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 & 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 >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.

Background: Taurolidine exhibits broad antimicrobial activity and is a component of a recently FDA approved catheter lock solution (DefenCath®, taurolidine 13,500 μg/mL and heparin 1000 Units/mL) indicated for reducing the risk of catheter-related bloodstream infections (CRBSI) in adult patients receiving chronic hemodialysis through a central venous catheter (HD-CVC). FDA approval was based on a Phase 3 randomized trial (LOCK-IT-100) in which DefenCath showed a 71% reduction in CRBSI risk among HD-CVC patients as compared with heparin alone. Although individual isolates from the clinical program were not available for testing, this study evaluated the in vitro antimicrobial activity of taurolidine against a set of recent clinical isolates representative of those recovered from the LOCK-IT-100 trial and/or those commonly associated with CRBSI. Methods: 420 bacterial and 50 yeast isolates were selected from the SENTRY Antimicrobial Surveillance Program. All isolates were collected from the bloodstream of patients in the U.S. between 2018-2023. Isolates were tested for susceptibility to taurolidine and comparators using Clinical and Laboratory Standards Institute (CLSI) broth microdilution guidelines. JMI Laboratories produced susceptibility test panels for testing. CLSI-recommended quality control strains were also tested concurrently. MIC values were determined after 24 hours. Results: Taurolidine exhibited broad antimicrobial activity against all isolates tested (see table). Against gram-positive bacteria, taurolidine MIC50/90 values ranged from 256-512/512-1,024 μg/mL for S. aureus, Coagulase-negative Staphylococcus, Enterococcus species, and Viridans group streptococci. This activity was maintained regardless of methicillin susceptibility for Staphylococcal isolates or vancomycin resistance among Enterococcal species. Against gram-negative bacteria, taurolidine MIC50/90 values ranged from 256-1,024/512-2,048 μg/mL for Enterobacterales, P. aeruginosa, S. maltophilia, A. baumannii-calcoaceticus, and B. cepacia. This activity was maintained in both multidrug resistant Enterobacterales and P. aeruginosa isolates. Among Candida isolates, taurolidine MIC50/90 values ranged from 256-512/512 μg/mL for C. glabrata and C. parapsilosis while taurolidine MIC50/90 values of 4,096/4,096 μg/mL were observed for C. albicans. Conclusions: Taurolidine activity was very similar among a large collection of gram-positive, gram-negative, and yeast organisms. MIC90 values for all species/groups were ≤2,048 μg/mL, except C. albicans where an MIC90 of 4,096 μg/mL was observed. The activity of taurolidine was unaffected by resistance to antibiotics (i.e. methicillin, vancomycin, or multi-drug resistance) among gram-positive or gram-negative organisms. Based on these data, catheter lock solutions containing the broad-spectrum antimicrobial taurolidine at 13,500 μg/mL have the potential to prevent CRBSI caused by a variety of species, including those observed in the recent LOCK-IT-100 clinical trial and other common bloodstream pathogens

The negative predictive value of blaCTX-M on BCID2 for ceftriaxone resistance in E. coli and K. pneumoniae group was 97% and 94%, respectively. Creation of a genotypic antibiogram led to updated local guidance for clinicians to utilize for empiric treatment of Enterobacterales bloodstream infections identified via rapid diagnostics.

Background: Candida auris is often identified in healthcare settings through bilateral composite of axilla/groin skin swabs screening. Re-screening the same patient has demonstrated inconsistent results over time, complicating the understanding of longitudinal colonization and limiting confidence in negative Results: Previous studies have described identification of colonized patients using other anatomical sites. Here, we compare bilateral composite of nares/hands with bilateral composite of axilla/groin screenings in a cohort of hospitalized patients in Miami, Florida, to assess the use of screening other body sites for C. auris surveillance. Methods: This study took place in a 560-bed academic acute-care facility and included patients previously colonized with C. auris who were cohorted on a 30-bed unit. Bilateral composite samples from both the axilla/groin and nares/hands were obtained simultaneously. Swabs were collected at six different time points at biweekly intervals between March and May 2023 (Figure 1) and sent to the Centers for Disease Control and Prevention for testing with culture and Real-time PCR-based methods. Results: A total of 102 swabs (51 from each swab type) were collected from 19 patients who were each sampled a median of twice (IQR: 1-5). Among the 102 swabs, 35 of 51 (69%) axilla/groin swabs were positive compared with 45 of 51 (88%) nares/hands swabs using culture (Figure 2). Furthermore, 48 of 51 (94%) swabs were positive by culture for both methods, with 15 positive from the nares/hands and one positive from the axilla/groin (Figure 3). Among 11 patients who were tested ≥2 times with nares/hands swabs, 9/11 (81%) tested positive on all sequential swabs via culture and 10/11 (90%) tested positive via PCR (Ct threshold < 3 6.9). Among the same 11 patients but using the axilla/groin swabs, 3/11 (27%) patients tested positive on all sequential swabs using culture, and 5/11 (45%) tested positive using PCR (Figures 2-4). On average, samples collected from nares/hands swabs had lower Ct values (mean=27) compared to axilla/groin swabs (mean=31) (p-value=< 0.001) (Figure 5). Discussion: Identifying the swab site with most consistent C. auris detection is important for surveillance purposes. In our study, there were more positives and consistent positivity for nares/hands by both culture and PCR-based methods, as well as lower Ct values, suggesting that these swabs provide more reliable detection of C. auris colonization. Alternative screening methods deserve consideration as CDC continues to explore whether swabbing of other body sites (e.g., nares, hands) would improve accuracy and consistency when identifying colonized patients.

During 2016–2022, Medicare part D beneficiaries filled 8,674,460 clotrimazole-betamethasone dipropionate prescriptions. Annual rates were stable (30.9 prescriptions/1,000 beneficiary-years in 2022, enough for one in every 33 beneficiaries). Diagnostic testing was infrequent, particularly among internal medicine, family medicine, and general practitioners, suggesting potential opportunities to improve diagnostic and prescribing practices.

Background: Detection of outbreaks traditionally relies on passive surveillance, and often misidentify or miss outbreaks. Whole genome sequencing (WGS) surveillance has emerged as a proactive measure, enabling early detection of outbreaks and facilitating rapid intervention strategies. WGS surveillance has not been widely studied due to infrastructure, cost, and evidence barriers regarding its impact on reducing healthcare-associated infections (HAIs). This study represents findings from two years of a real-time WGS surveillance program called the Enhanced Detection System for Healthcare-associated Transmission (EDS-HAT). Methods: The study was conducted at UPMC Presbyterian hospital, a 694-bed tertiary care center. Patient isolates of select bacterial pathogens were collected and underwent WGS weekly from November 2021 to November 2023. Potential transmission was defined using single-nucleotide polymorphism thresholds (≤15 for all organisms except Clostridioides difficile). Genetically related clusters were reviewed weekly for epidemiological linkages (unit, personnel, or procedural commonalities) and appropriate interventions were initiated by the infection prevention and control team. We described the frequency of genetic relatedness and nature of epidemiological linkages. Results: Of 7,051 eligible unique patient organism isolates, 4,723 were deemed healthcare-associated and underwent WGS. EDS-HAT identified 478 (12.2%) isolates genetically related to ≥1 other isolate across 173 clusters. Epidemiological links were found in 278 (58.2%) isolates in 114 clusters, with the majority being unit-based (205 isolates, 71.9%); other epidemiological links included equipment or healthcare workers (32 isolates, 11.5%), external facilities (24 isolates, 8.6%), and shared endoscopes (17 isolates, 6.1%); all endoscope outbreaks were effectively contained at two patients. No epidemiological links could be identified for 200 (41.8%) isolates. Infection prevention initiated 134 interventions in 114 clusters, including 74 (55.2%) general staff notification and education, 25 (18.7%) enhanced cleaning efforts, 23 (17.2%) hand hygiene/personal-protective equipment compliance observations, 9 (6.7%) environmental cultures, and 3 (2.2%) enhanced microbiological surveillance. Following the detection of an epidemiological link and intervention, 94/101 (94.1%) outbreaks were effectively halted on the intervened route (Figure). Conclusion: This study demonstrates the feasibility and efficacy of EDS-HAT as an infection prevention tool. Early detection and intervention of outbreaks significantly enhance the capability of healthcare facilities to control and prevent the spread of HAIs. Investment in infrastructure and implementation costs will result in reducing pathogen transmission and improving patient safety in acute care settings.

Disclosure: Alexander Sundermann: Honoraria - Opgen

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of procedure-related, skin, and soft-tissue infections. Hospitalized patients who are colonized with MRSA are at a higher risk of developing invasive infections after discharge. Chlorhexidine, an antiseptic/disinfectant, has been used to reduce carriage and prevent infections in these patients. Studies have shown chlorhexidine resistance among MRSA strains. Chlorhexidine resistance is associated with qac genes, which encode multidrug efflux pumps that increase bacterial tolerance to disinfectant agents. The global distribution and prevalence of qacA and qacB genes are highly variable. One study reported that qacA and qacB genes could be found in 0.9% - 83.3% of clinical MRSA isolates worldwide. The goal of this study was to determine the prevalence of chlorhexidine resistance and identify the resistance-associated genes from our MRSA samples using whole genome sequencing (WGS). Methods: 474 MRSA samples were obtained from hospitals in Detroit, MI (287) and Cleveland, OH (187). Whole genome sequencing was performed using the NextSeq (Illumina Inc., CA) platform. The sequencing data was analyzed using ResFinder 4.1, a publicly available database that can be used to identify acquired genes and chromosomal mutations mediating antimicrobial resistance. The output was organized into a data sheet to visualize the presence of the genes of interest. Results: The qacA gene was present in only one MRSA sample from the Cleveland area hospital. In the samples from Detroit, 14 out of 287 showed disinfectant resistance genes. The qacA, qacB, and qacD were present in 1, 6, and 7 samples, respectively. The prevalence of any qac gene in the Cleveland area samples was 0.5%. Meanwhile, the prevalence of any qac gene in Detroit area samples was 4.9%. Among the 7 samples that have qacD gene, 6 samples have more than one copy of qacD. Conclusions: The prevalence of the “qac” gene varied widely based on the origin of the samples. Detroit area samples had more qac genes prevalence than Cleveland area samples. Chlorhexidine is a widely used antiseptic/disinfectant, and it plays a vital role in reducing carriage and preventing infection among hospitalized patients colonized with MRSA. Monitoring and addressing MRSA-reduced susceptibility to chlorhexidine is imperative for maintaining the effectiveness of infection control practices such as decolonization.

Background: Most healthcare facilities in the US apply contact precautions (CP) for patients with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) infection and/or colonization. Most individuals with MRSA or VRE colonization will clear over time; however, frontline clinicians rarely evaluate for discontinuation of CP, resulting in increased burden on infection preventionists (IPs). Automation of time- and test-based evaluation using clinical decision support systems (CDSS) embedded in electronic health records (EHR) may increase evaluation and discontinuation of CP when appropriate, while preserving IP resources. Methods: This quality improvement initiative was implemented at Mass General Brigham (MGB), an integrated healthcare system, where patients with MRSA or VRE infection/colonization are identified in the EHR with a corresponding “infection status” and CP applied. Following MGB policy (Figure 1), CDSS features included: 1) automated time-based resolution from 2/15/2023-11/13/2023 and 2) automated ordering of screening assays for patients eligible for test-based evaluation from 6/20/2023-11/14/2023 (Figure 2). Counts of CP discontinuation and automated ordering were performed. IPs at one MGB facility performing manual review of patients self-recorded the time spent evaluating for CP discontinuation. Using these time reports, the average time to complete these tasks and the projected time savings were calculated over the implementation period. Results: Four IPs recorded the time to review patients for CP discontinuation, including reviewing recent antimicrobial administration, microbiology results, ordering screening test(s), and contacting the primary team. Twenty-five patient encounters were timed with a mean of 4.7 minutes documented per encounter. Over a 9-month period after initiation of the automated time-based resolution, the monthly mean number of patients with CP for MRSA and VRE which were automatically discontinued was 247 and 100, respectively. Projected IP time savings over the same 9-month period for MRSA and VRE were 174.1 and 70.5 hours, respectively. Over a 5-month period after initiation of automated ordering of MRSA polymerase chain reaction (PCR)/culture, as well as VRE culture for test-based evaluation, the monthly mean number of MRSA culture, MRSA PCR, and VRE culture automatically ordered for patients on CP for MRSA and VRE were 176, 24, and 145, respectively. Projected IP time savings over the same 5-month period for MRSA and VRE were 78.3 and 56.8 hours, respectively.

Conclusion: Healthcare systems that enhance their EHR with CDSS to automate CP evaluations may improve frontline clinician workflow, patient flow and bed capacity, while optimizing use of IP resources.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogen responsible for nosocomial and community-acquired infections with high morbidity and mortality1. MRSA nasal colonization is a major risk factor for developing infection in the hospital setting2,3. Decolonization of MRSA carriers is a strategy to decrease recurrence or to prevent new MRSA infections3,4. Decolonization with nasal mupirocin 2% and chlorhexidine baths has been shown to decrease the risk of MRSA infection after hospital discharge3. Mupirocin is an RNA synthetase inhibitor with activity against MRSA5. Resistance of MRSA isolates to mupirocin has been described previously6. As topical disinfectants play a crucial role in prevention of MRSA infection in a variety of settings, it is important to monitor the emergence of resistance. The goal of this study was to determine the prevalence of mupirocin resistance among MRSA samples isolated from two different regions in the United States (U.S). Methods: Our study had a total of 474 MRSA samples that were obtained from hospitals in Detroit, MI (287 samples) and Cleveland, OH (187 samples). After whole genome sequencing using NextSeq (Illumina Inc., CA) platform the data was analyzed using ResFinder 4.1, to identify antimicrobial resistance which can be either acquired or chromosomally mediated mutations. To visualize the presence of genes of interest the resistance genes were tallied on a spread sheet. Results: Mupirocin resistance gene was detected in five of 287 (1.74%) MRSA samples from the Detroit hospitals, all of which were associated with the mupA gene. Samples collected from the Cleveland area hospital demonstrated mupirocin resistance in seven samples of 187 (3.74%), all associated again with the mupA gene. One sample from the Detroit group showed resistance to both mupirocin and chlorhexidine. Conclusions: Prevalence of mupirocin resistance gene varied between the two hospital locations. Resistance to mupirocin has been documented in association with mutations in the mupA gene as well as chromosomal point mutations that can lead to either low or high-level resistance7,8. Although the mechanisms are not fully clear, mupA gene has been associated with high-level resistance9. Mupirocin resistance among MRSA isolates has increased over time9. MRSA infections remain an important etiology of nosocomial and community-acquired infections and common practice to combat this issue is universal decolonization with mupirocin10. It is critical to understand and monitor for development of mupirocin resistance as mupirocin remains one of the most effective tools to prevent invasive infection with MRSA in many patient populations.

Central line-associated bloodstream infections (CLABSI) pose a significant patient risk. To address incorrect classifications of infectious events as CLABSI, the surveillance process was changed from using finalized blood culture to preliminary blood culture results as trigger of timely, in-depth reviews. This improved the detection of true CLABSI events.

Background: Invasive Staphylococcus aureus infections cause significant morbidity and mortality in neonatal intensive care unit (NICU) infants.1 Colonization (asymptomatic carriage in the nose, skin, or gut) is a risk factor for subsequent invasive infection (e.g., pneumonia, bone infections, bloodstream infections, etc.). Active surveillance and decolonization measures for S. aureus-colonized infants have been associated with decreased invasive infection rates. 2-4 Methods: A methicillin-resistant S. aureus (MRSA) surveillance and decolonization program, consisting of admission and weekly MRSA nasal cultures followed by intranasal mupirocin plus chlorhexidine baths for colonized infants, was implemented in our level IV NICU with 150 beds in 2006.5 Due to poor compliance with decolonization protocols5, existing practices were reviewed and multiple interventions to increase compliance were implemented in 2018. These renewed efforts included revision of the existing MRSA decolonization protocol, updating the associated electronic medical record order set, re-education of unit staff, and weekly review by the Infection Prevention (IP) and NICU leadership teams to ensure the decolonization protocol was followed for newly colonized infants. Mean MRSA bloodstream infection (BSI) rates were calculated quarterly pre- (January 2014-December 2017) and post- (January 2018-December 2023) implementation of renewed efforts and compared via unpaired t-test. In July 2020 a similar methicillin-susceptible S. aureus (MSSA) surveillance and decolonization program was implemented with an associated revision of existing documents, education campaign, and weekly review of infants with new MSSA colonization. Mean MSSA BSI rates pre- (July 2018-June 2020) and post- (July 2020-December 2023) implementation were compared via unpaired t-test. Results: Renewed implementation of MRSA surveillance and decolonization was associated with a sustained decrease in the mean MRSA BSI rate (Figure 1): 0.10 per 1000 patient-days pre-implementation, 0.03 post-implementation (p=0.02). Following implementation of MSSA surveillance and decolonization, there was no statistically significant change in the mean MSSA BSI rate (Figure 2): 0.20 per 1000 patient-days pre-implementation, 0.15 post-implementation (p=0.32). Conclusions: Implementation of a robust MRSA surveillance and decolonization program in the NICU was associated with a sustained decrease in invasive MRSA infections. No change in invasive MSSA infection rates was observed following implementation of a similar protocol for MSSA. Additional research is needed to better understand the role of MSSA surveillance and decolonization in the NICU.

References: 1. Ericson, J.E., et al., JAMA Pediatr, 2015. 2. Popoola, V.O., et al., ICHE, 2016. 3. Kotloff, K.L., et al., Pediatrics, 2019. 4. Voskertchian, A., et al., ICHE, 2018. 5. Reich, P.J., et al. Clin Microbiol Infect, 2016.

Background: Whole genome sequencing (WGS) is a relatively new method for analyzing outbreaks and modes of transmission, particularly for multidrug resistant bacteria. This study sought to investigate clusters of patients with genetically related Vancomycin-Resistant Enterococcus spp. (VRE) bacteremia for shared hospital environmental exposures. Methods: All VRE blood culture isolates from patients from July 1, 2021 to June 30, 2022 underwent Illumina WGS. Core single nucleotide polymorphisms (SNPs) were identified, and multi-locus sequence typing (MLST) was performed across the VRE isolates. Clusters were defined as isolates with 15 or fewer core genome SNPs and were investigated for potential transmission routes. For each cluster, patients were evaluated in the 12 weeks before and after the first VRE isolate for shared hospital environmental exposures (hospital unit, patient rooms, procedural rooms, and radiology suites). Hospital units were comprised of patient rooms located geographically together on the same floor of the hospital. Results: A total of 82 VRE isolates underwent WGS. Thirty-eight (46%) clustered genetically with at least one other isolate. Clusters included 2 to 15 patients per group and represented 10 distinct MLST subgroups (Figure 1). Nine hundred and thirty-nine hospital environmental exposures were identified across the 38 patients. For each cluster, there was a total of 341 (36.3%) shared exposures. Shared environmental exposures occurred in radiology suites (35, 38.5%), patient rooms (32, 35.6%) and procedural rooms (23, 25.6%). Of the patients who shared the same hospital unit, 10 (31.3%) had the same patient room with 7 (70%) of them being in the emergency department (ED). Overall, the ED represented 7 (21.9%) of the shared hospital units. Each cluster had at least one shared hospital environmental exposure found. Conclusions: Use of WGS can help investigate outbreak clusters of resistant organisms such as VRE. In this study, nearly half of all VRE blood isolates were able to be segregated into clusters with at least one other isolate. Although VRE colonization of hospital rooms is well described, patient rooms represented the smallest proportion of shared hospital environmental exposures. This study thus suggests other environmental transmission routes such as radiology suites and procedural rooms warrant closer investigation.

Background: Nursing homes (NHs) have high prevalence of multi-drug resistant organisms (MDROs) with rates exceeding those in hospitals. This study proposes quantifying patients’ risk of MDRO colonization and creating a risk profile for the NH patient populations to assist in reducing MDRO burden in health care facilities. Methods: We assessed a risk classification model using data from a prospective cohort study (2018 Pathways study). Patient sample included 783 newly admitted patients followed for up to 180 days and 9,587 samples collected from patients during 2,089 visits. Individual risk factors of MDRO colonization were assessed using unadjusted logistic regression, and patients were risk classified based on number of risk factors. Multivariate regression was performed to obtain odds of MDRO colonization for patient risk groups adjusting for patient age, sex, race, and length of NH stay (LOS). The risk classification tool developed using Pathways data was also tested among a sample of NH residents from Veterans Administration (N=190). Results: The patient sample (Pathways data) was 43.2% male, 37.2% Black with a mean age 74 years. 69.3% were colonized with a MDRO during the study. In unadjusted regression, recent antibiotic use (p<.001), open wounds (p<.05), use of urinary catheter or feeding tube (p<.001), functional disability (p<.001), diabetes (p<.01), and preadmission hospital stay over 14 days (p<.001) were associated with colonization, while Charlson comorbidity score, age, sex, and race were not. In adjusted analysis (c-statistic=0.75), a patient’s colonization risk increased with the number of risk factors (Figure 1), with 47.2% expected colonization among patients with none of the risk factors and 86.7% expected colonization among patients with four or more risk factors. The risk classification model had similar performance among male and female patients, and among Black and White patients (Figure 2). Secondary analysis using data obtained from separate, Veterans Administration facilities provided preliminary validation of the risk scoring tool. The model had acceptable fit (c-statistic=0.71). Veterans with four or more risk factors had 87.8% expected probability of MDRO colonization compared with 39.6% colonization among those without any risk factors. Veterans with less than four risk factors also had higher colonization, but these differences were not statistically significant. Conclusions. Despite system-wide efforts to reduce MDRO burden, prevalence of MDRO colonization remains high in NHs. The risk classification tool can assist in early identification of most vulnerable NH patients to direct targeted interventions such as education, enhanced environmental cleaning, and active surveillance.

Disclosure: Lona Mody: NIH, VA, CDC, Kahn Foundation; Honoraria: UpToDate; Contracted Research: Nano-Vibronix