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ObjectivesThe role of follow-up blood cultures (FUBCs) in the management of Gram-negative bacteraemia (GNB) is poorly understood. We aimed to determine the utility of FUBCs in identifying patients with increased mortality risk.MethodsAn observational study with a prospectively enrolled cohort of adult inpatients with GNB was conducted at Duke University Health System from 2002 to 2015. FUBCs were defined as blood cultures performed from 24 hours to 7 days from initial positive blood culture.ResultsAmong 1702 patients with GNB, 1164 (68%) had FUBCs performed. When performed, FUBCs were positive in 20% (228/1113) of cases. FUBC acquisition was associated with lower all-cause in-hospital mortality (108/538, 20%, vs. 176/1164, 15%; p 0.01) and attributable in-hospital mortality (78/538, 15%, vs. 98/1164, 8%; p

We present extended X-ray absorption fine structure (EXAFS) spectra and modeling of a series of structurally tunable quasi-one-dimensional mixed-valence platinum-halide linear chain materials, [Pt(en2)][Pt(en2)X2](ClO4)4 with X = Cl, Br, I. The materials exhibit a commensurate charge density wave with fractional charge states on alternating platinum ions in the chain, as well as a Peierls distortion with alternating platinum-halide bond lengths. The amplitude of the charge density wave and, correspondingly, the extent of the Peierls distortion are controlled by the identity of the bridging halide ion. We have carried out ab initio multiple scattering calculations using the FEFF9 code to relate the oriented Pt LIII EXAFS spectra to the tunable electronic and structural properties. The spectral modeling reveals distinct photoelectron threshold energy values for the two inequivalent platinum ions in each of the mixed-valence chains, with values that vary systematically with fractional valence state. The difference in the photoelectron threshold energies of the two inequivalent platinum ions within each material correlates directly with the amplitude of the charge density wave, reflecting the decrease in charge density wave strength through the halide series X = Cl, Br, and I. We use dynamical matrix modeling to relate the experimentally determined mean-square relative displacement parameters for the metal-halide bond distances to the chain-axis vibrational modes that modulate the charge density wave structure. In addition, we discuss the EXAFS fitting results for the Pt-I bond lengths in the [Pt(en2)][Pt(en2)I2](ClO4)4 complex in comparison to previous, mutually inconsistent structural determinations for this material.

Abstract Plants used for treating endo- and ectoparasites of rabbits and poultry in British Columbia included Arctium lappa (burdock), Artemisia sp. (wormwood), Chenopodium album (lambsquarters) and C. ambrosioides (epazote), Cirsium arvense (Canada thistle), Juniperus spp. (juniper), Mentha piperita (peppermint), Nicotiana sp. (tobacco), Papaver somniferum (opium poppy), Rubus spp. (blackberry and raspberry relatives), Symphytum officinale (comfrey), Taraxacum officinale (common dandelion), Thuja plicata (western redcedar) and Urtica dioica (stinging nettle).

Abstract Background Developing and evaluating new technology that enables researchers to recover gene-expression levels of colonic cells from fecal samples could be key to a non-invasive screening tool for early detection of colon cancer. The current study, to the best of our knowledge, is the first to investigate and report the reproducibility of fecal microarray data. Using the intraclass correlation coefficient (ICC) as a measure of reproducibility and the preliminary analysis of fecal and mucosal data, we assessed the reliability of mixture density estimation and the reproducibility of fecal microarray data. Using Monte Carlo-based methods, we explored whether ICC values should be modeled as a beta-mixture or transformed first and fitted with a normal-mixture. We used outcomes from bootstrapped goodness-of-fit tests to determine which approach is less sensitive toward potential violation of distributional assumptions. Results The graphical examination of both the distributions of ICC and probit-transformed ICC (PT-ICC) clearly shows that there are two components in the distributions. For ICC measurements, which are between 0 and 1, the practice in literature has been to assume that the data points are from a beta-mixture distribution. Nevertheless, in our study we show that the use of a normal-mixture modeling approach on PT-ICC could provide superior performance. Conclusions When modeling ICC values of gene expression levels, using mixture of normals in the probit-transformed (PT) scale is less sensitive toward model mis-specification than using mixture of betas. We show that a biased conclusion could be made if we follow the traditional approach and model the two sets of ICC values using the mixture of betas directly. The problematic estimation arises from the sensitivity of beta-mixtures toward model mis-specification, particularly when there are observations in the neighborhood of the the boundary points, 0 or 1. Since beta-mixture modeling is commonly used in approximating the distribution of measurements between 0 and 1, our findings have important implications beyond the findings of the current study. By using the normal-mixture approach on PT-ICC, we observed the quality of reproducible genes in fecal array data to be comparable to those in mucosal arrays.

Abstract Background The use of medicinal plants is an option for livestock farmers who are not allowed to use allopathic drugs under certified organic programs or cannot afford to use allopathic drugs for minor health problems of livestock. Methods In 2003 we conducted semi-structured interviews with 60 participants obtained using a purposive sample. Medicinal plants are used to treat a range of conditions. A draft manual prepared from the data was then evaluated by participants at a participatory workshop. Results There are 128 plants used for ruminant health and diets, representing several plant families. The following plants are used for abscesses: Berberis aquifolium/Mahonia aquifolium Echinacea purpurea, Symphytum officinale, Bovista pila, Bovista plumbea, Achillea millefolium and Usnea longissima. Curcuma longa L., Salix scouleriana and Salix lucida are used for caprine arthritis and caprine arthritis encephalitis.Euphrasia officinalis and Matricaria chamomilla are used for eye problems. Wounds and injuries are treated with Bovista spp., Usnea longissima, Calendula officinalis, Arnica sp., Malva sp., Prunella vulgaris, Echinacea purpurea, Berberis aquifolium/Mahonia aquifolium, Achillea millefolium, Capsella bursa-pastoris, Hypericum perforatum, Lavandula officinalis, Symphytum officinale and Curcuma longa. Syzygium aromaticum and Pseudotsuga menziesii are used for coccidiosis. The following plants are used for diarrhea and scours: Plantago major, Calendula officinalis, Urtica dioica, Symphytum officinale, Pinus ponderosa, Potentilla pacifica, Althaea officinalis, Anethum graveolens, Salix alba and Ulmus fulva. Mastitis is treated with Achillea millefolium, Arctium lappa, Salix alba, Teucrium scorodonia and Galium aparine. Anethum graveolens and Rubus sp., are given for increased milk production.Taraxacum officinale, Zea mays, and Symphytum officinale are used for udder edema. Ketosis is treated with Gaultheria shallon, Vaccinium sp., and Symphytum officinale. Hedera helix and Alchemilla vulgaris are fed for retained placenta. Conclusion Some of the plants showing high levels of validity were Hedera helix for retained placenta and Euphrasia officinalis for eye problems. Plants with high validity for wounds and injuries included Hypericum perforatum, Malva parviflora and Prunella vulgaris. Treatments with high validity against endoparasites included those with Juniperus communis and Pinus ponderosa. Anxiety and pain are well treated with Melissa officinalis and Nepeta caesarea.

Abstract This paper investigates the commonalities in ethnoveterinary medicine used for horses between Trinidad (West Indies) and British Columbia (Canada). These research areas are part of a common market in pharmaceuticals and are both involved in the North American racing circuit. There has been very little research conducted on medicinal plants used for horses although their use is widespread. The data on ethnoveterinary medicines used for horses was obtained through key informant interviews with horse owners, trainers, breeders, jockeys, grooms and animal care specialists in two research areas: Trinidad and British Columbia (BC). A participatory validation workshop was held in BC. An extensive literature review and botanical identification of the plants was also done. In all, 20 plants were found to be used in treating racehorses in Trinidad and 97 in BC. Of these the most-evidently effective plants 19 of the plants used in Trinidad and 66 of those used in BC are described and evaluated in this paper. Aloe vera, Curcuma longa and Ricinus communis are used in both research areas. More research is needed in Trinidad to identify plants that respondents claimed were used in the past. Far more studies have been conducted on the temperate and Chinese medicinal plants used in BC and therefore these ethnoveterinary remedies reflect stronger evidence of efficacy.

Background: Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections., Methods: This was a retrospective cohort of all patients with an ID consult within an academic health system from 1 January 2014 through 31 December 2023, including community, general, and transplant ID consult services., Results: There were 60 820 inpatient ID consults (17 235 community, 29 999 general, and 13 586 transplant) involving 37 848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (P < .001). In total, 7.5% of patients receiving an ID consult died during admission and 1006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (P < .001). Six-month mortality was 9% for all nonobstetric admissions versus 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID. In total 2866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. A total of 16.3% of patients had a do-not-resuscitate order during the index hospitalization; 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult., Conclusions: Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: We aimed to determine whether automated identification of antibiotic targeting suspected urinary tract infection (UTI) shortened the time to antimicrobial stewardship (AS) intervention., Design: Retrospective before-and-after study., Setting: Tertiary and quaternary care academic medical center., Patients: Emergency department (ED) or admitted adult patients meeting best practice alert (BPA) criteria during pre- and post-BPA periods., Methods: We developed a BPA to alert AS pharmacists of potential ASB triggered by the following criteria: ED or admitted status, antibiotic order with genitourinary indication, and a preceding urinalysis with ≤ 10 WBC/hpf. We evaluated the median time from antibiotic order to AS intervention and overall percent of UTI-related interventions among patients in pre-BPA (01/2020-12/2020) and post-BPA (04/15/2021-04/30/2022) periods., Results: 774 antibiotic orders met inclusion criteria: 355 in the pre- and 419 in the post-BPA group. 43 (35 UTI-related) pre-BPA and 117 (94 UTI-related) post-BPA interventions were documented. The median time to intervention was 28 hours (IQR 18-65) in the pre-BPA group compared to 16 hours (IQR 2-34) in the post-BPA group ( P < 0.01). Despite absent pyuria, there were six cases with gram-negative bacteremia presumably from a urinary source., Conclusions: Automated identification of antibiotics targeting UTI without pyuria on urinalysis reduced the time to stewardship intervention and increased the rate of UTI-specific interventions. Clinical decision support aided in the efficiency of AS review and syndrome-targeted impact, but cases still required AS clinical review., Competing Interests: S.D.A. reports support from the Centers from Disease Control and Prevention (grant nos. 5U54CK000616-02 and SHEPheRD 75D30121D12733-D5-E003), National Institutes of Health (National Institute of Diabetes and Digestive and Kidney Diseases grant no. K12DK100024), the Society for Healthcare Epidemiology of America, and as well as prior consulting fees from Locus Biosciences, Sysmex America, GlaxoSmithKline, bioMérieux, and the Infectious Diseases Society of America. Additionally, S.D.A is an employee of GSK/ViiV Health care as of July 1, 2024 and holds stock in GlaxoSmithKline., (© The Author(s) 2024.)

In a multihospital cohort study of 3392 patients, positive urinalysis parameters had poor positive predictive value for diagnosing urinary tract infection (UTI). Combined urinalysis parameters (pyuria or nitrite) performed better than pyuria alone for ruling out UTI. However, performance of all urinalysis parameters was poor in older women., Competing Interests: Potential conflicts of interest. S. D. A. and R. N. report support from the Centers for Disease Control and Prevention (SHEPheRD 75D30121D12733-D5-E003) and the Duke Claude D. Pepper Older Americans Independence Center (National Institute on Aging grant number P30AG028716). S. D. A. also reports support from the Society for Healthcare Epidemiology of America, as well as consulting fees from Locus Biosciences (ended), Sysmex America (ended), GlaxoSmithKline, bioMérieux, and the Infectious Diseases Society of America.. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Cardiac fibroblasts are pivotal regulators of cardiac homeostasis and are essential in the repair of the heart after myocardial infarction (MI), but their function can also become dysregulated, leading to adverse cardiac remodelling involving both fibrosis and hypertrophy. MicroRNAs (miRNAs) are noncoding RNAs that target mRNAs to prevent their translation, with specific miRNAs showing differential expression and regulation in cardiovascular disease. Here, we show that miR-214-3p is enriched in the fibroblast fraction of the murine heart, and its levels are increased with cardiac remodelling associated with heart failure, or in the acute phase after experimental MI. Tandem mass tagging proteomics and in-silico network analyses were used to explore protein targets regulated by miR-214-3p in cultured human cardiac fibroblasts from multiple donors. Overexpression of miR-214-3p by miRNA mimics resulted in decreased expression and activity of the Piezo1 mechanosensitive cation channel, increased expression of the entire lysyl oxidase (LOX) family of collagen cross-linking enzymes, and decreased expression of an array of mitochondrial proteins, including mitofusin-2 (MFN2), resulting in mitochondrial dysfunction, as measured by citrate synthase and Seahorse mitochondrial respiration assays. Collectively, our data suggest that miR-214-3p is an important regulator of cardiac fibroblast phenotypes and functions key to cardiac remodelling, and that this miRNA represents a potential therapeutic target in cardiovascular disease., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Frequently used physical therapy (PT) equipment is difficult to disinfect due to equipment material and shape. The efficacy of standard disinfection of PT equipment is poorly understood., Methods: We completed a 2-phase prospective microbiological analysis of fomites used in PT at our hospital from September 2022 to October 2023. For both phases, study fomites were obtained after usage and split into symmetrical halves for sampling. In phase 1, sides were sampled following standard disinfection. In phase 2, sides were randomized 1:1 to intervention or control. Samples were obtained before and after the intervention, a disinfection cabinet using Ultraviolet C (UV-C) and 6% nebulized hydrogen peroxide. We defined antimicrobial-resistant clinically important pathogens (AMR CIP) as methicillin-resistant staphylococcus aureus (MRSA), Vancomycin Resistant Enterococcus (VRE), and Multidrug resistant (MDR)-Gram-negatives and non-AMR CIP as methicillin-sensitive staphylococcus aureus (MSSA), Vancomycin sensitive Enterococcus (VSE), and Gram-negatives. Three assessments were made: 1) contamination following standard disinfection (phase 1), 2) contamination postintervention compared to no disinfection (phase 2) and, 3) contamination following standard disinfection compared to postintervention (phase 1 vs phase 2 intervention)., Results: The median total colony-forming units (CFU) from 122 study fomite samples was 1,348 (IQR 398-2,365). At the sample level, 52(43%) and 15(12%) of samples harbored any clinically important pathogens (CIPs) or AMR CIPs, respectively. The median CFU was 0 (IQR 0-55) in the intervention group and 977 (409-2,547) in the control group ( P < .00001)., Conclusion: Following standard disinfection, PT equipment remained heavily contaminated including AMR and non-AMR CIPs. Following the intervention, PT equipment was less contaminated and harbored no AMR CIPs compared to control sides supporting the efficacy of the intervention on difficult-to-disinfect PT fomites.

Background: A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates., Objectives: We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic., Methods: We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups., Results: Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%., Conclusions: These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To determine whether removal of default duration, embedded in electronic prescription (e-script), influenced antibiotic days of therapy., Design: Interrupted time-series analysis., Setting: The study was conducted across 2 community hospitals, 1 academic hospital, 3 emergency departments, and 86 ambulatory clinics., Patients: Adults prescribed a fluoroquinolone with a duration <31 days., Interventions: Removal of standard 10-day fluoroquinolone default duration and addition of literature-based duration guidance in the order entry on December 19, 2017. The study period included data for 12 months before and after the intervention., Results: The study included 35,609 fluoroquinolone e-scripts from the preintervention period and 31,303 fluoroquinolone e-scripts from the postintervention period, accounting for 520,388 cumulative fluoroquinolone DOT. Mean durations before and after the intervention were 7.8 (SD, 4.3) and 7.7 (SD, 4.5), a nonsignificant change. E-scripts with a 10-day duration decreased prior to and after the default removal. The inpatient setting showed a significant 8% drop in 10-day e-scripts after default removal and a reduced median duration by 1 day; 10-day scripts declined nonsignificantly in ED and ambulatory settings. In the ambulatory settings, both 7- and 14-day e-script durations increased after default removal., Conclusion: Removal of default 10-day antibiotic durations did not affect overall mean duration but did shift patterns in prescribing, depending on practice setting. Stewardship interventions must be studied in the context of practice setting. Ambulatory stewardship efforts separate from inpatient programs are needed because interventions cannot be assumed to have similar effects.

Background and Objectives: The messenger RNA (mRNA)-based coronavirus disease 2019 vaccines approved for use in children <5 years of age have different antigen doses and administration schedules that could affect vaccine immunogenicity and effectiveness. We sought to compare the strength and breadth of serum binding and neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) elicited by monovalent mRNA-based coronavirus disease 2019 vaccines in young children., Methods: We conducted a prospective cohort study of children 6 months to 4 years of age who completed primary series vaccination with monovalent mRNA-1273 or BNT162b2 vaccines. Serum was collected 1 month after primary vaccine series completion for the measurement of SARS-CoV-2-specific humoral immune responses, including antibody binding responses to Spike proteins from an ancestral strain (D614G) and major variants of SARS-CoV-2 and antibody neutralizing activity against D614G and Omicron subvariants (BA.1, BA.4/5)., Results: Of 75 participants, 40 (53%) received mRNA-1273 and 35 (47%) received BNT162b2. Children receiving either primary vaccine series developed robust and broad SARS-CoV-2-specific binding and neutralizing antibodies, including to Omicron subvariants. Children with a previous history of SARS-CoV-2 infection developed significantly higher antibody binding responses and neutralization titers to Omicron subvariants, which is consistent with the occurrence of identified infections during the circulation of Omicron subvariants in the region., Conclusions: Monovalent mRNA-1273 and BNT162b2 elicited similar antibody responses 1 month after vaccination in young children. In addition, previous infection significantly enhanced the strength of antibody responses to Omicron subvariants. The authors of future studies should evaluate incorporation of these vaccines into the standard childhood immunization schedule.

Purpose: Patients with suspected UTIs are categorized into 3 clinical phenotypes based on current guidelines: no UTI, asymptomatic bacteriuria (ASB), or UTI. However, all patients may not fit neatly into these groups. Our objective was to characterize clinical presentations of patients who receive urine tests using the "continuum of UTI" approach., Materials and Methods: This was a retrospective cohort study of a random sample of adult noncatheterized inpatient and emergency department encounters with paired urinalysis and urine cultures from 5 hospitals in 3 states between January 01, 2017, and December 31, 2019. Trained abstractors collected clinical (eg, symptom) and demographic data. A focus group discussion with multidisciplinary experts was conducted to define the continuum of UTI, a 5-level classification scheme that includes 2 new categories: lower urinary tract symptoms/other urologic symptoms and bacteriuria of unclear significance. The newly defined continuum of UTI categories were compared to the current UTI classification scheme., Results: Of 220,531 encounters, 3392 randomly selected encounters were reviewed. Based on the current classification scheme, 32.1% (n = 704) had ASB and 53% (n = 1614) did not have a UTI. When applying the continuum of UTI categories, 68% of patients (n = 478) with ASB were reclassified as bacteriuria of unclear significance and 29% of patients (n = 467) with "no UTI" were reclassified to lower urinary tract symptoms/other urologic symptoms., Conclusions: Our data suggest the need to reframe our conceptual model of UTI vs ASB to reflect the full spectrum of clinical presentations, acknowledge the diagnostic uncertainty faced by frontline clinicians, and promote a nuanced approach to diagnosis and management of UTIs.

Objective: To analyze Clostridioides difficile testing in 3 hospitals in central North Carolina to validate previous racial health-disparity findings., Methods: We completed a retrospective analysis of inpatient C. difficile tests from 2015 to 2021 at 3 university-affiliated hospitals in North Carolina. We calculated the number of C. difficile tests per 1,000 patient days stratified by race: White, Black, and non-White, non-Black (NWNB). We defined a unique C. difficile test as one that occurred in an inpatient unit with a matching laboratory accession ID and on differing calendar days. Tests were evaluated overall, by hospital, by year, and by positivity rate., Results: In total, 35,160 C. difficile tests and 2,571,850 patient days across all 3 hospitals from 2015 to 2021 were analyzed. The median number of C. difficile tests per 1,000 patient days was 13.85 (interquartile range [IQR], 9.88-16.07). Among all C. difficile tests, 5,225 (15%) were positive. White patients were administered more C. difficile tests (14.46 per 1,000 patient days) than Black patients (12.96; P < .0001) or NWNB race patients (10.27; P < .0001). Black patients were administered more tests than NWNB patients ( P < .0001). White patients tested positive at a similar rate to Black patients (15% vs 15%; P = .3655) and higher than NWNB individuals (12%; P = .0061), and Black patients tested positive at a higher rate than NWNB patients ( P = .0024)., Conclusion: White patients received more C. difficile tests than Black and NWNB patient groups when controlling for race patient days. Future studies should control for comorbidities and investigate community onset of C. difficile by race and ethnicity.

Importance: Despite modest reductions in the incidence of hospital-onset Clostridioides difficile infection (HO-CDI), CDI remains a leading cause of health care-associated infection. As no single intervention has proven highly effective on its own, a multifaceted approach to controlling HO-CDI is needed., Objective: To assess the effectiveness of the Centers for Disease Control and Prevention's Strategies to Prevent Clostridioides difficile Infection in Acute Care Facilities Framework (hereafter, the Framework) in reducing HO-CDI incidence., Design, Setting, and Participants: This quality improvement study was performed within the Duke Infection Control Outreach Network from July 1, 2019, through March 31, 2022. In all, 20 hospitals in the network participated in an implementation study of the Framework recommendations, and 26 hospitals did not participate and served as controls. The Framework has 39 discrete intervention categories organized into 5 focal areas for CDI prevention: (1) isolation and contact precautions, (2) CDI confirmation, (3) environmental cleaning, (4) infrastructure development, and (5) antimicrobial stewardship engagement., Exposures: Monthly teleconferences supporting Framework implementation for the participating hospitals., Main Outcomes and Measures: Primary outcomes were HO-CDI incidence trends at participating hospitals compared with controls and postintervention HO-CDI incidence at intervention sites compared with rates during the 24 months before the intervention., Results: The study sample included a total of 2184 HO-CDI cases and 7 269 429 patient-days. In the intervention cohort of 20 participating hospitals, there were 1403 HO-CDI cases and 3 513 755 patient-days, with a median (IQR) HO-CDI incidence of 2.8 (2.0-4.3) cases per 10 000 patient-days. The first analysis included an additional 3 755 674 patient-days and 781 HO-CDI cases among the 26 controls, with a median (IQR) HO-CDI incidence of 1.1 (0.7-2.7) case per 10 000 patient-days. The second analysis included an additional 2 538 874 patient-days and 1751 HO-CDI cases, with a median (IQR) HO-CDI incidence of 5.9 (2.7-8.9) cases per 10 000 patient-days, from participating hospitals 24 months before the intervention. In the first analysis, intervention sites had a steeper decline in HO-CDI incidence over time relative to controls (yearly incidence rate ratio [IRR], 0.79 [95% CI, 0.67-0.94]; P = .01), but the decline was not temporally associated with study participation. In the second analysis, HO-CDI incidence was declining in participating hospitals before the intervention, and the rate of decline did not change during the intervention. The degree to which hospitals implemented the Framework was associated with steeper declines in HO-CDI incidence (yearly IRR, 0.95 [95% CI, 0.90-0.99]; P = .03)., Conclusions and Relevance: In this quality improvement study of a regional hospital network, implementation of the Framework was not temporally associated with declining HO-CDI incidence. Further study of the effectiveness of multimodal prevention measures for controlling HO-CDI is warranted.

Importance: Black patients are more likely than White patients to be restrained during behavioral crises in emergency departments (EDs). Although the perils of policing mental health for Black individuals are recognized, it is unclear whether or to what extent police transport mediates the association between Black race and use of physical restraint in EDs., Objective: To evaluate the degree to which police transport mediates the association between Black race and use of physical restraint in EDs., Design, Setting, and Participants: This retrospective, cross-sectional study used electronic health record data from ED visits by adults (aged ≥18 years) to 3 hospitals in the southeastern US and 10 in the northeastern US between January 1, 2015, and December 31, 2022. Data were analyzed from September 1, 2022, to May 30, 2023., Exposures: Race, ethnicity, and police transport to the hospital., Main Outcomes and Measures: The primary outcome variable was the presence of an order for restraints during an ED visit., Results: A total of 4 263 437 ED visits by 1 257 339 patients (55.5% of visits by female and 44.5% by male patients; 26.1% by patients 65 years or older) were included in the study. Black patients accounted for 27.5% of visits; Hispanic patients, 17.6%; White patients, 50.3%; and other or unknown race or ethnicity, 4.6%. In models adjusted for age, sex, site, previous behavioral or psychiatric history, and visit diagnoses, Black patients were at increased odds of experiencing restraint compared with White patients (adjusted odds ratio [AOR], 1.33 [95% CI, 1.28-1.37]). Within the mediation analysis, Black patients had higher odds of being brought to the hospital by police compared with all other patients (AOR, 1.38 [95% CI, 1.34-1.42]). Patients brought to the ED under police transport had increased odds of experiencing restraint compared with all other modes of transport (AOR, 5.51 [95% CI, 5.21-5.82]). The estimated proportion of use of restraints for Black patients mediated by police transport was 10.70% (95% CI, 9.26%-12.53%)., Conclusions and Relevance: In this cross-sectional study of ED visits across 13 hospitals, police transport may have mediated the association between Black race and use of physical restraint. These findings suggest a need to further explore the mechanisms by which transport to emergency care may influence disparate restrictive interventions for patients experiencing behavioral emergencies.

Introduction: Police involvement in patient transport to emergency medical care has increased over time, yet studies assessing racial inequities in transport are limited. This study evaluated the relationship between race and police transport to the emergency department for adult patients., Methods: This cross-sectional study evaluated adult (aged ≥18 years) visits at 13 different emergency departments across two regional hospital systems in the Southeastern and Northeastern U.S. from 2015 to 2022. Data were extracted from electronic health records. This analysis evaluated the association between race and transport by police transport using generalized linear multivariable mixed model with a binary logistic link for presence of police transport. Data were nested by patient and adjusted for site, demographics, and diagnostic visit characteristics., Results: Of 4,291,809 adult emergency department visits, 25,901 (0.6%) involved transport by police. Of the 25,901 visits in police-involved encounters, 10,513 (40.6%) patients were Black, and 9,827 (37.9%) were White. The adjusted model showed that Black patients were at higher odds of transport by police than White patients (AOR=1.64; 95% CI=1.57-1.72). Male sex, younger age (18-35 years), history of behavioral health diagnosis, and emergency department psychiatric or substance use disorders were independently associated with increased odds of police transport., Conclusions: This analysis revealed racial inequities in police-involved transport to emergency medical care, highlighting an urgent need to evaluate drivers of inequities and the ways in which police transport influences clinical outcomes., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Pandemic-associated stress may have exacerbated preexisting mental health and substance use disorders (MH/SUD) and caused new MH/SUD diagnoses which would be expected to lead to an increase in visits to emergency departments and hospital admissions for these conditions. This study assessed whether the proportion of hospital and emergency department encounters for MH/SUD diagnoses increased during the first year of the COVID-19 pandemic in the United States., Methods: We conducted a longitudinal (interrupted time series) analysis of 994,724 eligible encounters identified by electronic query between January 1, 2016 and March 31, 2021. Of these, 55,574 encounters involved MH/SUD diagnosis. The pre-pandemic period was defined as January 1, 2016 to March 31, 2020, and the pandemic period was defined as April 1, 2020 to March 31, 2021. All statistical analyses were performed with R., Results: No significant trend in MH/SUD encounters at baseline (rate ratio 1.00, 95% CI 0.99-1.01, p = 0.75) was observed. However, the onset of the pandemic was temporally associated with a significant level increase in the proportion of MH/SUD encounters relative to overall encounters (rate ratio 1.14, 95% CI 1.06-1.21, p<0.001) with no change in the overall trend (rate ratio 0.99, 95% CI 0.90-1.10, p = 0.89)., Conclusions: The significant pandemic-associated increase in the proportion of MH/SUD encounters relative to overall encounters was driven largely by sustained numbers of MH/ SUD encounters despite a decrease in total encounters. Increased support for mental health care is needed for these vulnerable patients during pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Der et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Percutaneous mechanical aspiration (PMA) of intravascular vegetations is a novel strategy for management of patients with infective endocarditis (IE) who are at high risk of poor outcomes with conventional cardiac surgery. However, clear indications for its use as well as patient outcomes are largely unknown., Objectives: To conduct a scoping review of the literature to summarize patient characteristics and outcomes of those undergoing PMA for management of IE., Methods: Two independent reviewers screened abstracts and full text for inclusion and independently extracted data., Data Sources: MEDLINE, Embase, and Web of Science., Study Eligibility Criteria: Studies published until February 21, 2023, describing the use of PMA for management of patients with cardiac implantable electronic device (CIED) or valvular IE were included., Assessment of Risk of Bias: As this was a scoping review, risk of bias assessment was not performed., Methods of Data Synthesis: Descriptive data was reported., Results: We identified 2252 titles, of which 1442 abstracts were screened, and 125 full text articles were reviewed for inclusion. Fifty-one studies, describing a total of 294 patients who underwent PMA for IE were included in our review. Over 50% (152/294) of patients underwent PMA to debulk cardiac implantable electronic device lead vegetations prior to extraction (152/294), and 38.8% (114/294) of patients had a history of drug use. Patient outcomes were inconsistently reported, but few had procedural complications, and all-cause in-hospital mortality was 6.5% (19/294)., Conclusions: While PMA is a promising advance in the care of patients with IE, higher quality data regarding patient outcomes are needed to better inform the use of this procedure., (Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome. Future studies will incorporate innovative methodologies with a focus on interventional clinical trials that have the potential to change clinical practice for difficult-to-treat infections, such as MRSA bloodstream infections., Competing Interests: Potential conflicts of interest. All authors report funding support from the ARLG of the NIH and the NIAID (UM1AI104681). S. B. D. reports grants or contracts paid to her institution from Gilead, Pfizer, F2G, Regeneron, Chan Zuckerberg Biohub, and NIAID/NIH; consulting fees paid directly to her from Genentech and Janssen/Johnson & Johnson (J&J); travel and meeting support from the Infectious Diseases Society of America (IDSA) to speak at IDWeek; a patent (US20100143379A1) for Mif agonists and antagonist and therapeutic uses thereof; a leadership role on the IDSA Antibacterial Resistance Committee, California Department of Public Health Hospital Acquired Infections Advisory Committee, and ARLG Innovations Group, Laboratory Center, Mentorship Committee, Gram-positive Committee, and Immunosuppressed Host Group; and payment directly to her for clinical events committee/adjudication committee participation from Shionogi, Basilea, and the Duke Clinical Research Institute.D. R. A. reports funding support from ContraFect and a leadership role on the ARLG Gram-positive Committee. A. B. reports funding support from the ARLG Early Faculty Seedling Award (NIAID UM1AI104681) and consulting fees from Roche. H. W. B. reports royalties from the Sanford Guide; consulting fees from the Sanford Guide, Antimicrobial Agents and Chemotherapy/American Society for Microbiology (ASM), and ID Clinics of North America/Elsevier; honoraria for Grand Rounds at Temple University; travel and meeting support for an IDWeek Lecture; membership as a voting member on the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria; and membership on the Board of Trustees at the College of the Holy Cross. B. C. reports grants or contracts paid to his institution from Moderna Vaccines and Merck Vaccines; royalties from UpToDate; consulting fees from Cowen Investments, Pfizer, Moderna, GSK, and Sanofi; payment as a medicolegal expert with multiple law firms; participation on the data and safety monitoring board (DSMB) or advisory board for Affinivax and GSK; and a leadership role as president of the Pediatric Infectious Diseases Society. S. E. C. reports grants or contracts paid to her institution from the Agency for Healthcare Research and Quality (AHRQ), the Centers for Disease Control and Prevention (CDC), the Patient-Centered Outcomes Research Institute, and the US Food and Drug Administration (FDA); consulting fees paid directly to her from the Duke Clinical Research Institute; participation on a DSMB for Debiopharm; and leadership roles as a board member of the National Foundation for Infectious Diseases and Globarl Antibiotic Research and Development Partnership North America (GARDP-NA). S. R. E. reports grants from the NIAID/NIH and De Gruyter (Editor-in-Chief for Statistical Communications in Infectious Diseases); royalties from Taylor & Francis; consulting fees from Genentech, AstraZeneca, Takeda, Microbiotix, J&J, Endologix, ChemoCentryx, Becton Dickinson, Atricure, Roviant, Neovasc, Nobel Pharma, Horizon, International Drug Development Institute (IDDI), SVB Leerink, Medtronic, Regeneron, Wake Forest University, Recor, Janssen, and IDDI; payments from Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION); meeting support from the FDA, Deming Conference on Applied Statistics, Clinical Trial Transformation Initiative, Council for International Organizations of Medical Sciences, International Chinese Statistical Association Applied Statistics Symposium, and Antimicrobial Resistance and Stewardship Conference; board member participation for the NIH, Breast International Group, University of Pennsylvania, Washington University, Duke University, Roche, Pfizer, Takeda, Akouos, Apellis, Teva, Vir, DayOneBio, Alexion, Tracon, Rakuten, AbbVie, Nuvelution, Clover, FHI Clinical, Lung Biotech, SAB Biopharm, Advantagene, Candel, and Novartis; and board positions with the American Statistical Association, Society for Clinical Trials, and Frontier Science Foundation. V. G. F. reports personal consulting fees from Novartis, Debiopharm, Genentech, Achaogen, Affinium, The Medicines Co, MedImmune, Bayer, Basilea, Affinergy, Janssen, ContraFect, Regeneron, Destiny, Amphliphi Biosciences, Integrated Biotherapeutics, C3J, Armata, Valanbio, Akagera, Aridis, Roche, and Pfizer; grants from NIH, MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck, Medical Biosurfaces, Locus, Affinergy, ContraFect, Karius, Genentech, Regeneron, Deep Blue, Basilea, and Janssen; royalties from UpToDate; stock options from Valanbio and ArcBio; honoraria from the IDSA for his service as Associate Editor of Clinical Infectious Diseases; travel support from ContraFect to the 2019 European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); and a sepsis diagnostics patent pending. S. A. F. reports grant or contracts from NIH (P50HD103525, U01AL116400, R21AI176063) and AHRQ (R01 HS024269), honoraria from ARLG, and provision of Clorox wipes for a clinical research study. B. J. K. reports grants from CDC and NIAID; honoraria from ARLG; and leadership roles in the CDC Microbiome Working Group, IDSA Journal Club, and ARLG. T. H. reports consulting fees from Tanabe-Mitsubishi Pharma and honoraria from Duke University and Cancer and Chemo Therapy. T. P. L. reports grants paid to his institution from Wockhardt; grants paid directly to him from Paratek, Cidara, Biofire Diagnostics, and Merck; payment directly to him for lectures from Shionogi, Ferring, Seres, and Melinta; consulting fees paid directly to him from AbbVie, Cidara Therapeutics, Ferring, ICPD, Genentech, J&J, Melinta, Merck, Roche, Shionogi, Spero, Venatrox, La Jolla, Seres, Paratek, GSK, and DoseMe; and payment for the development of educational presentations from the Mayo Clinic. L. G. M. reports grants or contracts from Merck, ContraFect, Paratek, Medline, and GSK. J. M. M. reports grants from Asociación Nacional de Investigación y Desarrollo, Fondo Nacional de Desarrollo Científico y Tecnológico FONDECYT (grant number 1211947). B. S. reports advisory board fees paid directly to him from Basilia. T. T. T. reports grants from NIH paid to her institution; travel and meeting support from IDSA; and a leadership role on the IDWeek Planning Committee and a role as a Gulf Coast Consortium Cluster Reviewer (both unpaid). N. A. T. reports grants from CDC and PDI, Inc; and consulting fees from Techspert. D. J. W. reports grants paid to his institution from CDC and NIH/NIAID; a leadership role on the IDSA Childhood Pneumonia Guidelines Committee; and receipt of equipment from bioMérieux for procalcitonin assays for an observational study. T. L. H. reports grants from Karius and NIH; royalties from UpToDate; consulting fees from Aridis, Pfizer, Lysovant, and Affinivax; and participation on a DSMB for the SNAP Trial and the advisory board for Basilea. C. A. A. reports grant funding to their institution from NIH/NIAID (1 Po1 AI152999, R01AI148342, R01 AI346337, T32 AI141349, K24 Ai121296, U19 AI44297, R01 AI150685, and R21 AI151536), MeMed Diagnostics Ltd, Entasis Therapeutics, Merck Pharmaceuticals, and Harris County Public Health; royalties paid to them from UpToDate; reimbursement from IDSA for attending IDWeek as a speaker and part of the organizing committee; reimbursement from ASM to attend ASM Microbe as a speaker; reimbursement from the Society for Healthcare Epidemiology of America (SHEA) to attend SHEA as a speaker; reimbursement from the European Society for Clinical Microbiology and Infectious Diseases to attend ECCMID as a speaker; reimbursement from Mérieux Foundation to attend ICARE course as faculty; reimbursement from Sociedad Chilea de Infectiologia, Sociedad Colombiana de Infectologia, Pan American Society for Infectious Diseases, and Brazilian Society for Infectious Diseases to attend the annual meeting and act as a speaker; was an unpaid participant on a DSMB with the World Health Organization and Antibacterial Pipeline Advisory Group; received payment for participation with the NIH Grant Review Study Sections; was a voluntary member of the board of directors of IDSA; and is the Editor-in-Chief of Antimicrobial Agents and Chemotherapy. B. E. M. reports royalties from UpToDate for online chapters; consulting fees from JRD, LLC (J&J), PPD Development, LP (GSK0 and Basilea Pharmaceutical International Ltd); participation on a DSMB with NIH Therapeutic and Prevention; and held the position of Governor of the Academy with the American Academy of Microbiology. C. L. reports grant payments to their institutions from NIAID/NIH (1R01AI151038-01) and Pfizer. M. H. S. reports advisory board fees from DoseMe; consulting fees from GSK and Entasis; and has an issued patent US10688195B2. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Ceftobiprole is a cephalosporin that may be effective for treating complicated Staphylococcus aureus bacteremia, including methicillin-resistant S. aureus ., Methods: In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated S. aureus bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new S. aureus bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments. Safety was also assessed., Results: Of 390 patients who underwent randomization, 387 (189 in the ceftobiprole group and 198 in the daptomycin group) had confirmed S. aureus bacteremia and received ceftobiprole or daptomycin (modified intention-to-treat population). A total of 132 of 189 patients (69.8%) in the ceftobiprole group and 136 of 198 patients (68.7%) in the daptomycin group had overall treatment success (adjusted difference, 2.0 percentage points; 95% confidence interval [CI], -7.1 to 11.1). Findings appeared to be consistent between the ceftobiprole and daptomycin groups in key subgroups and with respect to secondary outcomes, including mortality (9.0% and 9.1%, respectively; 95% CI, -6.2 to 5.2) and the percentage of patients with microbiologic eradication (82.0% and 77.3%; 95% CI, -2.9 to 13.0). Adverse events were reported in 121 of 191 patients (63.4%) who received ceftobiprole and 117 of 198 patients (59.1%) who received daptomycin; serious adverse events were reported in 36 patients (18.8%) and 45 patients (22.7%), respectively. Gastrointestinal adverse events (primarily mild nausea) were more frequent with ceftobiprole., Conclusions: Ceftobiprole was noninferior to daptomycin with respect to overall treatment success in patients with complicated S. aureus bacteremia. (Funded by Basilea Pharmaceutica International and the U.S. Department of Health and Human Services; ERADICATE ClinicalTrials.gov number, NCT03138733.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Two-step testing for Clostridioides difficile infection (CDI) aims to improve diagnostic specificity but may also influence reported epidemiology and patterns of treatment. Some providers fear that 2-step testing may result in adverse outcomes if C. difficile is underdiagnosed., Methods: Our primary objective was to assess the impact of 2-step testing on reported incidence of hospital-onset CDI (HO-CDI). As secondary objectives, we assessed the impact of 2-step testing on C. difficile-specific antibiotic use and colectomy rates as proxies for harm from underdiagnosis or delayed treatment. This longitudinal cohort study included 2 657 324 patient-days across 8 regional hospitals from July 2017 through March 2022. Impact of 2-step testing was assessed by time series analysis with generalized estimating equation regression models., Results: Two-step testing was associated with a level decrease in HO-CDI incidence (incidence rate ratio, 0.53 [95% confidence interval {CI}, .48-.60]; P < .001), a similar level decrease in utilization rates for oral vancomycin and fidaxomicin (utilization rate ratio, 0.63 [95% CI, .58-.70]; P < .001), and no significant level (rate ratio, 1.16 [95% CI, .93-1.43]; P = .18) or trend (rate ratio, 0.85 [95% CI, .52-1.39]; P = .51) change in emergent colectomy rates., Conclusions: Two-step testing is associated with decreased reported incidence of HO-CDI, likely by improving diagnostic specificity. The parallel decrease in C. difficile-specific antibiotic use offers indirect reassurance against underdiagnosis of C. difficile infections still requiring treatment by clinician assessment. Similarly, the absence of any significant change in colectomy rates offers indirect reassurance against any rise in fulminant C. difficile requiring surgical management., Competing Interests: Potential conflicts of interest. N. A. T. reports grant funding from the CDC, NIH/ARLG, and Rockefeller Foundation; research contract funding from PDI, Purio, and Basilea; and consulting fees for Techspert. D. J. A. reports grant funding from the CDC and Agency for Healthcare Research and Quality; contracts from CDC; interests as owner of Infection Control Education for Major Sports, LLC; and royalties from UpToDate. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Importance: Fewer than 5% of patients labeled with a penicillin allergy are truly allergic. The standard of care to remove the penicillin allergy label in adults is specialized testing involving prick and intradermal skin testing followed by an oral challenge with penicillin. Skin testing is resource intensive, limits practice to specialist-trained physicians, and restricts the global population who could undergo penicillin allergy delabeling., Objective: To determine whether a direct oral penicillin challenge is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy., Design, Setting, and Participants: This parallel, 2-arm, noninferiority, open-label, multicenter, international randomized clinical trial occurred in 6 specialized centers, 3 in North America (US and Canada) and 3 in Australia, from June 18, 2021, to December 2, 2022. Eligible adults had a PEN-FAST score lower than 3. PEN-FAST is a prospectively derived and internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies., Interventions: Patients were randomly assigned to either direct oral challenge with penicillin (intervention arm) or a standard-of-care arm of penicillin skin testing followed by oral challenge with penicillin (control arm)., Main Outcome and Measure: The primary outcome was a physician-verified positive immune-mediated oral penicillin challenge within 1 hour postintervention in the intention-to-treat population. Noninferiority was achieved if a 1-sided 95% CI of the risk difference (RD) did not exceed 5 percentage points (pp)., Results: A total of 382 adults were randomized, with 377 patients (median [IQR] age, 51 [35-65] years; 247 [65.5%] female) included in the analysis: 187 in the intervention group and 190 in the control group. Most patients had a PEN-FAST score of 0 or 1. The primary outcome occurred in 1 patient (0.5%) in the intervention group and 1 patient (0.5%) in the control group, with an RD of 0.0084 pp (90% CI, -1.22 to 1.24 pp). The 1-sided 95% CI was below the noninferiority margin of 5 pp. In the 5 days following the oral penicillin challenge, 9 immune-mediated adverse events were recorded in the intervention group and 10 in the control group (RD, -0.45 pp; 95% CI, -4.87 to 3.96 pp). No serious adverse events occurred., Conclusions and Relevance: In this randomized clinical trial, direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. In patients with a low-risk history, direct oral penicillin challenge is a safe procedure to facilitate the removal of a penicillin allergy label., Trial Registration: ClinicalTrials.gov Identifier: NCT04454229.

While interferon-gamma release assays (IGRAs) are widely used for detecting tuberculosis (TB) infection, tuberculin skin tests (TSTs) remain preferred for children under the age of 2 years. The preference for TST stems from concern over IGRA sensitivity in young children. However, TSTs are susceptible to false-positive results following Bacille Calmette-Guérin (BCG) vaccination, which is common in infancy, and exposure to nontuberculous mycobacteria. We reviewed available data for IGRA performance in children under age 2 years. Across four cohorts of high-risk children under age 2 (mostly case contacts or those born in tuberculosis endemic regions), 0 of 575 untreated children with negative IGRA test results progressed to tuberculosis disease-including 0 of 70 who were TST positive but IGRA negative. While neither TSTs nor IGRAs are perfectly sensitive for the diagnosis of tuberculosis infection, IGRAs are an acceptable alternative to TST in children <2 years of age., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Defective regulation of the alternative complement pathway (AP) causes excessive activation and promotes the inflammation and renal injury observed in atypical hemolytic-uremic syndrome (aHUS). The usefulness of heat-inactivated Factor B (HFB) in reducing AP activation was evaluated in: fluid-phase reactions, using purified complement proteins and Factor H (FH)-depleted serum; and in surface-activated reactions using human endothelial cells (ECs). C3a and Ba levels, measured by quantitative Western blots, determined the extent of fluid-phase activation. In reactions using C3, FB, and Factor D proteins, HFB addition (2.5-fold FB levels), reduced C3a levels by 60% and Ba levels by 45%. In reactions using FH-depleted serum (supplemented with FH at 12.5% normal levels), Ba levels were reduced by 40% with HFB added at 3.5-fold FB levels. The effectiveness of HFB in limiting AP convertase formation on activated surfaces was evaluated using stimulated ECs. Fluorescent microscopy was used to quantify endogenously released C3, FB, and C5 attached to EC-secreted ultra-large VWF strings. HFB addition reduced attachment of C3b by 2.7-fold, FB by 1.5-fold and C5 by fourfold. Our data indicate that HFB may be of therapeutic value in preventing AP-mediated generation of C3a and C5a, and the associated inflammation caused by an overactive AP., (© 2023. The Author(s).)

Our surveys of nurses modeled after the Capability, Opportunity, and Motivation Model of Behavior (COM-B model) revealed that opportunity and motivation factors heavily influence urine-culture practices (behavior), in addition to knowledge (capability). Understanding these barriers is a critical step towards implementing targeted interventions to improving urine-culture practices., Competing Interests: Dr Advani reports support from the Centers for Disease Control and Prevention (grant nos. 5U54CK000616-02 and SHEPheRD 75D30121D12733-D5-E003), the Society for Healthcare Epidemiology of America, and the Duke Claude D. Pepper Older Americans Independence Center (National Institute on Aging grant no. P30AG028716), as well as consulting fees from Locus Biosciences, Sysmex America, GlaxoSmithKline, bioMérieux, IPEC Experts (co-owner), and the Infectious Diseases Society of America., (© The Author(s) 2023.)

Background: Clinicians and laboratories routinely use urinalysis (UA) parameters to determine whether antimicrobial treatment and/or urine cultures are needed. Yet the performance of individual UA parameters and common thresholds for action are not well defined and may vary across different patient populations., Methods: In this retrospective cohort study, we included all encounters with UAs ordered 24 hours prior to a urine culture between 2015 and 2020 at 3 North Carolina hospitals. We evaluated the performance of relevant UA parameters as potential outcome predictors, including sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We also combined 18 different UA criteria and used receiver operating curves to identify the 5 best-performing models for predicting significant bacteriuria (≥100,000 colony-forming units of bacteria/mL)., Results: In 221,933 encounters during the 6-year study period, no single UA parameter had both high sensitivity and high specificity in predicting bacteriuria. Absence of leukocyte esterase and pyuria had a high NPV for significant bacteriuria. Combined UA parameters did not perform better than pyuria alone with regard to NPV. The high NPV ≥0.90 of pyuria was maintained among most patient subgroups except females aged ≥65 years and patients with indwelling catheters., Conclusion: When used as a part of a diagnostic workup, UA parameters should be leveraged for their NPV instead of sensitivity. Because many laboratories and hospitals use reflex urine culture algorithms, their workflow should include clinical decision support and or education to target symptomatic patients and focus on populations where absence of pyuria has high NPV.

Importance: Environmental contamination is a source of transmission between patients, health care practitioners, and other stakeholders in the acute care setting., Objective: To compare the efficacy of an enhanced daily disinfection strategy vs standard disinfection in acute care hospital rooms., Design, Setting, and Participants: This randomized clinical trial (RCT) was conducted in acute care hospital rooms at Duke University Hospital in Durham, North Carolina, from November 2021 to March 2022. Rooms were occupied by patients with contact precautions. Room surfaces (bed rails, overbed table, and in-room sink) were divided into 2 sides (right vs left), allowing each room to serve as its own control. Each side was randomized 1:1 to the intervention group or control group., Interventions: The intervention was a quaternary ammonium, salt-based, 24-hour continuously active germicidal wipe. It was applied in addition to routine disinfection for the intervention group. The control group received no intervention beyond routine disinfection., Main Outcomes and Measures: The primary outcome was the total contamination, measured in colony-forming units (CFUs) on the bed rails, overbed table, and sink on study day 1. The secondary outcomes were the proportion of sample areas with positive test results for clinically important pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and carbapenem-resistant Enterobacteriaceae; the similarity in baseline contamination between sample area sides on study day 0 before application of the intervention, and the proportion of sample areas with removed UV luminescent gel on study day 1., Results: A total of 50 study rooms occupied by 50 unique patients (median [IQR] age, 61 [45-69] years; 26 men [52%]) with contact precautions were enrolled. Of these patients, 41 (82%) were actively receiving antibiotics, 39 (78%) were bedridden, and 28 (56%) had active infections with study-defined clinically important pathogens. On study day 1, the median (IQR) total CFUs for the intervention group was lower than that for the control group (3561 [1292-7602] CFUs vs 5219 [1540-12 364] CFUs; P = .002). On study day 1, the intervention side was less frequently contaminated with patient-associated clinically important pathogens compared with the control side of the room (4 [14%] vs 11 [39%]; P = .04)., Conclusions and Relevance: Results of this RCT demonstrated that a quaternary ammonium, salt-based, 24-hour continuously active germicidal wipe decreased the environmental bioburden in acute care hospital rooms compared with routine disinfection. The findings warrant large-scale RCTs to determine whether enhanced daily disinfection strategies can decrease patient acquisition and adverse patient outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT05560321.

In orthopedic oncology, the implant of a megaprosthetic device is standard of care after large-scale tumor resection involving segmental removal of bone. Infection remains the leading cause of implant failure, often resulting in major morbidity. Perioperative antibiotic practices for megaprosthetic reconstructions are not standardized and are based on guidelines for conventional joint arthroplasties. This study aims to evaluate the efficacy of current prophylactic strategies for megaprosthetic reconstructions. We conducted a retrospective review of megaprosthetic reconstructions performed at Duke University from 2001 to 2021. Logistic regression with GEE was used to assess whether a prolonged course of postoperative antibiotics is associated with infection risk. We assessed the microbial profile and corresponding susceptibilities of megaprosthetic infections through record review. Additionally, we designed a pharmacokinetic subgroup analysis using liquid chromatography-tandem mass spectrometry to quantify antibiotic concentrations in surgical tissue. Wilcoxon rank-sum tests were used to correlate tissue concentrations with infection risk. Out of 184 cases, 23 (12.5%) developed infection within 1 year. Extended postoperative antibiotics were not significantly associated with infection risk ( P  = 0.23). Among 18 culture-positive cases, 4 (22.2%) were caused by cefazolin-susceptible organisms. Median bone and muscle concentrations of cefazolin among cases that developed postoperative infection (0.065 ng/mL and 0.2 ng/mL, respectively) were significantly lower than those of cases that did not (0.42 ng/mL and 1.95 ng/mL, P  < 0.01 and P  = 0.03). This study is the first to comprehensively assess aspects of perioperative prophylaxis for megaprosthetic reconstructions. Extending postoperative antibiotics did not reduce infection risk. We detected a high frequency of cefazolin nonsusceptible organisms among postoperative infections. Additionally, intraoperative antibiotic tissue concentrations may be predictive of later infection. Future studies ought to examine optimal drug choices and dosing strategies.

Background/aim: The number of coronavirus disease 2019 deaths and cases continues to increase globally. Novel therapies are urgently needed to treat patients with coronavirus disease 2019. We sought to provide a critical review of trials designed during the coronavirus disease 2019 pandemic. Our primary goal was to provide a critical review of the landscape of clinical trials designed to address the coronavirus disease 2019 pandemic. Specifically, we were interested in assessing the design of phase II/III and phase III interventional trials., Methods: We utilized the ClinicalTrials.gov database to include trials registered between 1 December 2019 and 11 April 2021 to survey the current landscape of clinical trials for coronavirus disease 2019. Variables extracted included: National Clinical Trial number, title, location, sponsor, study type, start date, completion date, gender group, age group, primary outcome, secondary outcome, overall status, and associated references., Results: About 57% of studies were interventional, 14.5% were phase III trials, and the majority of the therapeutic trials included hospitalized patients. There were 52 primary composite outcomes and 285 unique interventions spanning 10 drug classes. The outcomes, disease severity, and comparators varied substantially across trials, and the trials were often too small to be definitive., Conclusion: These findings are relevant as we strongly advocate for global coordination of efforts through the use of common platforms that enable harmonizing of endpoints, collection of common key variables and clear definition of disease severity to have clinically meaningful results from clinical trials.