scholarly journals Present and Future of Carbapenem-resistant Enterobacteriaceae (CRE) Infections

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 122 ◽  
Author(s):  
Suay-García ◽  
Pérez-Gracia
Keyword(s):  
Enzyme Production ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
The United States ◽  
Klebsiella Pneumoniae Carbapenemase ◽  
Carbapenem Resistant ◽  
Class D ◽  
Therapeutic Guidelines ◽  
Class B ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae (CRE) have become a public health threat worldwide. There are three major mechanisms by which Enterobacteriaceae become resistant to carbapenems: enzyme production, efflux pumps and porin mutations. Of these, enzyme production is the main resistance mechanism. There are three main groups of enzymes responsible for most of the carbapenem resistance: KPC (Klebsiella pneumoniae carbapenemase) (Ambler class A), MBLs (Metallo-ß-Lactamases) (Ambler class B) and OXA-48-like (Ambler class D). KPC-producing Enterobacteriaceae are endemic in the United States, Colombia, Argentina, Greece and Italy. On the other hand, the MBL NDM-1 is the main carbapenemase-producing resistance in India, Pakistan and Sri Lanka, while OXA-48-like enzyme-producers are endemic in Turkey, Malta, the Middle-East and North Africa. All three groups of enzymes are plasmid-mediated, which implies an easier horizontal transfer and, thus, faster spread of carbapenem resistance worldwide. As a result, there is an urgent need to develop new therapeutic guidelines to treat CRE infections. Bearing in mind the different mechanisms by which Enterobacteriaceae can become resistant to carbapenems, there are different approaches to treat infections caused by these bacteria, which include the repurposing of already existing antibiotics, dual therapies with these antibiotics, and the development of new ß-lactamase inhibitors and antibiotics.

scholarly journals Molecular Epidemiology of Carbapenemases in Enterobacteriales from Humans, Animals, Food and the Environment

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 693
Author(s):  
Gurleen Taggar ◽  
Muhammad Attiq Rheman ◽  
Patrick Boerlin ◽  
Moussa Sory Diarra
Keyword(s):  
Molecular Epidemiology ◽  
Resistance Genes ◽  
Control Strategies ◽  
Companion Animals ◽  
Hydrolytic Enzymes ◽  
Carbapenem Resistance ◽  
Carbapenem Resistant ◽  
Class D ◽  
Antimicrobial Resistance Genes ◽  
Class B

The Enterobacteriales order consists of seven families including Enterobacteriaceae, Erwiniaceae, Pectobacteriaceae, Yersiniaceae, Hafniaceae, Morganellaceae, and Budviciaceae and 60 genera encompassing over 250 species. The Enterobacteriaceae is currently considered as the most taxonomically diverse among all seven recognized families. The emergence of carbapenem resistance (CR) in Enterobacteriaceae caused by hydrolytic enzymes called carbapenemases has become a major concern worldwide. Carbapenem-resistant Enterobacteriaceae (CRE) isolates have been reported not only in nosocomial and community-acquired pathogens but also in food-producing animals, companion animals, and the environment. The reported carbapenemases in Enterobacteriaceae from different sources belong to the Ambler class A (blaKPC), class B (blaIMP, blaVIM, blaNDM), and class D (blaOXA-48) β-lactamases. The carbapenem encoding genes are often located on plasmids or associated with various mobile genetic elements (MGEs) like transposons and integrons, which contribute significantly to their spread. These genes are most of the time associated with other antimicrobial resistance genes such as other β-lactamases, as well as aminoglycosides and fluoroquinolones resistance genes leading to multidrug resistance phenotypes. Control strategies to prevent infections due to CRE and their dissemination in human, animal and food have become necessary. Several factors involved in the emergence of CRE have been described. This review mainly focuses on the molecular epidemiology of carbapenemases in members of Enterobacteriaceae family from humans, animals, food and the environment.

scholarly journals Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

2016 ◽  
Vol 64 (3) ◽  
pp. 257-264 ◽  
Author(s):  
Pranita D Tamma ◽  
Katherine E Goodman ◽  
Anthony D Harris ◽  
Tsigereda Tekle ◽  
Ava Roberts ◽  
...  
Keyword(s):  
Antibiotic Treatment ◽  
Resistance Mechanism ◽  
Severity Of Illness ◽  
Carbapenem Resistance ◽  
Resistance Mechanisms ◽  
P Value ◽  
Carbapenem Resistant ◽  
Type 3 ◽  
Encoding Genes ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) are associated with considerable mortality. As mechanisms of carbapenem resistance are heterogeneous, it is unclear if mortality differs based on resistance mechanisms. We sought to determine whether CRE resistance mechanism determination is prognostically informative. Methods We conducted an observational study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE compared with non-CP-CRE bacteremia. Clinical data were collected on all patients. A comprehensive DNA microarray-based assay was performed on all isolates to identify β-lactamase-encoding genes. Results There were 83 unique episodes of monomicrobial CRE bacteremia during the study period: 37 (45%) CP-CRE and 46 (55%) non-CP-CRE. The majority of CP-CRE isolates were blaKPC (92%), followed by blaNDM (5%) and blaOXA-48-type (3%). CP-CRE isolates were more likely to have meropenem minimum inhibitory concentrations (MICs) ≥16 µg/mL, while non-CP-CRE isolates were more likely to have meropenem MICs ≤1 µg/mL (P value < .001). A total of 18 (22%) patients died within 14 days, including 12 (32%) in the CP-CRE group and 6 (13%) in the non-CP-CRE group. Adjusting for severity of illness on day 1 of bacteremia, underlying medical conditions, and differences in antibiotic treatment administered, the odds of dying within 14 days were more than 4 times greater for CP-CRE compared with non-CP-CRE bacteremic patients (adjusted odds ratio, 4.92; 95% confidence interval, 1.01–24.81). Conclusion Our findings suggest that CP-CRE may be more virulent than non-CP-CRE and are associated with poorer outcomes. This underscores the added importance of delineating underlying resistance mechanisms of CRE to direct antibiotic treatment decisions.

scholarly journals Rising Threat of OXA-48 and other Carbapenemase Encoding Genes among Carbapenem Resistant Enterobacteriaceae in India

2020 ◽  
Vol 14 (3) ◽  
pp. 1917-1925
Author(s):  
Satyajeet K. Pawar ◽  
Shivaji T. Mohite ◽  
Kailash D. Datkhile ◽  
Madhavi N. Patil ◽  
Satish V. Kakade
Keyword(s):  
Diagnostic Methods ◽  
Contact Precautions ◽  
Carbapenem Resistant ◽  
Class D ◽  
Class B ◽  
Horizontal Spread ◽  
Phenotypic Methods ◽  
Hospital Acquired ◽  
Encoding Genes ◽  
Carbapenem Resistant Enterobacteriaceae

Members of Enterobacteriaceae family are responsible for both community and hospital acquired infections. Because of development of antimicrobial resistance carbapenem has remained as last resort of drug for treatment of infections caused by these bacteria.Mechanism for development of this resistance in carbapenem resistant Enterobacteriaceae (CRE) may due to production of carbapenemases, efflux mechanism or loss of outer membrane porins.The most common carbapenemase enzymes are Class A – KPC, Class B – NDM, VIM and IMP and Class D oxacillinase(OXA-48 like enzymes).In India, most prevalent carbapenemase encoding gene is NDM-1but there is rising threat of OXA-48 prevalence. Unlike the phenotypic methods, the genotypic methods are useful to discriminate the type of carbapenemase enzyme, specifically for OXA-48 like enzymes. Total 170 CRE isolates were subjected for multiplex PCR study for their molecular characterization. Of the 170 CRE isolates,68.2 % (n=116) were positive for NDM-1 gene while 44.1 % (n= 75) of the isolates showed presence of OXA-48 gene. VIM (2.3%), KPC (1.7 %) were responsible for carbapenemase production while none of the isolates showed presence of IMP gene. NDM-1 and OXA-48 coexisted in 21.2 % (n=36) of the total isolates. OXA-48 causes weak hydrolysis of carbapenem because of which it is under reported with routine diagnostic methods. Early detection of OXA-48 and other carbapenemase encoding genes, helps for contact precautions and effective therapy which prevents further escalation and horizontal spread of CRE.

scholarly journals 518. Comparing the Mortality of Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S249-S250
Author(s):  
Hyeonji Seo ◽  
Eunmi Yang ◽  
Seongman Bae ◽  
Hyemin Chung ◽  
Eunbeen Cho ◽  
...  
Keyword(s):  
Risk Factors ◽  
Combination Therapy ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Source Control ◽  
Definitive Treatment ◽  
Clinical Issue ◽  
Carbapenem Resistant ◽  
Independent Risk Factors ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background Carbapenem-resistant Enterobacteriaceae (CRE) infection is an emerging clinical issue. One of the mechanisms of carbapenem-resistance is carbapenemase production. This study aimed to identify whether clinical outcomes differ by CRE resistance mechanism and to evaluate risk factors for mortality in patients with CRE bacteremia. Methods We conducted a retrospective cohort study comparing 14-day mortality between patients with carbapenemase-producing (CP)-CRE and non-CP-CRE bacteremia during January 2011 to October 2018. Only monomicrobial Escherichia coli or Klebsiella pneumoniae bacteremia were included in the study. A modified carbapenem inactivation method was used for phenotypic detection of carbapenemase production. The presence of a variety of carbapenemase genes was evaluated by PCR with specific primers. Results Of 134 patients with monomicrobial CRE bacteremia, 48 (35.8%) were infected with CP-CRE, and 86 (64.1%) were infected with non-CP-CRE. The most common carbapenemase in CP-CRE isolates was KPC (66.7%), followed by NDM-1 (18.8%), OXA-48-like (10.4%), and VIM (4.1%). Baseline characteristics were similar between the two groups (Table 1). However, the CP-CRE group was significantly more likely to undergo removal of eradicable foci and to have meropenem MIC >8 µg/mL. A total of 33 (24.6%) patients died within 14 days, including 9 (18.8%) in the CP-CRE group and 24 (27.9%) in the non-CP-CRE group. Deceased patients were more likely to have a higher Pitt bacteremia score, nosocomial acquisition, ineradicable or not-eradicated foci, immunosuppressant use, inappropriate definitive treatment (Table 2). Combination therapy for definitive treatment was associated with decreased mortality. In a multivariate analysis including carbapenemase production, a higher Pitt bacteremia score (aOR, 5.15), ineradicable or not-eradicated foci (aOR, 4.05) and combination therapy for definitive treatment (aOR, 0.35) were independent risk factors for mortality. Conclusion Our study suggests that carbapenemase production is not a mortality risk factor in CRE bacteremia and provides additional evidence for early source control and combination therapy. Disclosures All authors: No reported disclosures.

scholarly journals Investigation and Containment of New Delhi Metallo-β-Lactamase (NDM)–Producing Carbapenem-Resistant Enterobacteriaceae (CRE) in a Hospital Intensive Care Unit

2020 ◽  
Vol 41 (S1) ◽  
pp. s305-s305
Author(s):  
Karoline Sperling ◽  
Amy Priddy ◽  
Nila Suntharam ◽  
Adam Karlen
Keyword(s):  
United States ◽  
Intensive Care Unit ◽  
Outpatient Surgery ◽  
The United States ◽  
Multidrug Resistant ◽  
New Delhi ◽  
Point Prevalence Study ◽  
Carbapenem Resistant ◽  
Multidrug Resistant Organisms ◽  
Carbapenem Resistant Enterobacteriaceae

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

scholarly journals Thirty-Day Laboratory-Based Surveillance for Carbapenem-Resistant Enterobacteriaceae in the Minneapolis-St. Paul Metropolitan Area

2014 ◽  
Vol 35 (4) ◽  
pp. 423-425 ◽  
Author(s):  
Edwin C. Pereira ◽  
Kristin M. Shaw ◽  
Paula M. Snippes Vagnone ◽  
Jane E. Harper ◽  
Alexander J. Kallen ◽  
...  
Keyword(s):  
United States ◽  
Metropolitan Area ◽  
The United States ◽  
Carbapenem Resistant ◽  
Over Time ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae (CRE) are a growing problem in the United States. We explored the feasibility of active laboratory-based surveillance of CRE in a metropolitan area not previously considered to be an area of CRE endemicity. We provide a framework to address CRE surveillance and to monitor changes in the incidence of CRE infection over time.

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 Multicenter Clinical and Molecular Epidemiological Analysis of Bacteremia Due to Carbapenem-Resistant Enterobacteriaceae (CRE) in the CRE Epicenter of the United States

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Michael J. Satlin ◽  
Liang Chen ◽  
Gopi Patel ◽  
Angela Gomez-Simmonds ◽  
Gregory Weston ◽  
...  
Keyword(s):  
New York ◽  
Empirical Therapy ◽  
Carbapenem Resistance ◽  
The United States ◽  
Resistance Mechanisms ◽  
Rapid Diagnostics ◽  
Multicenter Studies ◽  
Content Type ◽  
Medical Centers ◽  
Carbapenem Resistant

ABSTRACT Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or had undergone transplantation. The prevalences of carbapenem resistance among Klebsiella pneumoniae, Enterobacter spp., and Escherichia coli bacteremias were 9.7%, 2.2%, and 0.1%, respectively. Ninety percent of CRE were K. pneumoniae and 92% produced K. pneumoniae carbapenemase (KPC-3, 48%; KPC-2, 44%). Two CRE produced NDM-1 and OXA-48 carbapenemases. Sequence type 258 (ST258) predominated among KPC-producing K. pneumoniae (KPC-Kp). The wzi154 allele, corresponding to cps-2, was present in 93% of KPC-3-Kp, whereas KPC-2-Kp had greater cps diversity. Ninety-nine percent of CRE were ceftazidime-avibactam (CAZ-AVI)-susceptible, although 42% of KPC-3-Kp had an CAZ-AVI MIC of ≥4/4 μg/ml. There was a median of 47 h from bacteremia onset until active antimicrobial therapy, 38% of patients had septic shock, and 49% died within 30 days. KPC-3-Kp bacteremia (adjusted odds ratio [aOR], 2.58; P = 0.045), cancer (aOR, 3.61, P = 0.01), and bacteremia onset in the intensive care unit (aOR, 3.79; P = 0.03) were independently associated with mortality. Active empirical therapy and combination therapy were not associated with survival. Despite a decade of experience with CRE, patients with CRE bacteremia have protracted delays in appropriate therapies and high mortality rates, highlighting the need for rapid diagnostics and evaluation of new therapeutics.

scholarly journals Characterization of resistance mechanisms of Enterobacter cloacae Complex co-resistant to carbapenem and colistin

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Shixing Liu ◽  
Renchi Fang ◽  
Ying Zhang ◽  
Lijiang Chen ◽  
Na Huang ◽  
...  
Keyword(s):  
Lipid A ◽  
Efflux Pump ◽  
Resistance Mechanism ◽  
Carbapenem Resistance ◽  
Enterobacter Cloacae ◽  
Resistance Mechanisms ◽  
Colistin Resistance ◽  
Carbapenem Resistant ◽  
Horizontal Spread

Abstract Background The emergence of carbapenem-resistant and colistin-resistant ECC pose a huge challenge to infection control. The purpose of this study was to clarify the mechanism of the carbapenems and colistin co-resistance in Enterobacter cloacae Complex (ECC) strains. Results This study showed that the mechanisms of carbapenem resistance in this study are: 1. Generating carbapenemase (7 of 19); 2. The production of AmpC or ESBLs combined with decreased expression of out membrane protein (12 of 19). hsp60 sequence analysis suggested 10 of 19 the strains belong to colistin hetero-resistant clusters and the mechanism of colistin resistance is increasing expression of acrA in the efflux pump AcrAB-TolC alone (18 of 19) or accompanied by a decrease of affinity between colistin and outer membrane caused by the modification of lipid A (14 of 19). Moreover, an ECC strain co-harboring plasmid-mediated mcr-4.3 and blaNDM-1 has been found. Conclusions This study suggested that there is no overlap between the resistance mechanism of co-resistant ECC strains to carbapenem and colistin. However, the emergence of strain co-harboring plasmid-mediated resistance genes indicated that ECC is a potential carrier for the horizontal spread of carbapenems and colistin resistance.

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