producers, with discordant isolates being primarily Guiana extended-spectrum (GES)-type producers. To increase the sensitivity of the mCIM for GES-harboring isolates, a double inoculum, prolonged incubation, or both was evaluated, with each modification improving sensitivity to 100% (12/12). Upon eCIM testing, all Verona integrin-encoded metallo-β-lactamases (VIM; n = 27) and New Delhi metallo-β-lactamases (NDM; n = 13) tested had 100% concordance to their genotypic profiles, whereas all Klebsiella pneumoniae carbapenemase (KPC; n = 8) and GES (n = 12) isolates tested negative, as expected, in the presence of EDTA. The eCIM failed to identify all imipenemase (IMP)-producing (n = 22) and Sao Paulo metallo-β-lactamase (SPM)-producing (n = 14) isolates. KPC-, VIM-, and NDM-producing P. aeruginosa were well defined by the conventional mCIM and eCIM testing methods; additional modifications appear required to differentiate GES-, IMP-, and SPM-producing isolates.

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