Carbapenem-resistant Enterobacteriaceae Cases Research Articles

Insights and Opinions of Critical Care Healthcare Professionals in the Management of Carbapenem-resistant Enterobacteriaceae Cases and Antibiotic-Resistant Infections in the Intensive Care Unit Setting: A Survey-Based Approach.

A survey-based approach to managing antibiotic-resistant infections in the intensive care unit (ICU) setting, with a focus on carbapenem-resistant Enterobacteriaceae (CRE) cases, was conducted. Among CRE, New Delhi metallo-β-lactamase 1 (NDM-1) is a carbapenemase that is resistant to β-lactam antibiotics and has a broader spectrum of antimicrobial resistance than other carbapenemase types. The article explains that healthcare-associated infections (HAIs) are a significant problem, particularly in low- and middle-income countries, and that carbapenem in combination with other antibiotics are the most potent class of antimicrobial agents effective in treating life-threatening bacterial infections, including those caused by resistant strains. The survey aimed to gather critical care healthcare professionals (HCPs') opinions on their current practices in managing infections acquired in the hospital and ICU settings, with a focus on CRE cases, specifically NDM-1 and other antibiotic-resistant infections. Responses from critical care healthcare professionals, including online surveys and in-person interviews, to gain insights into the management of infections caused by multidrug-resistant bacteria. The findings related to the insights on the prevalence of bacterial flora, clinical experiences on efficacy and safety of meropenem sulbactam ethylenediaminetetraacetic acid (EDTA) (MSE) in CRE cases, and various combination therapies of antibiotics used to treat antibiotic-resistant infections in ICU setting were evaluated. Klebsiella pneumoniae bacteria were the most common bacteria in cultures, followed by Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii. NDM-1 was the type of carbapenemase found in around 50% of CRE patients. MSE is among the most preferred antibiotics besides colistin, polymyxin B, and ceftazidime avibactum for CRE cases and specifically for NDM-1 cases due to its high rate of efficacy and safety. The article concludes with a discussion on the antibiotics used in response to CRE cases, reporting that critical care HCP considers MSE with high efficacy and safe antibiotic combination and was used as both monotherapy and in combination with other antibiotics. The survey highlights the need for exploring and better understanding the role of MSE in the management of CRE infections, especially in NDM-1.

Susceptibility results discrepancy analysis between NHSN antimicrobial resistance (AR) Option and NEDSS Base System in Tennessee, July 2020–December 2021

Background: The NHSN Antimicrobial Resistance (AR) Option is an important avenue for acute-care hospitals to electronically report facilitywide antibiogram data. The NEDSS Base System (NBS) is the statewide surveillance system for mandatory reporting of all carbapenem-resistant Enterobacteriaceae (CRE) cases. The state health department (SHD) validated CRE case data reported through the AR Option to assess completeness and accuracy. Methods: NHSN AR Option data from July 2020–December 2021 for 24 facilities were validated by comparing reported CRE and susceptibility results to CRE isolates reported via the NBS. Isolates were matched based on specimen date, sex, birth month and day, pathogen, and specimen source. NHSN susceptibility results were dichotomized as “not resistant” and “resistant” to match the NBS results. Susceptibility discordance (differing proportions of resistant isolates) of matched pairs were evaluated using the McNemar exact test in SAS version 9.4 software. Results: The SHD identified 270 CRE cases from the NHSN and 1,254 unique CRE isolates from the NBS. Of the NHSN events, 72 (26.67%) were matched to the NBS. Among matched isolates, discordance was significant for doripenem (0 resistant isolates in the NHSN vs 13 in the NBS; P < .001) and imipenem (5 resistant isolates in the NHSN vs 23 in the NBS; P < .0001). Discordance was not significant for ertapenem nor meropenem. Sensitivity analyses maximized the match rate at 30.74% (83 matches) when NBS isolates from unknown sources were included and matching factors were specimen date and date of birth ± 1 day, and pathogen. Among all 6,325 CRE isolates in NBS, 290 (4.58%) did not have a specimen source provided. Of all 47,348 NHSN events, 7,624 (16.10%) had impossible patient birthdays. Conclusions: Many NHSN isolates could not be matched to NBS due to either isolates being missing from NBS or to data differences across the systems. This mismatch highlights the need for data validation and standardization at the point of entry for both systems. Discordant susceptibility outcomes raise concerns about using the NHSN as a method for facility and regional antibiogram data.Disclosures: None

Importance of carbapenem-resistant Enterobacteriaceae screening to prevent transmission within an acute-care hospital

Background: Carbapenem-resistant Enterobacteriaceae (CRE) present a serious public health risk because they are transmissible within the acute-care hospital setting, and they are associated with significant morbidity and mortality. Timely identification of CRE among hospitalized patients is essential to ensure that appropriate infection prevention measures are enforced to prevent transmission events. In 2022, 9 index CRE cases (5 Klebsiella pneumoniae carbapenemase (KPC)–producing and 4 New Delhi Metallo-β-lactamase (NDM)–producing cases) were identified within the University of Colorado Hospital (UCH) inpatient population. In response to index case identification, tracing was performed to identify patients with an epidemiologic link for targeted CRE screening to detect asymptomatic CRE carriage. Methods: In total, 645 patients were screened allowing for timely identification of CRE colonization within 6 patients (3-KPC; 1-OXA-48; 1-NDM; 1-KPC/OXA-48). Secondary case identification elicited additional evaluation of service team and mobile-device crossover between positive patients, as well as primary and ancillary treatment locations. Results: Investigations revealed 3 possible transmission events in 0.47% of the total screened population. Identification of secondary CRE cases prompted additional testing of exposed patients performed at 7-day intervals to capture a 21-day colonization period. In total, 95 additional patients were screened for CRE during secondary and tertiary CRE screening events. Discussion: Nursing staff collaboration and engagement were critical to achieving a high rate of compliance with CRE screening activities, not only collecting screening specimens but also providing explanation and reassurance to patients. Due to this partnership and diligence, UCH was able to achieve 77% compliance with initial CRE screening events. Secondary and tertiary CRE screening revealed testing compliance of 83% and 69%, respectively. To further reduce the risk of CRE transmission within hospitalized patients, UCH has implemented an enhanced cleaning process for high-risk patient rooms, which includes patients infected or asymptomatically colonized with CRE. This enhanced process is prompted based on CRE or infection status as documented in the electronic medical record (EMR), and it initiates a mandatory 2-phase cleaning process. Future plans include environmental testing audits to validate room decontamination and leveraging the EMR to capture pertinent healthcare and travel histories. Active engagement with public health partners will be pursued to enable molecular testing of high-risk touch points. Conclusions: Patient screening, enhanced decontamination, and monitoring activities are key elements to effectively prevent the spread of CRE within vulnerable patient populations and must be continuously evaluated for improvement opportunities.Disclosures: None

Colonization and Healthcare-Associated Infection of Carbapenem-Resistant Enterobacteriaceae, Data from Polish Hospital with High Incidence of Carbapenem-Resistant Enterobacteriaceae, Does Active Target Screening Matter?

The objective of the study was to analyse the incidence of carbapenem-resistant Enterobacteriaceae (CRE) at a provincial hospital from 2019-2021. Multiplex PCR was used to detect the presence of carbapenemase genes. There were 399 cases of CRE detected in total in the analysed period, including 104 healthcare-associated infections. Out of the isolated CRE, 97.7% were Klebsiella pneumoniae with OXA-48 or KPC genes. Overall, among the identified CRE genes, the most frequently present genes were the ones mediating oxacillinase OXA-48 (71%) and KPC (26%), and significantly less often New Delhi NDM metallo-β-lactamase (2.5%). Moreover, two isolates produced two carbapenemases, i.e., OXA-48 and KPC. The conducted research demonstrates that there is a constant need for continuous monitoring of the occurrence of CRE strains and the hospital antibiotic policy, as well as the implementation of procedures to prevent CRE transmission by medical personnel and hospital support staff.

SG-APSIC1209: Risk factors associated with mortality among carbapenem-resistant Enterobacteriaceae inpatient in a tertiary-care teaching hospital in Malaysia

Objectives: Carbapenem-resistant Enterobacteriaceae (CRE) is a multidrug-resistant gram-negative bacteria (MDR-GNB) that is rapidly emerging as a life-threatening nosocomial disease in many countries. We sought to identify the risk factors associated with mortality for carriage of CRE in patients at a tertiary-care teaching hospital. Methods: A retrospective observational study was conducted between January 2020 to December 2021 in a tertiary-care teaching healthcare facility, University Malaya Medical Centre in Malaysia. The study included all inpatients aged ≥18 years who had a CRE infection or were colonized during the study period. The genotype was identified by polymerase chain reaction (PCR). Statistical analysis of data including a multivariate logistic regression analysis was conducted using SPSS version 23.0 software. Results: In total, 176 cases of CRE (130 infection and 46 colonized) were identified, and the mortality rate was 31.8%. The main sources of CRE were rectal swab (61.9%), blood (11.9%), and respiratory sources (11.9%). Klebsiella pneumoniae (55.7%) was the predominant species, followed by Escherichia coli (21.6%). Among the isolates, 17.7% were non–CPE-CRE and 82.3% were CPE-CRE: NDM (69.3%) and OXA (10.8%). In multivariate analysis, the factors associated with mortality were older age (OR, 1.040; 95% CI, 1.012–1.069), longer length of stay (OR, 0.974; 95% CI, 0.955–0.994), use of central venous catheter (OR, 0.287; 95% CI, 0.094–0.878), and arterial lines (OR, 0.292; 95% CI, 0.095–0.891). Conclusion: Patients with CRE had a high mortality rate. Older age, longer duration of stay, indwelling CVC and arterial line were independent risk factors for death. Infection prevention and control measures to reduce CRE, such as active surveillance, contact precautions, compliance to intravenous catheter care bundles, healthcare worker education, and hand hygiene adherence, should be implemented.

Clinical and economic burden of bacteremia due to multidrug-resistant organisms in Korea: a prospective case control study

The socioeconomic and clinical burden of multidrug-resistant organisms (MDRO), including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Pseudomonas aeruginosa (MRPA), and carbapenem-resistant Enterobacteriaceae (CRE) have not yet been adequately addressed. We prospectively searched for MDRO bacteremia cases with matched controls from 10 hospitals across Korea during a 6-month period in 2017. Patients were classified into the MDRO, susceptible organism, and no-infection groups. The corresponding susceptible or no-infection controls had been selected according to predefined criteria. We collected clinical information and estimated the total additional medical cost due to MDRO infections using the multistate model. During the 6-month period, a total of 486 MDRO bacteremia cases (260, 87, 18, 20, and 101 cases of MRSA, MRAB, MRPA, CRE, and VRE, respectively) were identified. The 90-d mortality rates were 30.4%, 63.2%, 16.7%, 55.0%, and 47.5%, respectively. The additional costs caused by bacteremia were $15 768, $35 682, $39 908, $72 051, and $33 662 per MDRO type, respectively. Based on these 6-month data, the estimated annual number of bacteremia cases due to these five MDRO in Korea were 7979 (4070, 1396, 218, 461, and 1834 cases, respectively). Overall, this caused an estimated 3280 (1237, 882, 36, 254, and 871, respectively) deaths and cost $294 505 002 ($84 707 359, $74 387 364, $10 344 370, $45 850 215, and $79 215 694, respectively) (range $170,627,020-$416,094,679) in socioeconomic loss. A tremendous clinical and economic burden is caused by MDRO bacteremia compared with antibiotic-susceptible and no-infection groups. Substantial investment and efforts by related government agencies and medical staffs are needed.

A matrix management of prevention and control for carbapenem-resistant Enterobacteriaceae in an urban compact medical union

PurposeTo understand the epidemiological characteristics of nosocomial infection of carbapenem-resistant Enterobacteriaceae (CRE) in an urban medical union includes 10 medical hospitals with different number of beds in China. MethodsEpidemiological data on age, department, and infection of CRE cases detected from January 2014 to December 2021 were collected via a real-time hospital-infection monitoring system or manually for subsequent characterization. A multi-departmental and multi-disciplinary matrix (MMM) management of CRE was established and implemented within a medical union. ResultsA total of 1327 cases of CRE infection were detected during the 8 years, of which 352 were due to nosocomial infection, with an infection morbidity of 0.046% and a resistance rate of 10.79%. The morbidity of CRE infection showed a trend of year-to-year fluctuation. The morbidity of CRE infection was significantly higher in winter and spring than that in summer and autumn, significantly higher in men than in women (χ2 ​= ​55.891, p ​< ​0.001), and 3 times higher in elderly patients ≥65 years old than in patients <65 years old (χ2 ​= ​117.517, p ​< ​0.001). The morbidity of CRE infection after intervention with MMM management decreased significantly from 0.071% to 0.042% (χ2 ​= ​15.628, p ​< ​0.001). ConclusionsCRE prevention and control practice should be adapted to seasonal variations, gender and age differences. The effective prevention and control of CRE nosocomial infections can be achieved by implementing MMM management within a medical association.

Investigation and Analysis of Infection among Inpatients in a Tertiary Hospital in Shanghai.

Objectives This study is aimed at obtaining information about the prevalence of nosocomial infections (NIs) and the use of antibiotics in hospitalized patients and providing relevant references for further understanding, preventing, and controlling NIs. Methods The medical records of adult patients admitted to a hospital in Shanghai from November to December 2021 were analyzed. The patients were divided into the NI group, community-acquired infection (CAI) group, and uninfected or healed group according to their infection status. The survey results were summarized and analyzed. Results A total of 1485 patients were investigated, including 115 patients in the NI group, 172 patients in the CAI group, and 1198 patients in the uninfected or healed group. In the NI group, the main infection site was intra-abdominal tissue (49.6%), followed by lower respiratory tract (unrelated to application of catheters) (13%). There were 73 pathogens detected in the samples submitted from the NI group, mainly including 8 cases (11%) of Escherichia coli, 9 cases (12%) of Klebsiella pneumoniae, and 40 cases (55%) of negative microbiological test results. Thirteen of 115 patients with NIs had infections with drug-resistant bacteria, including 9 cases (69.2%) of CRE (carbapenem-resistant Enterobacteriaceae), 2 cases (15.38%) of VRE (vancomycin-resistant Enterococcus), 1 case (7.69%) of MRSA (methicillin-resistant Staphylococcus aureus), and 1 case (7.69%) of CRAB (carbapenem-resistant Acinetobacter baumannii). In terms of medication, single drug use accounted for the majority of the NI group (66.3%) and CAI group (60.6%); both groups had less frequent quadruple drugs. In the uninfected or healed group, single drug occupied 92.0%, and dual drug use accounted for 8.0%. Cefoperazone/sulbactam was the most commonly used antibacterial drug in the NI group (18.0%) and CAI group (17.6%), and piperacillin/tazobactam accounted for 14.0% and 17.6% in the two groups, respectively. In the uninfected or healed group, cefuroxime accounted for 59.8%, followed by cefoperazone/sulbactam (13.3%). Conclusion This study provides a scientific basis for effective control of NIs. Strict implementation of aseptic techniques, reduction of invasive operations, and rational use of anti-infective drugs can minimize the incidence of nosocomial infection to ultimately achieve effective prevention and control of NIs.

Evaluation of the Organotellurium Compound AS101 for Treating Colistin- and Carbapenem-Resistant Klebsiella pneumoniae.

Colistin- and carbapenem-resistant Enterobacteriaceae cases are increasing at alarming rates worldwide. Drug repurposing is receiving greater attention as an alternative approach in light of economic and technical barriers in antibiotics research. The immunomodulation agent ammonium trichloro(dioxoethylene-O,O’-)tellurate (AS101) was repurposed as an antimicrobial agent against colistin- and carbapenem-resistant Klebsiella pneumoniae (CRKP). 134 CRKP isolates were collected between 2012 and 2015 in Taiwan. The in vitro antibacterial activities of AS101 was observed through broth microdilution, time-kill assay, and electron microscopy. Pharmaceutical manipulation and RNA microarray were applied to investigate these antimicrobial mechanisms. Caenorhabditis elegans, a nematode animal model, and the Institute for Cancer Research (ICR) mouse model was employed for the evaluation of in vivo efficacy. The in vitro antibacterial results were found for AS101 against colistin- and CRKP isolates, with minimum inhibitory concentration (MIC) values ranging from <0.5 to 32 μg/mL. ROS-mediated antibacterial activity eliminated 99.9% of bacteria within 2–4 h. AS101 also extended the median survival time in a C. elegans animal model infected with a colistin-resistant CRKP isolate and rescued lethally infected animals in a separate mouse model of mono-bacterial sepsis by eliminating bacterial organ loads. These findings support the use of AS101 as an antimicrobial agent for addressing the colistin and carbapenem resistance crisis.

Neonates with Maternal Colonization of Carbapenemase-Producing, Carbapenem-Resistant Enterobacteriaceae: A Mini-Review and a Suggested Guide for Preventing Neonatal Infection.

Carbapenemase-producing, carbapenem-resistant Enterobacteriaceae (CP-CRE) are highly drug-resistant Gram-negative bacteria. They include New Delhi metallo-ß-lactamase (NDM)-producing carbapenemase (50.4% of all species in Ontario). Antibiotic challenges for resistant bacteria in neonates pose challenges of unknown dosing and side effects. We report two antenatally diagnosed CP-CRE colonization scenarios with the NDM 1 gene. The case involves extreme preterm twins who had worsening respiratory distress at birth requiring ventilator support, with the first twin also having cardiovascular instability. They were screened for CP-CRE, and a polymyxin antibiotic commenced. In the delivery room, neonatal intensive care unit (NICU) and the follow-up clinic, in collaboration with the interdisciplinary group, contact precautions and isolation procedures were instituted. None of the infants exhibited infection with CP-CRE. Consolidating knowledge with regard to CP-CRE and modifying human behavior associated with its spread can mitigate potential negative consequences. This relates to now and later, when travel and prolific human to human contact resumes, from endemic countries, after the current COVID-19 pandemic. Standardized efforts to curb the acquisition of this infection would be judicious given the challenges of treatment and continued emerging antibiotic resistance. Simple infection control measures involving contact precautions, staff education and parental cohorting can be useful and cost-effective in preventing transmission. Attention to NICU specific measures, including screening of at-risk mothers (invitro fertilization conception) and their probands, careful handling of breastmilk, judicious antibiotic choice and duration of treatment, is warranted. What does this study add? CP-CRE is a nosocomial infection with increasing incidence globally, and a serious threat to public health, making it likely that these cases will present with greater frequency to the NICU team. Only a few similar cases have been reported in the neonatal literature. Current published guidelines provide a framework for general hospital management. Still, they are not specific to the NICU experience and the need to manage the parents’ exposure and the infants. This article provides a holistic framework for managing confirmed or suspected cases of CP-CRE from the antenatal care through the NICU and into the follow-up clinic targeted at preventing or containing the spread of CP-CRE.

Prevalence of Carbapenem Resistant Enterobacteriaceae in a Tertiary Care Hospital of Gujarat, India

Introduction: Carbapenem Resistant Enterobacteriaceae (CRE) are major cause of community as well as healthcare associated infections and have limited treatment options. Measuring the magnitude of the problem of CRE, it is important for making strategies to lower its spread. Aim: To assess the incidence and prevalence rate of CRE in a tertiary care hospital of Gujarat, India. Materials and Methods: Retrospective data was collected for a period from 2014 to 2018 using Laboratory Information System (LIS). Prevalence of CRE was determined as number of CRE isolated per 100 Enterobacteriaceae isolated during the study period whereas incidence rate was determined as number of CRE cases per 1000 patient-days. Consumption of Carbapenems was calculated as Defined Daily Dose (DDD) per 1000 patient-days. Demographic data including age, gender, location in the hospital and sample type from which CRE was isolated was also analysed using Microsoft Excel. Results: The incidence of CRE cases per 1000 patient-days in 2014 to 2018 was 1.66, 2.11, 1.90, 2.26 and 1.91, respectively with an overall incidence of 1.99 per 1000 patient-days. The overall prevalence of CRE over a period of five years was found to be 29.07%. Klebsiellasp. was the most common CRE and had the highest percentage of Carbapenem resistance among all Enterobacteriaceae. Conclusion: The rate of CRE in present study was high and worrisome. Screening of the patient for CRE, source isolation and stringent implementation of infection control practices is required to confine the spread of CRE in this institute.

1425. Impact of Social Determinants on Racial Differences in Carbapenem-Resistant Enterobacteriaceae Incidence, Atlanta, 2012-2018

BackgroundPublic health prioritizes addressing social determinants of health to promote health equity. We hypothesized that social determinants of health, including poverty, are associated with racial disparity in the incidence of carbapenem-resistant Enterobacteriaceae (CRE).MethodsThe Georgia Emerging Infections Program conducted CDC-funded, active population-based CRE surveillance in metropolitan Atlanta (2017 population: 3.9 million) from 2012-2018. CRE cases were defined as Atlanta residents with a urine or normally sterile specimen growing E. coli, Klebsiella spp., or Enterobacter spp. resistant to ≥ 1 carbapenems (excluding ertapenem) and all third generation cephalosporins tested. Poverty, education and insurance levels by census tract of residence were obtained from the US Census Bureau’s 2017 American Community Survey. Race and end-stage renal disease (ESRD) were determined from chart review, and primary care provider (PCP) shortage area was obtained from the Health Resources and Services Administration. Age-adjusted incidence rate ratios were individually calculated using direct age standardization. Covariates were considered for inclusion in a multivariable Poisson regression model for the expected rate of CRE.ResultsAdjusting for age, CRE incidence was three times higher in blacks than whites. Higher CRE incidence was also observed among cases assigned > 40% below poverty level, > 15% below high school education, > 10% uninsured, and in a PCP shortage area (Table 1). CRE incidence was 58 times higher among ESRD cases than non-ESRD cases. In the multivariable model (Figure 1) addition of education, poverty or ESRD (p< 0.001), but not PCP access (p = 0.61) and insurance status (p=0.19), significantly reduced the racial difference in CRE incidence compared to race and age alone. Although controlling for age and either education, poverty level or ESRD reduced CRE among blacks, CRE incidence in blacks remained double that of whites.Figure 1. Comparison of race CRE incidence rate ratio adjusting for age alone (red line) to adjusting for age and individual social determinants (blue bars)” Table 1. Social Determinants Distribution and Age-Adjusted CRE Incidence Rate Ratio (N = 378) ConclusionPoverty level, ESRD and education only partially account for the racial differences seen in CRE incidence. While ESRD suggests a possible biologic component, persistent racial differences indicate the need for targeted public health interventions to address social determinants of health.Disclosures All Authors: No reported disclosures

Carbapenem-resistant Enterobacteriaceae epidemiology in Veterans' Affairs medical centers varies by facility characteristics.

This is an epidemiological study of carbapenem-resistant Enterobacteriaceae (CRE) in Veterans' Affairs medical centers (VAMCs). In 2017, almost 75% of VAMCs had at least 1 CRE case. We observed substantial geographic variability, with more cases in urban, complex facilities. This supports the benefit of tailoring infection control strategies to facility characteristics.

Epidemiology, risk factors and molecular analysis of carbapenem-resistant Enterobacteriaceae (CRE) in Mthatha, Eastern Cape, South Africa

Background: The emergence of carbapenem resistance in Enterobacteriaceae is an important threat to global health. Reported outcomes of infections with carbapenem-resistant Enterobacteriaceae (CRE) are poor. Commonly used antibiotics are generally inactive against CRE. Therefore, timely detection of CRE is of paramount importance. This study aimed to investigate the resistance genes responsible for CRE in Mthatha and to identify risk factors. Methods and materials: Study design – Prospective cohort study. Study period – 23 April to 27 September 2019. Setting – Eastern Cape province, SA. Study population – All adult and paediatric CRE patients. CRE case definition according to CDC 2018. ID and AST-bioMérieux Vitek 2 system. Detection of the blaOXA-48, blaKPC, blaNDM, and blaVIM by the RESIST-4 OKNV assay (Coris). Patients were interviewed to determine risk factors associated with CRE. Results: Forty-four non-duplicate CRE patients were identified during the study period from microbiology lab at NMAH. Enterobacteriaceae species: K. pneumoniae 22 (61.4%), E. cloacae 10 (22.7%), E. coli 2 (4.5%) and K. oxytoca, P. rettgeri and M. morganii 1 each (4.3%). Adult patient 29 (65.9%0 and paediatric 15 (34.1%). Race: all black patients except one white. CRE genes-blaOXA-48 22 (50%), blaNDM 8 (18.2%), two isolates (4.5%) with both blaOXA and blaNDM. We did not find any blaKPC and blaVIM in our setting and 12 (27.2%) isolates were negative for all OKNV. Outcomes: Demised 18 (40.9%), still admitted in the ward 1 (2.3%), discharged home on basis of clinical grounds 22 (50%) and 3 (6.8%) were transferred back to the district hospitals. HAI in 27 (61.4%) with VAP 8, HABSI 8, CAUTI 5, SSI 3 and CLABSI in 3. Risk factors for CRE acquisition were antibiotic exposure 25 (58.7%), ICU stay 7 (15.9%), received medical care in last 6 months 35 (79.6%) and none travelled outside RSA. HIV positive – 19 (43.2%). Conclusion: In out setting our CRE mortality rate is 40.9%, common CRE genotypes are blaOXA-48 and blaNDM. K. pneumoniae is the most common CRE-producing Enterobacteriaceae and antibiotic exposure is an important risk factor in Mthatha and surrounding areas.

Carbapenemase Production and Mortality Risk Among Carbapenem-Resistant Enterobacteriaceae Cases in Tennessee, United States

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are an urgent public health threat associated with poor patient outcomes. CRE that produce carbapenemase (CP-CRE) are of particular concern because the mechanism-conferring genes in plasmids can be transferred to other bacteria. CRE are reportable in Tennessee (TN); isolate submission is required for CP production and resistance mechanism testing. We aimed to compare patient characteristics and outcomes between CP-CRE and non–CP-CRE patients to guide potential public health interventions. Methods: A retrospective cohort study to compare 30-day mortality, and clinical characteristics of CP-CRE to non–CP-CRE patients was conducted. Laboratory data were gathered from CRE isolates of Tennessee residents from July 1, 2015, to June 30, 2018. The most recent Council of State and Territorial Epidemiologists CRE and CP-CRE case definition was used to confirm and classify cases. Healthcare exposures within 1 year prior to onset, demographic characteristics, and clinical characteristics were obtained by linking surveillance data with the inpatient and outpatient Tennessee hospital discharge data. Cases were also matched with Tennessee vital statistics data to determine all-cause 30-day mortality from the event date. We evaluated risk ratios of 30-day mortality with a multivariable regression model. Results: Among 1,034 CRE cases that had at least 1 isolate submitted to public health, 445 (43.0%) were CP-CRE and 589 (57.0%) were non–CP-CRE. Among CP-CRE isolates, the blaKPC gene was found in 434 (98.9%). CP-CRE cases were more likely to have isolates from normally sterile sites, to have an organism with elevated resistance to meropenem (minimum inhibitory concentration, &gt;16 µg/mL), to have prior admission to a long-term acute-care hospital, and to live in a nursing home (all P &lt; .001). Also, 77 CP-CRE cases (17.3%) and 56 non–CP-CRE cases (9.6%) died within 30 days of infection onset. The risk of 30-day mortality was 57% higher for CP-CRE (adjusted risk ratio, 1.57; 95% CI:, 1.10–2.23) compared to non–CP-CRE patients after adjusting for comorbidities, nursing home residence, and prior healthcare exposures. Conclusions: CP-CRE cases had poorer outcomes than non–CP-CRE cases. This may be related in part to a higher proportion of sterile site infections among CP-CRE cases; our study was underpowered to analyze this subpopulation of sterile site cases. We plan to continue monitoring and performing analyses as mortality and hospital discharge data from more recent years become available and as more cases accumulate.Funding: NoneDisclosures: None

Carbapenem-Resistant Enterobacteriaceae Resistant Only to Ertapenem: An Epidemiologically Distinct Cohort, Atlanta, 2016–2018

Background: Carbapenem-resistant Enterobacteriaceae (CRE), particularly carbapenemase-producing (CP) CRE, pose a major public health threat. In 2016, the phenotypic definition of CRE expanded to include ertapenem resistance to improve sensitivity for detecting CP-CRE. We compared characteristics of CRE resistant to ertapenem only (CRE-EO) to CRE resistant to ≥1 other carbapenem (CRE-O). Methods: The Georgia Emerging Infections Program performs active, population-based CRE surveillance in metropolitan Atlanta. CRE cases were defined as any Escherichia coli, Klebsiella pneumoniae, K. oxytoca, K. variicola, Enterobacter cloacae complex, or Enterobacter aerogenes resistant to ≥1 carbapenem by the clinical laboratory and isolated from urine or a sterile site between 2016 and 2018. Data were extracted from retrospective chart review and 90-day mortality from Georgia vital statistics for 2016–2017. Polymerase chain reaction (PCR) for carbapenemase genes was performed on a convenience sample of isolates by the CDC or Georgia Public Health Laboratory. We compared characteristics of CRE-EO cases to CRE-O cases using χ2 tests or t tests. Results: Among 927 CRE isolates, 553 (60%) were CRE-EO. CRE-EO were less frequently isolated from blood (5% vs 12%; P &lt; .01) and less commonly K. pneumoniae (21% vs 58%; P &lt; .01) than CRE-O. CRE-EO cases were more often women (65% vs 50%; P &lt; .01), had a lower Charlson comorbidity index (mean ± SD, 2.4±2.3 vs 3.0±2.6; P &lt; .01), and were less commonly at a long-term care facility (24% vs 31%) or hospital (15% vs 21%; P &lt; .01) in the 4 days prior to the CRE culture. CRE-EO were more susceptible to all antibiotics tested at the clinical laboratory (P &lt; .01) except for tigecycline (P = 1.0) (Table 1). Of the 300 (32%) isolates tested for carbapenemase genes, 98 (33%) were positive (7% CRE-EO vs 62% CRE-O; P &lt; .01). Of the CP isolates, we identified blaKPC in 93 cases (95%), blaNDM in 3 cases (3%), blaOXA-48-like in 2 cases (2%). CRE-EO cases had lower 90-day mortality (13% vs 21%; P &lt; .01). Conclusions: CRE-EO are epidemiologically distinct from CRE-O and are less likely to harbor carbapenemase genes. CRE-EO may require less intensive infection prevention interventions and have more therapeutic options.Funding: NoneDisclosures: None

Duodenoscope-Associated Outbreak of a Carbapenem Resistant Enterobacteriaceae

Background: We describe and evaluate our outbreak of carbapenem-resistant K. pneumoniae transmitted by contaminated duodenoscopes during endoscopic retrograde cholangiopancreatography (ERCP) procedures. Methods: An outbreak investigation was performed when Klebsiella pneumoniae carbapenemase-producing K. pneumoniae (KPC-KP) were identified from bile specimens of 4 patients. The investigation included medical record review, practice audits, and surveillance cultures of duodenoscopes and environmental sites. If available, clinical specimens were obtained from patients who had undergone ERCP in the previous 3 months. Carbapenem-resistant Enterobacteriaceae (CRE) screening cultures were performed to identify additional patients until no CRE cases were detected during 2 consecutive weeks. Pulsed-field gel electrophoresis (PFGE) of KPC-KP isolates was implemented. Results: In total, 12 cases were identified with exposure to duodenoscope from February 2019 through April 2019, including 6 cases with infections and 6 asymptomatic carriers. Case-control analysis showed that 2 specific duodenoscopes would be associated with the KPC-KP outbreak. Duodenoscope reprocessing procedures did not deviate from manufacturer recommendations for reprocessing. After ethylene oxide (EO) gas sterilization, the outbreak was terminated. Conclusions: Meticulous cleaning protocol and enhanced surveillance are necessary to prevent outbreaks of CRE. Notably, enhanced cleaning measures, such as sterilization for duodenoscopes, would be required after procedures with KPC-KP carriers.Funding: NoneDisclosures: None

Epidemiology and Microbiology of Outpatient Cases of Carbapenem-Resistant Enterobacteriaceae in Connecticut During 2018

Background: Little is known about the epidemiology, microbiology, and clinical management of carbapenem-resistant Enterobacteriaceae (CRE) in outpatient settings. In Connecticut, all clinical CRE isolates are submitted to the state public health laboratory (SPHL) for a customized panel of antimicrobial susceptibility and carbapenemase gene testing. We describe all outpatient cases of CRE in Connecticut in 2018, including location of presentation, risk factors, microbiology and aspects of treatment. Methods: Outpatient CRE cases were defined as CRE infection in a patient not hospitalized at the time of positive CRE culture or within 30 days after culture collection. Outpatient cases were identified from routine statewide CRE reporting by reviewing clinical and laboratory data. A questionnaire was sent to outpatient providers who ordered the cultures that yielded CRE to collect additional clinical information. Antimicrobial susceptibility and carbapenemase gene detection results from the SPHL were also summarized. Results: Among 53 outpatient CRE cases (1 blood, 52 urine), the most common organisms were Enterobacter (25, 47%), Klebsiella (12, 23%), and E. coli (11, 21%). Overall, 21 (39.6%) patients presented in primary care settings, 8 (15%) in urology offices, 6 (11%) in women’s health/OBGYN clinics; the remainder presented across various clinical settings (Fig. 1). Of 42 patients for whom clinical data were available, 45% had been hospitalized within the prior year and 19% had a chronic indwelling device. Among outpatient CRE cases, infectious diseases consultation was reported in 9.5% and lab consultation in none. Median patient age was 83 years. Of 36 CRE samples for which lab data were available, 9 (25%) were carbapenemase-producers (CP-CRE), of which 8 were blaKPC positive. Sensitivity rates to oral antimicrobials ranged from 43% to 75% (Table 1). Conclusions: CRE infections occur in several different outpatient settings, and formal ID consultation in the management of these patients is infrequent. These findings highlight the critical need for providers across different outpatient specialties to be familiar with the clinical management and infection control practices needed in caring for patients with CRE. Hospitalization within the year prior to presentation was frequent among patients who developed subsequent CRE-positive cultures. Most outpatient CP-CRE cases in CT are due to KPC production. Overall, sensitivity to oral antimicrobials frequently prescribed in outpatient settings is low, providing additional challenges to the outpatient management of patients with CRE infection. Fosfomycin, though only approved for E. coli infections, may be an acceptable antibiotic choice for the treatment of these patients.Funding: NoneDisclosures: None

Evaluation of Discrepancies in Carbapenem Minimum Inhibitory Concentrations Obtained at Clinical Laboratories Compared to a Public Health Laboratory

Background: Automated testing instruments (ATIs) are commonly used by clinical microbiology laboratories to perform antimicrobial susceptibility testing (AST), whereas public health laboratories may use established reference methods such as broth microdilution (BMD). We investigated discrepancies in carbapenem minimum inhibitory concentrations (MICs) among Enterobacteriaceae tested by clinical laboratory ATIs and by reference BMD at the CDC. Methods: During 2016–2018, we conducted laboratory- and population-based surveillance for carbapenem-resistant Enterobacteriaceae (CRE) through the CDC Emerging Infections Program (EIP) sites (10 sites by 2018). We defined an incident case as the first isolation of Enterobacter spp (E. cloacae complex or E. aerogenes), Escherichia coli, Klebsiella pneumoniae, K. oxytoca, or K. variicola resistant to doripenem, ertapenem, imipenem, or meropenem from normally sterile sites or urine identified from a resident of the EIP catchment area in a 30-day period. Cases had isolates that were determined to be carbapenem-resistant by clinical laboratory ATI MICs (MicroScan, BD Phoenix, or VITEK 2) or by other methods, using current Clinical and Laboratory Standards Institute (CLSI) criteria. A convenience sample of these isolates was tested by reference BMD at the CDC according to CLSI guidelines. Results: Overall, 1,787 isolates from 112 clinical laboratories were tested by BMD at the CDC. Of these, clinical laboratory ATI MIC results were available for 1,638 (91.7%); 855 (52.2%) from 71 clinical laboratories did not confirm as CRE at the CDC. Nonconfirming isolates were tested on either a MicroScan (235 of 462; 50.9%), BD Phoenix (249 of 411; 60.6%), or VITEK 2 (371 of 765; 48.5%). Lack of confirmation was most common among E. coli (62.2% of E. coli isolates tested) and Enterobacter spp (61.4% of Enterobacter isolates tested) (Fig. 1A), and among isolates testing resistant to ertapenem by the clinical laboratory ATI (52.1%, Fig. 1B). Of the 1,388 isolates resistant to ertapenem in the clinical laboratory, 1,006 (72.5%) were resistant only to ertapenem. Of the 855 nonconfirming isolates, 638 (74.6%) were resistant only to ertapenem based on clinical laboratory ATI MICs. Conclusions: Nonconfirming isolates were widespread across laboratories and ATIs. Lack of confirmation was most common among E. coli and Enterobacter spp. Among nonconfirming isolates, most were resistant only to ertapenem. These findings may suggest that ATIs overcall resistance to ertapenem or that isolate transport and storage conditions affect ertapenem resistance. Further investigation into this lack of confirmation is needed, and CRE case identification in public health surveillance may need to account for this phenomenon.Funding: NoneDisclosures: None

Regional Impact of a CRE Intervention Targeting High Risk Postacute Care Facilities (Chicago PROTECT)

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are endemic in the Chicago region. We assessed the regional impact of a CRE control intervention targeting high-prevalence facilities; that is, long-term acute-care hospitals (LTACHs) and ventilator-capable skilled nursing facilities (vSNFs). Methods: In July 2017, an academic–public health partnership launched a regional CRE prevention bundle: (1) identifying patient CRE status by querying Illinois’ XDRO registry and periodic point-prevalence surveys reported to public health, (2) cohorting or private rooms with contact precautions for CRE patients, (3) combining hand hygiene adherence, monitoring with general infection control education, and guidance by project coordinators and public health, and (4) daily chlorhexidine gluconate (CHG) bathing. Informed by epidemiology and modeling, we targeted LTACHs and vSNFs in a 13-mile radius from the coordinating center. Illinois mandates CRE reporting to the XDRO registry, which can also be manually queried or generate automated alerts to facilitate interfacility communication. The regional intervention promoted increased automation of alerts to hospitals. The prespecified primary outcome was incident clinical CRE culture reported to the XDRO registry in Cook County by month, analyzed by segmented regression modeling. A secondary outcome was colonization prevalence measured by serial point-prevalence surveys for carbapenemase-producing organism colonization in LTACHs and vSNFs. Results: All eligible LTACHs (n = 6) and vSNFs (n = 9) participated in the intervention. One vSNF declined CHG bathing. vSNFs that implemented CHG bathing typically bathed residents 2–3 times per week instead of daily. Overall, there were significant gaps in infection control practices, especially in vSNFs. Also, 75 Illinois hospitals adopted automated alerts (56 during the intervention period). Mean CRE incidence in Cook County decreased from 59.0 cases per month during baseline to 40.6 cases per month during intervention (P &lt; .001). In a segmented regression model, there was an average reduction of 10.56 cases per month during the 24-month intervention period (P = .02) (Fig. 1), and an estimated 253 incident CRE cases were averted. Mean CRE incidence also decreased among the stratum of vSNF/LTACH intervention facilities (P = .03). However, evidence of ongoing CRE transmission, particularly in vSNFs, persisted, and CRE colonization prevalence remained high at intervention facilities (Table 1). Conclusions: A resource-intensive public health regional CRE intervention was implemented that included enhanced interfacility communication and targeted infection prevention. There was a significant decline in incident CRE clinical cases in Cook County, despite high persistent CRE colonization prevalence in intervention facilities. vSNFs, where understaffing or underresourcing were common and lengths of stay range from months to years, had a major prevalence challenge, underscoring the need for aggressive infection control improvements in these facilities.Funding: The Centers for Disease Control and Prevention (SHEPheRD Contract No. 200-2011-42037)Disclosures: M.Y.L. has received research support in the form of contributed product from OpGen and Sage Products (now part of Stryker Corporation), and has received an investigator-initiated grant from CareFusion Foundation (now part of BD).