scholarly journals Epidemiologic and Microbiologic Characteristics of 28 Hospitalized Patients Cocolonized With Multiple Carbapenem-Resistant Enterobacteriaceae (CRE) in the United States

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

2016 ◽  
Vol 60 (7) ◽  
pp. 4073-4081 ◽  
Author(s):  
Kalyan D. Chavda ◽  
Liang Chen ◽  
Michael R. Jacobs ◽  
Robert A. Bonomo ◽  
Barry N. Kreiswirth

ABSTRACTThe emergence and spread ofKlebsiella pneumoniaecarbapenemase (KPC) amongEnterobacteriaceaepresents a major public health threat to the world. Although not as common as inK. pneumoniae, KPC is also found inEscherichia colistrains. Here, we genetically characterized 9 carbapenem-resistantE. colistrains isolated from six hospitals in the United States and completely sequenced theirblaKPC-harboring plasmids. The nine strains were isolated from different geographical locations and belonged to 8 differentE. colisequence types. SevenblaKPC-harboring plasmids belonged to four different known incompatibility groups (IncN, -FIA, -FIIK2, and -FIIK1) and ranged in size from ∼16 kb to ∼241 kb. In this analysis, we also identified two plasmids that have novel replicons: (i) pBK28610, which is similar to p34978-3 with an insertion of Tn4401b, and (ii) pBK31611, which does not have an apparent homologue in the GenBank database. Moreover, we report the emergence of a pKP048-like plasmid, pBK34397, inE. coliin the United States. Meanwhile, we also found examples of interspecies spread ofblaKPCplasmids, as pBK34592 is identical to pBK30683, isolated fromK. pneumoniae. In addition, we discovered examples of acquisition (pBK32602 acquired an ∼46-kb fragment including a novel replication gene, along with Tn4401band other resistance genes) and/or loss (pKpQIL-Ec has a 14.5-kb deletion compared to pKpQIL-10 and pBK33689) of DNA, demonstrating the plasticity of these plasmids and their rapid evolution in the clinic. Overall, our study shows that the spread ofblaKPC-producingE. coliis largely due to horizontal transfer ofblaKPC-harboring plasmids and related mobile elements into diverse genetic backgrounds.


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.


mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
José R. Mediavilla ◽  
Amee Patrawalla ◽  
Liang Chen ◽  
Kalyan D. Chavda ◽  
Barun Mathema ◽  
...  

ABSTRACT Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene bla NDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1 - and bla NDM-5 -harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. IMPORTANCE Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1 , was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin ( mcr-1 ) and carbapenem ( bla NDM-5 ) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms.


2020 ◽  
Vol 64 (5) ◽  
Author(s):  
Brian D. Johnston ◽  
Paul Thuras ◽  
Stephen B. Porter ◽  
Melissa Anacker ◽  
Brittany VonBank ◽  
...  

ABSTRACT Imipenem-relebactam (I-R) is a recently developed carbapenem–beta-lactamase inhibitor combination agent that can overcome carbapenem resistance, which has now emerged in Escherichia coli, including sequence type 131 (ST131) and its fluoroquinolone-resistant H30R subclone, the leading cause of extraintestinal E. coli infections globally. To clarify the likely utility of I-R for carbapenem-resistant (CR) E. coli infections in the United States, we characterized 203 recent CR clinical E. coli isolates from across the United States (years 2002 to 2017) for phylogroup, clonal group (including ST131, H30R, and the CTX-M-15-associated H30Rx subset within H30R), relevant beta-lactamase genes, and broth microdilution MICs for I-R and 11 comparator agents. Overall, I-R was highly active (89% susceptible), more so than all comparators except tigecycline and colistin (both 99% susceptible). I-R’s activity varied significantly in relation to phylogroup, clonal background, resistance genotype, and region. It was greatest among phylogroup B2, ST131-H30R, H30Rx, Klebsiella pneumoniae carbapenemase (KPC)-positive, and northeast U.S. isolates and lowest among phylogroup C, New Delhi metallo-β-lactamase (NDM)-positive, and southeast U.S. isolates. Relebactam improved imipenem’s activity against CR isolates within each phylogroup—especially groups A, B1, and B2—and particularly against isolates containing KPC. I-R remained substantially active against isolates coresistant to comparator agents, albeit somewhat less so than against the corresponding susceptible isolates. These findings suggest that I-R should be useful for treating most CR E. coli infections in the United States, largely independent of coresistance, although this likely will vary in relation to the local prevalence of specific E. coli lineages and carbapenem resistance mechanisms.


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


2006 ◽  
Vol 50 (9) ◽  
pp. 3098-3101 ◽  
Author(s):  
Shiri Navon-Venezia ◽  
Inna Chmelnitsky ◽  
Azita Leavitt ◽  
Mitchell J. Schwaber ◽  
David Schwartz ◽  
...  

ABSTRACT Carbapenem resistance in Escherichia coli is rare. We report four genetically unrelated carbapenem-resistant E. coli isolates cultured from four patients hospitalized in Tel Aviv Medical Center. PCR, sequencing, and Southern blot analysis identified KPC-2 as the imipenem-hydrolyzing enzyme in all four strains, carried on different plasmids with a possible common origin. This is the first discovery of KPC-2 in E. coli and the first report of this enzyme originating outside the United States.


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


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S823-S823
Author(s):  
Kendra Foster ◽  
Linnea A Polgreen ◽  
Brett Faine ◽  
Philip M Polgreen

Abstract Background Urinary tract infections (UTIs) are one of the most common bacterial infections. There is a lack of large epidemiologic studies evaluating the etiologies of UTIs in the United States. This study aimed to determine the prevalence of different UTI-causing organisms and their antimicrobial susceptibility profiles among patients being treated in a hospital setting. Methods We used the Premier Healthcare Database. Patients with a primary diagnosis code of cystitis, pyelonephritis, or urinary tract infection and had a urine culture from 2009- 2018 were included in the study. Both inpatients and patients who were only treated in the emergency department (ED) were included. We calculated descriptive statistics for uropathogens and their susceptibilities. Multi-drug-resistant pathogens are defined as pathogens resistant to 3 or more antibiotics. Resistance patterns are also described for specific drug classes, like resistance to fluoroquinolones. We also evaluated antibiotic use in this patient population and how antibiotic use varied during the hospitalization. Results There were 640,285 individuals who met the inclusion criteria. Females make up 82% of the study population and 45% were age 65 or older. The most common uropathogen was Escherichia Coli (64.9%) followed by Klebsiella pneumoniae (8.3%), and Proteus mirabilis (5.7%). 22.2% of patients were infected with a multi-drug-resistant pathogen. We found that E. Coli was multi-drug resistant 23.8% of the time; Klebsiella pneumoniae was multi-drug resistant 7.4%; and Proteus mirabilis was multi-drug resistant 2.8%. The most common antibiotics prescribed were ceftriaxone, levofloxacin, and ciprofloxacin. Among patients that were prescribed ceftriaxone, 31.7% of them switched to a different antibiotic during their hospitalization. Patients that were prescribed levofloxacin and ciprofloxacin switched to a different antibiotic 42.8% and 41.5% of the time, respectively. Conclusion E. Coli showed significant multidrug resistance in this population of UTI patients that were hospitalized or treated within the ED, and antibiotic switching is common. Disclosures All Authors: No reported disclosures


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