Emotion dysregulation is considered a transdiagnostic factor with importance for a range of neurodevelopmental and mental health issues, including attention deficit hyperactivity disorder (ADHD) symptoms, internalizing problems, and conduct problems. Emotion regulation skills are acquired from early in life and are thought to strengthen gradually over childhood. Children, however, acquire these skills at different rates and slower acquisition may serve as a marker for neurodevelopmental and mental health issues. The current study uses the UK Millennium Cohort Study, a large longitudinal study to evaluate whether developmental trajectories of emotion regulation across ages 3, 5, and 7 predict levels of ADHD symptoms, internalizing problems, and conduct problems at age 7. Both higher initial levels of and slower reductions in emotion dysregulation across ages 3, 5, and 7 predicted higher ADHD symptoms, conduct problems, and internalizing problems at age 7 in both male and female children. Our findings suggest that monitoring trajectories of emotion regulation over development could help flag at-risk children. Additionally, supporting the acquisition of emotion regulation skills in this critical period could be a promising transdiagnostic preventive intervention.

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

Background: Outpatient parenteral antimicrobial therapy (OPAT) provides a safe and effective alternative to prolonged hospitalization for patients with infectious diseases requiring elongated antimicrobial therapy. One study found that 35.6% of OPAT episodes met the composite definition for treatment failure, with unplanned extension of OPAT as the most common reason for treatment failure. Our study sought to identify factors predicting higher likelihood of extension of OPAT due to slow clinical response to treatment and determine how therapy extension relates to complications. Method: This retrospective cohort study included all patients aged ≥18 years discharged on OPAT between April 2022 and October 2022. Demographic, treatment, outcome, and complications data were extracted through chart review. The primary outcome was the proportion and predictors of OPAT extension due to slow clinical response to treatment. The secondary outcomes were OPAT complication rate, 30-day ED visit and 30-day readmission rates related to OPAT complications. We used univariable and multivariable logistic regression models for the primary outcome of slow clinical response requiring OPAT extension. Variables with p < 0.1 in the univariable analyses were included in the multivariable model. Result: 231 patients received OPAT during the six-month study. Among them, 40 (17.3%) patients required an extension of therapy. In univariable analysis, patients who had slow clinical response requiring extension of OPAT were more likely to have intraabdominal infection (odds ratio [OR], 2.435; 95% confidence interval[CI], 1.053–5.628), receipt of metronidazole (OR, 3.729; 95% CI, 1.413–9.842), and were more likely to be followed up through office visit (OR, 5.033; 95%CI, 1.164–21.759) or combination of office visit and telemedicine (OR, 2.223; 95%CI 1.041–4.747). Other variable comparisons are detailed in Figure 1. In the multivariable regression analysis, the independent predictor associated with extended of OPAT was follow-up via office visit (adjusted OR, 4.630; 95% CI, 1.024-20.694). Rates of complications related to intravenous access and antibiotic were similar between patients with and without extension; 15% vs. 11% (p=0.430) and 7.5% vs. 7.3% (p=1.000), respectively. There were no significant differences in 30-day ED visits and readmission rates between the 2 groups: 7.5% vs. 5.8%(p=0.715) and 12.5% vs. 7.3% (p=0.338). Conclusion: Our study highlights patient’s office visit follow-up is associated with the OPAT extension due to slow clinical response. However, extended therapy did not result in a significant increase in complications or hospital readmissions. These findings suggest the importance of careful patient selection and monitoring for OPAT, potentially guiding more efficient and targeted healthcare practices.

Background: Multiplex molecular tests for infectious diseases can provide highly sensitive results rapidly; however, these tests may more readily detect asymptomatic colonization. There are reports of non-FDA approved laboratory-developed multiplex tests for the diagnosis of urinary tract infections (UTI). Differentiating UTI from asymptomatic bacteriuria is challenging, especially in older adults. The increased sensitivity of multiplex tests may exacerbate this challenge. We sought to describe the use of multiplex testing for UTIs in Medicare claims. Methods: Multiplex testing was identified using carrier claims submitted by non-institutional providers using the Chronic Conditions Warehouse for 2016 – 2022. Because there are no CPT-4 codes specifying UTI multiplex testing, we included claims as described in Figure 1 and categorized claims based on the primary ICD-10-CM diagnosis. The payment amounts for line items related to testing for infectious agents were summed. Laboratories were counted using CLIA numbers listed on corresponding claims. Beneficiaries residing in a nursing home at the time of their claim were identified using stay information derived from the Minimum Dataset 3.0. For comparison, similar characteristics among carrier claims with a CPT-4 code indicating urine culture were also described. Results: Claims for unspecified multiplex molecular tests overall have increased, driven by increases in claims with a primary UTI diagnosis (from 8,521 in 2016 to 386,943 in 2022), while urine cultures have not (Figure 1). In 2022, 65% of all unspecified multiplex tests were linked to a diagnosis of UTI; UTI multiplex claims were associated with 647 laboratories. For UTI claims, the median cost per claim for line items related to multiplex testing was $589 compared to $13 for urine culture-related line items. Overall, 8% of UTI multiplex claims were for beneficiaries residing in a nursing home. Conclusions: Claims for non-FDA approved unspecified multiplex tests associated with a primary diagnosis of UTI have increased >45-times between 2016-2021 and have >45-times higher median costs than urine cultures. The use of this testing in the Medicare population, including nursing home residents, is of potential concern given that inappropriate treatment of asymptomatic bacteriuria has been described to be common in older adults. Research is needed to outline use cases where UTI multiplex testing may be beneficial. Appropriate use of diagnostic testing is important to minimize diagnostic errors and avoid unnecessary antibiotic use.

Background: Inappropriate Clostridioides difficile (C. difficile) laboratory testing is common in hospitals and leads to over diagnosis, unnecessary treatment, and elevated hospital onset C. difficile infection (HO-CDI) metrics. Diagnostic stewardship is essential to avoid inappropriate testing, but limited data exists on optional interventions. Methods: A diagnostic stewardship intervention targeting CDI testing comprised of education and prospective audit with feedback was performed a VA facility (inpatient, outpatient, and long-term care units). Education on appropriate indications for CDI testing was provided in pre-intervention (9/2022 to 5/2023) and intervention periods (6/2023 to 12/2023). During the intervention period, all CDI tests (positive or negative) were audited after completion in real-time by an Infectious Diseases physician and feedback was given to ordering providers and/or their supervising physician (if trainee) for all tests not meeting an appropriate indication. Appropriate indication was defined as ≥3 liquid stools in 24 hours or symptoms of fulminant disease. Testing was considered inappropriate if no clinical symptoms, patient received laxatives within 48 hours, test was performed for test-of-cure or within 7 days of a prior test with no clinical change, or delayed testing in patients with diarrhea on admission. The rate of HO-CDI per 10,000 bed days of care (BDOC) per LabID event was compared during the pre-intervention and intervention periods, and ordering appropriateness was compared for all tests and hospital onset tests before (3/2023-5/2023) and after (6/2023-12/2023) feedback was performed. Results: After starting audit and feedback, HO-CDI rate decreased from 3.92 per 10,000 BDOC to 0.99 per 10,000 BDOC (p=0.03). HO-CDI rate among tests that were inappropriate was 2.19 and 0.80 per 10,000 BDOC during the pre-intervention and intervention periods, respectively (p=0.40). Average overall tests per month decreased from 37.8 to 28.1 after the intervention. Rate of all inappropriate tests decreased from 16.25 to 7.96 per 10,000 BDOC (p=0.04) and rate of hospital onset inappropriate tests trended toward decrease from 9.29 to 4.77 tests per 10,000 BDOC (p=0.07). The most common reasons for inappropriate testing were < 3 episodes of diarrhea in 24 hours (54% pre-intervention, 65% intervention) and laxative use (57% pre-intervention, 45% intervention). No cases of delayed testing leading to worsened disease were identified during the intervention. Cost savings for decreased tests were estimated at $150-300 per month. Conclusion: An intervention comprised of education and real-time audit and feedback of all CDI tests obtained at a VA facility resulted in decreased inappropriate testing and reduced the rate of HO-CDI.

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.

Sub-glacial canyon features up to 580 m deep between flat terraces were identified beneath Devon Ice Cap during a 2023 radar echo sounding (RES) survey. The largest canyon connects a hypothesized brine network near the Devon Ice Cap summit with the marine-terminating Sverdrup outlet glacier. This canyon represents a probable drainage route for the hypothesized water system. Radar bed reflectivity is consistently 30 dB lower along the canyon floor than on the terraces, contradicting the signature expected for sub-glacial water. We compare these data with backscattering simulations to demonstrate that the reflectivity pattern may be topographically induced. Our simulated results indicated a 10 m wide canal-like water feature is unlikely along the canyon floor, but smaller features may be difficult to detect via RES. We calculated basal temperature profiles using a 2D finite difference method and found the floor may be up to 18°C warmer than the terraces. However, temperatures remain below the pressure melting point, and there is limited evidence that the canyon floor supports a connected drainage system between the DIC summit and Sverdrup Glacier. The terrain beneath Devon Ice Cap demonstrates limitations for RES. Future studies should evaluate additional correction methods near complex terrain, such as RES simulation as we demonstrate here.

Background: Urinary tract infections (UTIs) represent a prevalent indication for outpatient antibiotic usage, yet limited data exist regarding antibiotic prescriptions within urology specialties. This study aimed to assess antibiotic prescribing patterns in urology offices over a four-year period, providing insights for potential stewardship interventions. Methods: The analysis focused on antibiotic prescribing trends in adults between 2018 and 2021 during both visit and non-visit (e.g. telephone and chart messages) encounters across 15 ambulatory Urology clinics in an academic medical center in Western New York. Exclusions were made for antivirals, antiparasitics, antifungals, oral suspensions, selected non-UTI antibiotics, duplicate orders on the same day or week, and prescriptions exceeding 28 days. Prescriptions were categorized into single doses administered in the clinic and those prescribed for 2-28 days, with descriptive statistics and trend analyses conducted using SAS v9.14. Results: Over the four-year period, 54,282 prescriptions were analyzed. Of these, 26,944 (49.7%) were single doses administered in the clinic, predominantly for pre-procedure prophylaxis. The most commonly prescribed antibiotics for prophylaxis were fluoroquinolones (FQ) (47.5%), followed by ceftriaxone (19.2%), nitrofurantoin (13.2%), trimethoprim/sulfamethoxazole (8.6%), and gentamicin (4.2%). Among the 27,288 prescriptions for 2-28 days, 72.3% were from non-visit encounters, with 61.6% prescribed by advanced practice providers (APPs) (Figure 1). The mean number of prescriptions per patient was 2.07, with women receiving more prescriptions than men (2.39 vs. 1.88, P < 0.001). FQ remained the most commonly prescribed antibiotics during all encounters (23.7%), followed by nitrofurantoin (23.0%) (Figure 2). The antibiotic duration was longer for visit-based compared to non-visit-based prescriptions (mean 10 vs. 7 days, P < 0.001). Notably, there was a significant decrease in fluoroquinolone use between Q1 2018 and Q4 2019 for both male and female patients, followed by insignificant changes thereafter. Conclusions: Antibiotic use in urology outpatient settings is substantially underestimated if only prescriptions made during visit encounters are considered. More than two-thirds of prescriptions for 2-28 days were from non-visit encounters, with the majority originating from APPs. The average therapy duration exceeded guideline recommendations. Moreover, approximately half of the antibiotics were administered in the office for pre-procedure prophylaxis. To enhance antibiotic prescribing in these specialized clinics, interventions should focus on non-visit prescriptions and provide education for APPs, alongside adjustments to default durations in electronic orders. Further evaluation is essential to assess the appropriateness of single doses for pre-procedure prophylaxis.

Background: Clostridioides difficile PCR is extremely sensitive but cannot differentiate colonization versus active disease. Over diagnosis of C. difficile infection (CDI) has negative consequences including overuse of antibiotics targeting C. difficile, increased hospital-acquired (HA)-CDI rates, and increased healthcare costs. We describe the implementation of a Clinical Decision Support tool embedded in the C. difficile order and the result on testing, HA-CDI rates and healthcare costs. Methods: The C. difficile order was updated in June 2023 with 4 dynamic questions that reflex if specific criteria are identified in the electronic medical record in the prior 24 hours: less than 3 loose stools documented, receipt of laxative, opioid antagonist, oral contrast, or tube feed initiation. If any criteria are identified, an embedded alert triggers and the provider must choose “yes, high clinical suspicion” or “no (exit and cancel order)” in addition to providing an order indication. All inpatient C. difficile tests were reviewed from July 1 to Sept 30, 2022 (pre-update) and July 1 to Sept 30, 2023 (post-update). An order rate was calculated per 10,000 patient days as well as HA-CDI rate. Cost analysis was completed using direct lab costs and published costs of $35,000 per HA-CDI. Results of the order questions were reviewed post-update. Incident rate comparison was completed using medcalc. Results: Pre-update, 1147 tests were conducted, with an order rate of 104.3. Post-update, 919 tests were performed, with an order rate of 86.6. The positivity rate was 16.1% pre-update and 14.7% post-update. The incidence rate difference was 0.00177 (P 15 (145, 16%). 166 (18%) patients who received laxatives (18 positive, positivity rate 11%) were still tested. Conclusion: Implementation of a dynamic order led to a significant reduction in the total number of C. difficile PCR tests performed with associated reduction in HA-CDI and cost savings. Despite this, patients receiving laxatives were still being tested for C. difficile, highlighting the need for ongoing education and feedback. These results support the use of dynamic ordering for diagnostic stewardship, which can benefit both patients and hospitals.

Background: Coagulase-negative staphylococci (CoNS) are often considered contaminants when isolated from blood cultures. While criteria exist to distinguish true bacteremia from contamination (Table 1), clinical judgement is often necessary. Clinical microbiology laboratories have traditionally identified CoNS to the species level only if present in multiple cultures. There have been concerns that blood cultures positive for rare or less familiar CoNS species might be misinterpreted as true bacteremia. Tufts Medical Center (TMC) clinical microbiology laboratory started reporting all CoNS to the species level in January 2023. We studied the impact of species-level identification of CoNS on clinically relevant outcomes following this change. Methods: The study evaluated inpatients at TMC aged ≥ 18 years with CoNS isolated from blood cultures between July 2022 and June 2023. The primary outcome was the difference in anti-staphylococcal antibiotic utilization between the pre- and post-intervention groups. Secondary outcomes included differences in true bacteremia diagnosis, length of hospital stay, and mortality between the two groups. We also compared the performance of Souvenir’s criteria with clinical judgement at distinguishing contamination from true bacteremia. A total of 100 patients were included in the pre- and post-intervention groups to detect an estimated effect size of 15% with a power of 81%. Results: Most patients were male, White, and English speaking (Table 2). No differences were found between the two groups in terms of infectious disease consultation frequency, blood culture collection department, or the presence of central venous catheters (Table 2). Staphylococcus epidermidis was the predominant CoNS in the post-intervention group. Blood cultures were repeated before and after starting antibiotics in 24% and 74% (pre-intervention) and 18% and 84% (post-intervention) of cases, respectively. Anti-staphylococcus antibiotic use was the same in both groups (82%). The median antibiotic therapy duration was 4.5 days pre- vs 3 days post-intervention (p =0.39). There were no differences in hospital length of stay or mortality between the two groups (Table 3). The clinical diagnosis of true bacteremia was established in 28% of cases in the pre- vs 25% in the post-intervention group (p= 0.63). Compared to clinical judgement, Souvenir’s true bacteremia criteria demonstrated a sensitivity of 80.3%, negative PV of 91.9%, and positive PV of 55.2%. Conclusions: Species-level identification of CoNS positive blood cultures did not impact antibiotic utilization, diagnosis of true bacteremia, length of hospital stay, or mortality. Further studies with larger cohorts and prospective designs are needed to validate these findings and assess the long-term implications in patients.

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: The Uganda Ministry of Health (MoH) and implementing partners instituted an infection prevention and control (IPC) response strategy during the Uganda SVD outbreak in 2022 that involved rapid enhancement of screening capacity at HCFs. Rapid scale-up of screening for infectious diseases, such as SVD, is critical for early identification and triage of suspected or confirmed cases in HCFs. We describe the rapid deployment of a multimodal IPC strategy implemented in response to the SVD outbreak and the resulting impact on screening measures at HCFs. Methods: We implemented a multimodal IPC strategy in HCFs from five high risk districts to improve screening practices from November 2022–January 2023. The strategy included training health workers (HCWs) identified as IPC mentors; establishing screening areas; and providing screening supplies and communication materials. The three-day training utilized an MoH standardized training package with didactic and practice sessions. The mentors then cascaded screening information and skills to other HCWs through onsite trainings and mentorships and established screening areas. Baseline and endline (3 months after baseline) cross-sectional assessments were conducted using the MoH IPC Assessment Tool adapted from the WHO Ebola IPC Scorecard. The five main screening parameters assessed included presence of ≥ 1 meter distance between screener and the person screened, availability of a functional handwashing facility and infrared thermometer, correct record of each person’s temperature, and appropriate referral process for those suspected of having SVD to holding areas. IPC capacity was measured through the summation of each of these parameter results and calculated as an overall percentage. IBM SPSS Statistics 20 software was used for data analysis and a paired t-test done to determine any significant findings between mean scores (percentage) at baseline and endpoint. Results: A total of 296 IPC mentors were trained, screening information was cascaded to 3,899 HCWs, and screening areas were established in 1,135 HCFs. Based on the screening results from the MoH IPC assessment tool, capacity improved from 44% (SD=37) at baseline to 67% (SD=34) at endpoint. Screening capacity improved from baseline to endpoint among level II and public HCFs from 33% (SD=35) to 60% (SD=35) (p < 0 .05) and from 54% (SD=38) to 76% (SD=31) (p < 0 .05), respectively. Conclusion: Rapid implementation of a multimodal IPC strategy was successful in enhancing screening capacity across Uganda’s HCFs during a SVD response, which is critical for early identification of infected patients to interrupt transmission. This multimodal approach should be recommended for future response actions.

Previous approaches to modelling interval-censored data have often relied on assumptions of homogeneity in the sense that the censoring mechanism, the underlying distribution of occurrence times, or both, are assumed to be time-invariant. In this work, we introduce a model which allows for non-homogeneous behaviour in both cases. In particular, we outline a censoring mechanism based on a non-homogeneous alternating renewal process in which interval generation is assumed to be time-dependent, and we propose a Markov point process model for the underlying occurrence time distribution. We prove the existence of this process and derive the conditional distribution of the occurrence times given the intervals. We provide a framework within which the process can be accurately modelled, and subsequently compare our model to the homogeneous approach through a number of illustrative examples.

Background: Oral antimicrobial therapy for osteoarticular infections in adults is increasingly adopted; however, the preponderance of published data and experience with oral antibiotics involves agents such as fluoroquinolones, trimethoprim-sulfamethoxazole, and clindamycin. Data supporting the use of narrower-spectrum, stewardship-friendly oral antibiotics with favorable toxicities profiles (e.g. cefadroxil) are needed. Methods: We report a case series of adults who underwent surgery for monomicrobial Gram-positive osteomyelitis, native joint septic arthritis (NJSA), prosthetic joint infection (PJI), or other orthopedic hardware infection at our institution from January 2019 through January 2022 and who subsequently received at least two weeks of oral cefadroxil. We excluded patients who had polymicrobial infection or curative amputation, or who received cefadroxil only as suppressive antibiotic therapy (SAT). Our primary outcome of interest was treatment success during followup, defined as freedom from death, unplanned surgery for infection, or readmission for worsening infection. Results: We identified 22 patients who received cefadroxil for primary treatment of osteoarticular infection. The mean age was 57.6 years, mean weight 98.6 kg, 68% were male, and none had peripheral vascular disease. Infections included PJI in 12, NJSA in 8, osteomyelitis in 7, and other hardware infections in 5; some patients had multiple infectious syndromes. Methicillin-susceptible Staphylococcus aureus (MSSA) was the most common pathogen (73%), followed by streptococci (18%), other methicillin-susceptible staphylococci (14%), and Cutibacterium acnes (5%). Half of patients received 120kg who had device infections with MSSA, two of which were managed with implant retention, suggesting pharmacokinetic/pharmacodynamic factors and biofilm burden could influence treatment outcome. Limitations of this study include its small sample size, noncomparative nature, lengthy initial intravenous antibiotic durations, and limited durations of followup. These data suggest cefadroxil merits investigation for adult osteoarticular infection in larger comparative (and ideally, prospective randomized) studies.

Background: Candida auris, an emerging multidrug-resistant fungus, is often difficult to control in hospital outbreaks. We report the hospital investigation and findings of a transmission of C. auris from patients hospitalized in an adult unit to a pediatric unit, the first in Maryland. Methods: Between June and September 2023, C. auris was recovered from two patients admitted to an adult Neuroscience Intensive Care Unit (ICU) and a patient admitted to a pediatric ICU. Infection control initiated an investigation involving staff interviews, observations and chart reviews. Cases were defined as any patient with clinical or surveillance cultures growing C. auris. Point prevalence surveillance was conducted by collecting nares and composite axilla/groin swabs from patients on the affected units. Environmental cultures collected using moistened E-Swabs (Copan, Murrieta, CA) from shared supplies were plated on CHROMagar Candida (BD, Sparks, MD). C. auris isolates from patients hospitalized at the facility between February 2022 and October 2023 were analyzed by WGS for relatedness. WGS was performed using Illumina NextSeq 300 bp paired-end sequencing (Illumina, San Diego, CA). Single nucleotide polymorphism (SNP) analysis was performed by comparing raw reads to the reference C. auris B8441 genome for subsequent clustering analysis (Ares Genetics, Vienna, Austria). Results: WGS demonstrated isolates from two adults and one pediatric patient were less than three SNPs different, suggesting a shared isolate. One additional pediatric case was identified from surveillance cultures collected from 27 patients. Investigation into possible transmission routes revealed healthcare personnel serving both units, specifically clinical teams and continuous electroencephalography (cEEG) technologists. Additionally, cEEG equipment was used on both adult and pediatric patients and twelve equipment surface swabs and three samples each of measuring tape and gel were collected. C. auris was not isolated, however sensitivity of environmental sampling is unclear and suspicion for possible fomite/environmental transmission persisted. Other possible transmission routes included gaps in hand hygiene, isolation, disinfection of shared equipment, and reuse of single-use items. Interventions included improving and monitoring infection prevention practices, educating multi-disciplinary personnel and heightened environmental cleaning. Conclusion: This case highlights the feasibility of transmission of C. auris between patients admitted to a geographically distant unit. Our investigation revealed multiple possible routes of transmission including direct contact (from healthcare personnel or equipment) or indirect environmental sources. Prevention of hospital-associated C. auris transmission likely necessitates meticulous adherence to hand hygiene, contact precautions, and careful cleaning and disinfection of patient environments and equipment used by all disciplines.

Disclosure: Patricia Simner: Research Contracts: BD Diagnostics, OpGen Inc., Qiagen Sciences Inc, T2 Diagnostics, Accelerate Diagnostics; Research Collaborators:Ares Genetics, CosmosID, IDbyDNA, Illumina; Consulting: OpGen Inc., BD Diagnostics, Shionogi Inc., GeneCapture, Qiagen Sciences Inc, Entasis, Day Zero Diagnostics, Next Gen Diagnostics

We address the hypothesis that at early and late lactation milk presents low ethanol stability due to high acidity and ionic calcium values. Our aim was to evaluate the functional traits of milk (milk ethanol stability: MES, acidity and ionic calcium: iCa) according to lactation stage in different genetic groups. Raw milk samples were collected from Jersey (n = 271), Holstein (n = 248) and Jersey × Holstein crossbred cows (n = 82), raised on five commercial farms located in the state of Paraná, Brazil. Milk composition, somatic cell count (SCC), milk urea nitrogen (MUN), MES, pH, acidity and iCa were determined. Days in milk (DIM) were categorized into four classes: 1–60, 61–150, 151–305 and over 305 DIM. Data were submitted to analysis of variance. Fixed and random effects were incorporated into the model, in a repeated measures in time arrangement using the mixed models methodology. Significant interactions between DIM class and genetic groups were detected. The comparison between each combination of genetic group and DIM class showed that at the beginning of lactation, Holsteins produced milk with higher MES than Jersey and crossbreds. At 105–305 DIM Holstein milk presented higher MES than Jersey, while beyond 305 DIM Holstein milk showed higher MES than crossbred cows. At the beginning of lactation acidity was higher in Holstein milk and crossbreds compared with Jersey, while acidity was lower in Holstein milk compared with Jersey and crossbreds in the other lactation stages. Ionic calcium was highest after lactation peak for Holstein, but did not vary between lactation stages for Jersey and crossbreds. Functional characteristics of bovine raw milk such as MES, iCa and acidity varied between lactation stages in a distinct manner according to genetic groups. Early and end lactation stages are challenging in terms of low stability, especially for Jersey and crossbreds.

Background: Asymptomatic bacteriuria (ASB) is often treated with antibiotics despite recommendations against screening for and treating ASB in most populations. Some providers cite concern for progression of ASB to a symptomatic urinary tract infection (UTI) as the jultification for antibiotic use. While the 2019 Infectious Diseases Society of America (IDSA) ASB guidelines refute this concern, most evidence is derived from studies done in females, potentially limiting external validity. The purpose of this study is to compare the outcomes of patients with ASB who received antibiotic treatment versus those who did not in a primarily male population. Methods: This is a multi-center, retrospective, cohort study conducted by the 5 sites within the Veterans Affairs MidSouth Healthcare Network. Patients with a positive urine culture (defined as cultures with a colony forming unit count >100,000) collected from January 1, 2021 through December 31, 2021 were identified. ASB was determined via chart review using pre-determined criteria (positive culture in the absence of reported or documented signs or symptoms attributable to UTI as defined by the 2019 IDSA ASB guidelines). Additional data collected included antibiotic use, clinic visits and hospital admissions related to UTI or sepsis from a UTI. The primary outcome was the comparison of UTI incidence at 30 days, 6 months, and 1 year in those untreated versus treated with antibiotics. Secondary outcomes included a comparison of admissions with sepsis from UTI and adverse drug reactions (ADRs) between the cohorts. Continuous data were analyzed using a Student’s t-test. Discrete data were analyzed using either a Chi-squared or Fisher’s exact test. Results: The study population was primarily elderly (73 years, range 27-99 years) and male (79.7%). Of the 281 patients with ASB, 127 (45.2%) and 154 (54.8%) were untreated and treated, respectively. The incidence of UTI was 3% versus 1% (p = 0.41) at 30 days, 10% versus 12% (p = 0.61) at 6 months and 11% versus 12% (p = 0.94) at 12 months in the untreated and treated cohorts, respectively. There was no difference in admissions for UTI, sepsis from UTI or ADRs at 30 days. Conclusion: This study found no difference in the development of symptomatic UTI in veterans with untreated ASB compared to those treated with antibiotics. These findings align with current ASB guideline recommendations and support avoidance of unnecessary antibiotic use in the veteran population.