Extended-spectrum Β-lactamase-producing Enterobacterales Research Articles

Colonization by Extended-Spectrum β-Lactamase-Producing Enterobacterales and Bacteremia in Hematopoietic Stem Cell Transplant Recipients.

Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a risk factor for ESBL-E bloodstream infection (BSI) and to evaluate ESBL-E colonization in HSCT recipients. A retrospective analysis of ESBL-E colonization and BSI in HSCT patients was conducted from August 2019 to June 2022. Weekly swabs were collected and cultured on chromogenic selective media, with PCR identifying the β-lactamase genes. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) assessed the colonizing strains' similarities. Of 222 evaluated HSCT patients, 59.45% were colonized by ESBL-E, with 48.4% at admission. The predominant β-lactamase genes were blaTEM (52%) and blaSHV (20%). PFGE analysis did not reveal predominant clusters in 26 E. coli and 15 K. pneumoniae strains. WGS identified ST16 and ST11 as the predominant sequence types among K. pneumoniae. Thirty-three patients developed thirty-five Enterobacterales-BSIs, with nine being third-generation cephalosporin-resistant. No association was found between ESBL-E colonization and ESBL-BSI (p = 0.087). Although the patients presented a high colonization rate of ESBL-E upon admission, no association between colonization and infection were found. Thus, it seems that ESBL screening is not a useful strategy to assess risk factors and guide therapy for ESBL-BSI in HSCT-patients.

Comparison of Daily versus Admission and Discharge Surveillance Cultures for Multidrug-Resistant Organism Detection in an Intensive Care Unit.

Admission and discharge screening of patients for asymptomatic gut colonization with multidrug-resistant organisms (MDROs) is a traditional approach to active surveillance, but its sensitivity for detecting colonization is uncertain. Daily rectal or fecal swab samples and clinical data were collected over 12 months from patients in one 25-bed intensive care unit (ICU) in Chicago, IL USA and tested for the following multidrug-resistant organisms (MDROs): vancomycin-resistant enterococci (VRE); third-generation cephalosporin-resistant Enterobacterales, including extended-spectrum β-lactamase-producing Enterobacterales (ESBL); and carbapenem-resistant Enterobacterales (CRE). MDRO detection by (1) admission/discharge surveillance cultures or (2) clinical cultures were compared to daily surveillance cultures. Samples underwent 16S rRNA gene sequencing to measure the relative abundance of operational taxonomic units (OTUs) corresponding to each MDRO. Compared with daily surveillance cultures, admission/discharge cultures detected 91% of prevalent MDRO colonization and 63% of incident MDRO colonization among medical ICU patients. Only a minority (7%) of MDRO carriers were identified by clinical cultures. Higher relative abundance of MDRO-associated OTUs and specific antibiotic exposures were independently associated with higher probability of MDRO detection by culture. Admission and discharge surveillance cultures underestimated MDRO acquisitions in an ICU. These limitations should be considered when designing sampling strategies for epidemiologic studies that use culture-based surveillance.

Gut microbiome diversity and composition in individuals with and without extended-spectrum β-lactamase-producing Enterobacterales carriage: a matched case–control study in infectious diseases department

ObjectiveLittle is known about the effect of gut microbial and extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) carriage, particularly in the general population. The aim of this study was to identify microbiota signatures uniquely correlated with ESBL-E carriage. MethodsWe conducted a case–control study among individuals seeking care at the Sexual Health Clinic or Department of Infectious and Tropical Diseases, Saint-Antoine Hospital, Paris, France. Using coarsened exact matching, 176 participants with ESBL-carriage (i.e. cases) were matched 1:1 to those without ESBL-carriage (i.e. controls) based on sexual group, ESBL-E prevalence of countries travelled in <12 months, number of sexual partners in <6 months, geographic origin, and any antibiotic use in <6 months. 16S rRNA gene amplicon sequencing was used to generate differential abundances at the genus level and measures of α- and β-diversity. ResultsParticipants were mostly men (83.2%, n = 293/352) and had a median age of 33 years (interquartile range: 27–44). Nine genera were found associated with ESBL-E carriage: Proteus (p < 0.0001), Carnobacterium (p < 0.0001), Enterorhabdus (p 0.0079), Catonella (p 0.017), Dermacoccus (p 0.017), Escherichia/Shigella (p 0.021), Kocuria (p 0.023), Bacillus (p 0.040), and Filifactor (p 0.043); however, differences were no longer significant after Benjamini–Hochberg correction (q > 0.05). There were no differences between those with versus without ESBL-E carriage in measures of α-diversity (Shannon Diversity Index, p 0.49; Simpson Diversity Index, p 0.54; and Chao1 Richness Estimator, p 0.16) or β-diversity (Bray–Curtis dissimilarity index, p 0.42). DiscussionIn this large carefully controlled study, there is lacking evidence that gut microbial composition and diversity is any different between individuals with and without ESBL-E carriage.

712. Dynamics of Colonization with Multi-Drug Resistant Organisms and Clinical Outcomes in Critically Ill Patients: A Prospective Cohort Study

Abstract Background Critically ill patients have frequent intestinal colonization with multi-drug resistant organisms (MDRO). However, the duration of colonization and its impact on clinical outcomes are unknown. Methods We performed a prospective cohort study of adult patients admitted to ICUs at a tertiary care hospital. All patients had stool samples collected twice weekly for up to four weeks or until discharge from the ICU. Stool samples were cultured with selective media for vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), and carbapenem-resistant Enterobacterales (CRE). We characterized patient demographics and compared outcomes between patients with and without colonization. Results A total of 102 patients were included. Mean age was 62 years (SD±15), 62 (61%) were men, 67 (66%) were white, and 34 (33%) were admitted from a separate healthcare facility. Thirty-nine (38%) were colonized with ≥1 MDRO at ≥1 time point. There were no statistically significant differences in baseline characteristics between patients with and without colonization. Of the 39 patients with colonization, 23 (59%) were colonized with VRE at ≥1 time point, 18 (46%) with ESBL-E, and 7 (18%) with CRE; 8 (20%) were colonized with &amp;gt;1 organism (Figure 1). Notably, most patients (13/23 with VRE, 15/18 with ESBL-E, and 4/7 with CRE colonization) were colonized with each MDRO type at only one time point during their ICU stay (Figure 1). In-hospital mortality did not differ according to colonization status (21% with any colonization vs. 17% without, p=0.70). When assessing mortality according to specific MDRO type, VRE colonization was associated with in-hospital mortality (35% with VRE colonization vs. 14% without, p=0.02). Figure 1. Results of serial stool samples tested for target multi-drug resistant organisms in intensive care unit patients. Each horizontal line represents a different patient included in the study (N=102) and each circle represents a separate stool sample. Conclusion Nearly 40% of ICU patients were colonized with VRE, ESBL-E, and/or CRE, although colonization duration was generally limited, possibly reflecting antibiotic pressures and microbiome dynamics in critically ill patients. More research is needed to identify clinical, microbiome, and organism genomic factors that facilitate persistence and loss of colonization. Disclosures All Authors: No reported disclosures

Phenotypic and genotypic characterization of multidrug resistant and extended-spectrum β-lactamase-producing Enterobacterales isolated from clinical samples in the western region in Cameroon

BackgroundThe 2017 World Health Organization (WHO) report has listed extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) as critical pathogens for public health and requiring urgently new antibiotics. The aim of this study was to characterize phenotypically and genotypically ESBL-E isolated among clinical samples in Dschang, Cameroon.MethodsA cross-sectional study was conducted during a four-month periods from February to May 2022 in the two biggest hospitals of Dschang. Clinical samples were collected and cultured on Eosin Methylene Blue agar. Suspected growing colonies were biochemically identified using the Enterosystem Kit 18R. Antimicrobial susceptibility testing (AST) was done using the Kirby Bauer disc diffusion method and interpretated according to the CA-SFM recommendations. ESBL phenotypes were double screened using CHROMagar™ ESBL and double disk synergy test (DDST). The detection of resistance genes was performed using conventional and multiplex PCR methods. Results were analyzed with SPSS (version 21) and a p-value < 0.05 was considered statistically significant.ResultsA total of 152 Enterobacterales were isolated among 597 clinical samples including urine, blood, cervico-vaginal, urethral swabs and wound samples. The overall prevalence of ESBL-Enterobacterales was 29.61% (45/152). The most represented ESBL species were Escherichia coli (n = 23; 51.11%), Klebsiella pneumoniae (n = 8; 17.78%) and Citrobacter freundii (n = 6; 13.33%).ConclusionThis study reveals the high burden of ESBL-E among clinical samples in the regional hospital in Dschang with the most common species being E. coli and K. pneumoniae. It confirmed the high occurrence of blaCTX−M and blaTEM among ESBL-E. The study suggests that implementing antimicrobial stewardship program and real-time surveillance of antimicrobial resistance are needed in the Western region of Cameroon. Moreover, the implementation of infection prevention and control measures (IPC) is essential to curb the dissemination of these bacteria from community to hospital settings. Implementation of national action plan to fight against antimicrobial resistance at the local levels is urgently needed.

Is Carbapenem Therapy Necessary for the Treatment of Non-CTX-M Extended-Spectrum β-Lactamase-Producing Enterobacterales Bloodstream Infections?

Investigations into antibiotics for extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSIs) have focused on blaCTX-M genes. Patient outcomes from non-CTX-M-producing ESBL-E BSIs and optimal treatment are unknown. A multicenter observational study investigating 500 consecutive patients with ceftriaxone-resistant Enterobacterales BSIs during 2018-2022 was conducted. Broth microdilution and whole-genome sequencing confirmed antibiotic susceptibilities and ESBL gene presence, respectively. Inverse probability weighting (IPW) using propensity scores ensured patients with non-CTX-M and CTX-M ESBL-E BSIs were similar before outcome evaluation. 396 patients (79.2%) were confirmed to have an ESBL-E BSI. ESBL gene family prevalence was as follows: blaCTX-M (n = 370), blaSHV (n = 16), blaOXY (n = 12), and blaVEB (n = 5). ESBL gene identification was not limited to Escherichia coli and Klebsiella species. In the IPW cohort, there was no difference in 30-day mortality or ESBL-E infection recurrence between the non-CTX-M and CTX-M groups (odds ratio [OR], 0.99; 95% confidence interval [CI], .87-1.11; P = .83 and OR, 1.10; 95% CI, .85-1.42; P = .47, respectively). In an exploratory analysis limited to the non-CTX-M group, 86% of the 21 patients who received meropenem were alive on day 30; none of the 5 patients who received piperacillin-tazobactam were alive on day 30. Our findings suggest that non-CTX-M and CTX-M ESBL-E BSIs are equally concerning and associated with similar clinical outcomes. Meropenem may be associated with improved survival in patients with non-CTX-M ESBL-E BSIs, underscoring the potential benefit of comprehensive molecular diagnostics to enable early antibiotic optimization for ESBL-E BSIs beyond just blaCTX-M genes.

Infectious Diseases Society of America 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections.

The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), AmpC β-lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR-P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document. A panel of six infectious diseases specialists with expertise in managing antimicrobial-resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR-P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of resistance and availability of specific anti-infectives internationally, this document focuses on the treatment of infections in the United States. Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are also discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults. The field of antimicrobial resistance is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of antimicrobial resistant infections. This document is current as of December 31, 2022 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Increased Incidence and Risk Factors of Infections by Extended-Spectrum β-Lactamase-Producing Enterobacterales During the COVID-19 Pandemic: A Retrospective Case-Control Study.

To investigate changes in the incidence of infections by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) and analyzed whether there was an association between endogenous changes in the organism due to COVID-19 infection and the infections by ESBL-E. The study was a single-center retrospective case-control design. A total of 107 patients infected by ESBL-E during the COVID-19 pandemic were selected as the case group, while 214 uninfected patients selected by 1:2 propensity score matching (PSM) acted as the control group. Univariate analysis, LASSO logistic regression, and multivariate logistic regression were used to determine the risk factors for ESBL-E infection. An interrupted time series was used to analyze the changes in the incidence of ESBL-E infections in hospitalized patients during the COVID-19 pandemic. The incidence of infection with ESBL-E showed a significant increase during COVID-19 (3.42 vs 4.92 per 1000 patients, p = 0.003). The incidence of ESBL-E infections increased at an average rate of 0.45 per 1000 patients per week compared to the pre-pandemic period (p = 0.022). Multivariate logistic regression analysis showed that a length of hospitalization ≥ 15 days (OR: 2.98 (1.07-8.28), chronic kidney disease (OR: 4.25 (1.32-13.70), white blood cell (WBC) > 9.5×10^9/L (OR: 3.04 (1.54-6.01), use of hormonal drugs (OR: 2.38 (1.04-5.43), antibacterial drug use 1 type (OR: 5.38 (2.04-14.21), antibacterial drug use 2 types (OR: 23.05 (6.71-79.25) and antibacterial drug use ≥ 3 types (OR: 88.35 (8.55-912.63) were independent risk factors for infection with ESBL-E, while chronic obstructive pulmonary disease (COPD) was a protective factor (OR: 0.14 (0.03-0.66). COVID-19 was not an independent risk factor for infection by ESBL-E. During the COVID-19 pandemic, the incidence of infections by ESBL-E increased significantly. Increased exposure to traditional risk factors were the main reasons, however, COVID-19 was not an independent risk factor for ESBL-E infection.

The fecal carriage rate of extended-spectrum β-lactamase-producing or carbapenem-resistant Enterobacterales among Japanese infants in the community at the 4-month health examination in a rural city.

Extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is a great public health concern globally not only in hospitals but also in the community. To our knowledge, there have been few studies on the prevalence of ESBL-E and much less about carbapenem-resistant Enterobacterales (CRE) among children in the community, and there is no such study in Japan despite such situations. This study aimed to clarify their carriage status among Japanese infants in the community by taking the opportunity of the 4-month health checkup. This prospective analysis was conducted from April 2020 to March 2021 in Shimabara City, Nagasaki Prefecture, Japan. The research-related items were mailed to all subjects with official documents for the checkup. The fecal samples were obtained from the diaper by guardians beforehand and were collected with the questionnaire and then screened for ESBL-E and CRE by a clinical laboratory company with selective agars followed by identification and confirmation. Only the positive samples were analyzed about resistant genotypes. One hundred fifty infants aged 4-5 months, over half of the subjects, participated in this study. The overall ESBL-E carriage rate was 19.3% (n = 29), and no CRE carrier was detected among them. All identified ESBL-E were E. coli except for one K. pneumoniae. A significantly higher carriage rate was recorded among the infants born at "Hospital A" (25.0%) than the others (11.3%). Enterobacterales producing CTX-M-9 ± TEM were broadly distributed among the positive samples (65.5%), whereas the CTX-M-1 group was exclusively detected among those from "Hospital A". Recursive partitioning analysis suggested that delivery facilities might be an important factor for ESBL-E colonization, although the effect could be decreased as they grow. In contrast, no significant effect was observed for other factors such as parent(s) as healthcare worker(s), having a sibling(s), and the mode of delivery. This study revealed the ESBL-E and CRE carriage status of Japanese infants in the community for the first time, although the setting is somewhat limited. Our findings indicated that environmental factors, especially delivery facilities, influenced ESBL-E colonization among infants aged 4-5 months, implying the need for strengthening countermeasures against antimicrobial resistance at delivery facilities and communities outside the hospitals.

Community carriage of ESBL-producing Escherichia coli and Klebsiella pneumoniae: a cross-sectional study of risk factors and comparative genomics of carriage and clinical isolates.

The global prevalence of infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) is increasing, and for Escherichia coli, observations indicate that this is partly driven by community-onset cases. The ESBL-E population structure in the community is scarcely described, and data on risk factors for carriage are conflicting. Here, we report the prevalence and population structure of fecal ESBL-producing E. coli and Klebsiella pneumoniae (ESBL-Ec/Kp) in a general adult population, examine risk factors, and compare carriage isolates with contemporary clinical isolates. Fecal samples obtained from 4,999 participants (54% women) ≥40 years in the seventh survey of the population-based Tromsø Study, Norway (2015, 2016), were screened for ESBL-Ec/Kp. In addition, we included 118 ESBL-Ec clinical isolates from the Norwegian surveillance program in 2014. All isolates were whole-genome sequenced. Risk factors associated with carriage were analyzed using multivariable logistic regression. ESBL-Ec gastrointestinal carriage prevalence was 3.3% [95% confidence interval (CI) 2.8%-3.9%, no sex difference] and 0.08% (0.02%-0.20%) for ESBL-Kp. For ESBL-Ec, travel to Asia was the only independent risk factor (adjusted odds ratio 3.46, 95% CI 2.18-5.49). E. coli ST131 was most prevalent in both collections. However, the ST131 proportion was significantly lower in carriage (24%) versus clinical isolates (58%, P < 0.001). Carriage isolates were genetically more diverse with a higher proportion of phylogroup A (26%) than clinical isolates (5%, P < 0.001), indicating that ESBL gene acquisition occurs in a variety of E. coli lineages colonizing the gut. STs commonly related to extraintestinal infections were more frequent in clinical isolates also carrying a higher prevalence of antimicrobial resistance, which could indicate clone-associated pathogenicity.IMPORTANCEESBL-Ec and ESBL-Kp are major pathogens in the global burden of antimicrobial resistance. However, there is a gap in knowledge concerning the bacterial population structure of human ESBL-Ec/Kp carriage isolates in the community. We have examined ESBL-Ec/Kp isolates from a population-based study and compared these to contemporary clinical isolates. The large genetic diversity of carriage isolates indicates frequent ESBL gene acquisition, while those causing invasive infections are more clone dependent and associated with a higher prevalence of antibiotic resistance. The knowledge of factors associated with ESBL carriage helps to identify patients at risk to combat the spread of resistant bacteria within the healthcare system. Particularly, previous travel to Asia stands out as a major risk factor for carriage and should be considered in selecting empirical antibiotic treatment in critically ill patients.

Risk-factor analysis for extended-spectrum beta-lactamase-producing Enterobacterales colonization or infection: Evaluation of a novel approach to assess local prevalence as a risk factor.

To explore an approach to identify the risk of local prevalence of extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) on ESBL-E colonization or infection and to reassess known risk factors. Case-control study. Johns Hopkins Health System emergency departments (EDs) in the Baltimore-Washington, DC, region. Patients aged ≥18 years with a culture growing Enterobacterales between April 2019 and December 2021. Cases had a culture growing an ESBL-E. Addresses were linked to Census Block Groups and placed into communities using a clustering algorithm. Prevalence in each community was estimated using the proportion of ESBL-E among Enterobacterales isolates. Logistic regression was used to determine risk factors for ESBL-E colonization or infection. ESBL-E were detected in 1,167 of 11,224 patients (10.4%). Risk factors included a history of ESBL-E in the prior 6 months (aOR, 20.67; 95% CI, 13.71-31.18), exposure to a skilled nursing or long-term care facility (aOR, 1.64; 95% CI, 1.37-1.96), exposure to a third-generation cephalosporin (aOR, 1.79; 95% CI, 1.46-2.19), exposure to a carbapenem (aOR, 2.31; 95% CI, 1.68-3.18), or exposure to a trimethoprim-sulfamethoxazole (aOR, 1.54; 95% CI, 1.06-2.25) within the prior 6 months. Patients were at lower risk if their community had a prevalence <25th percentile in the prior 3 months (aOR, 0.83; 95% CI, 0.71-0.98), 6 months (aOR, 0.83; 95% CI, 0.71-0.98), or 12 months (aOR, 0.81; 95% CI, 0.68-0.95). There was no association between being in a community in the >75th percentile and the outcome. This method of defining the local prevalence of ESBL-E may partially capture differences in the likelihood of a patient having an ESBL-E.

Risk Factors, Temporal Dependence, and Seasonality of Human Extended-Spectrum β-Lactamases-Producing Escherichia coli and Klebsiella pneumoniae Colonization in Malawi: A Longitudinal Model-Based Approach.

Sub-Saharan Africa has the highest estimated death rate attributable to antimicrobial resistance, especially from extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E). However, the dynamics of human colonization in the community with ESBL-E are not well described. Inadequate water, sanitation, and hygiene infrastructure and associated behaviors are believed to play an important role in transmission of ESBL-E, and an improved understanding of the temporal dynamics of within-household transmission could help inform the design of future policies. In this 18-month study, using microbiological data and household surveys, we built a multivariable hierarchical harmonic logistic regression model to identify risk factors for colonization with ESBL-producing Escherichia coli and Klebsiella pneumoniae, reflecting household structure and temporal correlation of colonization status. Being male was associated with a lower risk of colonization with ESBL-producing E. coli (odds ratio [OR], 0.786; credible interval [CrI], .678-.910), whereas the use of a tube well or a borehole was associated with an increased risk (OR, 1.550; CrI, 1.003-2.394). For ESBL-producing K. pneumoniae, recent antibiotic exposure increased risk of colonization (OR, 1.281; CrI, 1.049-1.565), whereas sharing plates decreased that risk (OR, 0.672; CrI, .460-.980). Finally, the temporal correlation range of 8 to 11 weeks provided evidence that within-household transmission occurs within this time frame. We describe different risks for colonization with different enteric bacterial species. Our findings suggest interventions to reduce transmission targeted at the household level need to focus on improving water, sanitation, and hygiene infrastructure and associated behaviors, whereas at the community level, they should focus on both environmental hygiene and antibiotic stewardship.

Risk factors for predicting extended-spectrum β-lactamase-producing Enterobacterales (ESBLE) infections in non-urinary isolates.

With increases in antimicrobial resistance, it is crucial that patients receive appropriate antimicrobial therapy in a timely manner. Advancements in rapid diagnostics offer the ability to identify resistant organisms quickly. However, this technology is not always accessible and relies on correct specimen collection. While awaiting new microbiology methods, it may be beneficial to identify risk factors associated with common types of resistance. Specifically, extended-spectrum β-lactamase-producing Enterobacterales (ESBLE) are a rising threat globally. The primary objective of this retrospective case-control analysis was to identify factors associated with non-urinary ESBLE versus non-ESBLE infections. Patient cultures were randomly selected based on type of culture (blood, bacterial, or exudate) and organism (E. coli, K. pneumoniae, or K. oxytoca) to provide a 1:1 ratio of ESBLE to non-ESBLE infections. Baseline demographics and potential risk factors (malignancy, cirrhosis, acute kidney injury (AKI), and diabetes) were collected for each patient encounter. In the univariate analysis, risk factors that achieved a significant difference included cirrhosis, AKI, presence of urinary catheter, presence of center venous catheter, history of an ESBLE infection, hospital-acquired infection, and recent fluoroquinolone, cephalosporin, or beta-lactam use. The multivariate analysis showed that four factors were independently associated with an ESBLE infection: cirrhosis, urinary catheter, central venous catheter, and history of ESBLE. Having a history of an ESBLE had the highest adjusted odds ratio (aOR 12.49; 95% CI 4.71-33.15, P < .001) of the four factors. These results demonstrate that there may be benefit in incorporating select risk factors into clinical decision support tools to identify patients at highest risk of ESBLE infection.

2226. Analysis of Co-Resistance Among Klebsiella pneumoniae Urine Isolates From Female Outpatients in the United States

Abstract Background Over the past decade, extended spectrum β-lactamase producing Enterobacterales (ESBL) and multidrug resistance has risen among community-acquired uncomplicated urinary tract infections (uUTIs). This study was conducted to determine co-resistance among Klebsiella pneumoniae (K. pneumoniae) isolates in urine from female outpatients in the United States (US). Methods This was a retrospective, cross-sectional study of 30-day non-duplicate K. pneumoniae urine isolates from female outpatients (≥ 12 years of age) at 304 US facilities, with ≥ 3 months of data from 2011–2019 (Becton, Dickinson and Company [BD] Insights Research Database). K. pneumoniae isolates were defined as those that were ESBL-positive (ESBL+) (by commercial panel or not susceptible [NS] to ceftriaxone, cefotaxime, ceftazidime or cefepime), or NS if intermediate/resistant to any of the following: fluoroquinolones (FQs), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NFT). Co-resistance phenotypes were characterized in isolates NS to ≥ 2 of the 4 resistance phenotypes assessed. Results Among 250,719 non-duplicate K. pneumoniae isolates evaluated, 11,065 were ESBL+ (Table). Co-resistance among ESBL+ isolates was observed as follows: 54.9% to FQ; 65.7% to SXT; 75.5% to NFT; and 38.2% to all 4 resistance phenotypes. Of 10,962 isolates NS to FQ, co-resistance was observed as follows: 55.4% were ESBL+; 65.7% to SXT; 79.6% to NFT; and 38.6% to all 4 resistance phenotypes. Of 141,545 isolates NS to NFT, co-resistance was observed as follows: 5.9% were ESBL+; 6.2% to FQ; 11.8% to SXT; and 3.0% to all 4 resistance phenotypes. Among 23,887 isolates NS to SXT, co-resistance was observed as follows: 30.4% were ESBL+; 30.1% to FQ; 69.7% to NFT; and 17.7.% to all 4 resistance phenotypes. Table.Co-resistance phenotype combinations observed among Klebsiella pneumoniae isolates in urine from 2011–2019In total, 250,719 non-duplicate (30-day) Klebsiella pneumoniae isolates were evaluated.Note: Some isolates had overlapping susceptibilities/antimicrobial resistance types, hence individual phenotype totals do not reflect total number of isolates evaluated.Abbreviations: ESBL+, extended spectrum β-lactamase-producing or not susceptible to ceftriaxone, cefotaxime, ceftazidime or cefepime; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion The high prevalence of co-resistance in 30-day non-duplicate outpatient K. pneumoniae urinary isolates, particularly towards NFT (70–80% of isolates), limits the effective oral treatment options for uUTI. These analyses may help inform and optimize appropriate empiric treatment of female outpatients with uUTI in the US. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Janet Watts, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

2227. Prevalence, Regional Distribution, and Trends of Antimicrobial Resistance Among Female Outpatients With Urine Klebsiella pneumoniae Isolates: A Multicenter Evaluation

Abstract Background Infections caused by extended spectrum β-lactamase producing Enterobacterales (ESBLs), as well as antimicrobial resistance (AMR) and multi-drug resistance among uncomplicated urinary tract infections (uUTIs) in outpatients have risen in the past decade. The study objective was to determine the prevalence and geographic distribution of AMR among Klebsiella pneumoniae (K. pneumoniae) isolates in urine from female outpatients in the United States (US). Methods A retrospective, cross-sectional study of non-duplicate urine isolates from female outpatients (≥ 12 years of age) at 304 facilities, with ≥ 3 months of data, including initial isolates with distinct susceptibility patterns within 30 days of index urine samples, were used to assess regional AMR in 2019, and AMR trends from 2011 to 2019 (BD Insights Research Database, Franklin Lakes, NJ). K. pneumoniae isolates were identified as ESBL-positive (ESBL+) (confirmed by commercial panel or not susceptible [NS] to ceftriaxone, cefotaxime, ceftazidime, or cefepime), or NS if intermediate/resistant to any of the following: nitrofurantoin (NFT), trimethoprim/sulfamethoxazole (SXT), or fluoroquinolones (FQs). AMR prevalence and variation across US census regions was evaluated using logistic regression (with covariate adjustment) and generalized estimating equations. Results 44,056 non-duplicate K. pneumoniae isolates were evaluated in 2019 (Figure). For all microbiological phenotypes, there was significant variation in resistance for K. pneumoniae across all US census regions (p&amp;lt; 0.0001). Among 250,719 isolates evaluated from 2011 to 2019, AMR prevalence increased for all studied antimicrobials except for NFT NS (all p&amp;lt; 0.0041; Table). There was an increase in adjusted AMR rates by age groups with higher AMR rates for females ≥ 55 versus &amp;lt; 55, except for NFT, which showed the highest resistance in those aged &amp;lt; 55. Figure.Prevalence of antimicrobial resistance in Klebsiella pneumoniae isolates in 2019Abbreviations: ESBL+, extended spectrum β-lactamase-positive or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, fluoroquinolone; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole.Table.Klebsiella pneumoniae: model-estimated trends of relative average annual percentage change of antimicrobial resistance over time (2011 to 2019), by patient age, and by census region (N=250,719 isolates)All p values were p&amp;lt; 0.0001 apart from NFT trend over years, which was p=0.0041.*Relative average annual percentage change in resistance rate.Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; ESBL+, extended spectrum β-lactamase-positive or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion AMR prevalence in 2019 among non-duplicate K. pneumoniae isolates from urine in outpatients was notable. There were significant regional differences in resistance rates, which were higher in those aged ≥ 55 years, except for NFT. These analyses inform, and may be used to optimize, empiric treatment of uUTI. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Gang Ye, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

2050. Proportion of hospital-onset infections expressing antibiotic resistant (AR) phenotypes in US Hospitals, 2018 – 2020

Abstract Background Reports suggest the COVID-19 pandemic in 2020 was associated with increases in hospital-onset AR infections, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp., carbapenem-resistant Enterobacterales (E. coli, Klebsiella spp., and Enterobacter spp.) (CRE) and Acinetobacter spp. (CRAsp), extended-spectrum cephalosporin resistance suggestive of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), and multidrug-resistant Pseudomonas aeruginosa (MDR-PA). To evaluate whether trends were similar for susceptible and resistant strains, we estimated the proportions of these resistant phenotypes in U.S. hospitals. Figure 1.Proportion of hospital-onset pathogens expressing resistant phenotypes, 2018 – 2020 Methods We analyzed 2018–2020 hospital microbiology data in the Premier Healthcare and BD Insights Research Databases. Hospital-onset (HO) infections were those with positive cultures collected after hospital day 3. We used a raking procedure to produce weights to match national hospital characteristics, specifically: U.S. census division, bed size, teaching status, age, gender and urban/rural designation. We used a weighted means survey procedure for annual national estimates and generated annual comparisons with multivariable logistic regression adjusted by hospital characteristics. Results In 589 hospitals, the percentages of HO ESBL-E and CRAsp increased from 2019 to 2020 (Table). Among enterococci, the percentage with vancomycin resistance decreased. The percentages of MRSA, CRE, and MDR-PA did not change. Conclusion Our findings suggest pandemic-related factors, such as changes in antibiotic use or infection control, may have differentially affected susceptible and resistant phenotypes of hospital pathogens. Increases in the percentages of HO CRAsp and ESBL-E suggest these resistant phenotypes may have had a selective advantage over susceptible strains during the pandemic. In contrast, no changes in the percentages of HO MRSA or MDR-PA were observed, suggesting that infection rates increased similarly for resistant and susceptible strains. These findings underscore the importance of strategies to prevent hospital-associated infections and AR that are resilient to pandemic-related stresses on the healthcare system. Disclosures All Authors: No reported disclosures.

Systematic screening for digestive carriage of extended-spectrum β-lactamase-producing Enterobacterales (E-ESBL) at hospital readmission among patients with past history of E-ESBL colonization or infection

Extended-spectrum β-lactamase-producing Enterobacterales (E-ESBL) are commensal multidrug-resistant (MDR) bacteria of the digestive tract whose prevalence has risen sharply worldwide and in Europe over the past two decades. To assess digestive carriage at hospital readmission of a large cohort of 2509 patients with E-ESBL carriage over a five-year survey; 833 (33%) patients were readmitted at least once. A retrospective, single-centre survey conducted at a tertiary care hospital in France. Among patients with several hospital readmissions (range: 2-13), the proportion of patients still E-ESBL-colonized at hospital readmission, detected by systematic screening for E-ESBL colonization, was >80% within an 18-month period after prior hospitalization with the first E-ESBL isolation. There is a need to reconsider the continuation of systematic screening for E-ESBL colonization because of a high rate of patients still colonized at hospital readmission over a long period of time.

Impact of antibiotic intake on the incidence of extended-spectrum β-lactamase–producing Enterobacterales in sub-Saharan Africa: results from a community-based longitudinal study

ObjectivesThe global prevalence of intestinal extended-spectrum β-lactamase–producing Enterobacterales (ESBL-PE) is approximately 17% in communities, with significant variations among regions. This longitudinal study aimed to assess the impact of antibiotic intake on the incidence of intestinal ESBL-PE in Ghanaian pharmacy customers outside of hospitals. MethodsScreening for ESBL-PE was performed in four independent pharmacies in Kumasi, Ghana, using rectal swabs and an ESBL-PE–selective medium. Pharmacy customers purchasing antibiotics were recruited, and those buying non-antibiotic drugs served as controls. Participants who were negative for ESBL-PE provided follow-up swabs for up to 28 days. ResultsAt baseline, 302 (75%) of 404 participants were colonized with ESBL-PE. Sixty-three participants who were negative for ESBL-PE at baseline received per-protocol follow-up, including 28 individuals who took antibiotics and 35 controls. The cumulative proportions of ESBL-PE in the antibiotics and control groups were 71% (20/28) and 54% (19/35) at the first follow-up (p 0.258), 86% (24/28) and 80% (28/35) at the second follow-up (p 0.741) and 86% (24/28) and 94% (33/35) at the third follow-up (p 0.393), respectively. DiscussionThe rate of intestinal ESBL-PE carriage among pharmacy customers outside of hospitals was higher than expected at baseline and further increased during the 28 days of follow-up, irrespective of antibiotic intake. This alarming finding needs to be considered in the antibiotic treatment of outpatients and emphasizes the urgent need for improved prevention strategies, development of new antibiotic drugs and potential future elimination strategies. Further longitudinal studies on ESBL-PE in African communities, also outside of pharmacy settings, are required.

Multicenter evaluation of contamination of the healthcare environment near patients with Candida auris skin colonization

Background:Candida auris is an emerging multidrug-resistant yeast that is transmitted in healthcare facilities and is associated with substantial morbidity and mortality. Environmental contamination is suspected to play an important role in transmission but additional information is needed to inform environmental cleaning recommendations to prevent spread. Methods: We conducted a multiregional (Chicago, IL; Irvine, CA) prospective study of environmental contamination associated with C. auris colonization of patients and residents of 4 long-term care facilities and 1 acute-care hospital. Participants were identified by screening or clinical cultures. Samples were collected from participants’ body sites (eg, nares, axillae, inguinal creases, palms and fingertips, and perianal skin) and their environment before room cleaning. Daily room cleaning and disinfection by facility environmental service workers was followed by targeted cleaning of high-touch surfaces by research staff using hydrogen peroxide wipes (see EPA-approved product for C. auris, List P). Samples were collected immediately after cleaning from high-touch surfaces and repeated at 4-hour intervals up to 12 hours. A pilot phase (n = 12 patients) was conducted to identify the value of testing specific high-touch surfaces to assess environmental contamination. High-yield surfaces were included in the full evaluation phase (n = 20 patients) (Fig. 1). Samples were submitted for semiquantitative culture of C. auris and other multidrug-resistant organisms (MDROs) including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), extended-spectrum β-lactamase–producing Enterobacterales (ESBLs), and carbapenem-resistant Enterobacterales (CRE). Times to room surface contamination with C. auris and other MDROs after effective cleaning were analyzed. Results:Candida auris colonization was most frequently detected in the nares (72%) and palms and fingertips (72%). Cocolonization of body sites with other MDROs was common (Fig. 2). Surfaces located close to the patient were commonly recontaminated with C. auris by 4 hours after cleaning, including the overbed table (24%), bed handrail (24%), and TV remote or call button (19%). Environmental cocontamination was more common with resistant gram-positive organisms (MRSA and, VRE) than resistant gram-negative organisms (Fig. 3). C. auris was rarely detected on surfaces located outside a patient’s room (1 of 120 swabs; &lt;1%). Conclusions: Environmental surfaces near C. auris–colonized patients were rapidly recontaminated after cleaning and disinfection. Cocolonization of skin and environment with other MDROs was common, with resistant gram-positive organisms predominating over gram-negative organisms on environmental surfaces. Limitations include lack of organism sequencing or typing to confirm environmental contamination was from the room resident. Rapid recontamination of environmental surfaces after manual cleaning and disinfection suggests that alternate mitigation strategies should be evaluated.Funding: NoneDisclosures: None

Panorama of Bacterial Infections Caused by Epidemic Resistant Strains.

Antimicrobial resistance (AMR) represents a critical obstacle to public health worldwide, due to the high incidence of strains resistant to available antibiotic therapies. In recent years, there has been a significant increase in the prevalence of resistant epidemic strains, associated with this, public health authorities have been alarmed about a possible scenario of uncontrolled dissemination of these microorganisms and the difficulty in interrupting their transmission, as nosocomial pathogens with resistance profiles previously considered sporadic. They become frequent bacteria in the community. In addition, therapy for infections caused by these pathogens is based on broad-spectrum antibiotic therapy, which favors an increase in the tolerance of remaining bacterial cells and is commonly associated with a poor prognosis. In this review, we present the current status of epidemic strains of methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), MDR Mycobacterium tuberculosis, extended-spectrum β-lactamase-producing Enterobacterales (ESBL), Klebsiella pneumoniae carbapenemase (KPC), and—New Delhi Metallo-beta-lactamase-producing Pseudomonas aeruginosa (NDM).