Public Health and Hospital Collaboration Leads to Swift and Effective Containment Response to Novel Carbapenemase-Producing Carbapenem Resistant Enterobacteriaceae (CRE)

2018 ◽  
Vol 46 (6) ◽  
pp. S26
Author(s):  
Nailah Smith ◽  
Tracey Woodard ◽  
Thomas R. Talbot ◽  
Kathie Wilkerson ◽  
Pamela Talley ◽  
...  
Keyword(s):  
Public Health ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

scholarly journals 1194. Carbapenem-Resistant Enterobacteriaceae in Kentucky: Initial 6 Months of Mechanism Testing

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S361-S361
Author(s):  
Kevin Spicer ◽  
Katelyn Cox ◽  
Rachel Zinner ◽  
Andrea Flinchum
Keyword(s):  
Public Health ◽  
Rural Areas ◽  
Demographic Data ◽  
Acute Care Hospital ◽  
The United States ◽  
Care Hospital ◽  
Local Data ◽  
Carbapenem Resistant ◽  
State And Local ◽  
Carbapenem Resistant Enterobacteriaceae

Abstract Background A global rise in carbapenem-resistant Enterobacteriaceae (CRE) has been noted over the past two decades. State and local data on CRE are necessary to better inform public health interventions. Methods Reporting of CRE (i.e., Enterobacteriaceae resistant to any carbapenem or shown to produce a carbapenemase) was mandated in Kentucky in 2015. Voluntary submission of isolates to the Antibiotic Resistance Laboratory Network regional laboratory for carbapenemase testing began September 2017. Demographic data collected as part of reporting included age, sex, county of residence, and inpatient/outpatient status. Descriptive and chi-square analyses were performed. Results Between September 1, 2017 and February 28, 2018, 149 CRE were reported to the Kentucky Department for Public Health. Testing for presence of a carbapenemase was performed on 115 isolates (77.2%); 44 (38.3%) were carbapenemase producing (CP)-CRE and Klebsiella pneumoniae carbapenemase (KPC) was identified from 38 (86.4%). Also identified were Verona integron-encoded metallo-β-lactamase (VIM; 5, 11.4%) and New Delhi metallo-β-lactamase (NDM; 1, 2.3%). Identification of carbapenemase varied among genera: Citrobacter (3/4, 75%), Klebsiella (21/40, 52.5%), Serratia (2/5, 40%), Escherichia (6/20, 30%), Enterobacter (11/41, 26.8%), Proteus (0/4, 0%), other genera (1/2, 50%). CRE isolates from urban or suburban areas were more likely CP-CRE than were those from rural areas (30/65, 46.2% vs. 14/50, 28%, P = 0.047). Carbapenemase was identified more often among CRE isolates from currently hospitalized patients than from patients whose cultures were collected outside of an acute care hospital (37/70, 52.8% vs. 7/45, 15.6%; P < 0.001). Conclusion The percentage of CRE that were CP-CRE in Kentucky was comparable with that reported for the United States (38 vs. 32%). Klebsiella spp., the genera historically associated with CP-CRE, made up less than half of CP-CRE. CP isolates were identified from urban, suburban, and rural settings and more frequently from isolates collected in hospitals compared with the community. The additional epidemiology obtained as part of this reporting system has identified metropolitan areas of the state as targets for CRE prevention efforts. Disclosures All authors: No reported disclosures.

scholarly journals Structural Analysis of The OXA-48 Carbapenemase Bound to A “Poor” Carbapenem Substrate, Doripenem

Antibiotics ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 145 ◽  
Author(s):  
Krisztina M. Papp-Wallace ◽  
Vijay Kumar ◽  
Elise T. Zeiser ◽  
Scott A. Becka ◽  
Focco van den Akker
Keyword(s):  
Public Health ◽  
Crystal Structure ◽  
Salt Bridge ◽  
Hydrolytic Activity ◽  
Van Der Waals Interactions ◽  
Side Chain ◽  
Carbapenem Resistant ◽  
Mechanistic Basis ◽  
Further Development ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem-resistant Enterobacteriaceae are a significant threat to public health, and a major resistance determinant that promotes this phenotype is the production of the OXA-48 carbapenemase. The activity of OXA-48 towards carbapenems is a puzzling phenotype as its hydrolytic activity against doripenem is non-detectable. To probe the mechanistic basis for this observation, we determined the 1.5 Å resolution crystal structure of the deacylation deficient K73A variant of OXA-48 in complex with doripenem. Doripenem is observed in the Δ1R and Δ1S tautomeric states covalently attached to the catalytic S70 residue. Likely due to positioning of residue Y211, the carboxylate moiety of doripenem is making fewer hydrogen bonding/salt-bridge interactions with R250 compared to previously determined carbapenem OXA structures. Moreover, the hydroxyethyl side chain of doripenem is making van der Waals interactions with a key V120 residue, which likely affects the deacylation rate of doripenem. We hypothesize that positions V120 and Y211 play important roles in the carbapenemase profile of OXA-48. Herein, we provide insights for the further development of the carbapenem class of antibiotics that could render them less effective to hydrolysis by or even inhibit OXA carbapenemases.

scholarly journals Phylogenetically Diverse Escherichia Coli Strains From Chicken Co-Harbour Multiple Carbapenemase Encoding Genes (blaNDM-blaOXA-blaIMP)

2020 ◽  
Author(s):  
Erkihun Aklilu ◽  
Azian Harun ◽  
Kirnpal Kaur Banga Singh ◽  
Shamsaldeen Ibrahim ◽  
Nor Fadhilah Kamaruzzaman
Keyword(s):  
Public Health ◽  
Phylogenetic Diversity ◽  
Farm Animals ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Resistance Patterns ◽  
Phylogenetic Grouping ◽  
Encoding Genes ◽  
Potential Public Health ◽  
Carbapenem Resistant Enterobacteriaceae

Carbapenem resistant Enterobacteriaceae (CRE) has been public health risk in several countries and recent reports indicate the emergence of CRE in food animals. This study was conducted to investigate the occurrence, resistance patterns, and phylogenetic diversity of CRE E.coli from chicken. Routine bacteriology, PCR detection of E.coli species, multiplex PCR to detect carbapenemase encoding genes and phylogeny of CRE E. coli were conducted. The results show that 24.36 % (19/78) were identified as CRE based on the phenotypic identifications of which 17 were positive for the tested carabanemase genes. The majority, 57.99% (11/19) of the isolates harbored multiple carbapenemase genes. Four isolates harbored all blaNDM blaOXA, blaIMP, five and two different isolates harbored blaNDM and blaOXA, and blaOXA and blaIMP respectively. The Meropenem, Imipenem and Ertapenem MIC values for the isolates ranged from 2g/mL to ≥256g/mL. Phylogenetic grouping showed that the CRE E.coli isolates belonged to five different groups; groups A, B1, C, D and unknown. The detection of carbapenem resistant E.coli in this study shows that CRE is has become an emerging problem in farm animals, particularly, in poultry farms. This also implies the potential public health risks posed by CRE from chicken to the consumers.

scholarly journals A review on bacterial resistance to carbapenems: epidemiology, detection and treatment options

2020 ◽  
Vol 6 (3) ◽  
pp. FSO438 ◽  
Author(s):  
Ann A Elshamy ◽  
Khaled M Aboshanab
Keyword(s):  
Public Health ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Treatment Options ◽  
Carbapenem Resistance ◽  
Multidrug Resistant ◽  
Mechanisms Of Resistance ◽  
Carbapenem Resistant ◽  
Public Health Threat ◽  
Carbapenem Resistant Enterobacteriaceae

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.

Much to Do about Carbapenem-Resistant Enterobacteriaceae: Why Supplementing Surveillance May Be the Key to Stopping Spread

2014 ◽  
Vol 35 (8) ◽  
pp. 984-986 ◽  
Author(s):  
Christopher D. Pfeiffer ◽  
Zintars G. Beldavs
Keyword(s):  
Public Health ◽  
Acute Care ◽  
Artery Bypass ◽  
Vital Signs ◽  
Surgical Site Infections ◽  
Acute Care Hospitals ◽  
Colon Surgery ◽  
The United States ◽  
Carbapenem Resistant ◽  
Carbapenem Resistant Enterobacteriaceae

(See the article by Thaden et al, on pages 978–983.)It is critical to the future of public health to understand the burden of carbapenem-resistant Enterobacteriaceae (CRE) so that we can effectively target efforts to limit potential spread. The Centers for Disease Control and Prevention (CDC) classifies CRE as 1 of 3 “urgent” antibiotic resistance threats to public health because of the high mortality associated with CRE infection and its rapid dissemination in the United States.What is the current burden of CRE disease? We can glean a snapshot of the national epidemiology of CRE from the CDC’s national surveillance. Rapid geographic spread is evident in the CDC’s national map of CRE, which indicates that all but 3 states now have identified CRE. Incidence by facility type, procedure, device, and organism all have considerable variation, providing preliminary indications where future prevention efforts might best be focused. The 2013 CRE Vital Signs states that 3.9% of short-stay acute care hospitals and 17.8% of long-term acute care hospitals have identified cases of CRE infection among those with catheter-associated urinary tract infection (CAUTI) or central line–associated bloodstream infection (CLABSI). The CDC also reported that 10% of Klebsiella species in intensive care unit (ICU) CLABSIs, ICU CAUTIs, and surgical site infections after colon surgery or coronary artery bypass grafting in 2011 were carbapenem resistant. Although CRE have been reported in most states, it is increasingly clear that wide regional variation exists, from regions of hyperendemicity, such as parts of New York City, to regions apparently free of CRE, such as Maine.

Superbugs: Antibiotic Resistance Is Becoming a Major Public Health Concern

2016 ◽  
Vol 29 (2) ◽  
pp. 130-133 ◽  
Author(s):  
Patricia T. Alpert
Keyword(s):  
Public Health ◽  
Antibiotic Resistance ◽  
Clostridium Difficile ◽  
Current Treatment ◽  
Health Concern ◽  
Treatment Modalities ◽  
Public Health Concern ◽  
Carbapenem Resistant ◽  
Control And Prevention ◽  
Carbapenem Resistant Enterobacteriaceae

Antibiotic resistance has led to the development of so-called “superbugs” that no longer respond to the current treatment modalities. The array of antibiotics available to treat these infections is dwindling with very few antibiotics in the pipeline. This article discussed the pathogens the Centers for Disease Control and Prevention (CDC) has placed in their urgent category: (1) Clostridium difficile, (2) Carbapenem-resistant Enterobacteriaceae, and (3) Neisseria gonorrhoeae. In addition, a few suggestions for prevention of resistance are offered.

scholarly journals Carbapenemase Gene Profiles in Carbapenem-Resistant Enterobacteriaceae—United States, January 2018–August 2019

2020 ◽  
Vol 41 (S1) ◽  
pp. s149-s150
Author(s):  
Jennifer Huang ◽  
Amanda Pettinger ◽  
Katie Bantle ◽  
Amelia Bhatnagar ◽  
Sarah Gilbert ◽  
...  
Keyword(s):  
Public Health ◽  
United States ◽  
Drug Combination ◽  
The United States ◽  
Molecular Testing ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Gene Profiles ◽  
Carbapenemase Gene ◽  
Carbapenem Resistant Enterobacteriaceae

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant morbidity and mortality each year in the United States. Treatment options for these infections are often limited, in part due to carbapenemases, which are mobile β-lactam-hydrolyzing enzymes that confer multidrug resistance in CRE. As part of the CDC’s Containment Strategy for Emerging Resistance, public health laboratories (PHLs) in the CDC Antibiotic Resistance Laboratory Network (AR Lab Network) have worked to characterize clinical isolates of CRE for rapid identification of carbapenemase genes. These data are then used by public health and healthcare partners to promote patient safety by decreasing the spread of resistance. We summarize carbapenemase gene profiles in CRE, by genus and geography, using data collected through the AR Lab Network from January 2018 through August 2019. Methods: CRE isolates were submitted to 55 PHLs, including those of all 50 states, 4 large cities, and Puerto Rico, in accordance with each jurisdiction’s reporting laws. PHLs performed phenotypic and molecular testing on isolates to detect targeted, emerging carbapenemase genes and reported results to submitters. Carbapenemase-positive (CP) isolates were defined as PCR positive for ≥1 carbapenemase gene tested: blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48–LIKE. PHLs submitted results to CDC monthly. Genera other than Enterobacter, Klebsiella, and Escherichia coli are categorized as other genera in this analysis. Data were compiled and analyzed using SAS v 9.4 software. Results: From January 2018 to August 2019, the AR Lab Network tested 25,705 CRE isolates; 8,864 of 25,705 CRE (34%) were CP. Klebsiella spp represented the largest proportion of CP-CRE at 68% (n = 6,063), followed by E. coli (12%, n = 1,052), Enterobacter spp (11%, n = 981), and other genera (9%, n = 768). Figure 1a shows the composition of CP-CRE carbapenemase genes by genus. The most common carbapenemase and genus profiles were blaKPC in Klebsiella (74%; 5,562 of 7,561 blaKPC-positive) blaNDM in E. coli (43%; 372 of 868 blaNDM-positive) blaVIM in Enterobacter spp (35%; 25 of 72 blaVIM-positive), and blaIMP among other genera (90%; 92 of 102 blaIMP-positive). Common CP-CRE genes and genera also varied by geography (Fig. 1b). Conclusions: The AR Lab Network has greatly enhanced our nation’s ability to detect and characterize CP-CRE. Our data provide a snapshot of the organisms and regions where mobile carbapenemase genes are most often detected in CRE. Geographic variation in CP gene profiles provides actionable data to inform local priorities for detection and infection control and provide clinicians with situational awareness of the genes and organisms that are circulating in their region.Funding: NoneDisclosures: In this presentation, the authors discuss the drug combination aztreonam-avibactam and acknowledge that this drug combination is not currently FDA-approved.

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