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 ◽  
...  

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.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S237-S237
Author(s):  
Allison C Brown ◽  
Sarah Malik ◽  
Jennifer Huang ◽  
Amelia Bhatnagar ◽  
Rocio Balbuena ◽  
...  

Abstract Background Infections with metallo-β-lactamase (MBL)-producing organisms are emerging in the United States. Treatment options for these infections are limited. We describe MBL genes among carbapenemase positive carbapenem-resistant Enterobacteriaceae (CP-CRE) and Pseudomonas aeruginosa (CP-CRPA) isolates tested during the first two years of the Antibiotic Resistance Laboratory Network (AR Lab Network). Methods State and local public health laboratories tested CRE and CRPA isolates for organism identification, antimicrobial susceptibility, and PCR-based detection of blaKPC, blaNDM, blaOXA-48-like, blaVIM, and blaIMP carbapenemase genes. All testing results were sent to CDC at least monthly. Results Since January 2017, the AR Lab Network tested 21,733 CRE and 14,141 CRPA. CP-CRE were detected in 37% of CRE; 2% of CRPA were CP-CRPA. Among CP-CRE, 9% (686/8016) were MBL-producers (NDM, VIM, or IMP). Among MBL-producers, a blaNDM gene was detected most often (81%; 551/686). blaNDM were most common among Klebsiella spp. (47%; 261/551), blaIMP were most common among Providencia spp. (53%; 40/75), blaVIM was most common among Enterobacter spp. (19%; 25/62). Twelve percent (96) of MBL CP-CRE contained more than one carbapenemase gene. Among CP-CRPA, 73% (218/300) were MBL producers and blaVIM was the most common gene (62%; 186). Three (1%) MBL CP-CRPA contained more than one carbapenemase. Conclusion Increased testing of CRE and CRPA isolates through the AR Lab Network has facilitated early and rapid detection of hard-to-treat infections caused by MBL-producing organisms across the United States. The widespread distribution of MBL genes highlights the continued need for containment strategies that help prevent transmission between patients and among healthcare facilities. To support therapeutic decisions for severe infections caused by MBL-producing organisms, the AR Lab Network is now offering rapid susceptibility testing against aztreonam/avibactam, using digital dispenser technology. This testing program aims to close the gap between the availability of new drugs or drug combinations and the availability of commercial AST methods, thereby improving patient safety and antimicrobial stewardship. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 41 (S1) ◽  
pp. s25-s26
Author(s):  
Alicia Shugart ◽  
Garrett Mahon ◽  
Lauren Epstein ◽  
Jennifer Y. Huang ◽  
Gillian McAllister ◽  
...  

Background: Due to limited therapeutic options and potential for spread, carbapenem-resistant Enterobacteriaceae (CRE)-producing New Delhi metallo-β-lactamases (NDMs) are a public health priority. We investigated the epidemiology of NDM-producing CRE reported to the CDC to clarify its distribution and relative prevalence. Methods: The CDC’s Antibiotic Resistance Laboratory Network supports molecular testing of CRE for 5 carbapenemases nationally. Although KPC is the most common carbapenemase in the United States, non-KPC carbapenemases are a growing concern. We analyzed CRE with any of 4 non-KPC plasmid-mediated carbapenemases (NDM, VIM, IMP, or OXA-48 type) isolated from specimens collected from January 1, 2017, through June 30, 2019; only a patient’s first isolate per organism–carbapenemase combination was included. We excluded isolates from specimen sources associated with colonization screening (eg, perirectal). We compared the proportion of NDM-producing CRE to all non-KPC–producing CP-CRE between period A (January to June 2018) and period B (January to June 2019). Health departments and the CDC collected additional exposure and molecular information in selected states to better describe current NDM-producing CRE epidemiology. Results: Overall, 47 states reported 1,013 non–KPC-producing CP-CRE (range/state, 1–109 isolates; median, 11 isolates); 46 states reported 631 NDM-producing CRE (range/state, 1–84; median, 6). NDM-producing CRE increased quarterly from the third quarter of 2018 through the second quarter of 2019; CP-CRE isolates with other non-KPC carbapenemases remained stable (Fig. 1). In period A, 124 of 216 emerging CP-CRE had NDM (57.1%), compared with 255 of 359 emerging CP-CRE (71.0%) during period B (P = .1179). Among NDM-producing CRE, the proportion of Enterobacter spp increased from 10.5% in 2018 to 18.4% in 2019 (P = .0467) (Fig. 2). In total, 18 states reported more NDM-producing CRE in the first 6 months of 2019 than in all of 2018. Connecticut, Ohio, and Oregon were among states that conducted detailed investigations; these 3 states identified 24 NDM-producing CRE isolates from 23 patients in period B. Overall, 5 (21.7%) of 22 patients with history available traveled internationally ≤12 months prior to culture; 17 (73.9%) acquired NDM-producing CRE domestically. Among 15 isolates sequenced, 8 (53.3%) carried NDM-5 (6 E. coli, 1 Enterobacter spp and 1 Klebsiella spp) and 7 (46.7%) carried NDM-1 (6 Enterobacter spp and 1 Klebsiella spp). Species were diverse; no single strain type was shared by >2 isolates. Conclusions: Detection of NDM-producing CRE has increased across the AR Lab Network. Among states with detailed information available, domestic acquisition was common, and no single variant or strain predominated. Aggressive public health response and further understanding of current US NDM-CRE epidemiology are needed to prevent further spread.Disclosures: NoneFunding: None


2020 ◽  
Vol 41 (S1) ◽  
pp. s21-s21
Author(s):  
Shelley C. Rankin ◽  
Stephen D. Cole

Background: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) in companion animals will be a game changer for infection prevention and control strategies in veterinary and human healthcare facilities. CRE have emerged as an important cause of human healthcare-associated infections and are a major clinical and public health problem. Although reports of CRE from animals are still very rare, they have been documented in China, Europe, and the United States. Methods: In April 2019, a passive veterinary surveillance system identified the blaNDM-5 gene in an E. coli isolated from a dog in Philadelphia in July 2018. CRE are reportable to the Philadelphia Department of Public Health (PDPH), and in May 2019, the Matthew J. Ryan Veterinary Hospital at the University of Pennsylvania (MJRVH) reported a cluster of carbapenem-resistant E. coli (CR-E. coli) isolated from 14 animals to the PDHP. This cluster of 17 isolates, that all contained a blaNDM-5 gene, was the first report of a CR-E. coli outbreak at a US veterinary facility. The first isolate, E. coli 24213-18, was sequenced on the Pacific Biosciences (PacBio) Sequel Sequencer and has been uploaded to GenBank. Whole genome sequencing was performed on all 17 isolates using the Illumina MiSeq platform. Antimicrobial resistance genes were identified from the National Center for Biotechnology Information Pathogen Detection Isolates Browser using AMRFinder. Results: PacBio sequencing confirmed E. coli ST167 and identified a circular IncFII plasmid of 139,547 bp that contained the blaNDM-5 gene, along with many additional resistance genes. In June 2019, a retrospective review of hospital records was completed and showed that, from July 2018, 17 CR- E. coli were isolated from 14 animals. Conclusions: Control of CRE infections in human healthcare settings is challenging because the organisms colonize the gastrointestinal tract and can go undetected. The same issue is to be expected with companion animals. Healthcare-associated spread of CRE E. coli in a veterinary facility emphasizes the importance of rapidly identifying and characterizing carbapenem-resistant isolates from animals. Methods to control the spread of CRE in veterinary medical settings have not yet been studied, and related investigations will be critically important to limit the transmission of these pathogens in animal populations. The risk of transmission of CRE from animals to people is currently poorly understood. CRE will be a major challenge across all health fields as these organisms become more prevalent in the community. It is likely that a ‘One Health’ approach to surveillance, infection prevention, and antimicrobial stewardship will be required to limit the spread and potential global dominance of CRE.Funding: NoneDisclosures: None


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S299-S299
Author(s):  
Helio S Sader ◽  
Robert K Flamm ◽  
Michael A Pfaller ◽  
Mariana Castanheira

Abstract Background Bloodstream infections (BSIs) cause significant morbidity and mortality. We evaluated the frequency and antimicrobial susceptibility of bacteria causing BSIs in the United States. Methods A total of 9,210 bacterial isolates were consecutively collected (1/patient) from 33 US medical centers in 2015–2017 and tested for susceptibility by reference broth microdilution methods in a central laboratory (JMI Laboratories) as part of the International Network for Optimal Resistance Monitoring (INFORM) program. Whole-genome sequencing was performed on carbapenem-resistant Enterobacteriaceae (CRE). Results The most common organisms were S. aureus (SA; 24.3%), E. coli (EC; 20.8%), K. pneumoniae (KPN; 9.1%), coagulase-negative staphylococci (7.3%), E. faecalis (5.5%), P. aeruginosa (PSA; 4.7%), and β-hemolytic streptococci (4.7%). Overall, 50.0% of isolates were Gram-negative bacilli (GNB) and 41.4% were Enterobacteriaceae (ENT). All SA were susceptible (S) to dalbavancin (MIC90, 0.03 μg/mL), linezolid, tigecycline (TGC), and vancomycin; >99.9% S to daptomycin, 97.6% S to ceftaroline, and 57.8% S to oxacillin. The most active agents against ENT were CAZ-AVI (99.9% S; table), amikacin (AMK; 99.7% S), and the carbapenems meropenem (MEM) and doripenem (99.1% S). Ceftolozane-tazobactam (C-T; tested in 2017 only) was active against 96.9% of ENT. Ceftriaxone (CRO)-S rates were 83.0% and 86.5% among EC and KPN, respectively. CRO-non-S KPN exhibited low S rates to most agents, except CAZ-AVI (99.1% S), TGC (93.6%), AMK (93.8%), and colistin (COL; 93.4%). Among 28 CRE isolates (0.7% of ENT), 21 produced a KPC-like, 2 an NMD-like, and 1 a KPC-17 and an NDM-1. COL (100.0% S), C-T (98.7%S), CAZ-AVI (98.2% S), AMK (97.9% S), and tobramycin (95.6% S) were very active against PSA. CAZ-AVI and C-T remained active against most PSA isolates non-S to MEM (93.0 and 95.0% S, respectively) and/or piperacillin–tazobactam (P-T; 88.9 and 91.3% S) and/or CAZ (86.9 and 88.2% S). Conclusion GNB represented 50.0% of bacteria isolated from patients with BSIs and the most active agents against these organisms were CAZ-AVI and AMK. Various agents exhibited excellent overall coverage against Gram-positives, including dalbavancin, daptomycin, linezolid, and TGC. Disclosures H. S. Sader, Allergan: Research Contractor, Research support. R. K. Flamm, Allergan: Research Contractor, Research support. M. A. Pfaller, Allergan: Research Contractor, Research support. M. Castanheira, Allergan: Research Contractor, Research support.


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


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 ◽  
...  

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.


2020 ◽  
Vol 41 (S1) ◽  
pp. s62-s62
Author(s):  
Timileyin Adediran ◽  
Anthony Harris ◽  
J. Kristie Johnson ◽  
David Calfee ◽  
Loren Miller ◽  
...  

Background: As carbapenem-resistant Enterobacteriaceae (CRE) prevalence increases in the United States, the risk of cocolonization with multiple CRE may also be increasing, with unknown clinical and epidemiological significance. In this study, we aimed to describe the epidemiologic and microbiologic characteristics of inpatients cocolonized with multiple CRE. Methods: We conducted a secondary analysis of a large, multicenter prospective cohort study evaluating risk factors for CRE transmission to healthcare personnel gown and gloves. Patients were identified between January 2016 and June 2019 from 4 states. Patients enrolled in the study had a clinical or surveillance culture positive for CRE within 7 days of enrollment. We collected and cultured samples from the following sites from each CRE-colonized patient: stool, perianal area, and skin. A modified carbapenem inactivation method (mCIM) was used to detect the presence or absence of carbapenemase(s). EDTA-modified CIM (eCIM) was used to differentiate between serine and metal-dependent carbapenemases. Results: Of the 313 CRE-colonized patients enrolled in the study, 28 (8.9%) were cocolonized with at least 2 different CRE. Additionally, 3 patients were cocolonized with >2 different CRE (1.0%). Of the 28 patients, 19 (67.6%) were enrolled with positive clinical cultures. Table 1 summarizes the demographic and clinical characteristics of these patients. The most frequently used antibiotic prior to positive culture was vancomycin (n = 33, 18.3%). Among the 62 isolates from 59 samples from 28 patients cocolonized patients, the most common CRE species were Klebsiella pneumoniae (n = 18, 29.0%), Escherichia coli (n = 10, 16.1%), and Enterobacter cloacae (n = 9, 14.5%). Of the 62 isolates, 38 (61.3%) were mCIM positive and 8 (12.9%) were eCIM positive. Of the 38 mCIM-positive isolates, 33 (86.8%) were KPC positive, 4 (10.5%) were NDM positive, and 1 (2.6%) was negative for both KPC and NDM. Also, 2 E. coli, 1 K. pneumoniae, and 1 E. cloacae were NDM-producing CRE. Conclusion: Cocolonization with multiple CRE occurs frequently in the acute-care setting. Characterizing patients with CRE cocolonization may be important to informing infection control practices and interventions to limit the spread of these organisms, but further study is needed.Funding: NoneDisclosures: None


2020 ◽  
Vol 41 (6) ◽  
pp. 716-722
Author(s):  
Mimi R. Precit ◽  
Kelly Kauber ◽  
William A. Glover ◽  
Scott J. Weissman ◽  
Tashina Robinson ◽  
...  

AbstractBackground:Carbapenem-resistant Enterobacterales (CRE) are common causes of healthcare-associated infections and are often multidrug resistant with limited therapeutic options. Additionally, CRE can spread within and between healthcare facilities, amplifying potential harms.Objective:To better understand the burden, risk factors, and source of acquisition of carbapenemase genes in clinical Escherichia coli and Klebsiella spp isolates from patients in Washington to guide prevention efforts.Design:Multicenter prospective surveillance study.Methods:Escherichia coli and Klebsiella spp isolates meeting the Washington state CRE surveillance case definition were solicited from clinical laboratories and tested at Washington Public Health Laboratories using polymerase chain reaction (PCR) for the 5 most common carbapenemase genes: blaKPC, blaNDM, blaIMP, blaVIM, and blaOXA-48. Case patients positive by PCR were investigated by the public health department.Results:From October 2012 through December 2017, 363 carbapenem-resistant E. coli and Klebsiella spp isolates were tested. Overall, 45 of 115 carbapenem-resistant K. pneumoniae (39%), 1 of 8 K. oxytoca (12.5%), and 28 of 239 carbapenem-resistant E. coli (11.7%) were carbapenemase positive. Of 74 carbapenemase-positive isolates, blaKPC was most common (47%), followed by blaNDM (30%), blaOXA-48 (22%), and blaIMP (1%). Although all cases had healthcare exposure, blaKPC acquisition was associated with US health care, whereas non-blaKPC acquisition was associated with international health care or travel.Conclusions:We report that blaKPC, the most prevalent carbapenemase in the United States, accounts for nearly half of carbapenemase cases in Washington state and that most KPC-cases are likely acquired through in-state health care.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S361-S361
Author(s):  
Kevin Spicer ◽  
Katelyn Cox ◽  
Rachel Zinner ◽  
Andrea Flinchum

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.


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