Carbapenemase-producing Carbapenem-resistant Enterobacteriaceae Research Articles

Phenotypic antibiotic susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna State, northwest Nigeria.

Background. The increasing resistance of clinical Enterobacteriaceae isolates to commonly prescribed antibiotics has been reported around the world. Data are generally lacking on the prevalence and antibiotic susceptibility profile of clinical Enterobacteriaceae isolates from Kaduna, northwest Nigeria. This study thus aimed to determine the diversity and antibiotic resistance profile of clinical Enterobacteriaceae isolates recovered from clinical specimens from patients admitted to two selected healthcare institutions in Kaduna. Methods. This was a prospective cross-sectional study conducted between September and December 2021. Non-duplicate clinical bacterial isolates recovered from various specimens were collected and identified using rapid biochemical identification kits. The susceptibility of identified Enterobacteriaceae to various antibiotics and phenotypic detection of carbapenemase enzymes were thereafter determined. The data were analysed and visualized using R software version 4.3.1. Results. Of the 500 bacterial isolates recovered from specimens collected for the purpose of clinical bacteriology diagnostics, 108 (21.6 %) were identified as Enterobacteriaceae, with Pantoea agglomerans (52, 48.1 %) and Klebsiella oxytoca (19, 17.6 %) being the most prevalent. The isolates exhibited high resistance to azithromycin (69 %) and ceftazidime (42 %), while exhibiting low resistance to amikacin (7 %) and imipenem (10 %). Among the carbapenem-resistant Enterobacteriaceae (CRE) isolates, a significant proportion (12/17, 70.6 %) tested positive for carbapenemase activity. Conclusion. This study reports a high prevalence of multidrug-resistant Enterobacteriaceae in Kaduna, northwest Nigeria. The emergence of pathogenic P. agglomerans and an alarmingly high prevalence of carbapenemase-producing CRE were also observed. The presence of carbapenemase producers in an area with low carbapenem usage and resistance rates raises significant concerns. Continuous surveillance and robust antibiotic stewardship policies are imperative to preserve the efficacy of carbapenems in this region.

Epidemiological Characteristics and Drug-Resistance Genotype of CRE in Patients with Hematological Diseases in a Single Center of China

Patients with blood diseases have a significantly higher risk of infections and mortality rates compared with other type of patients. Referring to the 2019 CDC criteria for CRE, we examined the carbapenemase producing genotype and resistance characteristics of CRE strains (760 strains) in patients with hematological diseases. Among these, carbapenemase producing CRE (CP-CRE) accounts for 60.39% (459/760), non-carbapenemase producing CRE (non-CP-CRE) accounts for 39.61% (301/760). The data indicated that the most common bacteria in patients with hematologic disorders were Escherichia coli, Klebsiella pneumoniae and Enterbater cloacae, which primarily produced NDM-type metallo-β-lactamases. The rates of drug resistance in CP-CRE strains with MIC≥16 to Meropenem and Imipenem were 92.51% (420/454) and 86.12% (391/454), respectively. The drug resistance rates of non-CP-CRE strain with MIC≥16 to Meropenem and Imipenem were only 22.22% and 15.34%, respectively. Furthermore, we discovered that 36.88% (111/301) of non-CP-CRE strains were resistant to Ertapenem alone but still susceptible to Meropenem and Imipenem. The therapy of such CRE may differ significantly from that of other CRE strains, ETP-CRE may not be a typical CRE. In conclusion, Our data determined that the CRE colonized or infected in patients with hematological diseases was dominated by Escherichia coli and metallo-carbapease-producing types, among which the NDM genotypes was predominant. This is quite different from the domestic statistics, indicating that the CRE types infected by hematological disease patients are special and not consistent with other patients. We discovered that some patients with hematological diseases carried or were infected with ETP-CRE, which was sensitive to Meropenem and Imipenem. In terms of therapy, ETP-CRE strains may differ from other CRE in patients with hematological diseases，it may not be a typical CRE.

2779. Early Administration of Ceftazidime-Avibactam for Carbapenem-Resistant Enterobacterales Is Associated with Improved Clinical Success

Abstract Background Carbapenem-resistant Enterobacterales (CRE) are a significant public health threat. Ceftazidime-avibactam (CZA) retains activity against most carbapenemase-producing CRE and demonstrates favorable health outcomes compared to historically best available therapy. While early initiation of effective therapy is critical in serious infections, the impact of time to CZA initiation on CRE infection-related outcomes has yet to be assessed. Aim: to evaluate clinical outcomes of patients with CRE infections receiving early vs. late CZA as the first active β-lactam. Methods Multicenter, retrospective cohort of hospitalized adult patients from 2019-2022 with culture-positive CRE and infectious symptoms receiving early vs. late CZA as the first active β-lactam. Early and late CZA were defined as CZA administration within or after 48 hours of index culture collection, respectively. Primary outcome was a composite of clinical success defined as i) the absence of all-cause mortality or microbiological recurrence requiring therapy within 30 days from the end of CZA therapy and ii) continued infectious symptoms during CZA therapy. Results In total, 174 patients were included (≤48 hours n=52, >48 hours n=122). Median (IQR) age was 61 (53, 73) years and 56.3% were male. ICU admission rates were similar between early vs. late CZA (73.1% vs. 72.1%; P=0.921). Most common infection sources were respiratory (59.8%) and skin and skin structure (9.2%). Klebsiella pneumoniae was the most common CRE isolated (66%). The overall median (IQR) of CZA MIC was 2 (1,4). and there was no difference in the receipt of package insert CZA doses in the first 48 hours of CZA therapy between the early vs. late groups, respectively (1.9% vs. 5.2%; P=0.311). In total, 40/52 (76.9%) early and 68/122 (55.7%) late CZA patients met the clinical endpoint of clinical success (P< 0.001). The early and late CZA groups demonstrated similar ICU length of stay (LOS) (26 [9, 46] vs. 22 [12, 40]; P=0.431, respectively). Table 1. Baseline and Clinical Characteristics Conclusion In hospitalized adult patients with CRE infections, CZA administration within 48 hours of culture collection was associated with a higher rate of clinical success compared to CZA administered after 48 hours. Further studies in a larger patient cohort are warranted to verify these results. Disclosures Wesley D. Kufel, Pharm.D., BCPS, BCIDP, AAHIVP, Merck: Grant/Research Support Bryan White, PharmD, BCPS, BCIDP, Gilead Sciences: Advisor/Consultant Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant

Polyaniline-based 3D network structure promotes entrapment and detection of drug-resistant bacteria

Sensitive and accurate capture, enrichment, and identification of drug-resistant bacteria on human skin are important for early-stage diagnosis and treatment of patients. Herein, we constructed a three-dimensional hierarchically structured polyaniline nanoweb (3D HPN) to capture, enrich, and detect drug-resistant bacteria on-site by rubbing infected skins. These unique hierarchical nanostructures enhance bacteria capture efficiency and help severely deform the surface of the bacteria entrapped on them. Therefore, 3D HPN significantly contributes to the effective and reliable recovery of drug-resistant bacteria from the infected skin and the prevention of potential secondary infection. The recovered bacteria were successfully identified by subsequent real-time polymerase chain reaction (PCR) analysis after the lysis process. The molecular analysis results based on a real-time PCR exhibit excellent sensitivity to detecting target bacteria of concentrations ranging from 102 to 107 CFU/mL without any fluorescent signal interruption. To confirm the field applicability of 3D HPN, it was tested with a drug-resistant model consisting of micropig skin similar to human skin and Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (KPC-CRE). The results show that the detection sensitivity of this assay is 102 CFU/mL. Therefore, 3D HPN can be extended to on-site pathogen detection systems, along with rapid molecular diagnostics through a simple method, to recover KPC-CRE from the skin.Graphical

Multicentre genetic diversity study of carbapenem-resistant Enterobacterales: predominance of untypeable pUVA-like blaKPC bearing plasmids.

Carbapenem-resistant Enterobacterales (CRE) are an urgent public health threat. A better understanding of the molecular epidemiology and transmission dynamics of CRE is necessary to limit their dissemination within healthcare settings. We sought to investigate the mechanisms of resistance and spread of CRE within multiple hospitals in Maryland. From 2016 to 2018, all CRE were collected from any specimen source from The Johns Hopkins Medical Institutions. The isolates were further characterized using both phenotypic and genotypic approaches, including short- and/or long-read WGS. From 2016 to 2018, 302 of 40 908 (0.7%) unique Enterobacterales isolates were identified as CRE. Of CRE, 142 (47%) were carbapenemase-producing CRE with KPC (80.3%) predominating among various genera. Significant genetic diversity was identified among all CRE with high-risk clones serving as major drivers of clonal clusters. Further, we found the predominance of pUVA-like plasmids, with a subset harbouring resistance genes to environmental cleaning agents, involved in intergenus dissemination of blaKPC genes. Our findings provide valuable data to understand the transmission dynamics of all CRE within the greater Maryland region. These data can help guide targeted interventions to limit CRE transmission in healthcare facilities.

SG-APSIC1159: Control of hospital-acquired carbapenemase-producing carbapenem-resistant Enterobacteriaceae colonization: A descriptive study

Objectives: Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) are nosocomial pathogens, and control of CP-CRE transmission is one of the most important infection control issues healthcare organizations face today. Increasing colonization acquisition and clinical infections of CP-CRE occurred in our institution in 2019. In this observational study, we monitored CP-CRE acquisition following implementation of multimodal control measures, and we describe the impact of this intervention on clinical infections. Methods: Increased hospital-acquired CP-CRE colonization and clinical infections were observed in early 2019. Increased CP-CRE surveillance was implemented to include CP-CRE contacts, patients with lengths of stay >7 days, patients with a recent history of hospitalization in other hospitals, and renal dialysis patients. The following interventions were also implemented: (1) isolation or placing CP-CRE patients in cohorts in a designated multidrug-resistant organism (MDRO) ward; (2) emphasis on hand hygiene and contact precautions; (3) mandatory use of gown and gloves for predefined ‘high-risk’ nursing activities, including diaper changing, toilet assistance, wound dressing, and handling urine or stool; (4) enhanced environmental and equipment cleaning; (5) regular audit and feedback regarding compliance; and (6) weekly feedback on ward-level CP-CRE acquisition. CP-CRE colonization cases and clinical infections were tracked by infection prevention and control nurses. Results: The hospital-acquired CP-CRE colonization rate was 4.39 per 10,000 patient days in 2019; it decreased slightly to 3.61 in 2020 and remained steady at 3.77 in 2021. The predominant CP-CRE genes were NDM, OXA-48–like, and KPC. There were 12 hospital-acquired CP-CRE infections in 2019, a rate of 0.37 per 10,000 patient days. This incidence decreased to 6 infections in 2020 and 3 infections in 2021, with corresponding infection rates of 0.19 and 0.09 per 10,000 patient days, respectively. Conclusions: Control of CP-CRE remains extremely challenging in hospitals with multibed open wards. A bundle approach to infection control showed a gradual reduction in CP-CRE cases, with a significant impact on the prevention of clinical infections.

Epidemiological Characteristics of Carbapenemase Producing Carbapenem-Resistant Enterobacteriaceae Colonization

This study identified the epidemiological characteristics, including the size and major strains, of carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) and CP-CRE-related factors by comparing the characteristics of patients in the CP-CRE and non-CP-CRE groups and the CP-CRE and non-CRE groups. This secondary data analysis study included 24 patients in the CP-CRE group, 113 patients in the non-CP-CRE group, and 113 in the non-CRE group. The size and type of CP-CRE were analyzed in terms of frequency and percentage, and CP-CRE risk factors were identified using multiple logistic regression analysis. The rate of CP-CRE positivity among patients with CRE was 17.5%, and the most common causative organism in the CP-CRE group was Klebsiella pneumoniae (81.8%). There were no significant differences between patients in the CP-CRE and non-CP-CRE groups. When compared with the non-CRE group, the isolation of multidrug-resistant organisms except for CRE, particularly vancomycin-resistant Enterococcus, was confirmed as a major risk factor. To prevent CP-CRE acquisition, patients with multidrug-resistant organisms require treatment with more thorough adherence to CRE prevention and management guidelines.

780. Carbapenem-resistant Enterobacteriaceae (CRE) Contamination of In-room Sinks in a New Bed Tower

Abstract Background Time from opening of a new bed tower to CREcontamination of patient room hospital sinks is poorly understood. Methods A 26-bed patient care unit in a new bed tower was opened on 7/18/2020. Patients admitted to this unit underwent weekly rectal cultures to survey for carbapenemase-producing (CP) CRE. Additionally, infection preventionists performed routine surveillance of all clinical cultures for CP-CRE. In-room sinks were located opposite the patient headwall in each patient room and were cultured monthly beginning 9/14/2020 for 3 months. Samples were obtained from the drain cover, handles, and top of bowl using sponges soaked in neutralizing buffer and processed using the stomacher technique. The tailpipe was sampled using a flocked mini-tip swab soaked in neutralizing buffer; the p-trap water was sampled with sterile tubing attached to a 50mL syringe. All samples were plated on HARDYCHROM-ESBL and KPC Colorex medias and incubated at 37°C for 24 hours. Carbapenem resistance genes (NDM1, KPC, IMP, VIM and OXA48) were detected by multiplex PCR and species were confirmed using MALDI-TOF. Environmental pathogens with intrinsic carbapenem resistance and no detected carbapenem-resistance genes were excluded. Results Generally, patients admitted to study rooms were similar across samplings (Table 1). No CP-CRE-positive patients were identified from weekly screening or clinical cultures from the opening of the unit through the end of the study. On the first sampling we discovered KPC-positive Enterobacter cloacae complex on a drain cover (1,400 CFU) and two environmental pathogens housing IMP or KPC genes. On the second sampling we discovered five environmental pathogens housing IMP or KPC genes. On the third sampling we discovered two environmental pathogens housing the IMP gene in p-traps (Figure 1). Table 1. Patient Characteristics Figure 1. Bacterial species and carbapenem-resistance genes found over time Conclusion In a new bed tower open for 58 days with no evidence of CRE positive patients, CRE and CRE genes were discovered in in-room sinks in clinically important (KPC) and environmental pathogens (KPC, IMP). We observed transient colonization of sink drains with potentially important pathogens during a short observation period. Observation over longer time is required to determine transient versus persistent colonization and risk factors for persistent drain colonization. Disclosures All Authors: No reported disclosures

Difference in Susceptibility Between Carbapenemase- and Non–Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae

Background: Carbapenem-resistant Enterobacteriaceae (CRE) remain among the most urgent infectious threats according to the CDC Threats Reports. Although focus has often been placed on carbapenemase-producing phenotypes, there is increasing interest in distinguishing the optimal treatment and outcomes of carbapenemase-producing (CP) and non–carbapenemase-producing (NCP) CRE. We compare antimicrobial susceptibility patterns between CP-CRE and NCP-CRE isolated from patients at our academic medical center. Methods: All CRE isolates of Enterobacter cloacae, Escherichia coli, Klebsiella aerogenes, K. oxytoca, and K. pneumoniae in adult inpatients from 2010 to 2019 were included in this study. Susceptibility testing was performed using the BD Phoenix Automated System (BD Diagnostics, Sparks, MD). CLSI susceptibility break points were utilized in the susceptibility analyses of all antimicrobials tested. To determine carbapenemase production, isolates resistant only to ertapenem were considered NCP-CRE, and those resistant to both ertapenem and meropenem were considered CP-CRE. Statistical comparisons of susceptibility profiles were performed using either the χ2 test or the Fisher exact test. All data preprocessing and statistical analyses were performed using Python software. Results: Over the decade, we identified 291 CRE isolates (216 isolates resistant only to ertapenem and 75 resistant to ertapenem and meropenem). The ertapenem-resistant–only phenotype comprises ~66% of the total CRE population and is largely composed of E. cloacae (67%). As expected, most β-lactam susceptibilities were negligibly low between the 2 groups; however, other clinically relevant antimicrobials (aminoglycosides, fluoroquinolones, and sulfamethoxazole/trimethoprim) exhibited starkly different susceptibility profiles (P value Conclusions: These findings suggest that the most predominant CRE phenotype at our institution is not carbapenemase production. Evaluation of outcomes between CP- and NCP-CRE should be pursued further. The large differences in the MIC distributions may lead to differing outcomes for the affected patients.Funding: NoDisclosures: None

Klebsiella pneumoniae Carbapenemase (KPC)–Producing K. pneumoniae Contamination of an In-Room Sink in a New Bed Tower

Group Name: Duke Center for Antimicrobial Stewardship and Infection PreventionBackground: Wastewater drains in hospital patient rooms have been identified as environmental reservoirs for multidrug-resistant organisms, and they have been linked to outbreaks of carbapenem-resistant Enterobacteriaceae (CRE). We studied the colonization of wastewater drains in a new hospital bed tower. Methods: A patient care unit in a new bed tower opened on July 18, 2020. In-room sinks were located in each hospital room opposite the patient head wall. Patients admitted to this unit underwent weekly rectal cultures to survey for carbapenemase-producing CRE. Additionally, infection preventionists performed routine surveillance of all clinical cultures for CRE. Cultures were performed from all patient room sinks in this unit monthly beginning September 14, 2020. Samples were obtained from the drain cover, handles, and top of bowl using sponges soaked in neutralizing buffer and processed using the stomacher technique. The tail-pipe was sampled using a flocked mini-tip swab soaked in neutralizing buffer; the P-trap water was sampled with sterile tubing attached to a 50-mL syringe. All samples were plated on HARDYCHROM-ESBL and KPC Colorex media and were incubated at 37°C for 24 hours. Results: The first identified CRE-positive patient was admitted to the new unit on December 4, 2020; urine culture obtained at the time of admission grew KPC–producing Klebsiella pneumoniae (KPC-KP). The sink in this patient’s room had been sampled 3 prior times (most recently on November 9, 2020) and was negative for CRE. On December 7, 2020, KPC-KP was found on the drain cover (6,750 colony-forming units, CFU) and in the sink’s P-trap (1,840 CFU) of the index patient’s room during routine sink surveillance. Additional samples from other room surfaces were taken on December 9, 2020, and KPC-KP was recovered from the computer keyboard (452 CFU) and patient bedrails (880 CFU). The patient was discharged from this room December 13, 2020, and the room underwent enhanced terminal room cleaning including UV-C light. On the next routine sink sampling on January 4, 2021, KPC-KP was recovered again in the index room sink P-trap (9,800 CFU) but at no additional sites. MLST was performed, and all isolates were ST-258. Conclusions: In a new bed tower with no prior evidence of CRE-positive patients, the first identified case of a CRE (KPC-KP) in a patient resulted in widespread environmental contamination of the room after only 3 days of hospitalization and contamination of the in-room sink drain that persisted after 1 month. Given the ease with which CRE colonizes wastewater drains, new strategies are needed to mitigate drain colonization and to prevent CRE transmission to subsequent patients.Funding: NoDisclosures: None

Evaluation of carbapenem-resistant Enterobacteriaceae (CRE) guideline implementation in the Veterans Affairs Medical Centers using the consolidated framework for implementation research

BackgroundInfections caused by carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing (CP) CRE are difficult to treat, resulting in high mortality in healthcare settings every year. The Veterans Health Administration (VHA) disseminated guidelines in 2015 and an updated directive in 2017 for control of CRE focused on laboratory testing, prevention, and management. The Consolidated Framework for Implementation Research (CFIR) framework was used to analyze qualitative interview data to identify contextual factors and best practices influencing implementation of the 2015 guidelines/2017 directive in VA Medical Centers (VAMCs). The overall goals were to determine CFIR constructs to target to improve CRE guideline/directive implementation and understand how CFIR, as a multi-level conceptual model, can be used to inform guideline implementation.MethodsSemi-structured interviews were conducted at 29 VAMCs with staff involved in implementing CRE guidelines at their facility. Survey and VHA administrative data were used to identify geographically representative large and small VAMCs with varying levels of CRE incidence. Interviews addressed perceptions of guideline dissemination, laboratory testing, staff attitudes and training, patient education, and technology support. Participant responses were coded using a consensus-based mixed deductive-inductive approach guided by CFIR. A quantitative analysis comparing qualitative CFIR constructs and emergent codes to sites actively screening for CRE (vs. non-screening) and any (vs. no) CRE-positive cultures was conducted using Fisher’s exact test.ResultsForty-three semi-structured interviews were conducted between October 2017 and August 2018 with laboratory staff (47%), Multi-Drug-Resistant Organism Program Coordinators (MPCs, 35%), infection preventionists (12%), and physicians (6%). Participants requested more standardized tools to promote effective communication (e.g., electronic screening). Participants also indicated that CRE-specific educational materials were needed for staff, patient, and family members. Quantitative analysis identified CRE screening or presence of CRE as being significantly associated with the following qualitative CFIR constructs: leadership engagement, relative priority, available resources, team communication, and access to knowledge and information.ConclusionsEffective CRE identification, prevention, and treatment require ongoing collaboration between clinical, microbiology, infection prevention, antimicrobial stewardship, and infectious diseases specialists. Our results emphasize the importance of leadership’s role in promoting positive facility culture, including access to resources, improving communication, and facilitating successful implementation of the CRE guidelines.

Risk Factors Associated With Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Positive Cultures in a Cohort of US Veterans.

Carbapenem-resistant Enterobacteriaceae (CRE) cause approximately 13 100 infections, with an 8% mortality rate in the United States annually. Carbapenemase-producing CRE (CP-CRE) a subset of CRE infections infections have much higher mortality rates (40%-50%). There has been little research on characteristics unique to CP-CRE. The goal of the current study was to assess differences between US veterans with non-CP-CRE and those with CP-CRE cultures. A retrospective cohort of veterans with CRE cultures from 2013-2018 and their demographic, medical, and facility level covariates were collected. Clustered multiple logistic regression models were used to assess independent factors associated with CP-CRE. The study included 3096 unique patients with cultures positive for either non-CP-CRE or CP-CRE. Being African American (odds ratio, 1.44 [95% confidence interval, 1.15-1.80]), diagnosis in 2017 (3.11 [2.13-4.54]) or 2018 (3.93 [2.64-5.84]), congestive heart failure (1.35 [1.11-1.64]), and gastroesophageal reflux disease (1.39 [1.03-1.87]) were associated with CP-CRE cultures. There was no known antibiotic exposure in the previous year for 752 patients (24.3% of the included patients). Those with no known antibiotic exposure had increased frequency of prolonged proton pump inhibitor use (17.3%) compared to those with known antibiotic exposure (5.6%). Among a cohort of patients with CRE, African Americans, patients with congestive heart failure, and those with gastroesophageal reflux disease had greater odds of having a CP-CRE culture. Roughly 1 in 4 patients with CP-CRE had no known antibiotic exposure in the year before their positive culture.

A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan.

IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.

A method to quantify viable carbapenem resistant gram-negative bacteria in treated and untreated wastewater

Carbapenem resistance, particularly in Enterobacteriaceae, is an urgent threat to public health worldwide. Wastewater treatment plants are a critical control point for the spread of antimicrobial resistance into the environment yet, due in part to the lack of appropriate methods, the occurrence, identification and removal of carbapenem resistant bacteria has not been well characterized in wastewater matrices. This project was designed to provide a method for quantification of viable carbapenem resistant (CR) gram-negative bacteria (GNB) in raw sewage and treated wastewater effluents. A two-step procedure using membrane filtration and selective media supplemented with each of four carbapenems (doripenem, meropenem, imipenem, and ertapenem) was established for the quantification of CR GNB in wastewater matrices. Carbapenemase production was also assessed on individual bacterial colonies using two separate methods. Vitek®2 antimicrobial susceptibility test and disk diffusion assays were used to verify results from the supplemented media test and provide taxonomic identification. Treated and untreated wastewater samples from secondary and tertiary-stage wastewater treatment plants were analyzed for CR bacteria using the supplemented media procedure. Over 98% of all isolates selected from the carbapenem-supplemented media were verified as CR GNB. Carbapenemase production was observed in 80% of these isolates and 88% were multidrug resistant. All Enterobacteriaceae isolates from the supplemented media were verified as CR and 97% tested positive for carbapenemase production. The highest concentrations of CR GNB in wastewater were observed using the ertapenem-supplemented media. Doripenem-supplemented media showed the greatest specificity and selectivity for carbapenemase-producing CRE. Overall, the cumulative CR GNB in wastewater were reduced by approximately three- and five-log10 by the secondary and tertiary-stage WWTPs, respectively. This study establishes a method for characterization of viable CR GNB in wastewater matrices and demonstrates that current wastewater treatment technologies effectively reduce CR bacteria, including CRE, in sewage.

Risk Factors for Carbapenemase Producing-Carbapenem Resistant Enterobacteriaceae in Those With CRE Positive Cultures

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are gram-negative bacteria resistant to at least 1 carbapenem and are associated with high mortality (50%). Carbapenemase-producing CRE (CP-CRE) are particularly serious because they are more likely to transmit carbapenem resistance genes to other gram-negative bacteria and they are resistant to all carbapenem antibiotics. Few studies have evaluated risk factors associated with CP-CRE colonization. The goal of this study was to determine the risk factors associated with CP-CRE colonization in a cohort of US veterans. Methods: We conducted a retrospective cohort study of patients seen at VA medical centers between 2013 and 2018 who had positive cultures for CRE from any site, defined by resistance to at least 1 of the following carbapenems: imipenem, meropenem, doripenem, or ertapenem. CP-CRE was defined via antibiotic sensitivity data that coded the culture as being ‘carbapenemase producing,’ being ‘Hodge test positive,’ or ‘KPC producing.’ Only the first positive culture for CRE was included. Patient demographics (year of culture, age, sex, race, major comorbidities, infectious organism, culture site, inpatient status, and CP-CRE status) and facility demographics (rurality, geographic region, and facility complexity) were collected. Bivariate analysis and multiple logistic regression were performed to determine variables associated with CP-CRE versus non–CP-CRE. Results: In total, 3,322 patients were identified with a positive CRE culture: 546 (16.4%) with CP-CRE and 2,776 (83.63%) with non–CP-CRE. Most patients were men (95%) and were older (mean age, 71; SD, 12.5) and were diagnosed at a high-complexity VA medical center (65%). Most of the cultures were urine (63%), followed by sputum (13%), and blood (7%). Most were from inpatients (46%), followed by outpatients (42%), and long-term care facilities (12%). Multivariable analysis showed the following variables to be associated with CP-CRE positive cultures: congestive heart failure (P = .0136), African American (P = .0760), Klebsiella spp (P < .0001), GI cancers (P = .0087), culture collected in 2017 (P = .0004), and culture collected in 2018 (P < .0001). There were also significant differences CP-CRE frequencies by geographic region (P < .001). Discussion: CP-CRE diagnoses are relatively rare; however, the serious complications associated make them important infections to investigate. In our analysis, we found that congestive heart failure and gastric cancer were comorbidities strongly associated with CP-CRE. In 2017, the VA formalized their CP-CRE definition, which led to more accurate reporting. Conclusions: After the guideline was implemented, CP-CRE detection dramatically increased in noncontinental US facilities. More work should be done in the future to determine the different risk factors between non–CP-CRE and CP-CRE infections.Funding: NoneDisclosures: None

Leveraging the Electronic Medical Record to Identify Patients at Risk of Antibiotic Resistant Organisms

Background: Carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CP-CRE) pose a serious public health threat. The CDC guidelines for combating CP-CRE include a recommendation to screen selected high-risk patients. Objective: We describe a program to identify and screen patients at risk for CP-CRE. Setting: An academic, tertiary-care center with 1,297 licensed beds and 62,071 admissions per year. Methods: A report was created in the electronic medical record (EMR) to identify adult patients admitted in the previous 24 hours from countries and states with known CP-CRE transmission based on address and ZIP code. Patients with a known travel history outside the United States were also reviewed, but these data were inaccurate. Initially, a physician from Infection Prevention and Control (IPAC) placed orders for CP-CRE screening of these patients. Subsequently, a nursing protocol was developed to facilitate infection preventionists placing orders for CP-CRE screening earlier in the eligible patient’s hospital stay. An electronic communication is sent via the EMR alerting the patient care team to the order, the rationale for the order, and links to a tool kit with resources to help answer patient questions. A single perirectal swab is obtained by the nurse caring for the patient and is tested for Klebsiella pneumoniae carbapenemase (KPC), New Delhi metallo-β-lactamase (NDM), oxacillinase-48 (OXA-48), and Verona integron-encoded metallo-β-lactamase (VIM) by polymerase chain reaction (PCR). Results: From May 2018 to November 2019, 688 patients were screened for CP-CRE using the case-finding report and the nursing protocol. Overall, 9 patients with CP-CRE were identified: 1 KPC, 2 NDM, and 5 OXA-48, and 1 patient was identified to have both NDM and OXA-48. The yield of 1.3% from this screening is higher than that reported previously in the literature. Use of the nursing protocol has enabled IPAC to complete timely CP-CRE surveillance and prevent transmission to other patients. We are currently using a similar process to identify and screen persons at risk for the emerging infection Candida auris.Conclusions: The EMR can be leveraged for early identification and screening of patients with epidemiologically significant pathogens. Protocols within the EMR can be effectively replicated and modified to respond to emerging infections and changing surveillance guidelines.Funding: NoneDisclosures: Consulting fee-—Merck (Priya Sampathkumar)

Shifting Landscape of Healthcare-Associated Infection and Antimicrobial Resistant Infection Reporting Policy, 2005–2019

Background: Healthcare-associated infections (HAIs) are a serious threat to patient safety; they account for substantial morbidity, mortality, and healthcare costs. Healthcare practices, such as inappropriate use of antimicrobials, can also amplify the problem of antimicrobial resistance. Data collected to target HAI prevention and antimicrobial stewardship efforts and measure progress are an important resource for assuring transparency and accountability in healthcare, tracking adverse outcomes, investigating healthcare practices that may spread or protect against disease, detecting and responding to the spread of resistant pathogens, preventing infections, and saving lives. Methods: We discuss 3 healthcare-associated infection and antimicrobial Resistant infection (HAI-AR) reporting types: NHSN HAI-AR reporting, reportable diseases, and nationally notifiable diseases. HAI-AR reporting requirements outline facilities and data to report to NHSN and the health department to comply with state laws. Reportable diseases are those that facilities, providers, and laboratories are required to report to the health department. Nationally notifiable diseases are those reported by health departments to the CDC for nationwide surveillance and analysis as determined by Council of State and Territorial Epidemiologists (CSTE) and the CDC. Data presented are based on state and federal policy; NHSN data are based on CDC reporting statistics. Results: Since the 2005 launch of the CDC NHSN and publication of federal advisory committee HAI reporting guidance, most states have established policies stipulating healthcare facilities in their jurisdiction report HAIs and resistant infections to the NHSN to gain access to those data, increasing from 2 states in 2005, to 18 in 2010, and to 36 states, Washington, DC, and Philadelphia in 2019. Reporting policies and NHSN participation expanded greatly following the 2011 inception of CMS HAI quality reporting requirements, with several states aligning state requirements with CMS reporting. States listing carbapenem-resistant Enterobacteriaceae (CRE) as a reportable disease increased from 7 in 2013 to 41 states and the District of Columbia in 2019. Vancomycin-intermediate and vancomycin-resistant Staphylococcus aureus (VISA/VRSA) was added as a nationally notifiable disease in 2004, carbapenemase-producing CRE (CP-CRE) was added in 2018, and Candida auris clinical infections were added in 2019. The CDC and most jurisdictions with HAI reporting mandates issue public reports based on aggregate state data and/or facility-level data. States may also alert healthcare providers and health departments of emerging threats and to assist in notifying patients of potential exposure. Conclusions: Through efforts by health departments, facilities, patient advocates, partners, the CDC, and other federal agencies, HAI-AR reporting has steadily increased. Although reporting laws and data uses vary between jurisdictions, data provided serves as valuable tools to inform prevention.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 < .01) and less commonly K. pneumoniae (21% vs 58%; P < .01) than CRE-O. CRE-EO cases were more often women (65% vs 50%; P < .01), had a lower Charlson comorbidity index (mean ± SD, 2.4±2.3 vs 3.0±2.6; P < .01), and were less commonly at a long-term care facility (24% vs 31%) or hospital (15% vs 21%; P < .01) in the 4 days prior to the CRE culture. CRE-EO were more susceptible to all antibiotics tested at the clinical laboratory (P < .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 < .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 < .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

Harnessing Next-Generation Sequence Technology to Elucidate Healthcare-Associated Infection Transmission Pathways

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are multidrug-resistant bacteria that persist in healthcare environments, particularly in wastewater reservoirs where they can pose risks for patients. Healthcare-associated outbreaks of carbapenemase-producing (CP) CRE can be propagated via a single bacterial strain and/or mobile genetic element (MGEs) harboring a carbapenemase gene. Unlike chromosomally encoded carbapenemases, CP-MGEs can rapidly facilitate the spread of these carbapenemase genes across bacterial strains. From July 2017 to December 2018, the Florida Department of Health in Orange County investigated an outbreak of patients colonized with various bacterial genera of CP-CRE carrying the Klebsiella pneumoniae carbapenemase gene (blaKPC), indicating a potential MGE reservoir. WGS was performed to identify transmission pathways and linked cases, beyond what traditional testing provides. Methods: We selected a subset of blaKPC-harboring isolates for WGS on short- and long-read platforms (MiSeq, PacBio, MinION) to achieve high quality, complete genome and plasmid assemblies. Laboratory, clinical, and epidemiological data were combined to identify possible transmission events, common sources, and common MGEs. Results: Eleven clinical isolates from 5 genera (Citrobacter, Enterobacter, Klebsiella, Morganella, Providencia, and Serratia), and 10 environmental isolates collected from the pharmacy and medication room, ICU, and patient rooms and comprising 4 genera (Citrobacter, Enterobacter, Klebsiella, and Serratia) underwent WGS. Although short-read WGS elucidated additional subsets of closely related strains, high genomic diversity was also observed within some species: Citrobacter freundii: 13,483 single-nucleotide variants (SNVs), 67% core genome; Enterobacter spp: 3–18,563 SNVs; 34%; and K. pneumoniae: 8–18,460 SNVs, 80%. Further analysis using long-read hybrid assemblies revealed 2 unique blaKPC-harboring plasmids. The first plasmid, pDHQP20145-KPC3 (50 kb), contained the blaKPC-3 gene and was detected in both patient and environmental isolates across 3 of the 5 sequenced genera. The second plasmid, pDHQP201745-KPC2 (180 kb), contained the blaKPC-2 gene, and was found across 2 CP-CRE genera isolated from both patients and the environment, including isolates from the medication room sink drain and a patient who received compounded oral medications. Conclusion: WGS identified 2 blaKPC-harboring plasmids, including pDHQP20145-KPC3, which was found across 3 genera of CP-CRE isolated from patients and the environment, supporting prolonged transmission of KPC-producing CRE in this facility, and a CP-MGE driving transmission. The rapid spread of emerging, potentially mobile, antimicrobial resistance has increased our need to further explore the genomic environment of promiscuous MGEs. WGS can contribute to infection control beyond traditional subtyping methods, such as pulsed-field gel electrophoresis (PFGE), as MGEs increasingly represent an important driver of transmission.Funding: NoneDisclosures: None

Clinical and Microbiological Analysis of Risk Factors for Mortality in Patients with Carbapenem-Resistant Enterobacteriaceae Bacteremia

ObjectivesThe aims of this study were to identify whether the site of acquisition or the underlying carbapenem-resistant Enterobacteriaceae (CRE) resistance mechanism was associated with clinical outcomes, and to evaluate risk factors for 14-day mortality in patients with CRE bacteremia. Materials and methodsA retrospective cohort study was conducted at a 2700-bed tertiary center. All adult patients with monomicrobial carbapenem-resistant Escherichia coli or Klebsiella pneumoniae bacteremia from 2011 to 2018 were included. All blood isolates collected were tested with a modified carbapenem inactivation method for phenotypic detection of carbapenemase. ResultsOf 133 patients with monomicrobial CRE bacteremia, 63 (47.4%) were infected with carbapenemase-producing CRE (CP-CRE), and 70 (52.6%) with non-CP-CRE. Patients with community-onset infection (COI) were more likely to present with biliary or urinary tract infections, less likely to have ineradicable or non-eradicated foci and to receive appropriate empirical therapy, and marginally more likely to have CP-CRE compared with those with hospital-acquired infection (HAI). However, 14-day mortality was significantly lower in COI than HAI (7% vs 29%, P = 0.01). Patients who died were more likely to have had a higher APACHE II score, ineradicable or non-eradicated foci, and a lower chance of having received appropriate antibiotic treatment. Multivariate analysis revealed that HAI, high APACHE II score, and inappropriate antibiotic treatment were independent risk factors for mortality. Carbapenemase production did not affect mortality. ConclusionsThe results of this study indicate that timely, appropriate treatment is essential for managing CRE bacteremia, regardless of carbapenemase production, particularly in critically ill patients with hospital-acquired bacteremia.