scholarly journals Diverse Mechanisms of Resistance in Carbapenem-Resistant Enterobacteriaceae at a Health Care System in Silicon Valley, California

2018 ◽  
Author(s):  
Fiona Senchyna ◽  
Rajiv Gaur ◽  
Johanna Sandlund ◽  
Cynthia Truong ◽  
Guillaume Tremintin ◽  
...  
Keyword(s):  
Health System ◽  
Silicon Valley ◽  
Carbapenem Resistance ◽  
Gene Encoding ◽  
Major Health ◽  
Mechanism Of Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Underlying Mechanisms ◽  
Carbapenem Resistant Enterobacteriaceae

AbstractCarbapenem-resistant Enterobacteriaceae (CRE) are emerging as a major health threat in North America. The mechanism of resistance to carbapenems has therapeutic and public health implications. We comprehensively characterized the underlying mechanisms of carbapenem resistance in CRE isolates recovered between 2013 and 2016 at a health system in Northern California. Genotypic methods were used to detect carbapenemases and plasmid-encoded cephalosporinases, and mass spectrometry was used to quantify relative porin levels for OmpC and OmpF and their analogs. MICs for imipenem-relebactam, meropenem-vaborbactam, ceftazidime-avibactam, and ceftolozane-tazobactam were measured. Whole genome sequencing was used for strain typing. A carbapenemase gene encoding blaOXA-48 like, blaNDM, blaKPC, blaSME, blaIMP, and blaVIM was detected in 38.7% (24/62) of CRE isolates. Porin levels was down at least 2-fold in 91.9% (57/62) of isolates. Including carbapenemase genes and porin loss, the mechanism of resistance was identified in 95.2% (59/62) of CRE isolates. Of the carbapenemase gene-positive isolates, blaKPC -positive isolates were 100% susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam; blaOXA-48 like-positive isolates were 100% susceptible to ceftazidime-avibactam; and blaSME-positive isolates were 100% susceptible to meropenem-vaborbactam and ceftolozane-tazobactam. 100% (38/38), 92.1% (35/38), 89.5% (34/38), and 31.6% (12/38) of carbapenemase gene-negative CRE isolates were susceptible to ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, and ceftolozane-tazobactam, respectively. None of the CRE strains were genetically identical. In conclusion, at this health system in Silicon Valley, carbapenemase-producing CRE occurred sporadically and were mediated by diverse mechanisms. Nucleic acid testing for blaOXA-48 like, blaNDM, blaKPC, blaIMP, and blaVIM was sufficient to distinguish between carbapenemase-producing and non-producing CRE and accurately predicted susceptibility to ceftazidime-avibactam, meropenem-vaborbactam and imipenem-relebactam.

scholarly journals Plasmidome analysis of carbapenem-resistant Enterobacteriaceae isolated in Vietnam

2020 ◽  
Author(s):  
Aki Hirabayashi ◽  
Koji Yahara ◽  
Satomi Mitsuhashi ◽  
So Nakagawa ◽  
Tadashi Imanishi ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Genomic Epidemiology ◽  
Carbapenem Resistant ◽  
Oxford Nanopore ◽  
Carbapenemase Gene ◽  
Long Read ◽  
Severe Infections ◽  
Oxford Nanopore Technologies ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae (CRE) represent a serious threat to public health due to limited management of severe infections and high mortality. The rate of resistance of Enterobacteriaceae isolates to major antimicrobials, including carbapenems, is much higher in Vietnam than in Western countries, but the reasons remain unknown due to the lack of genomic epidemiology research. A previous study suggested that carbapenem resistance genes, such as the carbapenemase gene bla NDM-1 , spread via plasmids among Enterobacteriaceae in Vietnam. In this study, we performed detection and molecular characterization of bla NDM-1 -carrying plasmids in CRE isolated in Vietnam, and identified several possible cases of horizontal transfer of plasmids both within and among species of bacteria. Twenty-five carbapenem-resistant isolates from Enterobacteriaceae clinically isolated in a reference medical institution in Hanoi were sequenced on Illumina short-read sequencers, and 12 isolates harboring bla NDM-1 were sequenced on an Oxford Nanopore Technologies long-read sequencer to obtain complete plasmid sequences. Most of the plasmids co-carried genes conferring resistance to clinically relevant antimicrobials, including third-generation cephalosporins, aminoglycosides, and fluoroquinolones, in addition to bla NDM-1 , leading to multidrug resistance of their bacterial hosts. These results provide insight into the genetic basis of CRE in Vietnam, and could help control nosocomial infections.

The prevalence of carbapenemase genes and plasmid-mediated quinolone resistance determinants in carbapenem-resistant Enterobacteriaceae from five teaching hospitals in central China

2013 ◽  
Vol 142 (9) ◽  
pp. 1972-1977 ◽  
Author(s):  
L. HU ◽  
Q. ZHONG ◽  
Y. SHANG ◽  
H. WANG ◽  
C. NING ◽  
...  
Keyword(s):  
Klebsiella Oxytoca ◽  
Carbapenem Resistance ◽  
Quinolone Resistance ◽  
Central China ◽  
Teaching Hospitals ◽  
Resistance Determinants ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
High Prevalence ◽  
Carbapenem Resistant Enterobacteriaceae

SUMMARYWe investigated the prevalence of β-lactamase genes and plasmid-mediated quinolone resistance (PMQR) determinants in 51 carbapenem-resistant Enterobacteriaceae (CRE) from five teaching hospitals in central China. The prevalence of carbapenem resistance in Enterobacteriaceae was 1·0% (51/5012). Of 51 CRE, 31 (60·8%) isolates were positive for one tested carbapenemase gene, while 10 (19·6%) were simultaneously positive for two tested carbapenemase genes. The positive rates of blaKPC-2, blaNDM-1, blaIMP-4, blaIMP-26 and blaIMP-8 were 54·9%, 17·6%, 11·8%, 11·8% and 3·9%, respectively. Of 10 CRE with two carbapenemase genes, three, five, one and one were positive for blaKPC-2 and blaIMP-4, blaKPC-2 and blaIMP-26, blaKPC-2 and blaIMP-8, and blaKPC-2 and blaNDM-1, respectively. Eight of nine blaNDM-1-positive isolates lacked carbapenemases by the modified Hodge test, while 27/28 isolates harbouring blaKPC-2 were positive for carbapenemases determined by this test; 41·2% of the CRE-positive isolates also harboured ESBL genes in various combinations (three and two positive for blaKPC-2 also carried blaDHA-1 and blaCMY-2). The positive rates of qnrS1, qnrA1, qnrB and aac-(6/)-Ib-cr in CRE were 25·5%, 9·8%, 23·5% and 15·7%, respectively. In particular, 7/9 isolates harbouring blaNDM-1 were positive for these quinolone resistance genes, of which five carried qnrS1 and two carried qnrS1 and qnrB4. All but two of 29 Klebsiella pneumoniae isolates were grouped into 20 clonal clusters by PFGE, with the predominant cluster accounting for four blaKPC-2-positive isolates distributed in the same hospital. We conclude that there is a high prevalence of blaNDM-1 and PMQR determinants in CRE isolates in central China. Multiple resistance determinants in various combinations co-exist in these strains and we report for the first time the co-existence of blaKPC-2 and blaIMP-26 in a strain of Klebsiella oxytoca.

scholarly journals CRISPR-Cas9-Mediated Carbapenemase Gene and Plasmid Curing in Carbapenem-Resistant Enterobacteriaceae

2020 ◽  
Vol 64 (9) ◽  
Author(s):  
Mingju Hao ◽  
Yuzhang He ◽  
Haifang Zhang ◽  
Xiao-Ping Liao ◽  
Ya-Hong Liu ◽  
...  
Keyword(s):  
Clinical Intervention ◽  
Carbapenem Resistance ◽  
Plasmid Curing ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Fold Reduction ◽  
Carbapenemase Gene ◽  
Enterobacter Hormaechei ◽  
Generation Sequencing ◽  
Carbapenem Resistant Enterobacteriaceae

ABSTRACT Combating plasmid-mediated carbapenem resistance is essential to control and prevent the dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Here, we conducted a proof-of-concept study to demonstrate that CRISPR-Cas9-mediated resistance gene and plasmid curing can effectively resensitize CRE to carbapenems. A novel CRISPR-Cas9-mediated plasmid-curing system (pCasCure) was developed and electrotransferred into various clinical CRE isolates. The results showed that pCasCure can effectively cure blaKPC, blaNDM, and blaOXA-48 in various Enterobacteriaceae species of Klebsiella pneumoniae, Escherichia coli, Enterobacter hormaechei, Enterobacter xiangfangensis, and Serratia marcescens clinical isolates, with a >94% curing efficiency. In addition, we also demonstrated that pCasCure can efficiently eliminate several epidemic carbapenem-resistant plasmids, including the blaKPC-harboring IncFIIK-pKpQIL and IncN pKp58_N plasmids, the blaOXA-48-harboring pOXA-48-like plasmid, and the blaNDM-harboring IncX3 plasmid, by targeting their replication and partitioning (parA in pKpQIL) genes. However, curing the blaOXA-48 gene failed to eliminate its corresponding pOXA-48-like plasmid in clinical K. pneumoniae isolate 49210, while further next-generation sequencing revealed that it was due to IS1R-mediated recombination outside the CRISPR-Cas9 cleavage site resulting in blaOXA-48 truncation and, therefore, escaped plasmid curing. Nevertheless, the curing of carbapenemase genes or plasmids, including the truncation of blaOXA-48 in 49210, successfully restore their susceptibility to carbapenems, with a >8-fold reduction of MIC values in all tested isolates. Taken together, our study confirmed the concept of using CRISPR-Cas9-mediated carbapenemase gene and plasmid curing to resensitize CRE to carbapenems. Further work is needed to integrate pCasCure in an optimal delivery system to make it applicable for clinical intervention.

scholarly journals Phenotypic Detection of Carbapenemase Production in Carbapenem-Resistant Enterobacteriaceae by Modified Hodge Test and Modified Strip Carba NP Test

2021 ◽  
Author(s):  
Nisha Patidar ◽  
Nitya Vyas ◽  
Shanoo Sharma ◽  
Babita Sharma
Keyword(s):  
Carbapenem Resistance ◽  
Nonparametric Test ◽  
Multidrug Resistant ◽  
Clinical Samples ◽  
Chi Square ◽  
Carbapenem Resistant ◽  
The Social ◽  
Significant Difference ◽  
High Degree ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Objective Carbapenems are last resort antibiotics for multidrug-resistant Enterobacteriaceae. However, resistance to carbapenem is increasing at an alarming rate worldwide leading to major therapeutic failures and increased mortality rate. Early and effective detection of carbapenemase producing carbapenem-resistant Enterobacteriaceae (CRE) is therefore key to control dissemination of carbapenem resistance in nosocomial as well as community-acquired infection. The aim of present study was to evaluate efficacy of Modified strip Carba NP (CNP) test against Modified Hodge test (MHT) for early detection of carbapenemase producing Enterobacteriaceae (CPE). Material and Methods Enterobacteriaceae isolated from various clinical samples were screened for carbapenem resistance. A total of 107 CRE were subjected to MHT and Modified strip CNP test for the detection of CPE. Statistical Analysis It was done on Statistical Package for the Social Sciences (SPSS) software, IBM India; version V26. Nonparametric test chi-square and Z-test were used to analyze the results within a 95% level of confidence. Results Out of 107 CRE, 94 (88%) were phenotypically confirmed as carbapenemase producer by Modified strip CNP test and 46 (43%) were confirmed by Modified Hodge Test (MHT). Thirty-eight (36%) isolates showed carbapenemase production by both MHT and CNP test, 56 isolates (52%) were CNP test positive but MHT negative, eight (7%) isolates were MHT positive but CNP test negative and five (5%) isolates were both MHT and CNP test negative. There is statistically significant difference in efficiency of Modified CNP test and MHT (p < 0.05). Conclusion Modified strip CNP test is simple and inexpensive test which is easy to perform and interpret and gives rapid results in less than 5 minutes. It has high degree of sensitivity and specificity. Modified strip CNP test shows significantly higher detection capacity for carbapenemase producers as compared with MHT.

scholarly journals 1348. In vitro Activity of Plazomicin, a Next-Generation Aminoglycoside, Against Carbapenemase-Producing Klebsiella pneumoniae

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S412-S413
Author(s):  
Michael R Jacobs ◽  
Caryn E Good ◽  
Ayman M Abdelhamed ◽  
Daniel D Rhoads ◽  
Kristine M Hujer ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Carbapenem Resistance ◽  
Vitro Activity ◽  
In Vitro Activity ◽  
Next Generation ◽  
Aminoglycoside Resistance ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Research Grant

Abstract Background Plazomicin is a next-generation aminoglycoside with in vitro activity against multidrug-resistant Gram-negative species, including carbapenem-resistant isolates. The Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE) is a federally funded, prospective multicenter consortium of 20 hospitals from nine US healthcare systems to track carbapenem-resistant Enterobacteriaceae. Methods Minimum inhibitory concentrations (MICs) of plazomicin were determined by broth microdilution according to current CLSI guidelines against a collection of 697 carbapenem-resistant Klebsiella pneumoniae with defined carbapenem resistance mechanisms, including KPC and OXA carbapenemases. Isolates were submitted by participating CRACKLE centers. Results Carbapenemases present in study isolates included KPC-2 (n = 323), KPC-3 (n = 364), KPC-4 (n = 2), OXA-48 like (n = 7), and NDM (n = 1). Plazomicin MICs ranged from ≤0.12 to &gt;32 mg/L, with MIC50 and MIC90 values of 0.25 and 1 mg/L, respectively (figure). MICs of 689 (98.8%) isolates were ≤4 mg/L, while MICs of the remaining eight isolates were &gt;32 mg/L. Plazomicin MICs were related to specific carbapenemases present in isolates: of eight isolates with MICs &gt;32 mg/L, seven contained OXA-48 like and one contained KPC-3, suggesting that these isolates possess an aminoglycoside-resistance mechanism on the same plasmid as their carbapenemase gene, such as a 16S ribosomal RNA methyltransferase, against which plazomicin is not active. Conclusion Plazomicin has good in vitro potency against a collection of carbapenemase-producing K. pneumoniae, with MIC90 value of 1 mg/L and MICs of ≤4 mg/L for 98.9% of isolates. Disclosures M. R. Jacobs, Achaogen: Investigator, Research grant. Shionogi: Investigator, Research grant. L. Connolly, Achaogen, Inc.: Consultant, Consulting fee. K. M. Krause, Achaogen: Employee, Salary. S. S. Richter, bioMerieux: Grant Investigator, Research grant. BD Diagnostics: Grant Investigator, Research grant. Roche: Grant Investigator, Research grant. Hologic: Grant Investigator, Research grant. Diasorin: Grant Investigator, Research grant. Accelerate: Grant Investigator, Research grant. Biofire: Grant Investigator, Research grant. D. Van Duin, achaogen: Scientific Advisor, Consulting fee. shionogi: Scientific Advisor, Consulting fee. Allergan: Scientific Advisor, Consulting fee. Astellas: Scientific Advisor, Consulting fee. Neumedicine: Scientific Advisor, Consulting fee. Roche: Scientific Advisor, Consulting fee. T2 Biosystems: Scientific Advisor, Consulting fee.

scholarly journals Near-infrared Spectroscopy evaluations for rapid differentiation of carbapenem resistant Enterobacteriaceae from susceptible strains

2020 ◽  
Author(s):  
Bushra Alharbi ◽  
Maggy T. Sikulu-Lord ◽  
Anton Lord ◽  
Hosam M Zowawi ◽  
Ella Trembizki
Keyword(s):  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Predictive Accuracy ◽  
Bacterial Species ◽  
Carbapenem Resistance ◽  
Accurate Identification ◽  
Carbapenem Resistant ◽  
Global Threat ◽  
Carbapenem Resistant Enterobacteriaceae

AbstractAntimicrobial resistance (AMR) caused by Carbapenem-Resistant Enterobacteriaceae (CRE) is a global threat. Accurate identification of these bacterial species with associated AMR is critical for their management. While highly accurate methods to detect CRE are available, they are costly, timely and require expert skills making their application infeasible in low-resource settings. Here, we investigated the potential of Near-infrared Spectroscopy (NIRS) for a range of applications; i) the detection and differentiation of isolates of two pathogenic Enterobacteriaceae species, Klebsiella pneumoniae and Escherichia coli and, ii) the differentiation of carbapenem resistant and susceptible K. pneumoniae. NIRS has successfully differentiated between K. pneumoniae and E. coli isolates with a predictive accuracy of 89.04% (95% CI; 88.7-89.4%). K. pneumoniae isolates harbouring carbapenem resistance determinants were differentiated from susceptible K. pneumoniae strains with an accuracy of 85% (95% CI; 84.2-86.1%). To our knowledge, this is the largest demonstration of a proof of concept for the utility and feasibility of NIRS for rapidly differentiating between K. pneumoniae from E.coli as well as from carbapenem resistant K. pneumoniae from susceptible strains.

scholarly journals Investigation of Carbapenemase Genes in Carbapenem Resistant Enterobacterales Isolates: First KPC Report From Dokuz Eylul University Hospital

2021 ◽  
Author(s):  
Şeyda Şilan Okalin ◽  
Ayşe Nur Sarı Kaygısız ◽  
Mahmut Cem Ergon ◽  
İbrahim Mehmet Ali Öktem
Keyword(s):  
Treatment Options ◽  
Carbapenem Resistance ◽  
Tracheal Aspirate ◽  
University Hospital ◽  
Chain Reaction ◽  
Specific Primers ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Carbapenemase Gene ◽  
Polymerase Chain

Objective: In recent years, increasing carbapenem resistance of Enterobacterales bacteria limits treatment options, considerably. The main mechanism of this resistance is the production of carbapenemase enzymes. The aim of this study is to determine carbapenemase gene types in Enterobacterales isolates from our hospitalized patients and assess the clonal associations of the isolates with KPC gene. Method: A total of 48 clinical Enterobacterales isolates resistant to at least one carbapeneme and received between January 2019 and March 2019 were included in the study. Sample types were consisted of urine, blood, tracheal aspirate, wound and sputum. Of these isolates, three were Escherichia coli while 45 were Klebsiella pneumoniae. Types of carbapenemases were investigated by polymerase chain reaction, using specific primers for VIM, IMP, NDM, KPC and OXA-48 genes. PFGE was performed to determine the clonal associations between blaKPC positive K. pnemoniae isolates. Results: According to the results, blaOXA-48 (n=2) and blaKPC (n=1) were found to be present among E. coli isolates. Regarding 45 K. pneumoniae isolates; only blaOXA-48 and only blaNDM were present in 30 and two isolates, respectively. Seven K. pneumoniae isolates were found positive for both blaOXA-48 and blaNDM. Remaining K. pneumoniae isolates (n=6) harboured only blaKPC. None of the isolates were positive for blaIMP and blaVIM. PFGE analysis showed four isolates had the same pulsotype (A), while two had different pulsotypes (B-C). Conclusion: To our knowledge, this is the first report of KPC gene isolated in Dokuz Eylul University Hospital.

scholarly journals Prevalence of Carbapenem Resistant Enterobacteriaceae in a Tertiary Care Hospital of Gujarat, India

2021 ◽  
Author(s):  
Chirag Manojkumar Modi ◽  
Suman Praveen Singh ◽  
Yagnesh Gajanand Pandya ◽  
Chirag Premjibhai Patel ◽  
Rupal Minesh Patel
Keyword(s):  
Tertiary Care Hospital ◽  
Demographic Data ◽  
Treatment Options ◽  
Tertiary Care ◽  
Carbapenem Resistance ◽  
Defined Daily Dose ◽  
Sample Type ◽  
Care Hospital ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

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.

scholarly journals Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks

2017 ◽  
Vol 114 (5) ◽  
pp. 1135-1140 ◽  
Author(s):  
Gustavo C. Cerqueira ◽  
Ashlee M. Earl ◽  
Christoph M. Ernst ◽  
Yonatan H. Grad ◽  
John P. Dekker ◽  
...  
Keyword(s):  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
Phylogeographic Structure ◽  
Aggressive Approach ◽  
Beta Lactamases ◽  
Carbapenem Resistant ◽  
Local Transmission ◽  
California Hospital ◽  
Carbapenem Resistant Enterobacteriaceae ◽  
The Continuum

Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to the antibiotic era. Multiple different species can exhibit resistance due to many different mechanisms, and many different mobile elements are capable of transferring resistance between lineages. We prospectively sampled CRE from hospitalized patients from three Boston-area hospitals, together with a collection of CRE from a single California hospital, to define the frequency and characteristics of outbreaks and determine whether there is evidence for transfer of strains within and between hospitals and the frequency with which resistance is transferred between lineages or species. We found eight species exhibiting resistance, with the majority of our sample being the sequence type 258 (ST258) lineage ofKlebsiella pneumoniae. There was very little evidence of extensive hospital outbreaks, but a great deal of variation in resistance mechanisms and the genomic backgrounds carrying these mechanisms. Local transmission was evident in clear phylogeographic structure between the samples from the two coasts. The most common resistance mechanisms were KPC (K. pneumoniaecarbapenemases) beta-lactamases encoded byblaKPC2,blaKPC3, andblaKPC4, which were transferred between strains and species by seven distinct subgroups of the Tn4401element. We also found evidence for previously unrecognized resistance mechanisms that produced resistance when transformed into a susceptible genomic background. The extensive variation, together with evidence of transmission beyond limited clonal outbreaks, points to multiple unsampled transmission chains throughout the continuum of care, including asymptomatic carriage and transmission of CRE. This finding suggests that to control this threat, we need an aggressive approach to surveillance and isolation.

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