Epidemiology Of Carbapenem-resistant Enterobacteriaceae Research Articles

Active Surveillance of Patients Colonized with CRE: A Single-Center Study Based on a Combined Molecular/Culture Protocol.

Background/Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) are types of bacteria that need urgent attention globally. Active surveillance programs at hospitals are essential for the early identification of CRE carriers and the timely adoption of infection control measures. We aimed to analyze the epidemiology of CRE identified by multiplex RT-PCR in rectal swabs of patients upon admission to high-risk wards and to compare data obtained from both molecular and culture CRE screening. Methods: A total of 2861 rectal swabs, prospectively collected within 12-24 h of admission, underwent molecular screening for identification of K. pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), Verona integron-mediated metallo-β-lactamase (VIM), imipenemase (IMP), and OXA-48 (AllplexTM Entero-DR Assay). Only samples that tested positive or invalid underwent culture testing (Agar MacConkey and CHROMID® CARBA plates, bioMérieux, Craponne, France). Results: A total of 118 out of 2861 (about 4%) were positive for at least one carbapenem-resistant gene by a molecular approach (MA), with KPC, NDM, and VIM having the highest prevalence. Culture testing confirmed the presence of carbapenemase in 89 samples (75.4%), showing a disagreement rate of about 25% between the two methods, which, unfortunately, rises up to 60% for VIM. The dominant bacterial species were K. pneumoniae and E. coli (MALDI-TOF mass spectrometry). Conclusions: Our data underlined the need for the molecular screening of CRE carriers in order to implement active surveillance protocol in critical care settings and to improve infection control measures.

Carbapenem-resistance worldwide: a call for action - correspondence.

Carbapenem-resistance worldwide: a call for action - correspondence.

Molecular Characterization and Epidemiology of Carbapenem-Resistant Enterobacteriaceae Isolated from Pediatric Patients in Guangzhou, Southern China.

Carbapenem-resistant Enterobacteriaceae (CRE) are spreading worldwide, posing a serious public health concern. However, the data on CRE strains that cause infections in children in Guangzhou remain limited. Therefore, this study aimed to investigate the epidemiology of CRE, drug resistance, and resistance mechanisms in children in Guangzhou, Southern China. In total, 54 nonrepetitive CRE strains were collected in pediatric patients at three centers in Guangzhou, Southern China, from January 2016 to August 2018. CRE isolates were used for further studies on antimicrobial susceptibility, the modified Hodge test (MHT), the modified carbapenem inactivation method (mCIM), and drug resistance genes. Multilocus sequence typing (MLST) was used to elucidate the molecular epidemiology of K. pneumoniae. The isolated CRE strains include 34 K. pneumoniae (63.0%), 10 E. coli (18.5%), 4 Enterobacter cloacae (7.4%), and 6 Proteus mirabilis (11.1%) strains. The strains were isolated mainly from the blood (31.5%, n = 17), sputum (31.5%, n = 17), and urine (16.7%, n = 9). All CRE isolates were highly resistant to the third- or fourth-generation cephalosporins, carbapenems, and β-lactam + β-lactamase inhibitors (94.4%-96.3%). In addition, the resistance rates to amikacin, ciprofloxacin, levofloxacin, tigecycline, and colistin were 5.6%, 14.8%, 16.7%, 9.3%, and 0%, respectively. Carbapenemase was detected in 35 (64.8%) of the CRE isolates. The most dominant carbapenemase gene was bla NDM (n = 17, 48.6%), followed by bla IMP (n = 13, 37.1%) and bla OXA-23 (n = 4, 11.4%). Other carbapenemase genes (bla KPC, bla sim, bla Aim, bla GES, bla Gim, bla OXA-2 , and bla OXA-48 ) and the mcr-1 gene were not detected. MLST analysis showed high diversity among the K. pneumoniae, and ST45 (11.7%, 4/34) was the dominant sequence type. This study revealed bla NDM was the most dominant carbapenemase gene in children in Guangzhou. Infection control measures need to be taken for the prevention and treatment of CRE infections.

First report of Molecular Epidemiology of Carbapenem Resistant Enterobacteriaceae from a Tertiary Level Hospital in Rajasthan, Western India

Background: Carbapenem Resistant Enterobacteriaceae (CRE) are emerging at an alarming rate and pose a significant global threat. Objective: To conduct phenotypic and genotypic characterization of CRE strains from Rajasthan, Western India. Methodology: This was a prospective observational study conducted in Department of Microbiology, Dr S.N. Medical College, Jodhpur, Rajasthan from October to December 2018. All clinical samples received during the study period were processed and bacterial identification and antimicrobial susceptibility tests were performed according to standard microbiological guidelines. A total of 14 non duplicate carbapenem resistant clinical isolates of E coli and K pneumoniae were included in the study and subjected to Rapidec Carba NP test. Carbapenemase‑ encoding genes were amplified by multiplex polymerase chain reaction (PCR). PCR amplified products from three random isolates were subjected to Sanger sequencing. Results: Amikacin remained active against 36% isolates. All isolates were found to be susceptible to colistin and tigecycline. Carbapenemase production by Rapidec Carba NP test was noted in all (14/14) study isolates. All isolates were found to harbour ≥ 1 carbapenemase gene. The most common resistance gene observed was blaoxa (86%) followed by blaNDM (79%). None of the CRE isolates included in our study showed production of KPC enzymes. The sequences were analysed using BLAST analysis and were confirmed to be matching to OXA-48/181 and NDM-1. Conclusions: Growing carbapenem resistance is an important issue which needs urgent attention and blaOXA is an emerging mechanism of resistance among clinical CRE isolates in our setting Keywords: Carbapenem resistant Enterobacteriaceae, Phenotypic tests, Carbapenemase gene, Polymerase chain reaction

Genomically diverse carbapenem resistant Enterobacteriaceae from wild birds provide insight into global patterns of spatiotemporal dissemination

Carbapenem resistant Enterobacteriaceae (CRE) are a threat to public health globally, yet the role of the environment in the epidemiology of CRE remains elusive. Given that wild birds can acquire CRE, likely from foraging in anthropogenically impacted areas, and may aid in the maintenance and dissemination of CRE in the environment, a spatiotemporal comparison of isolates from different regions and timepoints may be useful for elucidating epidemiological information. Thus, we characterized the genomic diversity of CRE from fecal samples opportunistically collected from gulls (Larus spp.) inhabiting Alaska (USA), Chile, Spain, Turkey, and Ukraine and from black kites (Milvus migrans) sampled in Pakistan and assessed evidence for spatiotemporal patterns of dissemination. Within and among sampling locations, a high diversity of carbapenemases was found, including Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-beta-lactamase (NDM), oxacillinase (OXA), and Verona integron Metallo beta-lactamase (VIM). Although the majority of genomic comparisons among samples did not provide evidence for spatial dissemination, we did find strong evidence for dissemination among Alaska, Spain, and Turkey. We also found strong evidence for temporal dissemination among samples collected in Alaska and Pakistan, though the majority of CRE clones were transitory and were not repeatedly detected among locations where samples were collected longitudinally. Carbapenemase-producing hypervirulent K. pneumoniae was isolated from gulls in Spain and Ukraine and some isolates harbored antimicrobial resistance genes conferring resistance to up to 10 different antibiotic classes, including colistin. Our results are consistent with local acquisition of CRE by wild birds with spatial dissemination influenced by intermediary transmission routes, likely involving humans. Furthermore, our results support the premise that anthropogenically-associated wild birds may be good sentinels for understanding the burden of clinically-relevant antimicrobial resistance in the local human population.

Cost-effectiveness of carbapenem-resistant Enterobacteriaceae (CRE) surveillance in Maryland.

We analyzed the efficacy, cost, and cost-effectiveness of predictive decision-support systems based on surveillance interventions to reduce the spread of carbapenem-resistant Enterobacteriaceae (CRE). We developed a computational model that included patient movement between acute-care hospitals (ACHs), long-term care facilities (LTCFs), and communities to simulate the transmission and epidemiology of CRE. A comparative cost-effectiveness analysis was conducted on several surveillance strategies to detect asymptomatic CRE colonization, which included screening in ICUs at select or all hospitals, a statewide registry, or a combination of hospital screening and a statewide registry. We investigated 51 ACHs, 222 LTCFs, and skilled nursing facilities, and 464 ZIP codes in the state of Maryland. The model was informed using 2013-2016 patient-mix data from the Maryland Health Services Cost Review Commission. This model included all patients that were admitted to an ACH. On average, the implementation of a statewide CRE registry reduced annual CRE infections by 6.3% (18.8 cases). Policies of screening in select or all ICUs without a statewide registry had no significant impact on the incidence of CRE infections. Predictive algorithms, which identified any high-risk patient, reduced colonization incidence by an average of 1.2% (3.7 cases) without a registry and 7.0% (20.9 cases) with a registry. Implementation of the registry was estimated to save $572,000 statewide in averted infections per year. Although hospital-level surveillance provided minimal reductions in CRE infections, regional coordination with a statewide registry of CRE patients reduced infections and was cost-effective.

Whole-Genome Sequencing for Molecular Characterization of Carbapenem-Resistant Enterobacteriaceae Causing Lower Urinary Tract Infection among Pediatric Patients.

Antibiotic resistance is a growing public health problem globally, incurring health and cost burdens. The occurrence of antibiotic-resistant bacterial infections has increased significantly over the years. Gram-negative bacteria display the broadest resistance range, with bacterial species expressing extended-spectrum β-lactamases (ESBLs), AmpC, and carbapenemases. All carbapenem-resistant Enterobacteriaceae (CRE) isolates from pediatric urinary tract infections (UTIs) between October 2015 and November 2019 (n = 30). All isolates underwent antimicrobial resistance phenotypic testing using the Phoenix NMIC/ID-5 panel, and carbapenemase production was confirmed using the NG-Test CARBA 5 assay. Whole-genome sequencing was performed on the CREs. The sequence type was identified using the Achtman multi-locus sequence typing scheme, and antimicrobial resistance markers were identified using ResFinder and the CARD database. The most common pathogens causing CRE UTIs were E. coli (63.3%) and K. pneumoniae (30%). The most common carbapenemases produced were OXA-48-like enzymes (46.6%) and NDM enzymes (40%). Additionally, one E. coli harbored IMP-26, and two K. pneumoniae possessed mutations in ompK37 and/or ompK36. Lastly, one E. coli had a mutation in the marA porin and efflux pump regulator. The findings highlight the difference in CRE epidemiology in the pediatric population compared to Qatar’s adult population, where NDM carbapenemases are more common.

Changing US Epidemiology of NDM-Producing Carbapenem-Resistant Enterobacteriaceae, 2017–2019

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

Epidemiology of carbapenem-resistant Enterobacteriaceae in hospitals of a large healthcare system in Miami, Florida from 2012 to 2016: Five years of experience with an internal registry

Carbapenem-resistant Enterobacteriaceae (CRE) is an urgent public health threat globally. Limited data are available regarding the epidemiology of CRE in South Florida. We describe the epidemiology of CRE within a large public healthcare system in Miami, FL, the experience with an internal registry, active surveillance testing, and the impact of infection prevention practices. Retrospective cohort study in 4 hospitals from a large healthcare system in Miami-Dade County, FL from 2012 to 2016. The internal registry included all CRE cases from active surveillance testing from rectal and/or tracheal screening occurring in the intensive care units of 2 of the hospitals and clinical cultures across the healthcare system. All CRE cases were tagged in the electronic medical record and automatically entered into a platform for automatic infection control surveillance. The system alerted about new cases, readmissions, and transfers. A total of 371 CRE cases were identified. The overall prevalence was 0.077 cases per 100 patient-admissions; the admission prevalence was 0.019 per 100 patient-admissions, and the incidence density was 1.46 cases per 10,000 patient-days. Rates increased during the first 3 years of the study and declined later to a lower level than at the beginning of study period. Active surveillance testing and the use of an internal registry facilitated prompt identification of cases contributing to control increasing rates of CRE by rapid implementation of infection prevention strategies.

Fecal Carriage and Epidemiology of Carbapenem-Resistant Enterobacteriaceae Among Hospitalized Patients in a University Hospital.

PurposeTo determine the prevalence and epidemiology of fecal carriage of carbapenem-resistant Enterobacteriaceae (CRE), antimicrobial susceptibility, carbapenemase phenotype/genotype, and the colistin-resistance gene mcr-1 in a university hospital in China.MethodsA comprehensive study of the fecal carriage of CRE in 704 patients was performed. Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) were applied to elucidate the molecular epidemiology of the isolates.ResultsIn total, 60 CRE were detected in the 704 stool samples (8.5%), including 42 Klebsiella pneumoniae, 7 Escherichia coli, 3 Citrobacter freundii, 3 Klebsiella oxytoca, 3 Enterobacter cloacae, 1 Enterobacter aerogenes, and 1 Raoultella planticola. Fifty-five CRE isolates were positive for the carbapenemase phenotype, of which 39 were Klebsiella pneumoniae carbapenemase (KPC) producers. Thirty KPC-producing K. pneumoniae sequence type (ST) 11 isolates were identified and 28 were grouped into one cluster with a similarity of ≥85%, of predominately intensive care unit (ICU) strains. Three KPC-producing ST1889 strains were isolated from the pediatric ward, all indistinguishable and resistant to tigecycline. All CRE were susceptible to colistin and negative for mcr-1.ConclusionThis study revealed a predominant fecal carriage of the KPC-producing K. pneumoniae ST11 clone, with several indistinguishable strain clusters, and the emergence of ST1889 in a Chinese university hospital. This evidence of cross-infection supports the urgent need for the implementation of infection control measures to prevent CRE dissemination.

493. Laboratory Evaluation and Epidemiology of Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Department of Veterans Affairs, 2017

BackgroundCarbapenemase-producing (CP)-carbapenem-resistant Enterobacteriaceae (CRE) pose a major threat to public health and are a priority target of national prevention and control efforts including within Department of Veterans Affairs (VA). The laboratory evaluation and epidemiology of CRE in VA is uncertain.MethodsUsing data from the Veterans Health Administration Corporate Data Warehouse, we identified all Veterans with ≥1 CRE result obtained during 2017 and reviewed their electronic health record. Two case definitions were used: (1) 2015 CDC CRE (Enterobacteriaceae resistant to any carbapenem or with documented carbapenemase production) and (2) 2017 VA CP-CRE (E. coli, Klebsiella spp., and Enterobacter spp. resistant to imipenem, meropenem, or doripenem or with documented carbapenemase production). Patients harboring carbapenemase-producers detected by rectal screening tests only were included. We reviewed patient charts whose isolates met both CRE definitions, extracting detailed microbiologic and travel data for the first positive 2017 result.ResultsWe identified 904 unique Veterans with CRE; 577 (64%) patients had results meeting both CRE case definitions while 327 (36%) had results meeting CDC CRE criteria only (Figure 1). Of the 458 patients with clinical isolates meeting both case definitions, urine specimens predominated (64%) and were associated with the lowest crude 90-day mortality (16%); mortality was highest amongst patients with respiratory tract cultures (40%) and bloodstream isolates (34%) (Figure 2). Nearly half (48%) of VA CP-CRE were tested for carbapenemases (76% in-house; 24% send-out); of these, 75%tested positive with 78% being a KPC, 1% NDM, and 21% unspecified (Figure 3). Additionally, all 119 CRE carriers with an identified gene had KPC. Only 7 patients (1%) had documented overseas travel.ConclusionCurrently the incidence of CP-CRE in the nation’s largest healthcare system is low relative to other problem pathogens such as MRSA and Clostridioides difficile but is associated with a high crude mortality especially with respiratory and bloodstream isolates. KPC comprised almost all carbapenemases identified. This provides an initial, granular snapshot of CRE in VA to serve as a roadmap for ongoing CP-CRE prevention and control. Disclosures All authors: No reported disclosures.

496. Carbapenem-resistant Enterobacter: A Case-Case–Control Investigation

Background. BackgroundThe World Health Organization has declared carbapenem-resistant Enterobacteriaceae (CRE) as a worldwide public health threat. Analyzing the epidemiology of CRE was derived from cohorts consisting primarily of Klebsiella pneumoniae isolates. The second most frequent CRE is Enterobacter (CREn), but its molecular and clinical epidemiology differ from that of K. pneumoniae, and it has not been analyzed while implementing updated methodological tools and design.MethodsA matched case-case–control investigation was conducted at Shamir (Assaf Harofeh) Medical Center, Israel, for calendar years 2007–2017. Each CREn case was matched to a carbapenem-susceptible Enterobacter (CSEn) case and to an uninfected control (1:1:1 ratio). Logistic and Cox regression-matched analyses were conducted in order to study predictors and outcomes of CREn colonization and/or infection, respectively.ResultsThe study included 216 cases (72 in each group). Numerous predictors were significantly associated with CREn as per bivariable analyses, but the only independent significant predictors were: (1) recent (3 months) exposure to fluoroquinolones (aOR=2.94, P = 0.04), (2) intensive care unit stay in current hospitalization prior to culture (aOR=3.56, P = 0.003), and (3) a rapidly fatal McCabe score (aOR=0.471, P = 0.01). Patients with CREn suffered from significant delays in instituting appropriate antimicrobials (P = 0.03), and for those who survived the hospitalization, were more frequently discharged to a long-term care facility after being admitted to the index hospitalization from home (aOR=3.3, P = 0.02).ConclusionThis case-case–control-matched investigation of CREn epidemiology, revealed a unique modifiable predictor, i.e., recent fluoroquinolone exposure, which could represent a target for stewardship intervention. The case-case–control-matched design allowed for the control of numerous confounders previously reported to be associated with CREn but may represent a risk factor for Enterobacter infection in general. As with other CRE, CREn carriers suffer from significant delays in initiation of appropriate antimicrobials and from worse outcomes.Disclosures All authors: No reported disclosures.

2145. Carbapenem-Resistant Enterobacteriaceae infections at the Maharaj Nakorn Chiang Mai Hospital

BackgroundNowadays, carbapenem-resistant enterobacteriaceae (CRE) infection has been spreading worldwide in a tertiary care hospital and causing globally health damage. In Thailand, the studies of the epidemiology of CRE are scarce. This study aimed to describe epidemiology, clinical characteristics and treatment outcome of CRE infection.MethodsA retrospective cohort study was conducted among patients admitted to the Maharaj Nakorn Chiang Mai Hospital between January 2014 and December 2016 who had clinical diagnosis of CRE infection. Characteristics between groups were compared using Chi-square, Fisher exact test or Student t-test, Mann–Whitney U test. Factors associated with mortality in univariate analysis were analyzed in the logistic regression model.ResultsAmong 241 patients who had clinical specimens grew CRE, 51 had infection. Twenty-five patients (49%) were previously hospitalized within 90 days and 42 patients (82.4%) had exposed to antibiotics before documented CRE infection. The most common sites of clinical isolates were urine (33.3%), sputum (29.4%), and blood (21.6%). The mortality rate was 47.1%, which 17 (33.3%) patients’ death was attributable to CRE infection. Factor associated with mortality was higher body temperature (OR 4.8, P = 0.005) and thrombocytopenia.ConclusionCRE infections cause high mortality. Strategies to prevent emergence through prudent uses of antibiotics and transmission through infection control measures should be implemented in order to reduce mortality.Disclosures All authors: No reported disclosures.

497. Changing Molecular Epidemiology of CRE from 2016–2018, Increase in the Unknown

BackgroundHistorically, endemic Klebsiella pneumoniae carbapenemase (KPC) has accounted for the majority of carbapenem-resistant Enterobacteriaceae (CRE) in Los Angeles County (LAC). The LAC Department of Public Health (DPH) initiated enhanced CRE surveillance in 2016 to determine CRE prevalence and track emerging non-KPC resistance mechanisms (IMP, NDM, OXA, and VIM) among CRE to describe characteristics and identify local epidemiology for novel multi-drug-resistant organism (N-MDRO) infection and colonization.MethodsCRE isolates were voluntarily submitted by local clinical laboratories for mechanism detection by LAC Public Health Laboratory via MALDI-TOF and Nanosphere BC-GN. Baseline isolates were collected in 2016. Results are then presented by year through 2018. For N-MDRO cases, LACDPH interviewed healthcare facility (HCF) staff and cases to obtain case characteristics. Data were analyzed via Microsoft Access and SAS.ResultsCRE surveillance isolates were voluntarily submitted by 31 labs representing 34% (34/96) LAC hospitals and 1 large regional lab serving 60% of skilled nursing facilities from January 2016 to December 2018. LACDPH tested 1438 CRE isolates during the study period, 1168 (81%) were carbapenemase producing (CP). The proportion of CP CRE and KPC CRE declined over the study period (Table 1). NDM was the most common non-KPC (n = 30) followed by OXA (n = 28). The proportion of CRE with no genotypic marker increased over the course of the study. Case characteristics were obtained from 41 non-KPC CP CRE cases; median age was 66 years (range: 6–94 years); 12 (29%) expired. Among the 41 cases, 20 (49%) had a central line; 11 (27%) had surgery; 14 (34%) had antibiotics in the 6 months prior to culture date. Of the 41 cases, 11 (27%) had international healthcare exposure within 12 months with an invasive procedure and/or antibiotics.ConclusionSurveillance in a large urban setting suggests the molecular epidemiology of CRE is changing, with declining prevalence of KPC, increasing metallo-β-lactamase CP, and large proportion of isolates without resistance markers detected. Given the worrisome trends in non-KPC CRE, more systematic surveillance is warranted, potentially using more robust molecular epidemiology. Disclosures All authors: No reported disclosures.

Carbapenem-Resistant Enterobacteriaceae in Solid Organ Transplantation: Management Principles.

Carbapenem-resistant Enterobacteriaceae (CRE) have emerged as a worldwide problem. Given their degree of immunosuppression and the level of contact with the healthcare system, solid organ transplant (SOT) recipients are at a disproportionately higher risk of acquisition, colonization, and infection with CRE, and outcomes from infection tend to be worse compared to non-transplant patients. Therapeutic options are limited for CRE infections although several newer agents have recently been approved for use. How well these agents perform in the setting of immunosuppression and SOT is unclear. We sought to review the epidemiology of CRE in SOT and the management principles. CRE infections are becoming an increasing problem in SOT, and donor-derived infections present a challenge in the peri-transplant period. Newer treatments for CRE are emerging that are less toxic and potentially more effective than prior CRE-active agents, but supportive clinical data are limited. Newer beta-lactamase inhibitors have good activity against KPC carbapenemases, but they lack activity against metallo-beta-lactamases (e.g., NDM). Promising data is emerging with newer agents that have activity against most carbapenemases, but, again, clinical data is needed. Combination therapy in addition to optimal pharmacokinetic and pharmacodynamics may go some way to improve outcomes against these difficult-to-treat organisms. Other novel therapies that prevent the emergence of resistance (oral beta-lactamase inhibitors) and eradication of resistant Gram-negative colonization (fecal microbiota transplant) may eventually become part of a bundle approach to reduce CRE infections in the future. As in non-transplant patients, CRE infections in the transplant setting are challenging to treat and prevent. Infection prevention and control remains crucial to prevent widespread dissemination, and unique challenges exist with donor-derived CRE and how best to manage recipients in the peri-transplant period. Newer treatments are now in early-phase clinical studies, and in vitro activity data are supportive for several agents providing hope for improved outcomes with these typically difficult-to-treat and highly morbid infections in transplant recipients.

Epidemiology of carbapenem-resistant Enterobacteriaceae: a 5-year experience at a tertiary care hospital.

PurposeThe incidence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing worldwide. Ertapenem resistance is mediated by non-carbapenemase mechanisms, and has less of an effect on susceptibility to imipenem and meropenem. This study aimed to study the epidemiology of CRE, and to compare risk factors and related mortality between non-susceptibility to ertapenem alone Enterobacteriaceae (NSEE), with non-susceptibility to other carbapenems (imipenem, meropenem, or doripenem) Enterobacteriaceae (NSOCE) at a tertiary care hospital in Thailand.MethodsAll CRE isolated were identified between December 2011 and December 2016. Quarterly incidence rate was estimated. Hospital-wide carbapenem consumption was calculated as defined daily doses (DDD). Relationships between hospital-wide carbapenem consumption and incidence of CRE were tested. Factors associated with NSEE and NSOCE, and risk factors associated with 14- and 30-day mortality in patients with CRE infection were determined.ResultsThe quarterly CRE incidence increased significantly from 3.37 per 100,000 patient-days in the last quarter of 2011 to 32.49 per 100,000 patient-days in the last quarter of 2016. (P for trend <0.001). Quarterly hospital-wide carbapenem consumption increased 1.58 DDD per 1,000 patient-days (P for trend=0.004). The Poisson regression showed the expected increase of CRE incidence was 1.02 per 100,000 patient-days for a 1 DDD per 1,000 patient-days increase in carbapenem consumption (P<0.001). There were 40 patients with NSEE and 134 patients with NSOCE in the 5-year study period. The NSEE group had significantly lower carbapenem exposure compared with the NSOCE group (adjusted odds ratio: 0.25; P=0.001). No difference in 14-day and 30-day all-cause mortality between the two groups was observed.ConclusionThe incidence of CRE has risen significantly at our institution. Previous carbapenem use was associated with NSOCE. This hospital-wide carbapenem use was significantly associated with the increasing incidence of CRE.

Epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) and comparison of the phenotypic versus genotypic screening tests for the detection of carbapenemases at a tertiary level, academic hospital in Johannesburg, South Africa

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant infections and pose a threat to the viability of available antibiotics. Understanding the epidemiology of these infection...

Epidemiology of carbapenem-resistant Enterobacteriaceae (CRE) and comparison of the phenotypic versus genotypic screening tests for the detection of carbapenemases at a tertiary level, academic hospital in Johannesburg, South Africa

Background: Carbapenem-resistant Enterobacteriaceae (CRE) cause significant infections and pose a threat to the viability of available antibiotics. Understanding the epidemiology of these infections will assist in guiding appropriate treatment and infection prevention and control (IPC) practices in an institution. In addition, the phenotypic carbapenemase-producing Enterobacteriaceae (CPE) screening tests are widely used in South Africa. However, there is no published literature on their performance against PCR in that setting. Therefore, CRE epidemiology and performance of the Modified Hodge with Imipenem and Imipenem + EDTA combined disk tests (CDT) was evaluated at a tertiary academic hospital in Johannesburg.Method: A retrospective collection of data was performed. Data from January 2015 to December 2016 of all clinical isolates that were CRE OR carbapenem-susceptible Enterobacteriaceae with at least one positive CPE screening test were collected. Information collected included the ward areas from which samples were sent, specimen type that cultured CRE, CRE identification and carbapenem MIC results, phenotypic and genotypic CPE results.Results: Certain ward areas recurred as predominant areas with CRE infection in the two-year period. The prominent sample types that cultured CRE, the predominant Enterobacteriaceae species and carbapenemases identified corresponded with national surveillance data. The predominant carbapenemase type and level of carbapenem resistance conferred changed within one year. The Hodge test performed poorly for carbapenemase detection. The CDT detected metallo-β-lactamases adequately.Conclusion: In this study, the use of the MHT to screen for CPEs performed poorly. Continued surveillance will (i) lead to an understanding of the patient population (including infection type) affected, (ii) detect changes in the carbapenemase profiles, and (iii) inform infection prevention and control and appropriate clinical management.

Diversity of the epidemiology of carbapenemase-producing Enterobacteriaceae in long-term acute care rehabilitation settings from an area of hyperendemicity, and evaluation of an intervention bundle

Long-term acute care rehabilitation facilities (LTACRFs) are affected by carbapenem-resistant Enterobacteriaceae (CRE) in endemic areas. However, the contribution of different subpopulations of patients has not been investigated in these settings. To study the epidemiology of CRE in an LTACRF, and the effect of an infection control intervention. A surveillance programme was implemented in a large Italian LTACRF. The intervention included screening for CRE carriage at admission and weekly (for negative patients), and enforcement of contact precautions plus cohorting (in wards and rehabilitation areas) for presumed and confirmed carriers. Prevalence and incidence of CRE colonization and the number of CRE bacteraemias were monitored over one year. Overall, 1084 patients underwent screening (adherence 89.8%). At admission, 11.6% of patients were colonized, and 9.9% of those negative at admission subsequently became colonized. These percentages were significantly higher among patients with severe brain injuries (SBIs) who were exposed to a higher intensity of care (44.1% vs 8.6% and 63.5% vs 6.8%, respectively). The majority of CRE bacteraemias occurred in the SBI ward. The intervention was associated with a decline in the incidence of CRE colonization in the SBI ward (from 17.7 to 7.2 acquisitions/100 at-risk patient-weeks), but not in other wards. All CRE isolates were Klebsiella pneumoniae carbapenemase-producing K.pneumoniae. A peculiar CRE epidemiology was observed in a LTACRF from Italy, with very high rates of carriage and cross-transmission in SBI patients. A simplified infection control bundle was effective at reducing the incidence of CRE colonization in the SBI ward.

Israeli National Policy for Carbapenem-Resistant Enterobacteriaceae Screening, Carrier Isolation and Discontinuation of Isolation.

Since 2006, Israel has been confronting an outbreak of carbapenem-resistant Enterobacteriaceae (CRE), and in 2007 Israel implemented a national strategy to contain spread. The intervention was initially directed toward acute-care hospitals and later expanded to include an established reservoir of carriage in long-term-care hospitals. It included regular reporting of CRE cases to a central registry and daily oversight of management of the outbreak at the institutional level. Microbiological methodologies were standardized in clinical laboratories nationwide. Uniform requirements for carrier screening and isolation were established, and a protocol for discontinuation of carrier status was formulated. In response to the evolving epidemiology of CRE in Israel and the continued need for uniform guidelines for carrier detection and isolation, the Ministry of Health in 2016 issued a regulatory circular updating the requirements for CRE screening, laboratory diagnosis, molecular characterization, and carrier isolation, as well as reporting and discontinuation of isolation in healthcare institutions nationwide. The principal elements of the circular are contained herein. Infect Control Hosp Epidemiol 2018;39:85-89.