Emergence and Spread of Enterobacterales with Multiple Carbapenemases after COVID-19 Pandemic.

Resistance to carbapenems in Enterobacterales has become a matter of the highest concern in the last decade. Recently, Enterobacterales harboring multiple carbapenemases were detected in three hospital centers in Croatia and in the outpatient setting, posing a serious therapeutic challenge for clinicians. In this study, we analyzed eight Klebsiella pneumoniae and two Enterobacter cloacae complex isolates with multiple carbapenemases, with regard to antibiotic susceptibility, ß-lactamase production and plasmid content. The isolates demonstrated uniform resistance to amoxicillin/clavulanate, piperacillin/tazobactam, cefuroxime, ceftazidime, cefotaxime, ceftriaxone and ertapenem. Among novel ß-lactam/inhibitor combinations, ceftazidime/avibactam exhibited moderate activity, with 50% of isolates susceptible. All isolates demonstrated resistance to imipenem/cilastatin/relebactam, and all but one to ceftolozane/tazobactam. Four isolates exhibited a multidrug-resistant phenotype (MDR), whereas six were allocated to an extensively drug-resistant phenotype (XDR). OKNV detected three combinations of carbapenemases: OXA-48+NDM (five isolates), OXA-48+VIM (three isolates) and OXA-48+KPC (two isolates). Inter-array testing identified a wide variety of resistance genes for ß-lactam antibiotics: blaCTX-M-15, blaTEM, blaSHV, blaOXA-1, blaOXA-2, blaOXA-9, aminoglycosides: aac6, aad, rmt, arm and aph, fluoroquinolones: qnrA, qnrB and qnrS, sulphonamides: sul1 and sul2 and trimethoprim: dfrA5, dfrA7, dfrA14, dfrA17 and dfrA19. mcr genes were reported for the first time in Croatia. This study demonstrated the ability of K. pneumoniae and E. cloacae to acquire various resistance determinants under the selection pressure of antibiotics widely used during the COVID-19 pandemic. The novel inter-array method showed good correlation with OKNV and PCR, although some discrepancies were found.

Trends in hospital acquired New Delhi metallo-beta-lactamase-producing Enterobacterales in Tuscany (Italy) from 2019 to 2021: impact of the COVID-19 pandemic.

OBJECTIVES: In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) in hospitalized patients has increasingly been observed since 2018, leading in 2019 to the implementation of enhanced control measures successfully reducing transmission. We describe the NDM-CRE epidemiology during the COVID-19 pandemic in Tuscany. METHODS: Data on NDM-CRE patients hospitalized in five Tuscan hospitals were collected from January 2019 to December 2021. Weekly rates of NDM-CRE cases on hospital days in medical and critical-care wards were calculated. In March-December 2020, NDM-CRE rates were stratified by COVID-19 diagnosis. Multi-variate regression analysis was performed to assess outcomes' differences among two periods analysed and between COVID-19 populations. RESULTS: Since March 2020, an increase in NDM-CRE cases was observed, associated with COVID-19 admissions. COVID-19 patients differed significantly from non-COVID-19 ones by several variables, including patient features (age, Charlson index) and clinical history and outcomes (NDM-CRE infection/colonization, intensive care unit stay, length of stay, mortality). During the pandemic, we observed a higher rate of NDM-CRE cases per hospital day in both non-COVID-19 patients (273/100,000) and COVID-19 patients (370/100,00) when compared with pre-pandemic period cases (187/100,00). CONCLUSIONS: Our data suggest a resurgence in NDM-CRE spread among hospitalized patients in Tuscany during the COVID-19 pandemic, as well as a change in patients' case-mix. The observed increase in hospital transmission of NDM-CRE could be related to changes in infection prevention and control procedures, aimed mainly at COVID-19 management, leading to new challenges in hospital preparedness and crisis management planning.

Placing Antimicrobial Resistance in the Context of Competing Public Health Priorities in Sub-Saharan Africa, a Perspective from Malawi

Antimicrobial resistance is a major threat to human health that is predicted to impact most heavily on sub-Saharan Africa, however there is a lack of clinical outcome data from drug-resistant infections in this setting. There are reasons to expect the COVID-19 pandemic to have both positive and negative impacts on AMR in Africa. We have recruited a series of prospective longitudinal cohorts from Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi and the surrounding communities in the Southern Region of Malawi. The data from these cohorts has been used to describe the aetiology of febrile illness, the burden of antimicrobial resistance in this setting and the distribution of extended spectrum beta-lactamase producing bacteria in humans, animals and the environment. Amongst a cohort of patients presenting to QECH unwell with febrile illness, 67% were living with human immunodeficiency virus (HIV). We identified a diagnosis in 145 of 225 (64%) participants, most commonly tuberculosis (TB;34%) followed by invasive bacterial infections (17%), arboviral infections (13%), and malaria (9%). In a second cohort with drug resistant infection, resistance to third-generation cephalosporins was associated with an increased probability of in-hospital mortality (hazard ratio [HR] 1.44, 95% CI 1.02-2.04), longer hospital stays (1.5 days, 1.0-2.0) and decreased probability of discharge alive (HR 0.31, 0.22-0.45). In the community cohorts, a paucity of environmental health infrastructure and materials for safe sanitation was identified across all sites and ESBL-Enterobacterales were isolated from 41.8% of human stool, 29.8% of animal stool and 66.2% of river water samples and was associated with the wet season, living in urban areas, advanced age and in household-animal interactions. Life threatening febrile illness is common in Blantyre however, diagnostics are few, however the COVID-19 pandemic has led to rapid expansion of diagnostic capacity. We are, however frequently treating the wrong bugs with ceftriaxone, further there was significant expansion of azithromycin demand and usage during the pandemic. Current management of sepsis has not been optimised and ceftriaxone use is promoting carriage of ESBL bacteria out of the hospital and ESBL E. coli and K. pneumoniae are ubiquitous in the community, where environmental hygiene infrastructure and community antimicrobial stewardship are critically lacking.Copyright © 2023

Epidemiology of multidrug-resistant organisms before and during COVID-19 in Hong Kong.

Background: The coronavirus disease 2019 (COVID-19) has influenced antimicrobial consumption and incidence of multidrug-resistant organisms (MDROs). We aimed to study the epidemiology of MDROs before and during the COVID-19 pandemic in Hong Kong. Methods: With the maintenance of infection control measures, we described the trend of MDRO infections, including methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter species (CRA), and extended-spectrum-beta-lactamase-(ESBL)-producing Enterobacterales, in a healthcare region with 3100-bed before (1 January 2016 to 31 December 2019, period 1) and during COVID-19 (1 January 2020 to 30 September 2022, period 2), together with the antimicrobial consumption using piecewise Poisson regression. The epidemiological characteristics of newly diagnosed COVID-19 patients with or without MDRO infections were analyzed. Results: Between period 1 and 2, we observed a significant increase in the trend of CRA infections (P<0.001), while there was no significant increase in the trend of MRSA (P=0.742) and ESBL-producing Enterobacterales (P=0.061) infections. Meanwhile, a significant increase in the trend of carbapenems (P<0.001), extended-spectrum beta-lactam-beta-lactamase inhibitor combinations (BLBI) (P=0.045), and fluoroquinolones (P=0.009) consumption was observed. The observed opportunity (23,540 ± 3703 vs 26,145 ± 2838, p=0.359) and compliance (81.6% ± 0.5% vs 80.1% ± 0.8%, P=0.209) of hand hygiene per year was maintained. In a multivariable model, older age, male sex, referral from residential care home for the elderly, presence of indwelling device, presence of endotracheal tube, and use of carbapenems, use of BLBI, use of proton pump inhibitors and history of hospitalization in the past 3 months were associated with higher risks of infections by MDROs among COVID-19 patients. Conclusion: Infection control measures may control the surge of MDROs despite an increasing trend of antimicrobial consumption.

Determining the impact of professional body recommendations on the screening of acquired carbapenemase-producing Enterobacterales in England.

Introduction: Acquired carbapenemase-producing Gram-negative bacteria are an increasing public health concern globally and have been mandatory to report in England since October 2020. However, in light of the COVID-19 (SARS-CoV-2) pandemic, the Royal College of Pathologists (RCPath) released new guidance "for reducing the need for screening of CRE (carbapenem-resistant Enterobacterales) […] in low-risk areas", without defining "low risk". Methods: To assess the impact of the RCPath recommendations on screening of carbapenemase-producing Enterobacterales (CPE), an online Select Survey was sent to all NHS acute hospitals in England. The initial survey distribution was between March and April 2021 and the survey was relaunched between November 2021 and March 2022. Results: In total, 54 hospitals completed the survey, representing 39.1% of 138 eligible Trusts. All hospitals had a CPE screening policy in place, and the majority of these reflect UKHSA's Framework of actions to contain CPE. Of the 23 hospitals who reported a reduction in CPE screening, only three (13.0%) indicated that this was due to the RCPath recommendations, with 21 (91.3%) indicating that there had been a natural reduction in the number of patients admitted to the Trust who would have previously been screened due to the COVID-19 pandemic. Conclusion: For most surveyed hospitals, CPE screening was not reduced due to the RCPath recommendations. However, the results highlighted that there is a large amount of individual variation in CPE screening practices and diagnostic testing between hospitals.

Advances in molecular diagnostic tests for community-acquired pneumonia

The use of a timely and appropriate antibiotic therapy, which requires early and accurate microorganisms' detection in pneumonia. Currently, the identification of microorganisms in pneumonia is limited by the low sensitivity and long response time of standard culture-based diagnostic tools. For this reason, treatment in pneumonia is empirical. An inadequate empirical treatment is related to poor outcomes in patients with pneumonia. The microbiological diagnosis is key to improve the outcomes in patient with pneumonia. Over the past years there was a significant advance in the molecular diagnosis of infectious diseases including pneumonia. Also the impact of the COVID-19 pandemic has impacted the development and application of these new molecular techniques. This review summarizes the advances in molecular diagnosis of community-acquired pneumonia.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Things that dropped off during COVID

Introduction: The COVID-19 pandemic placed a renewed focus on transmission of respiratory infections in healthcare settings. However, little is known about the direct and indirect impacts on surveillance and infection prevention and control activities to limit transmission of other communicable diseases such as multidrug-resistant organisms (MDROs). Method(s): We conducted retrospective cross-sectional audits of compliance with routine screening and cleaning practices for MDROs (including vancomycin-resistant enterococci [VRE] and extended-spectrum beta-lactamase-[ESBL]-producing and carbapenemase-producing [CPE] Enterobacterales) in a tertiary hospital, where patients admitted to high-risk wards are screened upon admission and weekly. We correlated this with observed transmission events and an organisation-wide point-prevalence survey for MDRO colonisation. Result(s): Compliance with routine MDRO screening practices was lower than pre-pandemic. Additionally, interventions to limit environmental contamination with CPE had been neglected during the pandemic. This corresponded with an increase in CPE transmission. Audits of clinical staff infection prevention and control practices found missed opportunities to screen and identify colonised patients, as well as curtailed control measures during the pandemic, both correlating with MDRO transmission. Conclusion(s): Ongoing engagement of staff and senior decision makers in healthcare facilities is critical to maintaining infection control standards. At our institution, we found a lapse in standards during the COVID-19 pandemic was associated with an increase in MDRO transmission.Copyright © 2022

Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel ß-Lactam-Metallo-ß-Lactamase Inhibitors.

Virulent Enterobacterale strains expressing serine and metallo-ß-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop ß-lactamase inhibitors to counter this resistance. Currently, serine ß-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-ß-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived ß-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-ß-lactamase (NDM-1) and Verona Integron-encoded Metallo-ß-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 µM, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).

Evaluation and analysis of rates of bacterial co-infections and antimicrobial usage in COVID-19 patients: a retrospective cohort analysis

Background: The coronavirus disease 2019 (COVID- 19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread over the world. Although there are minimal microbiological and antibiotic data on COVID-19, bacterial co-infections have been related to poor outcomes in respiratory viralinfections. Adequate antibiotic use in conformity withantibiotic stewardship (ABS) recommendations is necessary during the pandemic. Material and procedure: We conducted a retrospective single-center cohort analysis of 140 adulthospitalised patients (ages 17-99) with confirmed COVID-19 who were admitted between February 16, 2021, and April 22, 2021, and who were discharged onMay 6, 2021. From 140 COVID-19 participants, the following clinical data was gathered: Men made up 63.5 percent of the participants, with a median age of 63.5 years (range 17-99). Results: According to local ABS recommendations, the most commonly administered antibiotic regimen was ampicillin/sulbactam (41.5 percent) with a median length of 6 (range 1-13) days. Urine antigen testing for Legionella pneumophila and Streptococcus peumoniaewas negative in all of the patients. In critically ill patients hospitalised to intensive care units (n = 50), co-infections with Enterobacterales (34.0%) and Aspergillus fumigatus (18.0%) were discovered. Blood cultures obtained at admission had a diagnostic yield of 4.2 percent. Conclusion: While bacterial and fungal co-infections are rare in COVID-19 patients, they are widespread in critically ill individuals. More investigation into the impact of antimicrobial therapy on therapeutic success in COVID-19 patients is essential to prevent antibiotic abuse. COVID-19 management might be improved with the aid of ABS standards. It's also necessary to look at the microbiological patterns of infectious consequences in COVID-19 individuals who are severely unwell.

Impact of COVID 19 on bacterial respiratory isolates (2018-2021) from a UK tertiary cardio-thoracic ICU

Aim: To study the impact of COVID-19 admissions during 1st and 2nd surges on bacteriology of ICU respiratory isolates. Method(s): Retrospective time trend analysis of bacterial respiratory isolates from a single centre, tertiary cardiothoracic ICU (CT-ICU) from patients admitted from Jan 2018- June 2021. We compared pre-COVID-19 (January 2018- March 2020) and COVID-19 periods (April 2020- June 2021) and surge periods (surge 1: March 2020- June 2020, surge 2: January- March 2021) to similar time frames in previous years. Chi-square test used to compare proportions. Result(s): 4974 respiratory isolates (Sputum-4230, BAL-563, ET secretions-181) included. During surge 2, culture positivity and gram-negative rates tripled from baseline (20% to 75%;p<0.05). Comparing the pre- pandemic to pandemic period, rates of Klebsiella sp, Acinetobacter sp and Stenotrophomonas sp increased from 12% to 21.3%, 2.4% to 6.2% and 10.5% to 14.3% respectively, while Pseudomonas sp dropped from 30.7% to 23.1% (all p<0.05). MDR Pseudomonas increased significantly from 38.9% to 47.9% (p<0.05), with a non-significant increase in MRSA (5.2% to 9.3%;p=0.34) and MDR enterobacterales (22.6% to 23%;p=0.48). Conclusion(s): This is the first report from a UK CTICU showing a marked epidemiological shift in the bacteriology of respiratory isolates in terms of organism profile, increase in culture positivity and MDR Pseudomonas rates during the pandemic. Analyzing trends on longevity of the findings will help guide changes to infection control and antibiotic policies. This emphasizes the importance of unit specific ecology in choosing appropriate timely antimicrobial therapy and therefore improving patient outcome.

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

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

Emergence of Hyper-Epidemic Clones of Enterobacterales Clinical Isolates Co-Producing KPC and Metallo-Beta-Lactamases during the COVID-19 Pandemic.

BACKGROUND: The global spread of carbapenemase-producing Enterobacterales has become an epidemiological risk for healthcare systems by limiting available antimicrobial treatments. The COVID-19 pandemic worsened this scenario, prompting the emergence of extremely resistant microorganisms. METHODS: Between March 2020 and September 2021, the NRL confirmed 82 clinical Enterobacterales isolates harboring a combination of blaKPC and MBL genes. Molecular typing was analyzed by PFGE and MLST. Modified double-disk synergy (MDDS) tests were used for phenotypic studies. RESULTS: Isolates were submitted from 28 hospitals located in seven provinces and Buenos Aires City, including 77 K. pneumoniae, 2 K. oxytoca, 2 C. freundii, and 1 E. coli. Almost half of K. pneumoniae isolates (n = 38; 49.4%), detected in 15 hospitals, belong to the CC307 clone. CC11 was the second clone, including 29 (37.7%) isolates (22, ST11 and 7, ST258) from five cities and 12 hospitals. Three isolates belonging to CC45 were also detected. The carbapenemase combinations observed were as follows: 55% blaKPC-2 plus blaNDM-5; 32.5% blaKPC-2 plus blaNDM-1; 5% blaKPC-3 plus blaNDM-1; 5% blaKPC-2 plus blaIMP-8; and 2.5% strain with blaKPC-2 plus blaNDM-5 plus blaOXA-163. Aztreonam/avibactam and aztreonam/relebactam were the most active combinations (100% and 91% susceptible, respectively), followed by fosfomycin (89%) and tigecycline (84%). CONCLUSIONS: The MDDS tests using ceftazidime-avibactam/EDTA and aztreonam/boronic acid disks improved phenotypic classification as dual producers. The successful high-risk clones of K. pneumoniae, such as hyper-epidemic CC307 and CC11 clones, drove the dissemination of double carbapenemase-producing isolates during the COVID-19 pandemic.

NDM-producing Enterobacterales prevalence associated to COVID-19 in a tertiary hospital.

Colonizations/Infections caused by carbapenem-resistant Enterobacterales are of great clinical and epidemiological importance due to their rapid dissemination and high mortality rates. In this scenario, the use of antibiotics intensified by the COVID-19 pandemic has brought about a great warning on the real impact that this pandemic could have on antimicrobial management programs and long-term antimicrobial resistance rates. The objective of this study was to evaluate the increase of New Delhi Metallo ß-Lactamase (NDM)-producing Enterobacterales cases in COVID-19 units of a complex Brazilian tertiary hospital. This retrospective observational study included all patients admitted to the hospital identified as colonized or infected by NDM-producing Gram negative bacilli (GNB), from January 2017 to April 2021. Forty-two NDM-producing Enterobacterales were identified in 39 patients. The rate of NDM cases per total surveillance cultures increased progressively between 2017 and 2021 (chi-2 for trend, p < 0.0001) and was associated with a higher occurrence specifically in COVID units (Fisher exact, p < 0.0001). The molecular investigation of the NDM-producing Klebsiella pneumoniae strains revealed the emergence of diverse clones during the COVID-19 period, also with possible evidence of horizontal transmission among patients within COVID units. NDM-producing Enterobacterales with multiple and different clonalities in the COVID-19 units also raised questions about the importance of other factors besides horizontal clonal transfer, including the increase of antimicrobial consumption by these patients.

The Clash of the Titans: COVID-19, Carbapenem-Resistant Enterobacterales, and First mcr-1-Mediated Colistin Resistance in Humans in Romania.

(1) Background: Antibiotic resistance and coronavirus disease-19 (COVID-19) represent a dual challenge in daily clinical practice, inducing a high burden on public health systems. Hence, we aimed to dynamically evaluate the impact of COVID-19 on patients with carbapenem-resistant Enterobacterales (CRE) urinary tract infections (UTIs), as well as the antibiotic resistance trends after the onset of the pandemic. (2) Methods: We conducted a prospective study including patients with CRE UTIs who were enrolled both pre- and during the pandemic from 2019 to 2022. We further performed a standardized and comparative clinical, paraclinical, and microbiological assessment between patients with and without COVID-19. (3) Results: A total of 87 patients with CRE UTIs were included in this study (46 pre-pandemic and 41 during the pandemic, of which 21 had associated Severe Acute Respiratory Syndrome Coronavirus-2 infection). Klebsiella pneumoniae was the main etiological agent of the UTIs, with the majority of strains (82.7%) being carbapenemase producers (mainly OXA-48 producers), while five of the 34 colistin-resistant isolates were harboring the mobile colistin resistance-1 (mcr-1) gene. COVID-19 patients presented a significantly worse outcome with higher rates of intensive care unit (ICU) admissions (66.7% for COVID patients vs. 18.2% for non-COVID patients, p < 0.001), while the fatality rates were also considerably higher among patients with concomitant viral infection (33.3% vs. 12.1%, p < 0.001). Besides COVID-19, additional risk factors associated with increased mortality were urinary catheterization, sepsis with K. pneumoniae, impaired liver and kidney function, and an inappropriate initial empiric antibiotic therapy. (4) Conclusions: COVID-19 showed a pronounced negative impact on patients with CRE UTIs, with significantly longer hospitalizations and higher ICU admissions and mortality rates.

Trends in the Incidence of Carbapenem-Resistant Enterobacterales (CRE) and Carbapenemase Producing CRE (CP-CRE) in Davidson and Surrounding Counties, Tennessee, 2016-2021

Background. The spread of Carbapenem-resistant Enterobacterales (CRE) continue to be a public health threat. Tennessee has participated in the Multidrug-Resistant Gram-Negative Bacilli Surveillance Initiative (MuGSI) since 2014. We investigated our data to describe the trends of CRE and CP-CRE and their changes during the COVID-19 outbreak. Methods. Population-based surveillance targeting selected CRE organisms was conducted in Davidson County and seven surrounding counties in Tennessee. A CRE case was defined as isolation of Escherichia coli, Klebsiella spp., or Enterobacter spp. resistant to >=1 carbapenem from a normally sterile body site or urine, in a surveillance area resident. A case was identified as incident if it was reported for the first time in the surveillance year or was a subsequent report of a case >=30 days after the last report. The Tennessee state public health laboratory tests for carbapenemase production on CRE isolates received from clinical laboratories. The data analysis was conducted using SAS software version 9.4. Results. 474 incident CRE cases were reported from 2016 to 2021. Females made up 68.63% and the average age was 65 years for both sexes. The incidence rate of CRE cases increased throughout study period and the rate in 2021 was 1.8-fold of 2016 (lowest rate for the study period) (P-value< 0.001). The incidence rate of CP-CRE increased in 2017 and 2018 compared to 2016 (p-value=0.01). The incidence rate for CP-CRE declined to the lowest level in 2020 (0.3 per 100,000 population). In 2021, the CP-CRE rate significantly increased compared to 2020 (p-value=0.02). The carbapenemase production (CP) positivity rate was also significantly higher in 2017(28.8%), 2018 (26.6%), and 2021 (25.8%) compared to the year 2020 where the positivity rate was the lowest (10.0%) (P-value< 0.05). Conclusion. The transmission of CP-CRE cases decreased during the years prior to the COVID-19 outbreak despite the steady increase in CRE cases. The transmission of CP-CRE gained momentum during the COVID outbreak as evidenced by an increased infection rate and CP positivity rate in 2021. Renewed focus on implementing coordinated infection prevention strategies is likely to contribute to reducing the spread of antimicrobial-resistant pathogens. (Figure Presented).

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

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 beta-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. 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. (Figure Presented).

Healthcare-Associated Infection Surveillance During the COVID-19 Pandemic in New Mexico

Background. The COVID-19 pandemic changed accessibility of care and practices within healthcare environments. This period has been associated with healthcare-associated infection outbreaks and shifts in healthcare-associated infectious disease epidemiology. This study's objective is to describe changes in rates and characteristics of antimicrobial-resistant gram negative and Clostridioides difficile (CD) infections during the COVID-19 pandemic in Bernalillo County, New Mexico. Methods. The NM EIP, a collaboration between University of New Mexico and theNMDOH, conducts ongoing laboratory- and population-based surveillance of infectious disease including Clostridium difficile, extended-spectrum beta lactamase (ESBL-E) and carbapenemase-producing gram negative bacteria (CRE). Stata statistical software was used for retrospective analysis of rates and characteristics on NM EIP data from Bernalillo county, NM between 2016 and 2021. Results. Reported C. difficile rates decreased from 76 to 49 cases/month and ESBL-producing Enterobacterales decreased from 145 to 86 cases/month during the pandemic period from March-December 2020 compared with the prior 14 months. Monthly case counts for 2020 are lowest during initial public health orders for the state of New Mexico. Rates of CRE remained constant between 2018-2021. The proportion of CDI cases originating from long-term care facilities decreased significantly from 17.2% to 10.4% (p=0.006) while the proportion attributable to hospital inpatient and community populations remained constant. The proportion of ESBL-E cases from sterile sample sites increased from 3.1% to 4.9% (p=0.05) and the proportion of patients who died within 30 days or prior to discharge increased from 2.2% to 3.2% (p=0.019). Conclusion. Rates and characteristics of CD and ESBL-E infections in Bernalillo countyNMchanged significantly during the COVID-19 pandemic, while rates of CRE remained constant. It is still unclear whether this is related to changes in actual disease rates due to risk factor exposure (healthcare), or if this trend reflects changes in careseeking behavior and/or reporting of cases. (Figure Presented).

On-going impact of the SARS-CoV-2 pandemic on the evolution of carbapenemase-producing Enterobacterales in Ontario, Canada

Background. The spread of carbapenemase-producing Enterobacterales (CPE) is global threat. Numerous outbreaks of CPE have been reported during the COVID-19 pandemic. We describe the impact of of the SARS-CoV-2 pandemic on the emergence of CPE in south-central Ontario, Canada. Incidence of clinical isolates of CPE and isolates with different CPE genes in Toronto/Peel region, 2017-2021. The upper panel shows the incidence of patients with clinical isolates of CPE by year and quarter from q4 2007 to q1 2022. The lower panel shows the incidence of patients with clinical isolates with different carbapenemase genes by fiscal year during the same period. Methods. TIBDN has performed population-based surveillance for CPE in Toronto/Peel region (pop 4.5M) from first identified isolate in 2007. All laboratories test/refer all carbapenem non-susceptible Enterobacterial isolates for identification of CPE. Hospital charts are reviewed and patients/physicians interviewed. Population data are obtained from Statistics Canada. Results. From 10/2007 to 3/31/2022, 1367 persons colonized or infected with CPE were identified. Theirmedian age was 68.7yrs (IQR 54-78yrs);761 (56%) weremale. 772 (56%) were colonized when first identified;115 (8.4%) were bacteremic at identification or subsequently developed bacteremia. The most common organisms were E. coli (651, 48%), K. pneumoniae (436, 32%), Enterobacter spp. (146, 11%), Citrobacter spp (62, 5%);the most common genes were NDM+/-OXA-48 (722, 53%), OXA-48-like (341, 25%), KPC (225, 16%), VIM(44, 3%). The incidence of CPE infections increased steadily until 3/2020 then declined by 61%and remained stable until 3/2022 (Figure, upper panel). The declinewas greater for E. coli (56%decrease), K. pneumoniae (62%) than for Enterobacter spp. (30%) and other species (19%). It occurred in all genes in 2020;however, KPC containing organisms increased again in 2021 (Figure, lower panel). Conclusion. The advent of the COVID-19 pandemic was associated with an immediate, substantial decline in the incidence of patients with CPE in our population area. This decline occurred in both isolates with genes usually occurring in cases imported from other countries, and in those usually occurring in cases associated with transmission within Canadian hospitals. Decreased travel and enhanced infection prevention and control in hospitals may both have contributed to reductions in CPE during the pandemic. (Figure Presented).

Last resort beta-lactam antibiotics for treatment of New-Delhi Metallo-Beta-Lactamase producing Enterobacterales and other Difficult-to-Treat Resistance in Gram-negative bacteria: A real-life study.

Introduction: Novel last resort beta-lactam antibiotics are now available for management of infections due to New-Delhi Metallo-Beta-Lactamase (NDM) producing Enterobacterales and non-fermenters with Difficult-to-Treat Resistance. However, data regarding the use of imipenem-cilastatin-relebactam (IMI-REL), cefiderocol (CFD) and ceftazidime-avibactam plus aztreonam (CAZ-AVI-ATM) are scarce in real-life settings. This study aimed to describe the use of last resort beta-lactam antibiotics, the microbiology and the outcome, in patients hospitalized in a tertiary hospital. Methods: We conducted a monocentric observational cohort study from 2020/01/01, to 2022/08/31. We screened all patients admitted to Nimes University Hospital who have received ≥ 1 dose of last resort beta-lactam antibiotics during the study period, using the Pharmacy database. We included patients treated with IMI-REL, CFD and CAZ-AVI-ATM. The primary endpoint was the infection-free survival rate. We also calculated rates of microbiological and clinical cure, recurrent infection, death and adverse events. Results: Twenty-seven patients were included in the study and 30 treatment courses were analyzed: CFD (N=24; 80%), CAZ-AVI-ATM (N=3; 10%) and IMI-REL (N=3; 10%). Antibiotics were used in 21 males (70%) and 9 females (30%) with a median age at 65-year-old [50-73.5] and a median Charlson index at 1 [0-2]. Almost all the patients had ≥ 1 risk factor for carbapenem resistant bacteria, a half of them was hospitalized for severe COVID-19, and most of antibiotic courses (N=26; 87%) were associated with ICU admission. In the study population, the probability of infection-free survival at day-90 after last resort beta-lactam therapy initiation was 48.4% CI95% [33.2-70.5]. Clinical failure rate was at 30%, microbiological failure rate at 33% and mortality rate at 23%. Adverse events were documented in 5 antibiotic courses (17%). In details, P. aeruginosa were mainly treated with CFD and IMI-REL, S. maltophilia with CFD and CAZ-AVI-ATM, A. baumannii with CFD, and NDM producing-K. pneumoniae with CAZ-AVI-ATM and CFD. After a treatment course with CFD, CAZ-AVI-ATM and IMI-REL, the probability of infection-free survival was 48% CI95% [10.4-73.5], 33.3% CI95% [6.7-100], 66.7% CI95% [30-100], respectively. Discussion/conclusion: Use of last resort beta-lactam antimicrobials in real-life settings was a safe and efficient therapeutic option for severe infections related to Gram-negative bacteria with Difficult-to-Treat Resistance.