The landscape of antibody binding in SARS-CoV-2 infection.

The search for potential antibody-based diagnostics, vaccines, and therapeutics for pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has focused almost exclusively on the spike (S) and nucleocapsid (N) proteins. Coronavirus membrane (M), ORF3a, and ORF8 proteins are humoral immunogens in other coronaviruses (CoVs) but remain largely uninvestigated for SARS-CoV-2. Here, we use ultradense peptide microarray mapping to show that SARS-CoV-2 infection induces robust antibody responses to epitopes throughout the SARS-CoV-2 proteome, particularly in M, in which 1 epitope achieved excellent diagnostic accuracy. We map 79 B cell epitopes throughout the SARS-CoV-2 proteome and demonstrate that antibodies that develop in response to SARS-CoV-2 infection bind homologous peptide sequences in the 6 other known human CoVs. We also confirm reactivity against 4 of our top-ranking epitopes by enzyme-linked immunosorbent assay (ELISA). Illness severity correlated with increased reactivity to 9 SARS-CoV-2 epitopes in S, M, N, and ORF3a in our population. Our results demonstrate previously unknown, highly reactive B cell epitopes throughout the full proteome of SARS-CoV-2 and other CoV proteins.

Effect of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the United States : A Simulation Modeling Approach.

BACKGROUND: Across the United States, various social distancing measures were implemented to control the spread of coronavirus disease 2019 (COVID-19). However, the effectiveness of such measures for specific regions with varying population demographic characteristics and different levels of adherence to social distancing is uncertain. OBJECTIVE: To determine the effect of social distancing measures in unique regions. DESIGN: An agent-based simulation model. SETTING: Agent-based model applied to Dane County, Wisconsin; the Milwaukee metropolitan (metro) area; and New York City (NYC). PATIENTS: Synthetic population at different ages. INTERVENTION: Different times for implementing and easing social distancing measures at different levels of adherence. MEASUREMENTS: The model represented the social network and interactions among persons in a region, considering population demographic characteristics, limited testing availability, "imported" infections, asymptomatic disease transmission, and age-specific adherence to social distancing measures. The primary outcome was the total number of confirmed COVID-19 cases. RESULTS: The timing of and adherence to social distancing had a major effect on COVID-19 occurrence. In NYC, implementing social distancing measures 1 week earlier would have reduced the total number of confirmed cases from 203 261 to 41 366 as of 31 May 2020, whereas a 1-week delay could have increased the number of confirmed cases to 1 407 600. A delay in implementation had a differential effect on the number of cases in the Milwaukee metro area versus Dane County, indicating that the effect of social distancing measures varies even within the same state. LIMITATION: The effect of weather conditions on transmission dynamics was not considered. CONCLUSION: The timing of implementing and easing social distancing measures has major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Hepatitis C virus infections among people aged 15-44, United States, 2009-2018.

OBJECTIVES: To estimate the prevalence, characteristics, and gender differences among people aged 15-44 years who are living with current HCV infections in the United States. DESIGN AND SAMPLE: We conducted a cross-sectional, secondary data analysis using data from people who participated in National Health and Nutrition Examination Survey (NHANES) cycles in 2009-2018. MEASUREMENTS: Sociodemographic, social behavior, and clinical factors that had been identified as related to having HCV, barriers to receiving HCV screening, care, or treatment, and health conditions that increase the risks of developing HCV-related complications were studied. A weighted-data analysis approach was used to generate descriptive statistics. RESULTS: The estimated, weighted prevalence of current HCV infections was 0.3% (95% CI, 0.2-0.4), representing approximately 363,161 people (95% CI, 301,402-424, 920). Females were more likely than males to have an unknown risk factor and reported worse overall health. Males were more likely to have comorbidities such as obesity or diabetes that put them at risk for developing life-threatening complications. CONCLUSIONS: Increased public health attention with gender-specific actions are needed to address the health needs of the thousands of people aged 15-44 years who are living with current HCV infections across the United States.

Effectiveness of a mobile antiretroviral pharmacy and HIV care intervention on the continuum of HIV care in rural Uganda.

Adherence to antiretroviral therapy (ART) is critical in order to achieve viral suppression. We designed an intervention, Mobile Antiretroviral Therapy and HIV care (MAP-HC) in rural southwestern Uganda aimed to reduce travel distance and hypothesized that MAP-HC would improve ART adherence and rates of viral load suppression. The study was conducted at two district hospitals, among patients who lived >5 km from the hospital. For each hospital, we identified 4 health centers in the catchment area to serve as site for the mobile pharmacy. Each site was visited once a month to provide ART refills and adherence counseling. We measured patient waiting time, adherence and viral load suppression before and after the intervention. The proportion of patients who missed an ART dose in the last 30 days dropped from 20% to 8.5% at 12 months post-intervention (p = 0.009) and those with detectable viral load dropped from 19.9% to 7.4% (p = 0.001), however, mean waiting time increased from 4.48 to 4.76 h (p = 0.13). Mobile pharmacy intervention in rural Uganda is feasible and resulted in improvement in adherence and viral load suppression. Although it did not reduce patient waiting time at the clinic, we recommend scale-up in rural areas where patients face transportation challenges.

Promoting Safe Injection Practices, Substance Use Reduction, Hepatitis C Testing, and Overdose Prevention Among Syringe Service Program Clients Using a Computer-Tailored Intervention: Pilot Randomized Controlled Trial.

BACKGROUND: Syringe service programs (SSPs) are safe, highly effective programs for promoting health among people who inject drugs. However, resource limitations prevent the delivery of a full package of prevention services to many clients in need. Computer-tailored interventions may represent a promising approach for providing prevention information to people who inject drugs in resource-constrained settings. OBJECTIVE: The aim of this paper is to assess the effect of a computer-tailored behavioral intervention, called Hep-Net, on safe injection practices, substance use reduction, overdose prevention, and hepatitis C virus (HCV) testing among SSP clients. METHODS: Using a social network-based recruitment strategy, we recruited clients of an established SSP in Wisconsin and peers from their social networks. Participants completed a computerized baseline survey and were then randomly assigned to receive the Hep-Net intervention. Components of the intervention included an overall risk synthesis, participants' selection of a behavioral goal, and an individualized risk reduction exercise. Individuals were followed up 3 months later to assess their behavior change. The effect of Hep-Net on receiving an HCV screening test, undergoing Narcan training, reducing the frequency of drug use, and sharing drug equipment was assessed. The individual's readiness to change each behavior was also examined. RESULTS: From 2014 to 2015, a total of 235 people who injected drugs enrolled into the Hep-Net study. Of these, 64.3% (151/235) completed the follow-up survey 3-6 months postenrollment. Compared with the control group, individuals who received the Hep-Net intervention were more likely to undergo HCV testing (odds ratio [OR] 2.23, 95% CI 1.05-4.74; P=.04) and receive Narcan training (OR 2.25, 95% CI 0.83-6.06; P=.11), and they shared drug equipment less frequently (OR 0.06, 95% CI 0.55-0.65; P<.001). Similarly, individuals who received the intervention were more likely to advance in their stage of readiness to change these 3 behaviors. However, intervention participants did not appear to reduce the frequency of drug use or increase their readiness to reduce drug use more than control participants, despite the fact that the majority of the intervention participants selected this as the primary goal to focus on after participation in the baseline survey. CONCLUSIONS: Implementing computer-based risk reduction interventions in SSPs may reduce harms associated with the sharing of injection equipment and prevent overdose deaths; however, brief computerized interventions may not be robust enough to overcome the challenges associated with reducing and ceasing drug use when implemented in settings centered on the delivery of prevention services. TRIAL REGISTRATION: ClinicalTrials.gov NCT02474043; https://clinicaltrials.gov/ct2/show/NCT02474043. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/resprot.4830.

Effect of Patient Navigation on Transitions of HIV Care After Release from Prison: A Retrospective Cohort Study.

Antiretroviral therapy is successfully administered to people living with HIV while they are incarcerated in most US prison systems, but interruptions in treatment are common after people are released. We undertook an observational cohort study designed to examine the clinical and psychosocial factors that influence linkage to HIV care and viral suppression after release from a single state prison system. In this report we describe baseline characteristics and 6-month post-incarceration HIV care outcomes for 170 individuals in Wisconsin. Overall, 114 (67%) individuals were linked to outpatient HIV care within 180 days of release from prison, and of these, 90 (79%) were observed to have HIV viral suppression when evaluated in the community. The strongest predictor of linkage to care in this study was participation in a patient navigation program: Those who received patient navigation were linked to care 84% of the time, compared to 60% of the individuals who received only standard release planning (adjusted OR 3.69, 95% CI 1.24, 10.96; P < 0.01). Findings from this study demonstrate that building and maintaining intensive patient navigation programs that support individuals releasing from prison is beneficial for improving transitions in HIV care.

Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?

BACKGROUND: Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients. METHODS: Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups. RESULTS: Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics. CONCLUSIONS: Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

Associations of gut microbiome richness and diversity with objective and subjective sleep measures in a population sample.

STUDY OBJECTIVES: Alterations in gut microbiota composition have been associated with several conditions, and there is emerging evidence that sleep quantity and quality are associated with the composition of the gut microbiome. Therefore, this study aimed to assess the associations between several measures of sleep and the gut microbiome in a large, population-based sample. METHODS: Data were collected from participants in the Survey of the Health of Wisconsin from 2016 to 2017 (N = 720). Alpha diversity was estimated using Chao1 richness, Shannon's diversity, and Inverse Simpson's diversity. Beta diversity was estimated using Bray-Curtis dissimilarity. Models for each of the alpha-diversity outcomes were calculated using linear mixed effects models. Permutational multivariate analysis of variance tests were performed to test whether gut microbiome composition differed by sleep measures. Negative binomial models were used to assess whether sleep measures were associated with individual taxa relative abundance. RESULTS: Participants were a mean (SD) age of 55 (16) years and 58% were female. The sample was 83% non-Hispanic white, 10.6% non-Hispanic black, and 3.5% Hispanic. Greater actigraphy-measured night-to-night sleep duration variability, wake-after-sleep onset, lower sleep efficiency, and worse self-reported sleep quality were associated with lower microbiome richness and diversity. Sleep variables were associated with beta-diversity, including actigraphy-measured night-to-night sleep duration variability, sleep latency and efficiency, and self-reported sleep quality, sleep apnea, and napping. Relative abundance of several taxa was associated with night-to-night sleep duration variability, average sleep latency and sleep efficiency, and sleep quality. CONCLUSIONS: This study suggests that sleep may be associated with the composition of the gut microbiome. These results contribute to the body of evidence that modifiable health habits can influence the human gut microbiome.

Does empirical Clostridium difficile infection (CDI) therapy result in false-negative CDI diagnostic test results?

BACKGROUND: Patients with suspected Clostridium difficile infection (CDI) often receive empirical therapy prior to collection of stool specimens for diagnostic testing. The likelihood that such empirical therapy might result in false-negative CDI test results is unknown. METHODS: We conducted a prospective study of CDI patients to determine the time to conversion of CDI test results, including polymerase chain reaction (PCR) for toxin B genes, glutamate dehydrogenase, and toxigenic culture, from positive to negative during CDI therapy. We evaluated the frequency of and risk factors for persistence of positive CDI tests. For patients receiving empirical therapy, we assessed the frequency of conversion of positive CDI test results at the time of the test order to negative by the time clinical staff collected stool specimens for testing. RESULTS: For 51 CDI patients, PCR, glutamate dehydrogenase, and toxigenic culture results converted to negative at similar rates. For PCR, 14%, 35%, and 45% of positive CDI tests converted to negative after 1, 2, and 3 days of treatment, respectively. Increased age and infection with North American pulsed-field gel electrophoresis strains were associated with persistent positive PCR results. For CDI patients diagnosed at the time of the test order, conversion to negative PCR results by the time clinical stool specimens were collected occurred in 4 of 9 (44%) patients who were prescribed empirical CDI therapy versus 0 of 23 (0%) who were not (P = .004). CONCLUSIONS: Empirical treatment for suspected CDI cases may result in false-negative PCR results if there are delays in stool specimen collection.

Easily modified factors contribute to delays in diagnosis of Clostridium difficile infection: a cohort study and intervention.

Although rapid laboratory tests are available for diagnosis of Clostridium difficile infection (CDI), delays in completion of CDI testing are common in clinical practice. We conducted a cohort study of 242 inpatients tested for CDI to determine the timing of different steps involved in diagnostic testing and to identify modifiable factors contributing to delays in diagnosis. The average time from test order to test result was 1.8 days (range, 0.2 to 10.6), with time from order to stool collection accounting for most of the delay (mean, 1.0 day; range, 0 to 10). Several modifiable factors contributed to delays, including not providing stool collection supplies to patients in a timely fashion, rejection of specimens due to incorrect labeling or leaking from the container, and holding samples in the laboratory for batch processing. Delays in testing contributed to delays in initiation of treatment for patients diagnosed with CDI and to frequent prescription of empirical CDI therapy for patients with mild to moderate symptoms whose testing was ultimately negative. An intervention that addressed several easily modified factors contributing to delays resulted in a significant decrease in the time required to complete CDI testing. These findings suggest that health care facilities may benefit from a review of their processes for CDI testing to identify and address modifiable factors that contribute to delays in diagnosis and treatment of CDI.

Alcohol use and HIV serostatus of partner predict high-risk sexual behavior among patients receiving antiretroviral therapy in South Western Uganda.

BACKGROUND: Antiretroviral treatment restores the physical and immunological function for patients with HIV/AIDS and the return of sexual desire. The frequency and correlates of sexual activity among patients receiving ART have not been widely studied. There is concern that widespread availability of ART may result in sexual disinhibition including practice of high-risk sexual behavior. We determined the correlates of sexual activity and high-risk sexual behavior in an ART-treated population in rural and urban Uganda. METHODS: We conducted a cross-sectional study among 329 ART-treated adult patients at two hospitals, one located in rural and another in urban western Uganda. We collected data on sexual activity, frequency of condom use, pregnancy, viral load (VL) and CD4. Patients were considered sexually active if they had had sexual intercourse in the last 6 months. Any unprotected sex was considered high-risk sex. A two-stage logistic regression was performed to determine factors associated with sexual activity and high-risk sex among those sexually active. RESULTS: Overall, 222 (67%) patients were women, 138 (41.2%) had been on ART for at least one year, and 168 (51.4%) were sexually active of whom 127 (75.6%) used condoms at the last intercourse. Younger age (<=30 years) (Odds ratio; OR=2.3, 95% CI 1.2, 4.2), higher monthly income (OR=4.1, 95% CI 2.4, 7.4), and being married (OR=22.7, 95% CI 8.2, 62.9) were associated with being sexually active. Undetectable VL, CD4 count and treatment duration were not significantly associated with sexual activity. Among the sexually active, alcohol consumption (OR=3.3, 95% CI 1.2, 9.1) and unknown serostatus of partner (OR=5.8, 95% CI 1.5, 21.4) were significant predictors of high-risk sexual behavior. The frequency of unprotected sex at the last intercourse was 25.9% and 22.1% among the men and women respectively and was not significantly different (p value for chi square test =0.59). CONCLUSION: Younger persons receiving ART are more likely to be sexually active. ART clients are more likely to engage in unprotected sex when sero-status of partner is unknown or report use of alcohol. Counseling on alcohol use and disclosure of sero-status may be useful in reducing high risk sexual behavior.

Change in alcohol consumption during the Covid-19 pandemic and associations with mental health and financial hardship: results from a survey of Wisconsin patients with cancer.

PURPOSE: Alcohol consumption increases health risks for patients with cancer. The Covid-19 pandemic may have affected drinking habits for these individuals. We surveyed patients with cancer to examine whether changes in drinking habits were related to mental health or financial effects of the pandemic. METHODS: From October 2020 to April 2021, adult patients (age 18-80 years at diagnosis) treated for cancer in southcentral Wisconsin were invited to complete a survey. Age-adjusted percentages for history of anxiety or depression, emotional distress, and financial impacts of Covid-19 overall and by change in alcohol consumption (non-drinker, stable, decreased, or increased) were obtained via logistic regression. RESULTS: In total, 1,875 patients were included in the analysis (median age 64, range 19-87 years), including 9% who increased and 23% who decreased drinking. Compared to stable drinkers (32% of sample), a higher proportion of participants who increased drinking alcohol also reported anxiety or depression (45% vs. 26%), moderate to severe emotional distress (61% vs. 37%) and viewing Covid-19 as a threat to their community (67% vs. 55%). Decreased (vs. stable) drinking was associated with higher prevalence of depression or anxiety diagnosis, emotional distress, and negative financial impacts of the pandemic. Compared to non-drinkers (36% of sample), participants who increased drinking were more likely to report emotional distress (61% vs. 48%). CONCLUSIONS: Patients with cancer from Wisconsin who changed their alcohol consumption during the Covid-19 pandemic were more likely to report poor mental health including anxiety, depression, and emotional distress than persons whose alcohol consumption was stable. IMPLICATIONS FOR CANCER SURVIVORS: Clinicians working with cancer survivors should be aware of the link between poor mental health and increased alcohol consumption and be prepared to offer guidance or referrals to counseling, as needed.

Utility of perirectal swab specimens for diagnosis of Clostridium difficile infection.

For 139 patients tested for Clostridium difficile infection by polymerase chain reaction, the sensitivity, specificity, positive predictive value, and negative predictive value of testing perirectal swabs vs stool specimens were 95.7%, 100%, 100%, and 99.1%, respectively. For selected patients, perirectal swabs provide an accurate toxigenic C. difficile detection strategy.

Individual Nutrition Is Associated with Altered Gut Microbiome Composition for Adults with Food Insecurity.

Diet is widely recognized as a key contributor to human gut microbiome composition and function. However, overall nutrition can be difficult to compare across a population with varying diets. Moreover, the role of food security in the relationship with overall nutrition and the gut microbiome is unclear. This study aims to investigate the association between personalized nutrition scores, variation in the adult gut microbiome, and modification by food insecurity. The data originate from the Survey of the Health of Wisconsin and the Wisconsin Microbiome Study. Individual nutrition scores were assessed using My Nutrition Index (MNI), calculated using data from food frequency questionnaires, and additional health history and demographic surveys. Food security and covariate data were measured through self-reported questionnaires. The gut microbiome was assessed using 16S amplicon sequencing of DNA extracted from stool samples. Associations, adjusted for confounding and interaction by food security, were estimated using Weighted Quantile Sum (WQS) regression models with Random Subset and Repeated Holdout extensions (WQSRSRH), with bacterial taxa used as components in the weighted index. Of 643 participants, the average MNI was 66.5 (SD = 31.9), and 22.8% of participants were food insecure. Increased MNI was significantly associated with altered gut microbial composition (ß = 2.56, 95% CI = 0.52−4.61), with Ruminococcus, Oscillospira, and Blautia among the most heavily weighted of the 21 genera associated with the MNI score. In the stratified interaction WQSRSRH models, the bacterial taxa most heavily weighted in the association with MNI differed by food security, but the level of association between MNI and the gut microbiome was not significantly different. More bacterial genera are important in the association with higher nutrition scores for people with food insecurity versus food security, including Streptococcus, Parabacteroides Faecalibacterium, and Desulfovibrio. Individual nutrition scores are associated with differences in adult gut microbiome composition. The bacterial taxa most associated with nutrition vary by level of food security. While further investigation is needed, results showed a higher nutrition score was associated with a wider range of bacterial taxa for food insecure vs. secure, suggesting nutritional quality in food insecure individuals is important in maintaining health and reducing disparities.

Assessing the relationship between physical activity and the gut microbiome in a large, population-based sample of Wisconsin adults.

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.

The Survey of the Health of Wisconsin (SHOW) Program: An Infrastructure for Advancing Population Health.

Introduction: The Survey of the Health of Wisconsin (SHOW) was established in 2008 by the University of Wisconsin (UW) School of Medicine and Public Health (SMPH) with the goals of (1) providing a timely and accurate picture of the health of the state residents; and (2) serving as an agile resource infrastructure for ancillary studies. Today, the SHOW program continues to serve as a unique and vital population health research infrastructure for advancing public health. Methods: SHOW currently includes 5,846 adult and 980 minor participants recruited between 2008 and 2019 in four primary waves. WAVE I (2008-2013) includes annual statewide representative samples of 3,380 adults ages 21 to 74 years. WAVE II (2014-2016) is a triannual statewide sample of 1,957 adults (age ≥18 years) and 645 children (age 0-17). WAVE III (2017) consists of follow-up of 725 adults from the WAVE I and baseline surveys of 222 children in selected households. WAVEs II and III include stool samples collected as part of an ancillary study in a subset of 784 individuals. WAVE IV consists of 517 adults and 113 children recruited from traditionally under-represented populations in biomedical research including African Americans and Hispanics in Milwaukee, Wisconsin. Findings to Date: The SHOW resource provides unique spatially granular and timely data to examine the intersectionality of multiple social determinants and population health. SHOW includes a large biorepository and extensive health data collected in a geographically diverse urban and rural population. Over 60 studies have been published covering a broad range of topics including, urban and rural disparities in cardio-metabolic disease and cancer, objective physical activity, sleep, green-space and mental health, transcriptomics, the gut microbiome, antibiotic resistance, air pollution, concentrated animal feeding operations and heavy metal exposures. Discussion: The SHOW cohort and resource is available for continued follow-up and ancillary studies including longitudinal public health monitoring, translational biomedical research, environmental health, aging, microbiome and COVID-19 research.

Unnecessary use of fluoroquinolone antibiotics in hospitalized patients.

BACKGROUND: Fluoroquinolones are among the most commonly prescribed antimicrobials and are an important risk factor for colonization and infection with fluoroquinolone-resistant gram-negative bacilli and for Clostridium difficile infection (CDI). In this study, our aim was to determine current patterns of inappropriate fluoroquinolone prescribing among hospitalized patients, and to test the hypothesis that longer than necessary treatment durations account for a significant proportion of unnecessary fluoroquinolone use. METHODS: We conducted a 6-week prospective, observational study to determine the frequency of, reasons for, and adverse effects associated with unnecessary fluoroquinolone use in a tertiary-care academic medical center. For randomly-selected adult inpatients receiving fluoroquinolones, therapy was determined to be necessary or unnecessary based on published guidelines or standard principles of infectious diseases. Adverse effects were determined based on chart review 6 weeks after completion of therapy. RESULTS: Of 1,773 days of fluoroquinolone therapy, 690 (39%) were deemed unnecessary. The most common reasons for unnecessary therapy included administration of antimicrobials for non-infectious or non-bacterial syndromes (292 days-of-therapy) and administration of antimicrobials for longer than necessary durations (234 days-of-therapy). The most common syndrome associated with unnecessary therapy was urinary tract infection or asymptomatic bacteriuria (30% of all unnecessary days-of-therapy). Twenty-seven percent (60/227) of regimens were associated with adverse effects possibly attributable to therapy, including gastrointestinal adverse effects (14% of regimens), colonization by resistant pathogens (8% of regimens), and CDI (4% of regimens). CONCLUSIONS: In our institution, 39% of all days of fluoroquinolone therapy were unnecessary. Interventions that focus on improving adherence with current guidelines for duration of antimicrobial therapy and for management of urinary syndromes could significantly reduce overuse of fluoroquinolones.

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. The primary outcomes were the number of confirmed COVID-19 cases and the timing of pandemic control, defined as the date after which only a small number of new cases occur. We also estimated the number of cases without vaccination. 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 0.1% of the population, vaccine effectiveness of 90%, and the adherence to nonpharmaceutical interventions is 65%, controlled spread could be achieved by July 2021 and August 2021, respectively versus in March 2022 in both regions without vaccine. If adherence to nonpharmaceutical interventions increases to 70%, controlled spread could be achieved by May 2021 and April 2021 in Dane County and Milwaukee, respectively. 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. The effect of SARS-CoV-2 variants was not considered. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

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.