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The gut and vaginal microbiome undergo changes during pregnancy which may be protective or harmful to the birthing person. Probiotics have been found to cause protective changes to the gut and vaginal microbiomes, with the potential to improve perinatal outcomes. This randomized control trial compares the vaginal and rectal microbiomes before and after an antenatal probiotic or placebo intervention, with a diverse group of pregnant people and a special focus on racial disparities. The vaginal and rectal microbiomes reveal non-significant increased Lactobacillus in the probiotics group, with a greater increase in participants who identified as Black. Potential implications and future studies are discussed.

Introduction Elevated glycosylated hemoglobin (HbA1c) in individuals with type 2 diabetes is associated with increased risk of hospitalization and death after acute COVID-19, however the effect of HbA1c on Long COVID is unclear.Objective Evaluate the association of glycemic control with the development of Long COVID in patients with type 2 diabetes (T2D).Research design and methods We conducted a retrospective cohort study using electronic health record data from the National COVID Cohort Collaborative. Our cohort included individuals with T2D from eight sites with longitudinal natural language processing (NLP) data. The primary outcome was death or new-onset recurrent Long COVID symptoms within 30–180 days after COVID-19. Symptoms were identified as keywords from clinical notes using NLP in respiratory, brain fog, fatigue, loss of smell/taste, cough, cardiovascular and musculoskeletal symptom categories. Logistic regression was used to evaluate the risk of Long COVID by HbA1c range, adjusting for demographics, body mass index, comorbidities, and diabetes medication. A COVID-negative group was used as a control.Results Among 7430 COVID-positive patients, 1491 (20.1%) developed symptomatic Long COVID, and 380 (5.1%) died. The primary outcome of death or Long COVID was increased in patients with HbA1c 8% to

Abstract Diarrhea claims >500,000 lives annually among children under five years of age in low- and middle-income countries. Mortality due to acute diarrhea (

Abstract The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin production of various C. difficile strains across different nutrient environments. Negative interactions influencing C. difficile growth are prevalent in an environment containing a single highly accessible resource and sparse in an environment containing C. difficile-preferred carbohydrates. C. difficile toxin production displays significant community-context dependent variation and does not trend with growth-mediated inter-species interactions. C. difficile strains exhibit differences in interactions with Clostridium scindens and the ability to compete for proline. Further, C. difficile shows substantial differences in transcriptional profiles in co-culture with C. scindens or Clostridium hiranonis. C. difficile exhibits massive alterations in metabolism and other cellular processes in co-culture with C. hiranonis, reflecting their similar metabolic niches. C. hiranonis uniquely inhibits the growth and toxin production of diverse C. difficile strains across different nutrient environments and robustly ameliorates disease severity in mice. In sum, understanding the impact of C. difficile strain variability and nutrient environments on inter-species interactions could help improve the effectiveness of anti-C. difficile strategies.

Summary: Background: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. Methods: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). Findings: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. Interpretation: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. Funding: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438.

Background: Guidelines recommend bundles with multiple infection control elements to prevent surgical site infections (SSI). Although effective in multiple research studies, little is known about the implementation of such complex bundles in the real-world clinical setting. Methods: A survey was distributed to the SHEA Research Network (SRN) hospitals during November 2022 – December 2023, to assess processes related to the implementation of SSI prevention bundles in colorectal surgery. Results: Of the 93 US and international hospitals within SRN, 49 completed the survey (53% response rate). The mean volume of colorectal surgeries per year was 377 (median 400). Figure 1 shows the individual elements of SSI prevention bundle reported as consistently used in most surgeries. There were no significant differences between hospitals with high vs. low volume (cut-off 400 surgeries), except for wound protectors or retractors, more likely to be used in high-volume hospitals (P = 0.047). A formal process for auditing adherence was reported by 71% of respondents for antibiotic prophylaxis, and 51% for skin prep, with the remaining elements audited < 50% of the time. Feedback of audited adherence to surgeons occurred < 50% of the time for all bundle elements, except antibiotic prophylaxis (59%). Table 1 shows the most common barriers reported as either successfully mitigated or still persistent at the time of the survey. High-volume hospitals were more likely to report persistent clinicians’ low bundle adherence (P = 0.016) and inadequate bundle adherence audit and feedback (P = 0.0016). Conclusion: Implementation of guideline-recommended colorectal SSI Prevention bundles remains highly variable. Further research aiming to develop strategies that optimize implementation and adherence is needed.

Background: Presenteeism when ill in healthcare personnel (HCP) can contribute to the spread of respiratory illness among HCP and patients. However, during the COVID-19 pandemic and now, there are substantial challenges preventing HCP from staying home when ill. We examined these challenges using the Systems Engineering Initiative for Patient Safety (SEIPS) framework. Method: As part of a larger anonymous electronic survey between 3/11/2022 and 4/12/2022 at an academic tertiary referral center, in inpatient and ambulatory settings where respondents were asked to describe factors impacting presenteeism when ill, we analyzed free-text responses using the SEIPS categories of tasks, tools/technology, person, organization, and physical environment. Result: 522 comments were received in response to the open-ended survey question asking individuals to describe any factors that would assist them in remaining home and/or help them get tested for COVID-19 when they have symptoms of a respiratory illness; 21 were excluded due to absent or incomplete response. Of the remaining responses (N = 501, Figure 1), 82% were associated with a single SEIPS component such as organization (N = 409), while other responses discussed factors that involved two SEIPS components, in no particular order (N = 92). A majority of the responses (N = 324, 55%) reported organizational barriers, frequently citing a strict sick call-in policy as well as a lack of protected time-off for COVID-19 testing or related absences. The next two most commonly identified components were physical environment (N= 88, 15%) and tasks (N = 72, 12%), mentioning barriers such as far distances to testing centers and prolonged waiting periods for testing Results: The person and tools/technology components were less commonly identified, with a frequency of 9% each. Conclusion: A number of systems level factors were identified that may impact the ability of HCP to stay home when ill. Interventions to help overcome HCP perceived barriers to staying home when experiencing respiratory symptoms should focus on the policies and practices within an organization. Communication from leadership should support staying home with respiratory symptoms by creating plans for coverage and back up consistently across all employee types in direct care.

Background: Blue light therapy (BLT) is a Food and Drug Administration cleared modality used in dermatology as an effective treatment of acne. The primary purpose of this study is to determine if there are dose-dependent antimicrobial effects of BLT against Cutibacterium acnes (C. acnes). Methods: A known strain of C. acnes was grown on chocolate agar in a controlled laboratory environment under anaerobic conditions for 1 week. After 1 week, 2-3 colonies of C. acnes were isolated and transferred to broth medium to incubate for 2 or 7 days. Broth vials (treatment arm) then underwent 1 of 6 different blue light dosing treatment regimens and a duplicate broth vial served as a control left open to the same environment. The BLT regimens were a single treatment of 25 J/cm2, 50 J/cm2, 75 J/cm2, 100 J/cm2, 2 serial treatments of 50 J/cm2 separated by 24 hours, or 2 serial treatments of 75 J/cm2 separated by 24 hours. The Omnilux Blue device (415 nm wavelength) was used for all BLT treatments and delivered, on average, 1.68 ± 0.004 J/min. Following treatment, the control and treatment broth samples were plated on chocolate agar and allowed to grow for 7 days. After 7 days, plates were counted and colony forming units (CFUs) were calculated. Six trials were completed for each BLT dosing regimen based on an a priori power analysis of 6 individual 2-sided t-tests. Comparisons in the primary outcome were made via mixed-effects analysis of variance with replicate as a random effect. Results: All BLT treatment regimens resulted in significantly fewer CFUs than their aggregate control plate CFUs (P

Objective: The effects of Coronavirus disease 2019 (COVID-19) infection and altered processes of care on nonelective coronary artery bypass grafting (CABG) outcomes remain unknown. We hypothesized that patients with COVID-19 infection would have longer hospital lengths of stay and greater mortality compared with COVID-negative patients, but that these outcomes would not differ between COVID-negative and pre-COVID controls. Methods: The National COVID Cohort Collaborative 2020-2022 was queried for adult patients undergoing CABG. Patients were divided into COVID-negative, COVID-active, and COVID-convalescent groups. Pre-COVID control patients were drawn from the National Surgical Quality Improvement Program database. Adjusted analysis of the 3 COVID groups was performed via generalized linear models. Results: A total of 17,293 patients underwent nonelective CABG, including 16,252 COVID-negative, 127 COVID-active, 367 COVID-convalescent, and 2254 pre-COVID patients. Compared to pre-COVID patients, COVID-negative patients had no difference in mortality, whereas COVID-active patients experienced increased mortality. Mortality and pneumonia were higher in COVID-active patients compared to COVID-negative and COVID-convalescent patients. Adjusted analysis demonstrated that COVID-active patients had higher in-hospital mortality, 30- and 90-day mortality, and pneumonia compared to COVID-negative patients. COVID-convalescent patients had a shorter length of stay but a higher rate of renal impairment. Conclusions: Traditional care processes were altered during the COVID-19 pandemic. Our data show that nonelective CABG in patients with active COVID-19 is associated with significantly increased rates of mortality and pneumonia. The equivalent mortality in COVID-negative and pre-COVID patients suggests that pandemic-associated changes in processes of care did not impact CABG outcomes. Additional research into optimal timing of CABG after COVID infection is warranted.

Abstract Social disparities continue to limit universal access to health care, directly impacting both lifespan and quality of life. Concomitantly, the gut microbiome has been associated with downstream health outcomes including the global rise in antibiotic resistance. However, limited evidence exists examining socioeconomic status (SES) associations with gut microbiome composition. To address this, we collected information on the community-level SES, gut microbiota, and other individual cofactors including colonization by multidrug-resistant organisms (MDROs) in an adult cohort from Wisconsin, USA. We found an association between SES and microbial composition that is mediated by food insecurity. Additionally, we observed a higher prevalence of MDROs isolated from individuals with low diversity microbiomes and low neighborhood SES. Our integrated population-based study considers how the interplay of several social and economic factors combine to influence gut microbial composition while providing a framework for developing future interventions to help mitigate the SES health gap.

Objectives To evaluate the effectiveness of COVID-19 vaccinations (initial and booster) during pre-Delta, Delta and Omicron dominant periods among pregnant people via (1) COVID-19 incident and severe infections among pregnant people who were vaccinated versus unvaccinated and (2) post-COVID-19 vaccination breakthrough infections and severe infections among vaccinated females who were pregnant versus non-pregnant.Design Retrospective cohort study using nationally sampled electronic health records data from the National COVID Cohort Collaborative, 10 December 2020 –7 June 2022.Participants Cohort 1 included pregnant people (15–55 years) and cohort 2 included vaccinated females of reproductive age (15–55 years).Exposures (1) COVID-19 vaccination and (2) pregnancy.Main outcome measures Adjusted HRs (aHRs) for COVID-19 incident or breakthrough infections and severe infections (ie, COVID-19 infections with related hospitalisations).Results In cohort 1, 301 107 pregnant people were included. Compared with unvaccinated pregnant people, the aHRs for pregnant people with initial vaccinations during pregnancy of incident COVID-19 were 0.77 (95% CI 0.62 to 0.96) and 0.88 (95% CI 0.73 to 1.07) and aHRs of severe COVID-19 infections were 0.65 (95% CI 0.47 to 0.90) and 0.79 (95% CI 0.51 to 1.21) during the Delta and Omicron periods, respectively. Compared with pregnant people with full initial vaccinations, the aHR of incident COVID-19 for pregnant people with booster vaccinations was 0.64 (95% CI 0.58 to 0.71) during the Omicron period. In cohort 2, 934 337 vaccinated people were included. Compared with vaccinated non-pregnant females, the aHRs of severe COVID-19 infections for people with initial vaccinations during pregnancy was 2.71 (95% CI 1.31 to 5.60) during the Omicron periods.Conclusions Pregnant people with initial and booster vaccinations during pregnancy had a lower risk of incident and severe COVID-19 infections compared with unvaccinated pregnant people across the pandemic stages. However, vaccinated pregnant people still had a higher risk of severe infections compared with non-pregnant females.

Air surveillance offers a potential means of monitoring airborne pathogens without the need for individual sampling. Here, the authors perform continuous air sampling in 15 community settings in the US for 29 weeks and demonstrate its feasibility for routine detection of SARS-CoV-2 and other respiratory pathogens.

Summary: Background: Surgical site infection prevention and treatment remains a challenge in healthcare settings globally. The routine use of intranasal mupirocin for decolonization has challenges and preoperative intranasal povidone-iodine decolonization is another option. The purpose of this quality improvement study was to assess if a one-time preoperative intranasal povidone-iodine application could reduce the risk of the likelihood of nasal carriage of Staphylococcus aureus after surgery. Methods: Ambulatory Surgery Center patients were enrolled in an intranasal povidone-iodine decolonization quality improvement study as they reported at the pre-operative holding area. Pre-decolonization intranasal samples were collected, followed by intranasal application of povidone-iodine. Patients waited for a minimum of 20 minutes after application before proceeding with surgery. Nasal samples were again collected after surgery. Each sample was tested for S. aureus colonization using the 16S rRNA-mecA-nuc triplex polymerase chain reaction, standard biochemical tests, and qualitative culturing. Findings: In the 98 patients enrolled, 36% of these patients had intranasal colonization with S. aureus by 16S rRNA-mecA-nuc triplex polymerase chain reaction before surgery. Using a qualitative culture technique, 28% of patients tested positive for S. aureus before surgery and 20% of patients tested positive for S. aureus after surgery (P = 0.039). Conclusion: Intranasal preoperative povidone-iodine is an effective strategy in the decolonization of S. aureus from the nares if properly implemented.

Objective: To characterize hospital-onset COVID-19 cases and to investigate the associations between these rates and population and hospital-level rates including trends in healthcare worker infections (HCW), community cases, and COVID-19 wastewater data. Design: Retrospective cohort study from January 1, 2021, to November 23, 2022. Setting: This study was conducted at a 589-bed urban Midwestern tertiary-care hospital system. Participants and interventions: The infection prevention team reviewed the electronic medical records (EMR) of patients who were admitted for >48 hours and subsequently tested positive for SARS-CoV-2 to determine whether COVID-19 was likely to be hospital-onset illness. Each case was further categorized as definite, probable, or possible based on viral sequencing, caregiver tracing analysis, symptoms, and cycle threshold values. Patients were excluded if there was a known exposure prior to admission. Clinical data including vaccination status were collected from the EMR. HCW case data were collected via our institution’s employee health services. Community cases and wastewater data were collected via the Wisconsin Department of Health Services database. Additionally, we evaluated the timing of changes in infection prevention guidance such as visitor restrictions. Results: In total, 156 patients met criteria for hospital-onset COVID-19. Overall, 6% of cases were categorized as definite, 24% were probable, and 70% were possible hospital-onset illness. Most patients were tested prior to a procedure (31%), for new symptoms (30%), and for discharge planning (30%). Also, 53% were symptomatic and 41% received treatment for their COVID-19. Overall, 38% of patients were immunocompromised and 27% were unvaccinated. Overall, 12% of patients died within 1 month of their positive SARS-CoV-2 test, and 11% required ICU admission during their hospital stay. Hospital-onset COVID-19 increased in fall of 2022. Specifically, October 2022 had 16 cases, whereas fall of 2021 (September–November) only had 3 cases total. Finally, similar peaks were observed in total cases by week between healthcare workers, county cases, and COVID-19 wastewater levels. These peaks correspond with the SARS-CoV-2 delta and omicron variant surges, respectively. Conclusions: Hospital-onset cases followed similar trends as population and hospital-level data throughout the study period. However, hospital-onset rate did not correlate as strongly in the second half of 2022 when cases were disproportionately high. Given that hospital-onset cases can result in significant morbidity, continued enhanced infection prevention efforts and low threshold for testing are warranted in the inpatient environment.

Background: The FIRST Trial is a 5-year study funded by the Agency for Healthcare Research and Quality. Our investigation is situated within a more extensive study to restrict fluoroquinolone antibiotics by requiring providers to obtain authorization from an infectious disease physician before prescribing fluoroquinolones. Our research team is performing a systematic evaluation to identify organizational characteristics and influencers of the fluoroquinolone preprescription authorization implementation process to understand variables that may facilitate or hinder implementation success. Methods: To address this critical gap, we present a qualitative analysis from our ongoing, multisite research project aimed at systematically assessing the adoption of an antimicrobial stewardship intervention in the form of an EHR-integrated best-practice alert (BPA) at each site to identify work system factors that impact uptake and variability in the implementation of the BPA at each location. The evaluation provides a detailed explanation of activities through the implementation process (eg, before implementation, during implementation, and after implementation) to assess how an organization effectively negotiates the phases and transitions, ultimately influencing the impact of the intervention. We have used a contextual determinant framework (CFIR) that has enabled us to perform a systematic and comprehensive exploration and identification of potential explanatory themes or variables to shed light on the complex social phenomenon of implementation. Results: Participants who will be a part of our poster presentation will learn about implementing a BPA, the potential barriers to implementation, and strategies for overcoming these barriers. Stakeholders within our study include site coordinators, medical doctors, nurses, pharmacists, and clinical informaticists. Our analysis synthesizes their experiences implementing and sustaining this evidence-based antimicrobial stewardship intervention. It includes (1) a detailed description of the process of change, (2) work-system factors (eg, inner setting and outer setting) that they believe influenced the success of the intervention, (3) barriers and facilitators (eg, CFIR constructs) within the implementation process; and (4) description of how these could have influenced the outcomes of interest (eg, implementation and intervention effectiveness). Conclusions: Our research is expected to advance patient safety research and initiatives by providing a more robust approach to performing systematic intervention evaluations. By outlining stakeholders’ experiences within our study, implementation leaders within healthcare systems will utilize our findings to aid them in their design and implementation process when designing and implementing similar types of healthcare interventions.

Background: Amid the COVID-19 pandemic, healthcare systems were stretched thin, with staffing shortages posing substantial challenges. Limiting spread of COVID-19 among healthcare professionals (HCP) is paramount to preventing exacerbation of such shortages, but strategies are highly dependent on HCP self-screening for symptoms and isolating when present. We examined HCP perceptions of barriers and factors that facilitate staying home when experiencing respiratory symptoms. Methods: At an academic tertiary-care referral center, in inpatient and ambulatory settings, we conducted an anonymous electronic survey between March 11, 2022, and April 12, 2022. Using logistic regression analysis, we analyzed predictors of employees reporting to work with respiratory symptoms using STATA and SAS software. Results: In total, 1,185 individuals including 829 clinical staff and 356 nonclinical staff responded to the survey. When excluding participants who reported working “remotely” (N = 381) and those who reported being unsure of whether they had worked with symptoms (N = 14), the prevalence of working with respiratory symptoms was 63%. There was no significant difference between clinical and nonclinical staff (OR, 1.1; 95% CI, 0.8–1.5; P = .60). Increasing number of years of service was protective against working with symptoms, achieving statistically significance in multivariable analysis after 16 years. Compared to those having worked

As agent-based models (ABMs) are increasingly used for modeling infectious diseases, model validation is becoming more crucial. In this study, we present an alternate approach to validating hospital ABMs that focuses on replicating hospital-specific conditions and proposes a new metric for validating the social-environmental network structure of ABMs. We adapted an established ABM representing Clostridioides difficile infection (CDI) spread in a generic hospital to a 426-bed Midwestern academic hospital. We incorporated hospital-specific layout, agent behaviors, and input parameters estimated from primary hospital data into the model, referred to as H-ABM. We compared the predicted CDI rate against the observed rate from 2013-2018. We used colonization pressure, a measure of nearby infectious agents, to validate the socio-environmental agent networks in the ABM. Finally, we conducted additional experiments to compare the performance of individual infection control interventions in the H-ABM and the generic model. We find that the H-ABM is able to replicate CDI trends during 2013-2018, including a roughly 46% drop during a period of greater infection control investment. High CDI burden in socio-environmental networks was associated with a significantly increased risk of C. difficile colonization or infection (Risk ratio: 1.37; 95% CI: [1.17, 1.59]). Finally, we found that several high-impact infection control interventions have diminished impact in the H-ABM. This study presents an alternate approach to validation of ABMs when large-scale calibration is not appropriate for specific settings and proposes a new metric for validating socio-environmental network structure of ABMs. Our findings also demonstrate the utility of hospital-specific modeling.

Abstract Understanding the principles of colonization resistance of the gut microbiome to the pathogen Clostridioides difficile will enable the design of defined bacterial therapeutics. We investigate the ecological principles of community resistance to C. difficile using a synthetic human gut microbiome. Using a dynamic computational model, we demonstrate that C. difficile receives the largest number and magnitude of incoming negative interactions. Our results show that C. difficile is in a unique class of species that display a strong negative dependence between growth and species richness. We identify molecular mechanisms of inhibition including acidification of the environment and competition over resources. We demonstrate that Clostridium hiranonis strongly inhibits C. difficile partially via resource competition. Increasing the initial density of C. difficile can increase its abundance in the assembled community, but community context determines the maximum achievable C. difficile abundance. Our work suggests that the C. difficile inhibitory potential of defined bacterial therapeutics can be optimized by designing communities featuring a combination of mechanisms including species richness, environment acidification, and resource competition.

The species composition of the human gut microbiota is related to overall health, and a healthy gut microbiome is crucial in maintaining colonization resistance against pathogens. Disruption of gut microbiome composition and functionality reduces colonization resistance and has been associated with several gastrointestinal and non-gastrointestinal diseases. One prime example is Clostridioides difficile infection (CDI) and subsequent recurrent infections that occur after the development of systemic antibiotic-related dysbiosis. Standard-of-care antibiotics used for both acute and recurrent infections do not address dysbiosis and often worsen the condition. Moreover, monoclonal antibodies, recommended in conjunction with standard-of-care antibiotics for the prevention of recurrent CDI in patients at high risk of recurrence, reduce recurrences but do not address the underlying dysbiosis. Fecal microbiota transplantation (FMT) is an evolving therapeutic strategy in which microbes are harvested from healthy donor stool and transplanted into the gut of a recipient to restore the gut microbiome. Although effective in the prevention of recurrent CDI, some existing challenges include screening and the standardization of stool acquisition and processing. Recent safety alerts by the US Food and Drug Administration raised concern about the possibility of transmission of multidrug-resistant organisms or severe acute respiratory syndrome coronavirus 2 via FMT. Increased knowledge that microbes are beneficial in restoring the gut microbiome has led to the clinical development of several newer biotherapeutic formulations that are more regulated than FMT, which may allow for improved restoration of the gut microbiome and prevention of CDI recurrence. This review focuses on mechanisms by which gut microbiome restoration could influence colonization resistance against the pathogen C. difficile. Plain language summary The Role of the Gut Microbiome in Clostridioides difficile Infection Introduction: A rich and diverse gut microbiome is key to immune system regulation and colonization resistance against pathogens. A disruption in the gut microbiome composition can make the gut more vulnerable to diseases such as Clostridioides difficile infection (CDI), caused by the bacterium C. difficile . CDI management presents a therapeutic dilemma, as it is usually treated with antibiotics that can treat the infection but also can damage the microbiome. Treatment of CDI using antibiotics can further reduce microbial diversity and deplete beneficial bacteria from the gut leading to a condition called dysbiosis. Antibiotic treatment can be followed by therapies that restore the gut microbiota, boost colonization resistance, and prevent the development of antimicrobial resistance. It is important to evaluate treatment options to determine their safety and effectiveness. Methods: The researchers provided an overview of the mechanisms that the gut microbiome uses to prevent colonization of the gut by pathogens. They subsequently reviewed the efficacy and shortcomings of the following treatments for CDI: - Antibiotics - Monoclonal antibodies - Fecal microbiota transplantation (FMT) Results: Commensal intestinal bacteria prevent colonization of the gut by pathogens using mechanisms such as: - Competition for key nutrients - Production of inhibitory bile acids - Short-chain fatty acid production - Lowering the luminal pH - Production of bacteriocins Antibiotic therapy is recommended as a standard treatment for CDI. However, patients are vulnerable to recurrent CDI after discontinuation of the therapy. Monoclonal antibodies that inactivate C. difficile toxins may be recommended along with antibiotics to prevent recurrent CDI. However, this approach does not restore the microbiome. FMT is one method of microbial restoration, where stool is harvested from a healthy donor and transplanted into a patient’s colon. Although FMT has shown some efficacy in the treatment of recurrent CDI, the procedure is not standardized. Safety concerns have been raised about the possibility of transmission of multidrug-resistant pathogens via FMT. Conclusion: Treatment methods that can efficiently restore the diversity of the gut microbiome are crucial in preventing recurrence of CDI.

Abstract Background Using patient audio recordings of medical visits to provide clinicians with feedback on their attention to patient life context in care planning can improve health care delivery and outcomes, and reduce costs. However, such an initiative can raise concerns across stakeholders about surveillance, intrusiveness and merit. This study examined the perspectives of patients, physicians and other clinical staff, and facility leaders over 3 years at six sites during the implementation of a patient-collected audio quality improvement program designed to improve patient-centered care in a non-threatening manner and with minimal effort required of patients and clinicians. Methods Patients were invited during the first and third year to complete exit surveys when they returned their audio recorders following visits, and clinicians to complete surveys annually. Clinicians were invited to participate in focus groups in the first and third years. Facility leaders were interviewed individually during the last 6 months of the study. Results There were a total of 12 focus groups with 89 participants, and 30 leadership interviews. Two hundred fourteen clinicians and 800 patients completed surveys. In a qualitative analysis of focus group data employing NVivo, clinicians initially expressed concerns that the program could be disruptive and/or burdensome, but these diminished with program exposure and were substantially replaced by an appreciation for the value of low stakes constructive feedback. They were also significantly more confident in the value of the intervention in the final year (p = .008), more likely to agree that leadership supports continuous improvement of patient care and gives feedback on outcomes (p = .02), and at a time that is convenient (p = .04). Patients who volunteered sometimes expressed concerns they were “spying” on their doctors, but most saw it as an opportunity to improve care. Leaders were supportive of the program but not yet prepared to commit to funding it exclusively with facility resources. Conclusions A patient-collected audio program can be implemented when it is perceived as safe, not disruptive or burdensome, and as contributing to better health care.

Abstract Background Proton pump inhibitors (PPIs) are among the most prescribed medications and are often used unnecessarily. PPIs are used for the treatment of heartburn and acid-related disorders. Emerging evidence indicates that PPIs are associated with serious adverse events, such as increased risk of Clostridioides difficile infection. In this study, we designed and piloted a PPI de-implementation intervention among hospitalized non-intensive care unit patients. Methods Using the Systems Engineering Initiative for Patient Safety (SEIPS) model as the framework, we developed an intervention with input from providers and patients. On a bi-weekly basis, a trainee pharmacist reviewed a random sample of eligible patients’ charts to assess if PPI prescriptions were guideline-concordant; a recommendation to de-implement non-guideline-concordant PPI therapy was sent when applicable. We used convergent parallel mixed-methods design to evaluate the feasibility and outcomes of the intervention. Results During the study period (September 2019 to August 2020), 2171 patients with an active PPI prescription were admitted. We randomly selected 155 patient charts for review. The mean age of patients was 70.9 ± 9 years, 97.4% were male, and 35% were on PPIs for ≥5 years. The average time (minutes) needed to complete the intervention was as follows: 5 to assess if the PPI was guideline-concordant, 5 to provide patient education, and 7 to follow-up with patients post-discharge. After intervention initiation, the week-to-week mean number of PPI prescriptions decreased by 0.5 (S

Background: Povidone-iodine and chlorhexidine gluconate are commonly used antiseptics that have broad antiviral properties, including against SARS-CoV-2. Nasal and oral antisepsis is a possible option to reduce viral transmission; however, effectiveness data are limited. The acceptability of this method for adjunct infection control is also unknown. We are conducting a clinical randomized controlled trial (NCT04478019) to evaluate the effectiveness and feasibility of nasal and oral antisepsis to prevent COVID-19. Methods: Healthcare and other essential workers with in-person job duties were recruited into a 10-week clinical trial. Participation did not require in-person activities: all communication was web- or telephone-based, supplies were shipped directly to the participant, and participants self-collected specimens. Participants completed a 3-week intervention and 3-week control phases and were randomized to the timing of these phases (Fig. 1). During the 3-week intervention phase, participants applied povidone-iodine nasal swabs 2 times per day and chlorhexidine gluconate oral rinse 4 times per day following the manufacturers’ instructions for use. Participants continued all usual infection control measures (eg, face masks, eye protection, gowns, hand hygiene) as required by their workplace. To measure effectiveness against viral transmission, participants collected midturbinate nasal swabs 3 times per week to measure SARS-CoV-2 viral load. Participants also self-reported COVID-19 tests they received and why (eg, symptoms or exposure). To assess acceptability, participants completed pre- and post-surveys about their perceived and actual experience with the interventions. Participants also self-reported adverse effects due to the intervention. Results: As of December 3, 2021, 221 participants (148 healthcare workers and 73 non–healthcare essential workers) had enrolled. Moreover, 20 adverse effects have been reported, including skin irritation, epistaxis, and mouth discoloration; 9 participants withdrew due to side effects. Laboratory analyses are ongoing to measure effectiveness in reducing SARS-CoV-2 viral load. We performed an interim analysis of intervention acceptability. Survey responses were given on a Likert scale of 1 (not at all) to 5 (extremely). Although 36% of respondents (n = 74) reported on the postsurvey that the intervention was less acceptable than they had expected on the presurvey, the overall acceptability measure was still relatively high (3.76) (Fig. 2). In addition, 76% of respondents reported that they would use the intervention in the future (n = 56). Conclusions: Participant recruitment is ongoing, and data continue to be collected to analyze effectiveness and feasibility. Preliminary data suggest that participants find the nasal and oral antisepsis intervention to be an acceptable option to complement standard infection control methods to prevent COVID-19.

Background: Surgical site infections (SSIs) incur up to $10 billion annually due to their excessive morbidity. SSI prevention bundles have had variable success in colorectal surgery. For example, at the University of Wisconsin Hospital, a 505-bed regional referral center, SSI rates have remained high despite the introduction of a 14-element SSI prevention bundle in 2016. To aid in the implementation of this complex bundle, the hospital started Strike Teams in 2019. We have described the impact of Strike Teams on colorectal SSI rates in our tertiary-care hospital. Methods: A Strike Team with key stakeholders from colorectal surgery (ie, surgeon, OR director, nurses, surgical technicians), anesthesia, pharmacy, infection prevention, and infectious disease was formed, supported by the hospital’s executive leadership. The Strike Team met monthly throughout 2019 to review each SSI case, discussed barriers to adherence for the SSI prevention bundle elements with implementation difficulties (Table 1), and proposed actionable feedback to increase adherence. The latter was disseminated to frontline clinicians by the teams’ surgical leaders during everyday clinical practice. The Strike Team was paused in 2020 due to resource reallocation in response to the COVID-19 pandemic. Monthly and quarterly SSI surveillance was conducted according to CDC guidance. Results: Colorectal SSI rates before, after, and during Strike Team activity are shown in Fig. 1. Adherence rates to the bundle elements targeted by the Strike Team are shown in Fig. 2. Conclusions: Adherence to the preferred antibiotic prophylaxis increased, although adherence to other bundle elements of focus did not change significantly. SSI rates decreased below our expectation while the Strike Team was active in our hospital, although SSI reduction was not sustained. Further research should study the effectiveness of Strike Teams as a long-term implementation strategy for SSI prevention in colorectal surgery.

In this study, the authors present an analysis of 247 full-genome SARS-CoV-2 sequences obtained from two communities in Wisconsin, USA, and report distinct patterns of viral spread. Their results suggest that patterns of SARS-CoV-2 transmission and spread may vary substantially, even between neighbouring communities.

Abstract Background Clostridioides difficile infection (CDI) is commonly associated with outcomes like recurrence and readmission. The effect of social determinants of health, such as ‘neighborhood’ socioeconomic disadvantage, on a CDI patient’s health outcomes is unclear. Living in a disadvantaged neighborhood could interfere with a CDI patient’s ability to follow post-discharge care recommendations and the success probability of these recommendations, thereby increasing risk of readmission. We hypothesized that neighborhood disadvantage was associated with 30-day readmission risk in Medicare patients with CDI. Methods In this retrospective cohort study, odds of 30-day readmission for CDI patients are evaluated controlling for patient sociodemographics, comorbidities, and hospital and stay-level variables. The cohort was created from a random 20% national sample of Medicare patients during the first 11 months of 2014. Results From the cohort of 19,490 patients (39% male; 80% white; 83% 65 years or older), 22% were readmitted within 30 days of an index stay. Unadjusted analyses showed that patients from the most disadvantaged neighborhoods were readmitted at a higher rate than those from less disadvantaged neighborhoods (26% vs. 21% rate: unadjusted OR = 1.32 [1.20, 1.45]). This relationship held in adjusted analyses, in which residence in the most disadvantaged neighborhoods was associated with 16% increased odds of readmission (adjusted OR = 1.16 [1.04, 1.28]). Conclusions Residence in disadvantaged neighborhoods poses a significantly increased risk of readmission in CDI patients. Further research should focus on in-depth assessments of this population to better understand the mechanisms underlying these risks and if these findings apply to other infectious diseases.

The gut microbiome is an important factor in human health and disease. While preliminary studies have found some evidence that physical activity is associated with gut microbiome richness, diversity, and composition, this relationship is not fully understood and has not been previously characterized in a large, population-based cohort. In this study, we estimated the association between several measures of physical activity and the gut microbiota in a cohort of 720 Wisconsin residents. Our sample had a mean age of 55 years (range: 18, 94), was 42% male, and 83% of participants self-identified as White. Gut microbial composition was assessed using gene sequencing of the V3-V4 region of 16S rRNA extracted from stool. We found that an increase of one standard deviation in weekly minutes spent in active transportation was associated with an increase in alpha diversity, particularly in Chao1's richness (7.57, 95% CI: 2.55, 12.59) and Shannon's diversity (0.04, 95% CI: 0.0008, 0.09). We identified interactions in the association between Inverse Simpson's diversity and physical activity, wherein active transportation for individuals living in a rural environment was associated with additional increases in diversity (4.69, 95% CI: 1.64, 7.73). We also conducted several permutational ANOVAs (PERMANOVA) and negative binomial regression analyses to estimate the relationship between physical activity and microbiome composition. We found that being physically active and increased physical activity time were associated with increased abundance of bacteria in the family Erysipelotrichaceae. Active transportation was associated with increased abundance of bacteria in the genus Phascolarctobacterium, and decreased abundance of Clostridium. Minutes in active transportation was associated with a decreased abundance of the family Clostridiaceae.

Gulf War Illness (GWI) affects 25-35% of the 1991 Gulf War Veteran (GWV) population. Patients with GWI experience pain, fatigue, cognitive impairments, gastrointestinal dysfunction, skin disorders, and respiratory issues. In longitudinal studies, many patients with GWI have shown little to no improvement in symptoms since diagnosis. The gut microbiome and diet play an important role in human health and disease, and preliminary studies suggest it may play a role in GWI. To examine the relationship between the gut microbiota, diet, and GWI, we conducted an eight-week prospective cohort study collecting stool samples, medications, health history, and dietary data. Sixty-nine participants were enrolled into the study, 36 of which met the case definition for GWI. The gut microbiota of participants, determined by 16S rRNA sequencing of stool samples, was stable over the duration of the study and showed no within person (alpha diversity) differences. Between group analyses (beta diversity) identified statistically significant different between those with and without GWI. Several taxonomic lineages were identified as differentially abundant between those with and without GWI (n = 9) including a greater abundance of Lachnospiraceae and Ruminococcaceae in those without GWI. Additionally, there were taxonomic differences between those with high and low healthy eating index (HEI) scores including a greater abundance of Ruminococcaceae in those with higher HEI scores. This longitudinal cohort study of GWVs found that participants with GWI had significantly different microbiomes from those without GWI. Further studies are needed to determine the role these differences may play in the development and treatment of GWI.

Introduction The composition of the nasal microbiota in surgical patients in the context of general anesthesia and nasal povidone-iodine decolonization is unknown. The purpose of this quality improvement study was to determine: (i) if general anesthesia is associated with changes in the nasal microbiota of surgery patients and (ii) if preoperative intranasal povidone-iodine decolonization is associated with changes in the nasal microbiota of surgery patients. Materials and methods One hundred and fifty-one ambulatory patients presenting for surgery were enrolled in a quality improvement study by convenience sampling. Pre- and post-surgery nasal samples were collected from patients in the no intranasal decolonization group (control group, n = 54). Pre-decolonization nasal samples were collected from the preoperative intranasal povidone-iodine decolonization group (povidone-iodine group, n = 97). Intranasal povidone-iodine was administered immediately prior to surgery and continued for 20 minutes before patients proceeded for surgery. Post-nasal samples were then collected. General anesthesia was administered to both groups. DNA from the samples was extracted for 16S rRNA sequencing on an Illumina MiSeq. Results In the control group, there was no evidence of change in bacterial diversity between pre- and post-surgery samples. In the povidone-iodine group, nasal bacterial diversity was greater in post-surgery, relative to pre-surgery (Shannon’s Diversity Index (P = 0.038), Chao’s richness estimate (P = 0.02) and Inverse Simpson index (P = 0.027). Among all the genera, only the relative abundance of the genus Staphylococcus trended towards a decrease in patients after application (FDR adjusted P = 0.06). Abundant genera common to both povidone-iodine and control groups included Staphylococcus, Bradyrhizobium, Corynebacterium, Dolosigranulum, Lactobacillus, and Moraxella. Conclusions We found general anesthesia was not associated with changes in the nasal microbiota. Povidone-iodine treatment was associated with nasal microbial diversity and decreased abundance of Staphylococcus. Future studies should examine the nasal microbiota structure and function longitudinally in surgical patients receiving intranasal povidone-iodine.

Abstract Objective: To compare clinical outcomes associated with appropriate and inappropriate management of asymptomatic bacteriuria (ASB) and urinary tract infection (UTI) among inpatients with neurogenic bladder (NB). Design: Multicenter, retrospective cohort. Setting: The study was conducted across 4 Veterans’ Affairs hospitals. Participants: The study included veterans with NB due to spinal cord injury or disorder (SCI/D), multiple sclerosis (MS), or Parkinson’s disease (PD) hospitalized between January 1, 2017, and December 31, 2018, with diagnosis of ASB or UTI. Interventions: In a medical record review, we classified ASB and UTI diagnoses and treatments as appropriate or inappropriate based on national guidelines. Main outcome measures: Frequencies of Clostridioides difficile infection, acute kidney injury, 90-day hospital readmission, postculture length-of-stay (LOS), and multidrug-resistant organisms in subsequent urine cultures were compared between those who received appropriate and inappropriate management. Results: We included 170 encounters with ASB (30%) or UTI (70%) diagnoses occurring for 166 patients. Overall, 86.1% patients were male, 47.6% had SCI/D and 77.6% used bladder catheters. All ASB encounters had appropriate diagnoses, and 96.1% had appropriate treatment. In contrast, 37 UTI encounters (31.1%) had inappropriate diagnoses and 61 (51.3%) had inappropriate treatment, including 30 encounters with true ASB. Among patients with SCI/D or MS, appropriate ASB or UTI diagnosis was associated with a longer postculture LOS (median, 14 vs 7.5 days; P = .02). We did not detect any significant associations between appropriate versus inappropriate diagnosis and treatment and other outcomes. Conclusions: Almost one-third of UTI diagnoses and half of treatments in hospitalized patients with NB are inappropriate. Opportunities exist to improve ASB and UTI management in patients with NB to minimize inappropriate antibiotic use.

Abstract Objectives: Contaminated surfaces in healthcare settings contribute to the transmission of nosocomial pathogens. Adequate environmental cleaning is important for preventing the transmission of important pathogens and reducing healthcare-associated infections. However, effective cleaning practices vary considerably. We examined environmental management services (EMS) staff experiences and perceptions surrounding environmental cleaning to describe perceived challenges and ideas to promote an effective environmental services program. Design: Qualitative study. Participants: Frontline EMS staff. Methods: From January to June 2019, we conducted individual semistructured interviews with key stakeholders (ie, EMS staff) at 3 facilities within the Veterans’ Affairs Healthcare System. We used the Systems Engineering Initiative for Patient Safety (SEIPS) framework (ie, people, environment, organization, tasks, tools) to guide this study. Interviews were audio-recorded, transcribed, and analyzed for thematic content. Results: In total, 13 EMS staff and supervisors were interviewed. A predominant theme that emerged were the challenges EMS staff saw as hindering their ability to be effective at their jobs. EMS staff interviewed felt they understand their job requirements and are dedicated to their work; however, they described challenges related to feeling undervalued and staffing issues. Conclusions: EMS staff play a critical role in infection prevention in healthcare settings. However, some do not believe their role is recognized or valued by the larger healthcare team and leadership. EMS staff provided ideas for improving feelings of value and job satisfaction, including higher pay, opportunities for certifications and advancement, as well as collaboration or integration with the larger healthcare team. Healthcare organizations should focus on utilizing these suggestions to improve the EMS work climate.

This article is a narrative of one patient’s experience during COVID-19. As a non-COVID patient, she shares her personal fears, the fears of others in her family and the fears of the healthcare professionals. These fears have made navigating the healthcare systems stressful for patients but also caused patients to avoid them completely. In some cases, this avoidance led to delayed diagnosis, missed diagnosis and death. When healthcare providers guide patients through the process of seeking in-person healthcare, the outcomes were more positive for everyone involved but especially for the patients and their care partners. The patient’s voice is needed to help healthcare professionals understand their fears and how to provide the best healthcare for all. Experience Framework This article is associated with the Patient, Family & Community Engagement lens of The Beryl Institute Experience Framework (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens.

ABSTRACT The aerodigestive tract (ADT) is the primary portal through which pathogens and other invading microbes enter the body. As the direct interface with the environment, we hypothesize that the ADT microbiota possess biosynthetic gene clusters (BGCs) for antibiotics and other specialized metabolites to compete with both endogenous and exogenous microbes. From 1,214 bacterial genomes, representing 136 genera and 387 species that colonize the ADT, we identified 3,895 BGCs. To determine the distribution of BGCs and bacteria in different ADT sites, we aligned 1,424 metagenomes, from nine different ADT sites, onto the predicted BGCs. We show that alpha diversity varies across the ADT and that each site is associated with distinct bacterial communities and BGCs. We identify specific BGC families enriched in the buccal mucosa, external naris, gingiva, and tongue dorsum despite these sites harboring closely related bacteria. We reveal BGC enrichment patterns indicative of the ecology at each site. For instance, aryl polyene and resorcinol BGCs are enriched in the gingiva and tongue, which are colonized by many anaerobes. In addition, we find that streptococci colonizing the tongue and cheek possess different ribosomally synthesized and posttranslationally modified peptide BGCs. Finally, we highlight bacterial genera with BGCs but are underexplored for specialized metabolism and demonstrate the bioactivity of Actinomyces against other bacteria, including human pathogens. Together, our results demonstrate that specialized metabolism in the ADT is extensive and that by exploring these microbiomes further, we will better understand the ecology and biogeography of this system and identify new bioactive natural products. IMPORTANCE Bacteria produce specialized metabolites to compete with other microbes. Though the biological activities of many specialized metabolites have been determined, our understanding of their ecology is limited, particularly within the human microbiome. As the aerodigestive tract (ADT) faces the external environment, bacteria colonizing this tract must compete both among themselves and with invading microbes, including human pathogens. We analyzed the genomes of ADT bacteria to identify biosynthetic gene clusters (BGCs) for specialized metabolites. We found that the majority of ADT BGCs are uncharacterized and the metabolites they encode are unknown. We mapped the distribution of BGCs across the ADT and determined that each site is associated with its own distinct bacterial community and BGCs. By further characterizing these BGCs, we will inform our understanding of ecology and biogeography across the ADT, and we may uncover new specialized metabolites, including antibiotics.

Whether a healthcare worker’s severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is community or hospital acquired affects prevention practices. We used virus sequencing to determine that infection of a healthcare worker who cared for 2 SARS-CoV-2–infected patients was probably community acquired. Appropriate personal protective equipment may have protected against hospital-acquired infection.

Background: Environmental sources have been implicated as a potential source for exogenous acquisition of Candida species, particularly the emerging multidrug-resistant Candida auris. However, limited information is available on environmental reservoirs of Candida species in healthcare facilities. Methods: During a 6-month period, cultures for Candida species were collected from high-touch surfaces in patient rooms and from portable equipment in 6 US acute care hospitals in 4 states. Additional cultures were collected from sink drains and floors in one of the hospitals and from high-touch surfaces, portable equipment, and sink drains in a hospital experiencing an outbreak due to C. auris. Candida species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectometry. Results: Candida species were recovered from patient rooms in 4 of the 6 hospitals. Seven of 147 patient room cultures (4.8%) and 1 of 57 (1.8%) portable equipment cultures were positive, with the most common species being C. parapsilosis. For the hospital where additional sites were sampled, Candida species were recovered from 8 of 22 (36.4%) hospital room floors and 4 of 17 (23.5%) sink drains. In the facility with a C. auris outbreak, Candida species were frequently recovered from sink drains (20.7%) and high-touch surfaces (15.4%), but recovery of C. auris was uncommon (3.8% of high-touch surfaces, 3.4% of sink drains, and 0% of portable equipment) and only present in rooms that currently or recently housed a patient with C. auris. Conclusion: Candida species often contaminate surfaces in hospitals and may be particularly common on floors and in sink drains. However, C. auris contamination was uncommon in a facility experiencing an outbreak, suggesting that current cleaning and disinfection practices can be effective in minimizing environmental contamination.

Abstract Background Hospital antimicrobial stewardship programs are especially critical in countries such as the Philippines, where antibiotic resistant infections are highly prevalent. At the study institution in Manila, Philippines, a Prior Approval for Restricted Antimicrobials (PARA) is required for non-infectious disease specialists to prescribe certain antimicrobials, including carbapenems. PARA request forms include specification of empiric or definitive therapy based on diagnostic tests. Recommended duration of therapy is typically 3 days for empiric use and 7 days for definitive, with possible extension upon specialist approval. Methods The study took place at an 800-bed tertiary hospital. We performed a retrospective review of patient medical records and laboratory reports dating from January 1 to December 31, 2016. Information related to patient demographics, carbapenem prescription, laboratory diagnosis, and therapy were compiled. Carbapenem prescriptions were classified as ‘adherent’ or ‘non-adherent’ according to clinical guidelines related to infection diagnosis, treatment duration, and de-escalation. Results Of the 185 patients on carbapenem therapy, Prescriptions of carbapenems were either definitive (n = 56), empiric (n = 127), or prophylactic (n = 2) as defined by the ordering provider. 69 out of 185 (37%) prescriptions were deemed non-adherent to guidelines, despite receiving approvals for their respective requests. Of these, 72% were non-adherent due to failure to de-escalate the carbapenem and 28% were non-adherent due to an incomplete course of therapy. Conclusion Despite initial PARA approval for carbapenem therapy, 37% of prescriptions were non-guideline-adherent, highlighting the ongoing challenges in implementing this type of stewardship strategy. In order to increase the effectiveness of PARA, additional approaches may be warranted, including the application of strict policies which reinforce follow-up of available culture results, justification of therapy extension, or referral to an infectious disease specialist.

Abstract Background Chlorhexidine gluconate (CHG) bathing of hospitalized patients may have benefit in reducing hospital-acquired bloodstream infections (HABSIs). However, the magnitude of effect, implementation fidelity, and patient-centered outcomes are unclear. In this meta-analysis, we examined the effect of CHG bathing on prevention of HABSIs and assessed fidelity to implementation of this behavioral intervention. Methods We undertook a meta-analysis by searching Medline, EMBASE, CINAHL, Scopus, and Cochrane’s CENTRAL registry from database inception through January 4, 2019 without language restrictions. We included randomized controlled trials, cluster randomized trials and quasi-experimental studies that evaluated the effect of CHG bathing versus a non-CHG comparator for prevention of HABSIs in any adult healthcare setting. Studies of pediatric patients, of pre-surgical CHG use, or without a non-CHG comparison arm were excluded. Outcomes of this study were HABSIs, patient-centered outcomes, such as patient comfort during the bath, and implementation fidelity assessed through five elements: adherence, exposure or dose, quality of the delivery, participant responsiveness, and program differentiation. Three authors independently extracted data and assessed study quality; a random-effects model was used. Results We included 26 studies with 861,546 patient-days and 5259 HABSIs. CHG bathing markedly reduced the risk of HABSIs (IRR = 0.59, 95% confidence interval [CI]: 0.52–0.68). The effect of CHG bathing was consistent within subgroups: randomized (0.67, 95% CI: 0.53–0.85) vs. non-randomized studies (0.54, 95% CI: 0.44–0.65), bundled (0.66, 95% CI: 0.62–0.70) vs. non-bundled interventions (0.51, 95% CI: 0.39–0.68), CHG impregnated wipes (0.63, 95% CI: 0.55–0.73) vs. CHG solution (0.41, 95% CI: 0.26–0.64), and intensive care unit (ICU) (0.58, 95% CI: 0.49–0.68) vs. non-ICU settings (0.56, 95% CI: 0.38–0.83). Only three studies reported all five measures of fidelity, and ten studies did not report any patient-centered outcomes. Conclusions Patient bathing with CHG significantly reduced the incidence of HABSIs in both ICU and non-ICU settings. Many studies did not report fidelity to the intervention or patient-centered outcomes. For sustainability and replicability essential for effective implementation, fidelity assessment that goes beyond whether a patient received an intervention or not should be standard practice particularly for complex behavioral interventions such as CHG bathing. Trial registration Study registration with PROSPERO CRD42015032523.

The aim of this research was to describe the incidence and treatments of mastitis and other common bovine diseases using one year of retrospective observational data (n = 50,329 cow-lactations) obtained from herd management software of 37 large dairy farms in Wisconsin. Incidence rate (IR) was defined as the number of first cases of each disease divided by the number of lactations per farm. Clinical mastitis (CM) remains the most diagnosed disease of dairy cows. Across all herds, the mean IR (cases per 100 cow-lactations) was 24.4 for clinical mastitis, 14.5 for foot disorders (FD), 11.2 for metritis (ME), 8.6 for ketosis (KE), 7.4 for retained fetal membranes (RFM), 4.5 for diarrhea (DI), 3.1 for displaced abomasum (DA), 2.9 for pneumonia (PN) and 1.9 for milk fever (MF). More than 30% of cows that had first cases of CM, DA, RFM, DI, and FD did not receive antibiotics. Of those treated, more than 50% of cows diagnosed with PN, ME and CM received ceftiofur as a treatment. The IR of mastitis and most other diseases was greater in older cows (parity ≥ 3) during the first 100 days of lactation and these cows were more likely to receive antibiotic treatments (as compared to younger cows diagnosed in later lactation). Cows of first and second parities in early lactation were more likely to remain in the herd after diagnosis of disease, as compared to older cows and cows in later stages of lactation. Most older cows diagnosed with CM in later lactation were culled before completion of the lactation. These results provide baseline data for disease incidence in dairy cows on modern U.S. dairy farms and reinforce the role of mastitis as an important cause of dairy cow morbidity.

Introduction Clostridioides difficile infection (CDI) is one of the most common healthcare-associated infections in the USA, having high incidence in intensive care units (ICU). Antibiotic use increases risk of CDI, with fluoroquinolones (FQs) particularly implicated. In healthcare settings, antibiotic stewardship (AS) and infection control interventions are effective in CDI control, but there is little evidence regarding the most effective AS interventions. Preprescription authorisation (PPA) restricting FQs is a potentially promising AS intervention to reduce CDI. The FQ Restriction for the Prevention of CDI (FIRST) trial will evaluate the effectiveness of an FQ PPA intervention in reducing CDI rates in adult ICUs compared with preintervention care, and evaluate implementation effectiveness using a human-factors and systems engineering model.Methods and analysis This is a multisite, stepped-wedge, cluster, effectiveness-implementation clinical trial. The trial will take place in 12 adult medical-surgical ICUs with ≥10 beds, using Epic as electronic health record (EHR) and pre-existing AS programmes. Sites will receive facilitated implementation support over the 15-month trial period, succeeded by 9 months of follow-up. The intervention comprises a clinical decision support system for FQ PPA, integrated into the site EHRs. Each ICU will be considered a single site and all ICU admissions included in the analysis. Clinical data will be extracted from EHRs throughout the trial and compared with the corresponding pretrial period, which will constitute the baseline for statistical analysis. Outcomes will include ICU-onset CDI rates, FQ days of therapy (DOT), alternative antibiotic DOT, average length of stay and hospital mortality. The study team will also collect implementation data to assess implementation effectiveness using the Systems Engineering Initiative for Patient Safety model.Ethics and dissemination The trial was approved by the Institutional Review Board at the University of Wisconsin-Madison (2018-0852-CP015). Results will be made available to participating sites, funders, infectious disease societies, critical care societies and other researchers.Trial registration number NCT03848689.

IntroductionThe recovery of other pathogens in patients with SARS-CoV-2 infection has been reported, either at the time of a SARS-CoV-2 infection diagnosis (co-infection) or subsequently (superinfection). However, data on the prevalence, microbiology, and outcomes of co-infection and superinfection are limited. The purpose of this study was to examine the occurrence of co-infections and superinfections and their outcomes among patients with SARS-CoV-2 infection.Patients and methodsWe searched literature databases for studies published from October 1, 2019, through February 8, 2021. We included studies that reported clinical features and outcomes of co-infection or superinfection of SARS-CoV-2 and other pathogens in hospitalized and non-hospitalized patients. We followed PRISMA guidelines, and we registered the protocol with PROSPERO as: CRD42020189763.ResultsOf 6639 articles screened, 118 were included in the random effects meta-analysis. The pooled prevalence of co-infection was 19% (95% confidence interval [CI]: 14%-25%, I2 = 98%) and that of superinfection was 24% (95% CI: 19%-30%). Pooled prevalence of pathogen type stratified by co- or superinfection were: viral co-infections, 10% (95% CI: 6%-14%); viral superinfections, 4% (95% CI: 0%-10%); bacterial co-infections, 8% (95% CI: 5%-11%); bacterial superinfections, 20% (95% CI: 13%-28%); fungal co-infections, 4% (95% CI: 2%-7%); and fungal superinfections, 8% (95% CI: 4%-13%). Patients with a co-infection or superinfection had higher odds of dying than those who only had SARS-CoV-2 infection (odds ratio = 3.31, 95% CI: 1.82-5.99). Compared to those with co-infections, patients with superinfections had a higher prevalence of mechanical ventilation (45% [95% CI: 33%-58%] vs. 10% [95% CI: 5%-16%]), but patients with co-infections had a greater average length of hospital stay than those with superinfections (mean = 29.0 days, standard deviation [SD] = 6.7 vs. mean = 16 days, SD = 6.2, respectively).ConclusionsOur study showed that as many as 19% of patients with COVID-19 have co-infections and 24% have superinfections. The presence of either co-infection or superinfection was associated with poor outcomes, including increased mortality. Our findings support the need for diagnostic testing to identify and treat co-occurring respiratory infections among patients with SARS-CoV-2 infection.

IntroductionVaccination programs aim to control the COVID-19 pandemic. However, the relative impacts of vaccine coverage, effectiveness, and capacity in the context of nonpharmaceutical interventions such as mask use and physical distancing on the spread of SARS-CoV-2 are unclear. Our objective was to examine the impact of vaccination on the control of SARS-CoV-2 using our previously developed agent-based simulation model.MethodsWe applied our agent-based model to replicate COVID-19-related events in 1) Dane County, Wisconsin; 2) Milwaukee metropolitan area, Wisconsin; 3) New York City (NYC). We evaluated the impact of vaccination considering the proportion of the population vaccinated, probability that a vaccinated individual gains immunity, vaccination capacity, and adherence to nonpharmaceutical interventions. We estimated the timing of pandemic control, defined as the date after which only a small number of new cases occur.ResultsThe timing of pandemic control depends highly on vaccination coverage, effectiveness, and adherence to nonpharmaceutical interventions. In Dane County and Milwaukee, if 50% of the population is vaccinated with a daily vaccination capacity of 0.25% of the population, vaccine effectiveness of 90%, and the adherence to nonpharmaceutical interventions is 60%, controlled spread could be achieved by June 2021 versus October 2021 in Dane County and November 2021 in Milwaukee without vaccine.DiscussionIn controlling the spread of SARS-CoV-2, the impact of vaccination varies widely depending not only on effectiveness and coverage, but also concurrent adherence to nonpharmaceutical interventions.

We studied farmworker practices and beliefs potentially contributing to transmission of bacteria and their associated antibiotic resistance genes (ARGs) among animals and farm workers to identify potential behavioral interventions to reduce the risk of bacterial transmission. Ten focus groups were conducted on eight Wisconsin dairy farms to assess potentially high-risk practices and farmworker knowledge and experiences with antibiotic use and resistance using the Systems Engineering in Patient Safety (SEIPS) framework. Farmworkers were asked to describe common on-farm tasks and the policies guiding these practices. We found workers demonstrated knowledge of the role of antibiotic stewardship in preventing the spread of ARGs. Worker knowledge of various forms of personal protective equipment was higher for workers who commonly reported glove-use. Additionally, workers knowledge regarding the importance of reducing ARG transmission varied but was higher than we had hypothesized. Programs to reduce ARG spread on dairy farms should focus on proper hand hygiene and personal protective equipment use at the level of knowledge, beliefs, and practices.

Recurrent Clostridiodes difficile infections (rCDIs) are a burdensome problem. Patients with a history of CDI that are prescribed antibiotics are at a high risk for recurrence. Fecal microbiota transplantation (FMT) has been shown to be an effective treatment for rCDI, though there is little information on the impact of FMT with antibiotics on the gut microbiome. We are conducting a clinical trial of FMT to prevent rCDI in patients with a history of CDI currently taking antibiotics. Our primary objective is to determine the effect of FMT on the gut microbiome during antibiotic exposure. Our secondary aim is to assess safety and feasibility of using FMT as a prophylaxis for CDI. We plan to enroll 30 patients into a phase II randomized, double-blind, placebo-controlled trial with three arms: (1) 5 FMT capsules per day during antibiotic treatment and for 7 days post antibiotic cessation, (2) a one-time dose of 30 FMT capsules 48–72 h post cessation of antibiotic treatment, or (3) 5 placebo capsules per day during antibiotic treatment and for 7 days post antibiotic treatment. Patients provide stool samples throughout the duration of the study and are cultured C. difficile. Sequencing of the V4 region of the 16S rRNA gene will be carried out to assess the gut microbiota. Results of this study will provide information on the impact of FMT on the gut microbiome as well as the necessary data to examine whether or not prophylactic FMT should be explored further as a way to prevent CDI recurrence.

Abstract Background Clostridium difficile infection (CDI) is understudied in limited resource settings. In addition, provider awareness of CDI as a prevalent threat is unknown. An assessment of current facilitators and barriers to CDI identification, management, and prevention is needed in limited resource settings to design and evaluate quality improvement strategies to effectively minimize the risk of CDI. Methods Our study aimed to identify CDI perceptions and practices among healthcare providers in South African secondary hospitals to identify facilitators and barriers to providing quality CDI care. Qualitative interviews (11 physicians, 11 nurses, 4 pharmacists,) and two focus groups (7 nurses, 3 pharmacists) were conducted at three district level hospitals in the Cape Town Metropole. Semi-structured interviews elicited provider perceived facilitators, barriers, and opportunities to improve clinical workflow from patient presentation through CDI (1) Identification, (2) Diagnosis, (3) Treatment, and (4) Prevention. In addition, a summary provider CDI knowledge score was calculated for each interviewee for seven components of CDI and management. Results Major barriers identified were knowledge gaps in characteristics of C. difficile identification, diagnosis, treatment, and prevention. The median overall CDI knowledge score (scale 0–7) from individual interviews was 3 [interquartile range 0.25, 4.75]. Delays in C. difficile testing workflow were identified. Participants perceived supplies for CDI management and prevention were usually available; however, hand hygiene and use of contact precautions was inconsistent. Conclusions Our analysis provides a detailed description of the facilitators and barriers to CDI workflow and can be utilized to design quality improvement interventions among limited resource settings.

Abstract Background Infection by Staphylococcus aureus (S. aureus) is a major cause of morbidity and mortality. Colonization by S. aureus increases the risk of infection. Little is known about decolonization strategies for S. aureus beyond antibiotics, however probiotics represent a promising alternative. A randomized controlled trial was conducted to determine the efficacy of Lactobacillus rhamnosus (L. rhamnosus) HN001 in reducing carriage of S. aureus at multiple body sites. Methods One hundred thirteen subjects, positive for S. aureus carriage, were recruited from the William S. Middleton Memorial Medical Center, Madison, WI, USA, and randomized by initial site of colonization, either gastrointestinal (GI) or extra-GI, to 4-weeks of oral L. rhamnosus HN001 probiotic, or placebo. Nasal, oropharyngeal, and axillary/groin swabs were obtained, and serial blood and fecal samples were collected. Differences in prevalence of S. aureus carriage at the end of the 4-weeks of treatment were assessed. Results The probiotic and placebo groups were similar in age, gender, and health history at baseline. S. aureus colonization within the stool samples of the extra-GI group was 15% lower in the probiotic than placebo group at the endpoint of the trial. Those in the probiotic group compared to the placebo group had 73% reduced odds (OR 0.27, 95% CI 0.07–0.98) of methicillin-susceptible S. aureus presence, and 83% reduced odds (OR 0.17, 95% CI 0.04–0.73) of any S. aureus presence in the stool sample at endpoint. Conclusion Use of daily oral L. rhamnosus HN001 reduced odds of carriage of S. aureus in the GI tract, however it did not eradicate S. aureus from other body sites. Trial registration ClinicalTrials.gov Identifier: NCT01321606. Registered March 21, 2011.

Abstract Background Heavy metals including lead and cadmium can disrupt the immune system and the human microbiota. and are increasingly of concern with respect to the propogation of antibiotic-resistence. Infection by methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of global morbidity and mortality. Heavy metal exposure may be associated with increased MRSA colonization and infection, and a decrease in methicillin-susceptible Staphylococcus aureus (MSSA) through co-selection mechanisms and natural selection of antibiotic resistance in the presence of heavy metals. This study examines the association between blood lead (Pb) and cadmium (Cd) level, and MRSA and MSSA nasal colonization. Methods All data used for this analysis came from the 2001–2004 National Health and Nutrition Examination Survey (NHANES). The analytical sample consisted of 18,626 participants aged 1 year and older. Multivariate logistic regression, including adjustment for demographic and dietary factors, was used to analyze the association between blood Pb and Cd, and nasal colonization by MRSA and MSSA. Results Prevalence of MRSA and MSSA carriage were 1.2%, and 29.3% respectively. MRSA was highest in women, individuals age 70 and older, who self-identified as black, had only a high school diploma, lived below 200% of the Federal Poverty Level, and had a history of smoking. While not significantly different from those colonized with MSSA, geometric mean blood Pb (1.74 μg/dL) and blood Cd (0.31 μg/L) were highest in those colonized with MRSA. Associations with MRSA colonization appeared to increase in a dose-dependent manner with increasing quartile of blood Pb level. Blood Cd level in the fourth quartile was also significantly associated with lower odds of MRSA colonization. Both metals were associated with lower odds of MSSA colonization. Conclusions Both MRSA and MSSA results suggest that general population levels of blood Pb but not Cd are associated with differences in nasal carriage of S. aureus. While further research is needed, reduction in heavy metal exposures such as lead, concurrently with maintaining a healthy microbiota may be two modifiable options to consider in the fight against antibiotic-resistance.

Abstract Background Inappropriate ordering and acquisition of urine cultures leads to unnecessary treatment of asymptomatic bacteriuria (ASB). Treatment of ASB contributes to antimicrobial resistance particularly among hospital-acquired organisms. Our objective was to investigate urine culture ordering and collection practices among nurses to identify key system-level and human factor barriers and facilitators that affect optimal ordering and collection practices. Methods We conducted two focus groups, one with ED nurses and the other with ICU nurses. Questions were developed using the Systems Engineering Initiative for Patient Safety (SEIPS) framework. We used iterative categorization (directed content analysis followed by summative content analysis) to code and analyze the data both deductively (using SEIPS domains) and inductively (emerging themes). Results Factors affecting optimal urine ordering and collection included barriers at the person, process, and task levels. For ED nurses, barriers included patient factors, physician communication, reflex culture protocols, the electronic health record, urinary symptoms, and ED throughput. For ICU nurses, barriers included physician notification of urinalysis results, personal protective equipment, collection technique, patient body habitus, and Foley catheter issues. Conclusions We identified multiple potential process barriers to nurse adherence with evidence-based recommendations for ordering and collecting urine cultures in the ICU and ED. A systems approach to identifying barriers and facilitators can be useful to design interventions for improving urine ordering and collection practices.

Abstract Background Healthcare facilities in low- and middle-income countries, including the Philippines, face substantial challenges in achieving effective infection control. Early stages of interventions should include efforts to understand perceptions held by healthcare workers who participate in infection control programs. Methods We performed a qualitative study to examine facilitators and barriers to infection control at an 800-bed, private, tertiary hospital in Manila, Philippines. Semi-structured interviews were conducted with 22 nurses, physicians, and clinical pharmacists using a guide based on the Systems Engineering Initiative for Patient Safety (SEIPS). Major facilitators and barriers to infection control were reported for each SEIPS factor: person, organization, tasks, physical environment, and technology and tools. Results Primary facilitators included a robust, long-standing infection control committee, a dedicated infection control nursing staff, and innovative electronic hand hygiene surveillance technology. Barriers included suboptimal dissemination of hand hygiene compliance data, high nursing turnover, clinical time constraints, and resource limitations that restricted equipment purchasing. Conclusions The identified facilitators and barriers may be used to prioritize possible opportunities for infection control interventions. A systems engineering approach is useful for conducting a comprehensive work system analysis, and maximizing resources to overcome known barriers to infection control in heavily resource-constrained settings.