The SHIELD Study: A preliminary analysis of nasal and oral antisepsis to prevent COVID-19

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.Funding: Professional Disposables International, Healthcare Division (PDIHC)Disclosures: None

The Strike Team as an implementation strategy for surgical infection prevention

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.Funding: NoneDisclosures: None

Anti-membrane Antibodies Persist at Least One Year and Discriminate Between Past Coronavirus Disease 2019 Infection and Vaccination.

BACKGROUND: The consequences of past coronavirus disease 2019 (COVID-19) infection for personal and population health are emerging, but accurately identifying distant infection is a challenge. Anti-spike antibodies rise after both vaccination and infection and anti-nucleocapsid antibodies rapidly decline. METHODS: We evaluated anti-membrane antibodies in COVID-19 naive, vaccinated, and convalescent subjects to determine if they persist and accurately detect distant infection. RESULTS: We found that anti-membrane antibodies persist for at least 1 year and are a sensitive and specific marker of past COVID-19 infection. CONCLUSIONS: Thus, anti-membrane and anti-spike antibodies together can differentiate between COVID-19 convalescent, vaccinated, and naive states to advance public health and research.

The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection.

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 bacteriocinsAntibiotic 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.

SARS-CoV-2 and other respiratory pathogens are detected in continuous air samples from congregate settings.

Two years after the emergence of SARS-CoV-2, there is still a need for better ways to assess the risk of transmission in congregate spaces. We deployed active air samplers to monitor the presence of SARS-CoV-2 in real-world settings across communities in the Upper Midwestern states of Wisconsin and Minnesota. Over 29 weeks, we collected 527 air samples from 15 congregate settings. We detected 106 samples that were positive for SARS-CoV-2 viral RNA, demonstrating that SARS-CoV-2 can be detected in continuous air samples collected from a variety of real-world settings. We expanded the utility of air surveillance to test for 40 other respiratory pathogens. Surveillance data revealed differences in timing and location of SARS-CoV-2 and influenza A virus detection. In addition, we obtained SARS-CoV-2 genome sequences from air samples to identify variant lineages. Collectively, this shows air sampling is a scalable, high throughput surveillance tool that could be used in conjunction with other methods for detecting respiratory pathogens in congregate settings.

Effectiveness of Mask-Wearing on Respiratory Illness Transmission in Community Settings: A Rapid Review.

OBJECTIVE: Respiratory illnesses, including coronavirus disease 2019 (COVID-19), have resulted in millions of deaths globally. Guidance on mask-wearing in community settings has been inconsistent. This review examined the effectiveness of mask-wearing on respiratory virus transmission in community settings. METHODS: A search was conducted for English language reports of randomized controlled trials of mask-wearing in the community and effect on laboratory-confirmed respiratory infections or influenza-like illness. Investigators abstracted study characteristics and assessed bias. Meta-analysis was conducted to calculate pooled risk estimates. RESULTS: Eleven studies were included. In 7 studies that evaluated influenza-like illness symptoms as an outcome (3029 participants), this study found mask-wearing associated with a decreased risk of influenza-like illness (overall risk ratio [RR], 0.83; 95% confidence interval [CI], 0.71 to 0.96). Studies examining laboratory-confirmed respiratory infections as an outcome (10,531 participants) showed no statistically significant association between mask-wearing and infections (RR, 1.04; 95% CI, 0.60-1.80). However, masking combined with enhanced hand hygiene was associated with a decreased risk for both influenza-like illness symptoms (RR, 0.88; 95% CI, 0.51-1.51) and laboratory-confirmed respiratory infection (RR, 0.79; 95% CI, 0.52-1.18). CONCLUSIONS: Masking in community settings decreases transmission of influenza-like illness. Mask-wearing combined with enhanced hand hygiene reduces transmission of influenza-like illness and laboratory-confirmed respiratory infection.

Association Between Immune Dysfunction and COVID-19 Breakthrough Infection After SARS-CoV-2 Vaccination in the US.

Importance: Persons with immune dysfunction have a higher risk for severe COVID-19 outcomes. However, these patients were largely excluded from SARS-CoV-2 vaccine clinical trials, creating a large evidence gap. Objective: To identify the incidence rate and incidence rate ratio (IRR) for COVID-19 breakthrough infection after SARS-CoV-2 vaccination among persons with or without immune dysfunction. Design, Setting, and Participants: This retrospective cohort study analyzed data from the National COVID Cohort Collaborative (N3C), a partnership that developed a secure, centralized electronic medical record-based repository of COVID-19 clinical data from academic medical centers across the US. Persons who received at least 1 dose of a SARS-CoV-2 vaccine between December 10, 2020, and September 16, 2021, were included in the sample. Main Outcomes and Measures: Vaccination, COVID-19 diagnosis, immune dysfunction diagnoses (ie, HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation), other comorbid conditions, and demographic data were accessed through the N3C Data Enclave. Breakthrough infection was defined as a COVID-19 infection that was contracted on or after the 14th day of vaccination, and the risk after full or partial vaccination was assessed for patients with or without immune dysfunction using Poisson regression with robust SEs. Poisson regression models were controlled for a study period (before or after [pre- or post-Delta variant] June 20, 2021), full vaccination status, COVID-19 infection before vaccination, demographic characteristics, geographic location, and comorbidity burden. Results: A total of 664 722 patients in the N3C sample were included. These patients had a median (IQR) age of 51 (34-66) years and were predominantly women (n = 378 307 [56.9%]). Overall, the incidence rate for COVID-19 breakthrough infection was 5.0 per 1000 person-months among fully vaccinated persons but was higher after the Delta variant became the dominant SARS-CoV-2 strain (incidence rate before vs after June 20, 2021, 2.2 [95% CI, 2.2-2.2] vs 7.3 [95% CI, 7.3-7.4] per 1000 person-months). Compared with partial vaccination, full vaccination was associated with a 28% reduced risk for breakthrough infection (adjusted IRR [AIRR], 0.72; 95% CI, 0.68-0.76). People with a breakthrough infection after full vaccination were more likely to be older and women. People with HIV infection (AIRR, 1.33; 95% CI, 1.18-1.49), rheumatoid arthritis (AIRR, 1.20; 95% CI, 1.09-1.32), and solid organ transplant (AIRR, 2.16; 95% CI, 1.96-2.38) had a higher rate of breakthrough infection. Conclusions and Relevance: This cohort study found that full vaccination was associated with reduced risk of COVID-19 breakthrough infection, regardless of the immune status of patients. Despite full vaccination, persons with immune dysfunction had substantially higher risk for COVID-19 breakthrough infection than those without such a condition. For persons with immune dysfunction, continued use of nonpharmaceutical interventions (eg, mask wearing) and alternative vaccine strategies (eg, additional doses or immunogenicity testing) are recommended even after full vaccination.

Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Asymptomatic Infections in 2 Large Academic Health Systems in Wisconsin.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) asymptomatic infections may play a critical role in disease transmission. We aim to determine the prevalence of asymptomatic SARS-CoV-2 infection at 2 hospital systems in 2 counties in Wisconsin. The SARS-CoV-2 prevalence was 1% or lower at both systems despite the higher incidence of coronavirus disease 2019 (COVID-19) in Milwaukee County.

A systems approach to understanding SARS-CoV-2 transmission among healthcare workers in a cluster.

Preventing transmission of COVID-19 between healthcare workers is essential to optimize patient, employee, and organizational outcomes. We used a systems engineering approach to analyze contact tracing interviews from a cluster of COVID-19 at our healthcare institution and identified modifiable and non-modifiable causes of transmission. Similar work system analyses may be useful to institutions in identifying multiple factors contributing to infection clusters among healthcare workers, and in developing layered infection prevention methods to further reduce transmission.

Distinct patterns of SARS-CoV-2 transmission in two nearby communities in Wisconsin, USA

Evidence-based public health approaches that minimize the introduction and spread of new SARS-CoV-2 transmission clusters are urgently needed in the United States and other countries struggling with expanding epidemics. Here we analyze 247 full-genome SARS-CoV-2 sequences from two nearby communities in Wisconsin, USA, and find surprisingly distinct patterns of viral spread. Dane County had the 12th known introduction of SARS-CoV-2 in the United States, but this did not lead to descendant community spread. Instead, the Dane County outbreak was seeded by multiple later introductions, followed by limited community spread. In contrast, relatively few introductions in Milwaukee County led to extensive community spread. We present evidence for reduced viral spread in both counties, and limited viral transmission between counties, following the statewide Safer-at-Home public health order, which went into effect 25 March 2020. Our results suggest that early containment efforts suppressed the spread of SARS-CoV-2 within Wisconsin.

Effectiveness of mRNA Covid-19 Vaccine among U.S. Health Care Personnel.

BACKGROUND: The prioritization of U.S. health care personnel for early receipt of messenger RNA (mRNA) vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), allowed for the evaluation of the effectiveness of these new vaccines in a real-world setting. METHODS: We conducted a test-negative case-control study involving health care personnel across 25 U.S. states. Cases were defined on the basis of a positive polymerase-chain-reaction (PCR) or antigen-based test for SARS-CoV-2 and at least one Covid-19-like symptom. Controls were defined on the basis of a negative PCR test for SARS-CoV-2, regardless of symptoms, and were matched to cases according to the week of the test date and site. Using conditional logistic regression with adjustment for age, race and ethnic group, underlying conditions, and exposures to persons with Covid-19, we estimated vaccine effectiveness for partial vaccination (assessed 14 days after receipt of the first dose through 6 days after receipt of the second dose) and complete vaccination (assessed ≥7 days after receipt of the second dose). RESULTS: The study included 1482 case participants and 3449 control participants. Vaccine effectiveness for partial vaccination was 77.6% (95% confidence interval [CI], 70.9 to 82.7) with the BNT162b2 vaccine (Pfizer-BioNTech) and 88.9% (95% CI, 78.7 to 94.2) with the mRNA-1273 vaccine (Moderna); for complete vaccination, vaccine effectiveness was 88.8% (95% CI, 84.6 to 91.8) and 96.3% (95% CI, 91.3 to 98.4), respectively. Vaccine effectiveness was similar in subgroups defined according to age (<50 years or ≥50 years), race and ethnic group, presence of underlying conditions, and level of patient contact. Estimates of vaccine effectiveness were lower during weeks 9 through 14 than during weeks 3 through 8 after receipt of the second dose, but confidence intervals overlapped widely. CONCLUSIONS: The BNT162b2 and mRNA-1273 vaccines were highly effective under real-world conditions in preventing symptomatic Covid-19 in health care personnel, including those at risk for severe Covid-19 and those in racial and ethnic groups that have been disproportionately affected by the pandemic. (Funded by the Centers for Disease Control and Prevention.).

Viral Sequencing to Investigate Sources of SARS-CoV-2 Infection in US Healthcare Personnel.

BACKGROUND: Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We posit that current infection control guidelines generally protect HCP from SARS-CoV-2 infection in a healthcare setting. METHODS: In this retrospective case series, we used viral genomics to investigate the likely source of SARS-CoV-2 infection in HCP at a major academic medical institution in the Upper Midwest of the United States between 25 March and 27 December 2020. We obtained limited epidemiological data through informal interviews and review of the electronic health record and combined this information with healthcare-associated viral sequences and viral sequences collected in the broader community to infer the most likely source of infection in HCP. RESULTS: We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or coworker (55 of 95 [57.9%]) and were genetically similar to viruses circulating concurrently in the community. We found that 10.5% of HCP infections (10 of 95) could be traced to a coworker. Strikingly, only 4.2% (4 of 95) could be traced to a patient source. CONCLUSIONS: Infections among HCP add further strain to the healthcare system and put patients, HCP, and communities at risk. We found no evidence for healthcare-associated transmission in the majority of HCP infections evaluated. Although we cannot rule out the possibility of cryptic healthcare-associated transmission, it appears that HCP most commonly become infected with SARS-CoV-2 via community exposure. This emphasizes the ongoing importance of mask wearing, physical distancing, robust testing programs, and rapid distribution of vaccines.

Review of the use of nasal and oral antiseptics during a global pandemic.

A review of nasal sprays and gargles with antiviral properties suggests that a number of commonly used antiseptics including povidone-iodine, Listerine®, iota-carrageenan and chlorhexidine should be studied in clinical trials to mitigate both the progression and transmission of SARS-CoV-2. Several of these antiseptics have demonstrated the ability to cut the viral load of SARS-CoV-2 by 3-4 log10 in 15-30 s in vitro. In addition, hypertonic saline targets viral replication by increasing hypochlorous acid inside the cell. A number of clinical trials are in process to study these interventions both for prevention of transmission, prophylaxis after exposure, and to diminish progression by reduction of viral load in the early stages of infection.

The impact of vaccination to control COVID-19 burden in the United States: A simulation modeling approach.

INTRODUCTION: Vaccination 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. METHODS: We 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. RESULTS: The 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. DISCUSSION: In 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.

Implementing daily chlorhexidine gluconate (CHG) bathing in VA settings: The human factors engineering to prevent resistant organisms (HERO) project.

BACKGROUND: Daily use of chlorhexidine gluconate (CHG) has been shown to reduce risk of healthcare-associated infections. We aimed to assess moving CHG bathing into routine practice using a human factors approach. We evaluated implementation in non-intensive care unit (ICU) settings in the Veterans Health Administration. METHODS: Our multiple case study approach included non-ICU units from 4 Veterans Health Administration settings. Guided by the Systems Engineering Initiative for Patient Safety, we conducted focus groups and interviews to capture barriers and facilitators to daily CHG bathing. We measured compliance using observations and skin CHG concentrations. RESULTS: Barriers to daily CHG include time, concern of increasing antibiotic resistance, workflow and product concerns. Facilitators include engagement of champions and unit shared responsibility. We found shortfalls in patient education, hand hygiene and CHG use on tubes and drains. CHG skin concentration levels were highest among patients from spinal cord injury units. These units applied antiseptic using 2% CHG impregnated wipes vs 4% CHG solution/soap. DISCUSSION: Non-ICUs implementing CHG bathing must consider human factors and work system barriers to ensure uptake and sustained practice change. CONCLUSIONS: Well-planned rollouts and a unit culture promoting shared responsibility are key to compliance with daily CHG bathing. Successful implementation requires attention to staff education and measurement of compliance.

COVID-19 in Health Care Personnel: Significance of Health Care Role, Contact History, and Symptoms in Those Who Test Positive for SARS-CoV-2 Infection.

OBJECTIVE: To identify significant factors that help predict whether health care personnel (HCP) will test positive for severe acute respiratory coronavirus 2 (SARS-CoV-2). PATIENTS AND METHODS: We conducted a prospective cohort study among 7015 symptomatic HCP from March 25, 2020, through November 11, 2020. We analyzed the associations between health care role, contact history, symptoms, and a positive nasopharyngeal swab SARS-CoV-2 polymerase chain reaction test results, using univariate and multivariable modelling. RESULTS: Of the symptomatic HCP, 624 (8.9%) were positive over the study period. On multivariable analysis, having a health care role other than physician or advanced practice provider, contact with family or community member with known or suspected coronavirus disease 2019 (COVID-19), and seven individual symptoms (cough, anosmia, ageusia, fever, myalgia, chills, and headache) were significantly associated with higher adjusted odds ratios for testing positive for SARS-CoV-2. For each increase in symptom number, the odds of testing positive nearly doubled (odds ratio, 1.93; 95% CI, 1.82 to 2.07, P<.001). CONCLUSION: Symptomatic HCP have higher adjusted odds of testing positive for SARS-CoV-2 based on three distinct factors: (1) nonphysician/advanced practice provider role, (2) contact with a family or community member with suspected or known COVID-19, and (3) specific symptoms and symptom number. Differences among health care roles, which persisted after controlling for contacts, may reflect the influence of social determinants. Contacts with COVID-19-positive patients and/or HCP were not associated with higher odds of testing positive, supporting current infection control efforts. Targeted symptom and contact questionnaires may streamline symptomatic HCP testing for COVID-19.

Decreasing ICU-associated Clostridioides difficile infection through fluoroquinolone restriction, the FIRST trial: a study protocol.

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.