Carbapenem-resistant Enterobacteriaceae Research Articles

In vitro evaluation of using ceftazidime/avibactam against carbapenem-resistant Acinetobacter baumannii

ObjectiveCarbapenem-resistant Acinetobacter baumannii (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant Enterobacterales, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB. MethodA clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC = 32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0–64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fibre infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined. ResultsAn AVI concentration-dependent reduction in CAZ MIC was observed (r2 = 0.99). CAZ MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI = 4 mg/L), and further to 8 mg/L (AVI = 16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r2 > 0.96). Bacterial suppression was observed >24 hours with the serum exposure, but not that from the ELF. ConclusionUsing multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.

Sunlight-Driven Photothermally Boosted Photocatalytic Eradication of Superbugs Using a Plasmonic Gold Nanoparticle-Decorated WO3 Nanowire-Based Heterojunction.

Superbug infections are currently one of the biggest global health problems in our society. Herein, we report the design of a plasmonic gold nanoparticle (GNP)-decorated WO3 nanowire-based heterojunction for the proficient usage of sunlight-based renewable energy to inactivate 100% superbugs via photothermally boosted photocatalytic action. Additionally, a synergistic photothermal and photocatalytic approach has been used for sunlight-driven complete eradication of carbapenem-resistant Enterobacteriaceae Escherichia coli (CRE E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) superbugs. Interestingly, photocatalytic activity of methylene blue (MB) dye degradation in the presence of 670 nm near-infrared light shows that photothermally boosted photocatalytic performance is much superior to that of only a photocatalytic or photothermal process. The observed higher photocatalytic performance for the heterojunction is because the plasmonic GNP enhanced the absorption capability at 670 nm and increased the temperature of the photocatalyst surface, which reduces the activation energy of the degradation reaction. Similarly, sunlight-driven photocatalytic experiments show 100% degradation of MB after 60 min of sunlight irradiation. Moreover, sunlight-based photocatalytic inactivation of MRSA and CRE E. coli experiments show 100% inactivation after 60 min of light irradiation.

Prevalence of carbapenem-resistant Enterobacterales with bla IMP-6 predominance in hospitals from 2018 to 2021 in Nara, Japan.

Despite the global health risk of carbapenem-resistant Enterobacterales (CRE), especially carbapenemase-producing Enterobacterales (CPE), Japan reports a significantly low frequency of CRE with a predominance of IMP-type carbapenemases. This study aimed to investigate the prevalence and characteristics of CRE isolated from hospitals in the city of Nara, Japan. We obtained 171 CRE isolates from 16 791 Enterobacterales isolated at 23 hospitals in Nara between January 2018 and December 2021. Isolates of CPE were characterized through antimicrobial susceptibility testing, the carbapenem inactivation method, PCR and DNA sequencing. Genotypic diversity of carbapenemase-producing Escherichia coli and Klebsiella pneumoniae was determined via MLST and PFGE. The prevalence of CRE between 2018 and 2021 was 1.02%, gradually decreasing from 1.13% to 0.74%. Ninety-nine isolates were identified as CPE, representing six species. Ninety-seven CPE isolates harboured bla IMP-6, while the remaining two carried either bla IMP-1 or bla IMP-19. Genotype analysis identified ST131 as the dominant genotype for E. coli, but none for K. pneumoniae. PFGE results suggested clonal spread of CPE in Hospital A, where CRE was isolated in high numbers (n = 44). In this study, CRE prevalence was marginally higher than previously reported in Japan, but still low in frequency. A predominance of Enterobacterales harbouring bla IMP-6 was confirmed in Nara. The spread of CPE at Hospital A suggested the possibility of a nosocomial outbreak due to bla IMP-6 transmission via plasmids or clonal spread. Continued monitoring is crucial for effective management of CRE prevalence in the region.

Risk factors and molecular epidemiology of intestinal colonization by carbapenem-resistant Gram-negative bacteria in patients with hematological diseases: a multicenter case‒control study.

Patients with hematological diseases are considered to be at high risk for intestinal colonization by carbapenem-resistant Gram-negative bacteria (CR-GNB). However, the epidemiological data regarding risk factors and molecular characteristics of intestinal colonized CR-GNB isolates in this population are insufficient in China. A multicenter case‒control study involving 4,641 adult patients with hematological diseases from 92 hospitals across China was conducted. Following culture of collected rectal swabs, mass spectrometry and antimicrobial susceptibility tests were performed to identify GNB species and CR phenotype. Risk factors were assessed through retrospective clinical information. Whole-genome sequencing was used to analyze the molecular characteristics of CR-GNB isolates. This trial is registered with ClinicalTrials.gov as NCT05002582. Our results demonstrated that among 4,641 adult patients, 10.8% had intestinal colonization by CR-GNB. Of these, 8.1% were colonized by carbapenem-resistant Enterobacterales (CRE), 2.6% were colonized by carbapenem-resistant Pseudomonas aeruginosa (CRPA), and 0.3% were colonized by carbapenem-resistant Acinetobacter baumannii (CRAB). The risk factors for CR-GNB colonization include male gender, acute leukemia, hematopoietic stem cell transplantation, β-lactam antibiotic usage, and the presence of non-perianal infections within 1 week. Compared with CRPA-colonized patients, patients using carbapenems were more likely to be colonized with CRE. NDM was the predominant carbapenemase in colonized CRE. This study revealed a high CR-GNB intestinal colonization rate among adult patients with hematological diseases in China, with CRE being the predominant one. Notably, a significant proportion of CRE exhibited metallo-β-lactamase production, indicating a concerning trend. These findings emphasize the importance of active screening for CR-GNB colonization in patients with hematological diseases.IMPORTANCECarbapenem-resistant Gram-negative bacteria (CR-GNB) has emerged as a significant threat to public health. Patients with hematological diseases are at high risk of CR-GNB infections due to their immunosuppressed state. CR-GNB colonization is an independent risk factor for subsequent infection. Understanding the risk factors and molecular characteristics of CR-GNB associated with intestinal colonization in patients with hematological diseases is crucial for empirical treatment, particularly in patients with febrile neutropenia. However, the epidemiology data are still insufficient, and our study aims to determine the intestinal colonization rate of CR-GNB, identify colonization risk factors, and analyze the molecular characteristics of colonized CR-GNB isolates.

Efficacy of ceftazidime/avibactam and plazomicin on carbapenem-resistant Klebsiella pneumoniae and Escherichia coli.

Carbapenem-resistant Enterobacterales (CRE) have become a major public health problem worldwide. The aim of this study was to investigate efficacy of ceftazidime/avibactam and plazomicin on carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates. Susceptibility of imipenem, meropenem, ertapenem, ceftazidime/avibactam and plazomicin was investigated by broth-microdilution method. Major carbapenemases NDM, VIM, IMP, KPC, OXA-48 as well as other β-lactamases namely, TEM, SHV, OXA-1-like, CTX-M, ACC, FOX, MOX, DHA, CIT, EBC, VEB, GES, PER were investigated by PCR. A total of 120 carbapenem-resistant isolates (60 E. coli and 60 K. pneumoniae) were included in this study and blaOXA-48-like was found in 78.33%, blaNDM in 26.66%, blaKPC in 7.5%, blaIMP in 5.83%, and blaVIM in 5%. Among 94 isolates with the blaOXA-48-like gene, 22.3% were resistant to ceftazidime/avibactam and 51.1% were resistant to plazomicin. Of 32 isolates with blaNDM, 31 (96.9%) were resistant to ceftazidime/avibactam and 30 (93.75%) were resistant to plazomicin, and both antibiotics had limited effects against blaNDM carriers (P < 0.001). Of the 12 isolates with blaNDM+OXA-48 combination, 11 (91.7%) were resistant to ceftazidime/avibactam and plazomicin. The effect of both antibiotics was significantly lower in strains with blaNDM+OXA-48 combination (P < 0.005).The most common carbapenemase genes in this study were blaOXA-48-like and blaNDM. Ceftazidime/avibactam demonstrated a good efficacy among OXA-48 producing K. pneumoniae and E. coli, however, plazomicin had a significantly lower antibacterial effect in our study. Both antimicrobial agents should be considered as an option by evaluating combined susceptibility results and gene patterns obtained by regional and global molecular data in the treatment of CRE infections.

Rectal screening for carbapenemase-producing Enterobacteriaceae in an intensive care unit in India

Rectal screening for carbapenemase-producing Enterobacteriaceae in an intensive care unit in India

Application of a Model Using Prior Healthcare Information to Predict Multidrug-Resistant Organism (MDRO) Carriage

Background: Early identification of patients colonized with MDROs can help healthcare facilities improve infection control and treatment. We evaluated whether a model previously validated to predict carbapenem-resistant Enterobacterales (CRE) carriage on hospital admission (area under the curve [AUC]=0.86, Lin et al. OFID 2019) would generalize to predict a patient’s likelihood of CRE and non-CRE MDRO colonization at the time of medical intensive care unit (MICU) admission. Methods: We analyzed data collected previously in a retrospective observational cohort study of patients admitted to Rush University Medical Center’s MICU from 1/2017-1/2018 and screened within the first two days for rectal MDRO colonization. Organisms of interest included CRE, carbapenem-resistant Pseudomonas aeruginosa (CRPA), vancomycin-resistant enterococci (VRE), and third-generation cephalosporin-resistant Enterobacterales (3GCR-E). Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization at admission was determined by routine clinical screening. Each patient’s first MICU admission during the study period was linked to Illinois’ hospital discharge database and assigned a CRE colonization risk probability using the existing model. Model covariates were age, and during the prior 365 days, number of short-term acute care hospitalizations (STACH) and mean STACH length of stay, number of long-term acute care hospitalizations (LTACH) and mean LTACH length of stay, prior hospital admission with an ICD-10 diagnosis code indicating bacterial infection, and current admission to LTACH. Predictive value of the model was evaluated by receiver operating characteristic (ROC) curves. Results: We analyzed 1237 MICU admissions. MDRO admission prevalence is shown in the Table. The model performed well to predict carriage of healthcare-associated MDROs, including CRE, CRPA, composite CR-MDROs (CRE &amp; CRPA), and VRE. However, the model performed poorly for MDROs with known community reservoirs, including 3GCR-E and MRSA (Table). In general, MDRO admission prevalence increased in parallel with predicted CRE colonization risk (Figure). The number needed to screen (NNS) to detect one healthcare-associated MDRO carrier was inversely related to the CRE colonization risk score. For example, NNS in the total cohort compared to those with CRE risk score of &gt;0.5% was: CRE 111 vs 32 patients, CRPA 333 vs 42 patients, composite CR-MDRO 83 vs 18 patients, and VRE 12 vs 4 patients. However, higher CRE risk score cutoff was inversely related to screening sensitivity. Conclusion: A prediction model using prior healthcare exposure information successfully discriminated patients likely to harbor healthcare-associated MDROs upon MICU admission. Prediction scores generated by a public-health accessible database could be used to target screening/isolation or enact protective measures for high-risk patients.

Carbapenemase-Producing Enterobacteriaceae detected in a Large Canadian Tertiary Care Hospital: Five-year retrospective study

Background: The prevalence of carbapenemase-producing Enterobacteriaceae (CPE) is increasing worldwide. In Canada, where rates of healthcare-associated (HA) transmission of CPE remains relatively low, there is a need to share early experience of universal screening programs and risk factors for HA acquisition. Method: In 2018, universal screening was introduced throughout our large Canadian tertiary care hospital across, all critical care and oncology units. Additionally, risk-factor based screening was applied in all other inpatient units, with further targeted screening of roommate exposures or all inpatients on unit following identification of a single HA case. A retrospective cohort study was carried out on CPE cases detected between January 2018 and December 2023. We assessed the proportion of HA CPE cases, defined as CPE identified in patients with prior admission to our facility or after &gt;72 hours after admission. HA cases were examined for relevant risk factors, including known roommate with CPE, the presence of other CPE on the unit, exposure to outbreak units, prior travel history, travel by a family member, and antibiotic exposure within the past 90 days. Result: A total of 150 CPE cases were identified, with 66 (44%) classified as HA. Among these HA cases, 14 (21%) were associated with presence of known case on the unit. The remaining 52 (79%) represented sporadic nosocomial cases without a known exposure or further transmission on the unit. Upon further retrospective review, 6 (9.2%) HA cases had documented travel history or exposure to a family member with recent travel to China, India, Sri Lanka, or the United States within the past year. Nearly all HA cases (62, 95.4%) had antibiotic exposure within 90 days of CPE detection; specifically, 47 (72.3%) received beta-lactams, 42 (64.6%) cephalosporin, 25 (38.5%) glycopeptide, 20 (30.8%) carbapenem, and 8 (12.3%) macrolide. Conclusion: HA CPE acquisition identified during the first 5-years of universal screening were mostly sporadic and not associated with known exposures or other risk factors. Receipt of prior antibiotics was present in nearly all cases.

Outbreak of New Delhi Metallo-β-lactamase-producing Escherichia coli in a Neonatal Intensive Care Unit, New York State

Background: Outbreaks of carbapenemase-producing (CP) organisms (CPOs), including carbapenem-resistant Enterobacterales (CRE), in neonatal intensive care units (NICUs) are not well documented. The Centers for Disease Control and Prevention (CDC) identifies CP-CRE as an urgent threat to United States (US) healthcare facilities. Wadsworth Center, the New York State (NYS) Department of Health’s (NYSDOH’s) public health laboratory, participates in CDC’s Antimicrobial Resistance Laboratory Network to provide CPO identification, characterization, and surveillance. NYSDOH investigated an outbreak of CP-CRE Escherichia coli (E. coli) infections in NICU patients reported by one hospital. Method: Hospital A reported a CRE E. coli outbreak in their NICU to NYSDOH, as required by NYS Sanitary Code. In response, epidemiologists reviewed case data, conducted case finding, and provided infection control guidance to the hospital. Hospital A continued NICU clinical surveillance and conducted colonization screening to detect additional cases of CRE E. coli. The Wadsworth Center Antimicrobial Resistance Laboratory Network tested isolates from affected patients for CP genes and performed whole genome sequencing (WGS) to determine the CP gene variant, multilocus sequence type (MLST), and relatedness by mutation event (ME) analysis. NYSDOH epidemiologists assessed Hospital A’s infection control practices in affected areas and provided recommendations. Result: Hospital A identified two CRE E. coli infections in NICU patients with overlapping admissions in June-July 2023. Retrospective surveillance identified a third CRE E. coli case in an adult medical intensive care unit patient on admission to Hospital A in June 2023, with prior hospitalization April-May 2023. WGS analysis identified the blaNDM-5 gene in all three CRE E. coli patient isolates. The two NICU patients’ isolates had the same MLST (361/650) and differed by 9 MEs, indicating relatedness to each other and not the adult patient’s (MLST 167/2). NICU patient colonization screening identified no additional blaNDM-5 E. coli cases. NYSDOH’s NICU infection control assessment found that both cases were in adjacent isolettes within three feet of each other. Clean isolettes, equipment, and supplies for new admissions were stored in the clinical care space, not in a separate clean area. Conclusion: CP-CRE is an urgent threat to US healthcare facilities, including hospital NICUs. Though the incidence and prevalence of CP-CRE blaNDM-5 E. coli are not well-defined in NY, single healthcare-associated cases in NICU populations represent an outbreak. The Wadsworth Center Antimicrobial Resistance Laboratory Network’s contributions complement traditional epidemiologic surveillance and investigation methods to provide more specific, comprehensive infection

Organism-specific Trends in Carbapenem-resistant Enterobacterales Infections in a Cohort of Hospitalized Patients, 2012–2022

Background: Carbapenem-resistant Enterobacterales (CRE) infections are an urgent public health threat. An estimated 12,700 CRE (including E. coli, Klebsiella spp., and Enterobacter spp.) infections occurred in the United States in 2020. While the estimated incidence of CRE infections has been relatively stable between 2012 and 2020, organism-specific trends, including those for organisms not typically included in CRE surveillance definitions, have not been described. We estimated the annual rate of carbapenem-resistant Enterobacterales infections, disaggregated by organism, from 2012 to 2022. Methods: Data on inpatient hospitalizations from a dynamic cohort of short-term acute care hospitals reporting microbiology data between 2012 and 2022 were obtained from the PINC AI Database and the BD Insights Research Database. We included patients with clinical isolates of E. coli, Enterobacter spp., Klebsiella spp., Citrobacter spp., Serratia marcescens, Proteus mirabilis, and Morganella spp. and sufficient susceptibility results to identify carbapenem resistance. We limited our analysis to incident isolates, defined as a patient’s first isolate of a given organism and carbapenem resistance phenotype in a 14-day period. We calculated the annual rate of carbapenem-resistant infections per 10,000 hospitalizations for each organism. Results: There were 3,018,792 incident isolates from 55.8 million hospitalizations included in the analysis. Overall, 31,226 incident carbapenem-resistant isolates were identified. The rate of carbapenem-resistant infections varied by organism and over time (Table 1). The rate of carbapenem-resistant Klebsiella spp. infections appeared to decline from 3.94 in 2012 to 2.44 infections per 10,000 hospitalizations in 2022. The rate of carbapenem-resistant Enterobacter spp. infections appeared to increase from 1.05 in 2012 to 1.44 infections per 10,000 hospitalizations in 2022. The rate of carbapenem-resistant E. coli infections also appeared to increase, from 0.61 in 2012 to 0.85 infections per 10,000 hospitalizations in 2022. Rates of carbapenem-resistant Proteus mirabilis, Morganella spp., Citrobacter spp., or Serratia marcescens infections were similar in 2022 compared to 2012. Conclusions: Disaggregating data by organism revealed heterogeneous trends, with apparent increases in rates of carbapenem-resistant Enterobacter spp. and E. coli infections and apparent decreases in rates of carbapenem-resistant Klebsiella spp. infections. Organism-specific CRE analyses may provide additional insight into CRE epidemiology.

Impact of Discontinuing Contact Precautions for Multidrug-resistant Gram-negative Enterobacteriaceae in a Large Health System

Background: Contact precautions (CP) to prevent transmission of multidrug-resistant gram-negative (MDRGN) Enterobacteriaceae are recommended, although studies of discontinuation of CP (DcCP) have found no change in healthcare associated infections (HAI) due to extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. Limited data exists on DcCP for MDRGN in a large health system. Methods: We performed a retrospective observational study analyzing the relationship between use of CP and HAI due to two definitions of MDRGN Enterobacteriaceae: ESBL, and non-susceptibility to ≥3 drug classes (3DC-GNR), with carbapenem resistant Enterobacteriaceae (CRE) serving as control. The study included all inpatient admissions from 2/2017 through 9/2022 at 21 acute care hospitals. Hospitals had latitude to determine CP practices based on local risk assessment, but in 2/2018, system-wide transmission-based precautions guidance was updated to recommend DcCP for MDRGN Enterobacteriaceae and in 12/2019 was updated to clarify DcCP specifically for ESBL and 3DC-GNR while continuing CP for carbapenem-resistant organism carriage. We interviewed infection preventionists to define when CP were used for CRE, ESBL, and 3DC-GNR Enterobacteriaceae. HAI were defined using National Healthcare Safety Network criteria including all HAI categories. We compared the incidence rate of HAI attributable to the two MDRGN types in hospital months with and without use of CP, with HAI due to CRE as a comparison group since all hospitals used CP for CRE throughout the study period. Results: The periods of CP use, by hospital, are shown in Figure 1. Throughout the study period, there were 987 HAI attributed to ESBL Enterobacteriaceae, 579 due to 3DC-GNR Enterobacteriaceae, and 329 due to CRE. Figure 2 shows the unadjusted aggregate rate of HAI for each of the three MRGN types, including among hospitals with and without CP in each month, for ESBL and 3DC-GNR. In months with and without CP, the rate of HAI was 1.482/10,000 and 1.093/10,000 patient days (incidence rate ratio [IRR], 1.356 [95% confidence interval, 1.195-1.540]) for ESBL Enterobacteriaceae. In months with and without CP, the rate of HAI was 1.071/10,000 and 0.493/10,000 patient days (IRR,2.173[95% confidence interval, 1.838-2.569]) for 3DC-GNR Enterobacteriaceae. Conclusion: DcCP was not associated with an increase in HAI due to ESBL and 3DC-GNR Enterobacteriaceae in aggregated facilities that self-selected for DcCP. Facilities that used CP were associated with significantly higher rates of ESBL and 3DC-GNR Enterobacteriaceae, a relationship that did not change as hospitals DcCP for these MDRGN. Further analyses are necessary to assess for a causal relationship.

Carbapenem-resistant Acinetobacter baumannii and Carbapenem-resistant Enterobacterales in US Dialysis Populations, 2016-2021

Background: Infections lead to high mortality among patients on chronic dialysis; knowledge of multi-drug resistant infections is limited. The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) in 10 U.S. sites and carbapenem-resistant Acinetobacter baumannii (CRAB) in 9 U.S. sites. We investigated clinical characteristics, healthcare exposures, and outcomes of CRE and CRAB cases in persons on chronic dialysis from 2016-2021. Methods: Among EIP catchment-area residents on chronic dialysis, we defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes (formerly Enterobacter aerogenes), Klebsiella oxytoca, Klebsiella pneumoniae, or Klebsiella variicola resistant to any carbapenem, from a normally sterile site or urine in a 30-day period. A CRAB case was defined as the first isolation of Acinetobacter baumannii complex resistant to any carbapenem (excluding ertapenem), from a normally sterile site or urine (or lower respiratory tract or wound since 2021) in a 30-day period. Medical records were reviewed. A case was considered colonized if the case culture had no associated infection type or colonization was documented in the medical record. Descriptive analyses, including analyses stratified by pathogen, were conducted. Results: Among 426 cases, 314 were CRE, and 112 were CRAB; most cases were male (235, 55.2%), Black (229, 53.8%), and 51-80 years old (320, 75.1%) (Table). An infection was associated with 363 (85.2%) case cultures; bloodstream infections (148; 40.8%), urinary tract infections (134; 36.9%), and pneumonia (17; 4.7%) were the most frequent. Overall, most cases had documented healthcare exposures (excluding outpatient dialysis) in the year before incident specimen collection, including: 366 (85.9%) hospitalizations, 235 (55.2%) surgeries, 209 (49.1%) long-term care facility stays, 54 (12.7%) long-term acute care facility stays. Additionally, 125 (29.3%) had an intensive care unit admission within the 7 days before incident specimen collection. Compared to CRE cases, a higher proportion of CRAB cases (a) had a long-term care facility stay (82/112 [73.2%] versus 127/314 [40.5%], P&lt;.0001) or hospitalization (103/112 [92%] versus 263/314 [83.8%], P = .03) within the preceding year and (b) died within 30 days of incident specimen collection (40/112 [35.7%] versus 64/314 [20.4%], P = .001). Discussion: Among CRE and CRAB cases in persons on chronic dialysis, healthcare exposures were common, and mortality was high. Additional efforts to better describe the burden of these organisms and associated risk factors in the dialysis population are needed for tailoring infection prevention strategies to this vulnerable.

Epidemiological and clinical characteristics of patients with carbapenem-resistant Enterobacterales in a university hospital of Colombia: Enzyme coproductions in rise

The distribution of carbapenemases in Carbapenem-Resistant Enterobacterales (CRE) has recently undergone a change in our region. According to the Colombian National Institute of Health, there is an increasing prevalence of NDM and NDM-KPC co-producing strains. We carried-out an ambispective cohort study of adult inpatients from Hospital Universitario San Ignacio (2021–2023), infected or colonized with CRE, in which carbapenemases immunochromatographic assay was performed. Out of the 150 patients included in the study, 71.3 % presented with an infection, and carbapenemases were detected in 92.7 % of these cases. Among them, KPC predominated (54 %), while 16.7 % demonstrated enzyme coproductions, mainly KPC-NDM. CRE infected patients had an 18.7 % 30-days mortality, but we could not demonstrate an association between type of carbapenemase and mortality rate (p = 0.82). Logistic regression analysis suggested that ICU admission was independently correlated to fatality (OR 5.08; CI 1.68–16.01). NDM and KPC-NDM presence in CRE poses a public health threat and a therapeutic challenge, with unknown mortality differences according to the carbapenemases pattern. Nevertheless, there was not an association between enzyme type and mortality.

Efficacy of Empiric Contact Precautions for Patients from High Risk Facilities

Background: Infection prevention surveillance revealed that patients admitted from two specific long term care facilities comprised the majority of multi-drug resistant organisms (MDRO) and scabies cases at our institution. Current practices include performing active surveillance for Candida auris and methicillin-resistant Staphylococcus aureus (MRSA) for specific high-risk patients, as surveillance for all MDROs and scabies is impractical. We therefore sought to create an admission screening process to efficiently identify patients from high-risk facilities (HRFs) and place them in pre-emptive contact precautions upon admission. Methods: Patients admitted from HRFs were identified on admission as part of the initial nursing assessment. For any positive responses, nursing received a Best Practice Advisory to place the patient in contact precautions and patient placement received an alert that the patient would require a private room. Infection Preventionists reviewed a report of all patients who screened positive and added a “High Risk Facility” banner to the chart. This banner remained for the duration of hospitalization and for every subsequent readmission and outpatient visit. We reviewed the electronic medical records of all patients with a HRF banner placed from March 8, 2023 to September 15, 2023 and abstracted data regarding the presence of scabies or any of the following MDROs before and after placement of the banner: C. auris, carbapenem-resistant enterobacterales (CRE), MRSA, vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Acinetobacter, and MDR Pseudomonas. Results: Of the 93 patients who had a HRF banner added during the study period, 31 (33.33%) were already known to have MDRO colonization at the time of admission to our facility. Thirty-three of the remaining 62 patients (53.22%) without known MDRO colonization were subsequently found to have MDRO colonization/infection or scabies infestation that may have required contact precautions during their index admission or a subsequent admission. This included 14 patients with C. auris, 2 with CRE, 3 with MDR Pseudomonas, 12 with MRSA, 12 with carbapenem-resistant Acinetobacter, and 2 with VRE. Patients were admitted for a median of 9 days before their diagnosis, and 36 of the 93 patients (38.71%) were re-admitted to our hospital during the study period. Conclusion: We found that empiric contact precautions based solely on exposure to specific HRFs facilitated earlier isolation by a median of 9 days. This approach should be considered in acute care hospitals with a high proportion of admissions from HRFs, especially when active and passive surveillance for MDROs is limited.

Uptake of Revised CLSI Breakpoints and Potential Impact among Hospitals Reporting to The NHSN AR Option, 2022

Background: Antimicrobial susceptibility testing (AST) is critical for detecting antimicrobial resistance (AR) and guiding antimicrobial treatment. The Clinical and Laboratory Standards Institute (CLSI) regularly publishes and revises breakpoints to guide the interpretation of AST results. In 2010–2019, CLSI has lowered many breakpoints for Enterobacterales and Pseudomonas aeruginosa. Timely implementation of updated breakpoints can vary across hospital laboratories, leading to shifts in the interpretation of AST results. This issue is a potential threat to the estimation of national prevalence estimates for AR and limits the comparability of AR data across hospitals. Hospitals submit AST data with clinical laboratory interpretations to the AR Option of CDC’s National Healthcare Safety Network (NHSN). NHSN tracks whether a hospital adopted the revised CLSI breakpoints for six organism-antimicrobial combinations involving AR phenotypes commonly associated with healthcare associated infections through hospital self-reporting status into a structured survey — 2022 NHSN Annual Hospital Survey (Table). For this analysis, we describe the uptake of revised CLSI breakpoints and compare cumulative antibiograms among hospitals that used various breakpoints. Methods: We included hospitals that completed the 2022 NHSN annual survey and submitted data to the NHSN AR Option for at least 9 months in 2022 by November 1, 2023. The percentage of hospitals that implemented CLSI breakpoints, published during 2010–2019, were determined for combinations of antibiotic class, organism, and CLSI revision year (Table). We calculated percent resistance (%R) as the number of isolates meeting AR phenotype definitions divided by the total number of Isolates tested for the following phenotypes: carbapenem-resistant Enterobacterales (CRE) which included E. coli, Klebsiella, and Enterobacter species; extended-spectrum cephalosporin-resistant Enterobacterales (ESC); carbapenem-non-susceptible P. aeruginosa; fluoroquinolone-resistant P. aeruginosa; and fluoroquinolone-resistant Enterobacterales. Results: Among the 741 hospitals included, 75%–93% implemented any of the six revised CLSI breakpoints (Table). The %R was higher among isolates from hospitals that adopted revised breakpoints compared to those that did not (p &lt; 0 .0001). The largest difference was observed for carbapenem-non-susceptible P. aeruginosa (14.91% vs 10.11%). Conclusions: The uptake of revised CLSI breakpoints varied across hospitals, organism-antimicrobial combinations, and CLSI versions. This analysis indicates that the prevalence of AR for corresponding phenotypes could be underestimated if data from hospitals using higher, outdated breakpoints are included. It is important for NHSN to continue tracking breakpoints used in individual hospitals and encourage hospitals to report complete data on the original AST results, such as MIC, to optimize the accuracy of national AR surveillance.

Clusters of emerging multidrug-resistant organisms in US health care facilities during the initial months of the SARS-CoV-2 pandemic

Outbreaks of emerging multidrug-resistant organisms (eMDROs), including carbapenem-resistant Enterobacterales, carbapenem-resistant Acinetobacter baumannii, and Candida auris, have been reported among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. We describe eMDRO clusters in SARS-CoV-2 units and associated infection control (IC) practices early in the SARS-CoV-2 pandemic. We conducted a retrospective survey of a convenience sample of health departments in 11 states to describe clusters of eMDROs that began before November 1, 2020 and involved SARS-CoV-2 units. Cluster characteristics and IC practices during the cluster period were assessed using a standardized outbreak report form, and descriptive analyses were performed. Overall, 18 eMDRO clusters (10 carbapenem-resistant Enterobacterales, 6 Cauris, 1 carbapenem-resistant Pseudomonas aeruginosa, and 1 carbapenem-resistant A baumannii) in 18 health care facilities involving 397 patients were reported from 10 states. During the cluster period, 60% of facilities reported a shortage of isolation gowns, 69% extended use of gowns, and 67% reported difficulty obtaining preferred disinfectants. Reduced frequency of hand hygiene audits was reported in 85% of acute care hospitals during the cluster period compared with before the pandemic. Changes in IC practices and supply shortages were identified in facilities with eMDRO outbreaks during the SARS-CoV-2 pandemic and might have contributed to eMDRO transmission.

Containment of a KPC-CRE Outbreak Associated with Premise Plumbing in a Long-Term Care Facility— Minnesota, 2022-2023

Background: On March 23, 2022, the Minnesota Department of Health (MDH) was notified of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella oxytoca isolated from a resident’s urine in long-term care facility A (LTCF-A). Carbapenem-resistant Enterobacterales (CRE) are reportable statewide with required isolate submission to MDH Public Health Laboratory (MDH-PHL), where carbapenemase production and mechanism identification is confirmed. Methods: MDH partnered with LTCF-A on a containment response, including infection prevention and control (IPC) measures, KPC-CRE education, and colonization screening. Rectal swabs were screened for carbapenemase genes by real-time PCR (Cepheid Xpert Carba-R), with positive specimens undergoing culture, isolation, and whole genome sequencing (WGS). MDH-PHL conducted WGS including multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis to describe genetic relationships among isolates. When screening indicated a potential environmental source, due to species diversity and ongoing resident transmission, an environmental screening plan was developed including collection of premise plumbing samples from room faucets, aerators, sinks, toilets, and shared shower drains. Results: KPC-CRE was detected in 23 residents (urine, n=2; rectal swab, n=21) during March 2022–November 2023. 21 isolates comprising 10 Enterobacterales species were cultured from KPC-positive screening specimens. SNP analysis performed on bacteria of the same species demonstrated 5 distinct clusters of relatedness comprising 2-3 residents per cluster (Cluster 1: Klebsiella oxytoca, n=3; Cluster 2: Klebsiella oxytoca, n=3; Cluster 3: Escherichia coli, n=2; Cluster 4: Klebsiella pneumoniae, n=2; Cluster 5: Raoultella planticola, n=2). 7 KPC-positive resident specimens did not yield a culturable organism. KPC-CRE was detected throughout the premise plumbing including 8 of 9 shared shower room drains and 6 of 75 resident room sink drains. WGS and SNP analysis suggest relatedness among resident and environmental KPC-CRE isolates. Gaps in IPC measures including hand hygiene, use of personal protective equipment (PPE), environmental cleaning and disinfection, and sink hygiene practices were observed during onsite assessments. Use of an EPA-registered biofilm disinfectant in facility drains and repeated environmental sampling has demonstrated a decrease in KPC-harboring bacteria within the premise plumbing, but not complete elimination. Conclusion: Containing the spread of KPC-CRE within LTCF-A has been challenging due to environmental reservoirs of KPC-CRE along with insufficient implementation of IPC practices. Continued colonization screening has been necessary to detect newly colonized residents and reinforce efforts to increase IPC compliance. Strict implementation and adherence to IPC measures, including those that minimize the spread of KPC-CRE from facility premise plumbing, are needed to fully halt KPC-CRE transmission within LTCF-A.

Variability of MDRO Reporting Across Tennessee Microbiology Laboratories

Background: Identification and timely reporting of multi-drug resistant organisms (MDROs) drives efficacy of infection prevention efforts. Data on MDRO reporting timeliness and inter-facility variability are limited. Facility-dependent variability in MDRO reporting across Tennessee was examined to identify opportunities for MDRO surveillance improvement. Methods: Data for reported Tennessee MDROs including carbapenem-resistant Enterobacterales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), Carbapenem-resistant Pseudomonas aeruginosa (CRPA) and Candida auris, were obtained from the southeast regional Antibiotic Resistance Laboratory Network (ARLN) from 2018-2022, excluding screening and colonization specimens. Variance in days accrued from specimen collection to ARLN receipt was analyzed using one-way analysis of variance (ANOVA) with Tukey’s test (SAS 9.4). Facilities were categorized as fast (1-10 days), slow (11-20 days), or delayed (21-100 days) reporters. Results: There were 9,569 MDRO isolates reported. CRPA was reported faster than other MDROs (p &lt; 0.001), while specimens from West Tennessee compared to other regions (p &lt; 0.001) (Figure) and blood cultures compared to other specimens were reported more slowly (p &lt; 0.001) (Table). There was no difference in reporting times for facilities using on-site microbiology laboratories versus reference laboratories (P = 0.062). Conclusion: MDRO reporting times varied across Tennessee by region, specimen, and organism. Future work to elucidate drivers of variability will consist of surveys and focused interviews with laboratory personnel to identify shared and unique barriers and opportunities for improvement.

Impact of Transitioning to Single-Patient Rooms on Prevention of Multidrug-Resistant Organisms in a Resource-Limited Facility

Background: Healthcare-associated infections (HAI) substantially increase hospital costs and lead to poor patient outcomes, particularly when caused by multidrug-resistant organisms (MDRO). To decrease MDRO transmission, isolation of colonized or infected patients in single rooms is recommended. However, single-patient isolation rooms are expensive to build and often unavailable in resource-limited hospitals. In 2023, an intensive care unit (ICU) at a large Brazilian tertiary hospital relocated from a space with an open floor plan to a newly built location with single-patient rooms. We evaluated the impact of this transition on acquisition of carbapenem-resistant Enterobacterales (CRE) colonization, HAI, and compliance with Hand Hygiene (HH) and Contact Precaution (CP) activities. Methods: We compared rates of CRE colonization acquisition, CRE colonization pressure, HAI, and compliance with HH and CP between pre- (March 1, 2022 – Feb 28, 2023) and post-implementation of single-rooms (March 1, 2023 - October 31, 2023) in a 12-bed surgical ICU. All patients were screened for CRE colonization on admission to the unit and weekly until discharge using rectal swab cultures. Colonization pressure was defined as the ratio of CRE-positive patient-days (PDs) to the total number of PDs. Rates of central-line associated blood-stream infections, ventilator-associated pneumonia, and catheter-associated urinary tract infections were monitored. HH and CP compliance were monitored weekly by infection prevention staff outside of the unit. Poisson regression and multiple linear regression were used to compare rates between pre- and post-implementation periods. Results: Healthcare acquisition of CRE colonization remainedstable between pre- and post-implementation (incidence rate ratio: 0.88 (95%CI, 0.73-1.05; P=0.16) despite an increase in CRE colonization pressure of 8.6% over baseline (from 7.84% pre- to 16.39% post-implementation (95% confidence interval [CI], 4.13-12.96%; P=.001)). The latter was driven by reduced turnover of CRE-colonized patients in the post-implementation period (mean patient-day reduced by 10.33; 95%CI, 3.06-17.61; P=0.006). Incidence of HAIs also remained stable (global incidence 3.12 vs 3.30, pre- and post-intervention, respectively; P=0.2). HH compliance was high prior to the transition (95.7%) and increased slightly but not significantly post-intervention (97.5%; P=0.3). CP compliance improved by 9.83%, especially in gown and glove changes after each patient interaction, from 90.62% pre- to 100% post-implementation (95%CI, 1.52-17.22; P=.02). Conclusion The move to an ICU with exclusively single-patient rooms was associated with increase in CP compliance. This could help explain why HAI incidence and healthcare acquisition of CRE colonization remained stable despite a significant increase in CRE colonization pressure.Disclosure: Matias Salomao: Speaker - Cepheid

Investigation of a Donor-derived Carbapenamase-producing Carbapenem-resistant Enterobacterales Hospital Outbreak

Carbapenamase-producing carbapenem-resistant Enterobacterales (CP-CRE) is an urgent public health threat for healthcare facilities. Solid organ transplant (SOT) recipients carry an increased risk for CRE infection and colonization due to prolonged exposures to antimicrobials, healthcare facilities and immunosuppression. CRE infection in SOT patients is associated with an increase in morbidity and mortality. Here, we describe a hospital outbreak investigation of three cases of New Delhi metallo-beta-lactamase (NDM) - CRE that led to novel findings with implications for further interdisciplinary investigations. An NDM-CRE infection in a critically-ill patient was identified during passive surveillance and prompted an investigation. Previous CP-CRE passive surveillance cases were reviewed. Rectal screening was performed for potentially exposed patients. 403 rectal swabs were tested for carbapenemase genes in active surveillance. Patients identified to have a new NDM-CRE isolate on active or passive surveillance were considered cases and underwent in-depth chart review including possible patient-to-patient exposures, hospital locations, procedures, devices, and consultations. NDM-CRE isolates were sent to the Minnesota Department of Health (MDH) for whole genome sequencing (WGS) to assess relatedness. Five NDM-CRE cases were identified, with all isolates harboring blaNDM including three NDM-Klebsiella pneumoniae (NDM-KP) cases (Figure 1). The first NDM-KP case, patient 1, developed mediastinal infection following lung transplantation. Review of United Network for Organ Sharing revealed that respiratory specimens from patient 1’s donor grew NDM-KP and a bronchial wash at the time of transplant yielded NDM-KP. The second NDM-KP case (patient 3) developed ventilator-associated pneumonia and was found to have used sequentially the same ventilator as patient 1. The third NDM-KP case (patient 4) was detected via rectal swab in active surveillance and shared wound care personnel in common with patients 1 and 3 (Figure 2). WGS demonstrated two single nucleotide polymorphisms (SNP) among all three isolates, strongly suggesting relatedness (Figure 3). Best practices for infection prevention were reviewed with wound care personnel. To date, no further NDM-KP isolates have been identified. Investigation was facilitated by in-depth chart review and WGS via the Central Region Antimicrobial Resistance Laboratory Network at MDH. Detection of the NDM-KP from a lung donor specimen appears genetically linked to clinical isolates in other patients, raising the possibility of a donor-derived hospital outbreak. This investigation is the first to describe a donor-derived NDM outbreak in a healthcare facility. Communication between organ procurement agencies, transplant centers, and infection prevention must be optimized to prevent CRE-associated morbidity in SOT receipts and CRE hospital outbreaks.