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To minimize the impacts of COVID-19 and to keep campus open, Cornell University’s Ithaca, NY, campus implemented a comprehensive process to monitor COVID-19 spread, support prevention practices, and assess early warning indicators linked to knowledge, behaviors, and attitudes of campus community members. The integrated surveillance approach informed leadership and allowed for prompt adjustments to university policies and practices through evidence-based decisions. This approach enhanced healthy behaviors and promoted the well-being and safety of all community members. (Am J Public Health. 2022;112(7):980–984. https://doi.org/10.2105/AJPH.2022.306838 )

Given the global threat of antimicrobial resistance, it is imperative that veterinary graduates are effective antimicrobial stewards. Veterinary students learn the principles of antimicrobial stewardship explicitly, through pre-clinical coursework, and implicitly, through the cases they each encounter on clinical rotations. We aimed to understand the influence of pre-clinical versus clinical learning on veterinary students’ knowledge and awareness of antimicrobial concepts to guide efforts to improve instruction in these areas. To assess knowledge acquisition and to explore student perceptions of antimicrobial stewardship, a standardized online survey was administered to Cornell University veterinary students at two timepoints: in August 2020 before clinical rotations ( N = 26 complete responses and N = 24 partial responses) and again in May 2021 after their clinical rotations ( N = 17 complete responses and N = 6 partial responses). Overall and section-specific confidence and knowledge scores were calculated, using pairwise deletion for incomplete responses. Students generally had low confidence in antimicrobial topics and correctly answered only half of knowledge questions correctly; they performed the best on antimicrobial resistance knowledge questions. There were no significant differences in knowledge or confidence after clinical rotations. On average, students had only read one antimicrobial stewardship guideline. Students reported that human health care providers contributed more to antimicrobial resistance than veterinarians. In conclusion, graduating veterinary students at our institution have significant knowledge gaps in critical principles that are essential to become antimicrobial stewards. Explicit instruction in antimicrobial stewardship is necessary in the pre-clinical and clinical coursework, and the practical use of antimicrobial stewardship guidelines should be emphasized.

Tylosin phosphate (TYL) is administered to more than 50% of U.S. beef cattle to reduce the incidence of liver abscesses but may increase the risk of macrolide–lincosamide–streptogramin-resistant bacteria disseminating from the feedlot. Limited evidence has been collected to understand how TYL affects the proportion of resistant bacteria in cattle or the feedlot environment. We created a mathematical model to investigate the effects of TYL administration on Enterococcus dynamics and examined preharvest strategies to mitigate the impact of TYL administration on resistance. The model simulated the physiological pharmacokinetics of orally administered TYL and estimated the pharmacodynamic effects of TYL on populations of resistant and susceptible Enterococcus within the cattle large intestine, feedlot pen, water trough, and feed bunk. The model parameters' population distributions were based on the available literature; 1000 Monte Carlo simulations were performed to estimate the likely distribution of outcomes. At the end of the simulated treatment period, the median estimated proportion of macrolide-resistant enterococci was only 1 percentage point higher within treated cattle compared with cattle not fed TYL, in part because the TYL concentrations in the large intestine were substantially lower than the enterococci minimum inhibitory concentrations. However, 25% of the simulated cattle had a >10 percentage point increase in the proportion of resistant enterococci associated with TYL administration, termed the TYL effect. The model predicts withdrawing TYL treatment and moving cattle to an antimicrobial-free terminal pen with a low prevalence of resistant environmental enterococci for as few as 6 days could reduce the TYL effect by up to 14 percentage points. Additional investigation of the importance of this subset of cattle to the overall risk of resistance transmission from feedlots will aid in the interpretation and implementation of resistance mitigation strategies.

Curbing the coronavirus disease 2019 (COVID-19) pandemic requires a thorough understanding of risk factors for transmission of SARS-CoV-2, the etiologic agent. Institutions of higher education present unique challenges for controlling disease spread because of features inherent to these settings. Our objective was to determine risk factors for SARS-CoV-2 infection among a university student population in the northeastern USA during the spring and fall 2021 semesters, using the case-control study design. Cases were defined as students with a newly diagnosed SARS-CoV-2 infection detected either through the robust PCR-based surveillance testing program on campus or through healthcare testing if symptoms compatible with COVID-19 were present. Controls were defined as students with negative SARS-CoV-2 status, based on consistently negative PCR results at the time of selection. A comprehensive questionnaire was administered to each student enrolled in the study, covering a broad range of campus life activities. A total of 446 cases and 1,185 controls were included in this study. Multivariable logistic regression analysis showed that recent party attendance (adjusted OR = 2.3, p.0001), recently visiting a bar (aOR = 1.6, p = .007), living in a campus residence hall (aOR = 1.6, p = .001), fraternity/sorority membership (aOR = 1.8, p = .002), and recent travel (aOR = 1.3, p = .04) were associated with being a COVID-19 case. Having an on-campus job was negatively associated with being a COVID-19 case (aOR = 0.6, p = .0003). Among cases, the most commonly reported symptoms were cough (43.9%), fatigue (38.1%) and sore throat (30.3%). These findings can be used to inform the development of COVID-19 mitigation strategies and public health outreach efforts in university settings, thus reducing SARS-CoV-2 transmission among students and helping to preserve the vital education and research missions of these institutions.

Dermatophytosis corresponds to a broad series of infections, mostly superficial, caused by a group of keratinophilic and keratinolytic filamentous fungi called dermatophytes. These mycoses are currently considered to be a major public health concern worldwide, particularly in developing countries such as those in the Middle East and North Africa (MENA) region. Here we compiled and discussed existing epidemiologic data on these infections in the MENA region. Most of the available studies were based on conventional diagnostic strategies and were published before the last taxonomic revision of dermatophytes. This has led to misidentifications, which might have resulted in the underestimation of the real burden of these infections in the MENA countries. Our analysis of the available literature highlights an urgent need for further studies based on reliable diagnostic tools and standard susceptibility testing methods for dermatophytosis, which represents a major challenge for these countries. This is crucial for guiding appropriate interventions and activating antifungal stewardship programs in the future.

International audience; Background: Although cost is often a barrier to providing optimal veterinary care, only a minority of pet owners use insurance to help cover veterinary costs. We sought to estimate consumer demand and preferences for pet insurance and how educating owners on treatment costs and disease risk affects pet insurance uptake.Methods: We surveyed 306 dog owners across the United States without pet insurance, including a choice experiment, used ordinary least squares regression to estimate the demand for pet insurance, and conjoint analysis to estimate the pet insurance feature preferences.Results: Pet insurance uptake increased by 12.3% after veterinary treatment cost and canine cancer risk information was presented to participants. We found that, on average, pet owners were willing to pay 24 dollars more per month for a preventive care service in pet insurance. Forty-four percent of participants were willing to spend up to 1000 dollars to prolong their pet's life a year, while 46% of the sample were willing to spend 3000 dollars or more.Conclusions: Our results suggest that providing pet owners’ information about the costs and likelihood of disease can increase their willingness to pay for pet insurance. Coverage of preventive care was the most valuable feature in pet insurance among those presented to dog owners.

Multidrug resistance (MDR) surveillance consists of reporting MDR prevalence and MDR phenotypes. Detailed knowledge of the specific associations underlying MDR patterns can allow antimicrobial stewardship programs to accurately identify clinically relevant resistance patterns. We applied machine learning and graphical networks to quantify and visualize associations between resistance traits in a set of 1,091 Staphylococcus aureus isolates collected from one New York hospital between 2008 and 2018. Antimicrobial susceptibility testing was performed using reference broth microdilution. The isolates were analyzed by year, methicillin susceptibility, and infection site. Association mining was used to identify resistance patterns that consisted of two or more individual antimicrobial resistance (AMR) traits and quantify the association among the individual resistance traits in each pattern. The resistance patterns captured the majority of the most common MDR phenotypes and reflected previously identified pairwise relationships between AMR traits in S. aureus. Associations between β-lactams and other antimicrobial classes (macrolides, lincosamides, and fluoroquinolones) were common, although the strength of the association among these antimicrobial classes varied by infection site and by methicillin susceptibility. Association mining identified associations between clinically important AMR traits, which could be further investigated for evidence of resistance coselection. For example, in skin and skin structure infections, clindamycin and tetracycline resistance occurred together 1.5 times more often than would be expected if they were independent from one another. Association mining efficiently discovered and quantified associations among resistance traits, allowing these associations to be compared between relevant subsets of isolates to identify and track clinically relevant MDR.

SUMMARYAntimicrobial drugs are used to treat pathogenic bacterial infections in animals and humans. The by-stander enteric bacteria of the treated host's intestine can become exposed to the drug or its metabolites reaching the intestine in antimicrobially active form. We consider which processes and variables need to be accounted for to project the antimicrobial concentrations in the host's intestine. Those include: the drug's fraction (inclusive of any active metabolites) excreted in bile; the drug's fractions and intestinal segments of excretion via other mechanisms; the rates and intestinal segments of the drug's absorption and re-absorption; the rates and intestinal segments of the drug's abiotic and biotic degradation in the intestine; the digesta passage time through the intestinal segments; the rates, mechanisms, and reversibility of the drug's sorption to the digesta and enteric microbiome; and the volume of luminal contents in the intestinal segments. For certain antimicrobials, the antimicrobial activity can further depend on the aeration and chemical conditions in the intestine. Model forms that incorporate the inter-individual variation in those relevant variables can support projections of the intestinal antimicrobial concentrations in populations of treated host, such as food animals. To illustrate the proposed modeling framework, we develop two examples of treatments of bovine respiratory disease in beef steers by oral chlortetracycline and injectable third-generation cephalosporin ceftiofur. The host's diet influences the digesta passage time, volume, and digesta and microbiome composition, and may influence the antimicrobial loss due to degradation and sorption in the intestine. We consider two diet compositions in the illustrative simulations. The examples highlight the extent of current ignorance and need for empirical data on the variables influencing the selective pressures imposed by antimicrobial treatments on the host's intestinal bacteria.

Background:Pseudomonas aeruginosa is an important nosocomial pathogen associated with intrinsic and acquired resistance mechanisms to major classes of antibiotics. To better understand clinical risk factors for drug-resistant P. aeruginosa infection, decision-tree models for the prediction of fluoroquinolone and carbapenem-resistant P. aeruginosa were constructed and compared to multivariable logistic regression models using performance characteristics. Methods: In total, 5,636 patients admitted to 4 hospitals within a New York City healthcare system from 2010 to 2016 with blood, respiratory, wound, or urine cultures growing PA were included in the analysis. Presence or absence of drug-resistance was defined using the first culture of any source positive for P. aeruginosa during each hospitalization. To train and validate the prediction models, cases were randomly split (60 of 40) into training and validation datasets. Clinical decision-tree models for both fluoroquinolone and carbapenem resistance were built from the training dataset using 21 clinical variables of interest, and multivariable logistic regression models were built using the 16 clinical variables associated with resistance in bivariate analyses. Decision-tree models were optimized using K-fold cross validation, and performance characteristics between the 4 models were compared. Results: From 2010 through 2016, prevalence of fluoroquinolone and carbapenem resistance was 32% and 18%, respectively. For fluoroquinolone resistance, the logistic regression algorithm attained a positive predictive value (PPV) of 0.57 and a negative predictive value (NPV) of 0.73 (sensitivity, 0.27; specificity, 0.90) and the decision-tree algorithm attained a PPV of 0.65 and an NPV of 0.72 (sensitivity 0.21, specificity 0.95). For carbapenem resistance, the logistic regression algorithm attained a PPV of 0.53 and a NPV of 0.85 (sensitivity 0.20, specificity 0.96) and the decision-tree algorithm attained a PPV of 0.59 and an NPV of 0.84 (sensitivity 0.22, specificity 0.96). The decision-tree partitioning algorithm identified prior fluoroquinolone resistance, SNF stay, sex, and length-of-stay as variables of greatest importance for fluoroquinolone resistance compared to prior carbapenem resistance, age, and length-of-stay for carbapenem resistance. The highest-performing decision tree for fluoroquinolone resistance is illustrated in Fig. 1. Conclusions: Supervised machine-learning techniques may facilitate prediction of P. aeruginosa resistance and risk factors driving resistance patterns in hospitalized patients. Such techniques may be applied to readily available clinical information from hospital electronic health records to aid with clinical decision making.Funding: NoneDisclosures: None

Background Tylosin is a commonly used in-feed antimicrobial and is approved in several countries to reduce the incidence of liver abscesses in beef cattle. Macrolides are critically important antimicrobials in human health and used to treat some foodborne bacterial diseases, such as Campylobacter jejuni and Salmonella. Feeding tylosin could select for resistant enteric bacteria in cattle, which could contaminate beef products at slaughter and potentially cause foodborne illness. We conducted a systematic review and meta-analysis to evaluate the impact of feeding tylosin to cattle on phenotypic and genotypic resistance in several potential zoonotic enteric bacteria: Enterococcus species, Escherichia coli, Salmonella enterica subspecies enterica, and Campylobacter species. This review was registered with PROSPERO (#CRD42018085949). Results Eleven databases were searched for primary research studies that fed tylosin at approved doses to feedlot cattle and tested bacteria of interest for phenotypic or genotypic resistance. We screened 1,626 citations and identified 13 studies that met the inclusion criteria. Enterococcus species were tested in seven studies, Escherichia coli was isolated in five studies, three studies reported on Salmonella, and two studies reported on Campylobacter species. Most studies relied on phenotypic antimicrobial susceptibility testing and seven also reported resistance gene testing. A random-effects meta-analyses of erythromycin-resistant enterococci from four studies had significant residual heterogeneity. Only two studies were available for a meta-analysis of tylosin-resistant enterococci. A semi-quantitative analysis demonstrated an increase in macrolide-resistant enterococci after long durations of tylosin administration (>100 days). Semi-quantitative analyses of other bacteria-antimicrobial combinations revealed mixed results, but many comparisons found no effect of tylosin administration. However, about half of these no-effect comparisons did not record the cumulative days of tylosin administration or the time since the last dose. Conclusions When fed at approved dosages for typical durations, tylosin increases the proportion of macrolide-resistant enterococci in the cattle gastrointestinal tract, which could pose a zoonotic risk to human beef consumers. Feeding tylosin for short durations may mitigate the impact on macrolide-resistant enterococci and further studies are encouraged to determine the effect of minimizing or eliminating tylosin use in beef cattle. There may also be an impact on other bacteria and other antimicrobial resistances but additional details or data are needed to strengthen these comparisons. We encourage authors of antimicrobial-resistance studies to follow reporting guidelines and publish details of all comparisons to strengthen future meta-analyses.

Background Sensitivity analysis is an essential step in mathematical modeling because it identifies parameters with a strong influence on model output, due to natural variation or uncertainty in the parameter values. Recently behavior pattern sensitivity analysis has been suggested as a method for sensitivity analyses on models with more than one mode of output behavior. The model output is classified by behavior mode and several behavior pattern measures, defined by the researcher, are calculated for each behavior mode. Significant associations between model inputs and outputs are identified by building linear regression models with the model parameters as independent variables and the behavior pattern measures as the dependent variables. We applied the behavior pattern sensitivity analysis to a mathematical model of tetracycline-resistant enteric bacteria in beef cattle administered chlortetracycline orally. The model included 29 parameters related to bacterial population dynamics, chlortetracycline pharmacokinetics and pharmacodynamics. The prevalence of enteric resistance during and after chlortetracycline administration was the model output. Cox proportional hazard models were used when linear regression assumptions were not met. Results We have expanded the behavior pattern sensitivity analysis procedure by incorporating model selection techniques to produce parsimonious linear regression models that efficiently prioritize input parameters. We also demonstrate how to address common violations of linear regression model assumptions. Finally, we explore the semi-parametric Cox proportional hazards model as an alternative to linear regression for situations with censored data. In the example mathematical model, the resistant bacteria exhibited three behaviors during the simulation period: (1) increasing, (2) decreasing, and (3) increasing during antimicrobial therapy and decreasing after therapy ceases. The behavior pattern sensitivity analysis identified bacterial population parameters as high importance in determining the trajectory of the resistant bacteria population. Conclusions Interventions aimed at the enteric bacterial population ecology, such as diet changes, may be effective at reducing the prevalence of tetracycline-resistant enteric bacteria in beef cattle. Behavior pattern sensitivity analysis is a useful and flexible tool for conducting a sensitivity analysis on models with varied output behavior, enabling prioritization of input parameters via regression model selection techniques. Cox proportional hazard models are an alternative to linear regression when behavior pattern measures are censored or linear regression assumptions cannot be met.

Antimicrobial use in food animals may increase antimicrobial resistance in their enteric bacteria that can be transferred to human microbiome. Over 70% of U.S. beef feedlots use non-ionophore in-feed antimicrobials for animal disease control, treatment, or growth promotion. The fraction of feedlots feeding chlortetracycline (CTC), mostly for disease control but also for treatment, has increased since the mid-1990s to present. Quantitative information on the antimicrobial selective pressure on the enteric bacteria of cattle fed CTC is lacking. Hence, the purpose of this study was to develop a deterministic mathematical model of the pharmacokinetics of ingested CTC in a beef steer and estimate the concentration of antimicrobially active (undegraded) CTC in the animal's large intestine. To evaluate the fit of the model to existing data, we also estimated the CTC concentrations in the central circulation, and fresh and aging manure from the steer. The model accounted for CTC abiotic degradation while in the gastrointestinal tract, absorption into the central circulation and tissues, biliary and renal excretion, and removal from the intestine by defecation. The model included an increase in the large intestine volume as the steer grew. We estimated that during CTC feeding to a 300-kg steer for growth promotion, the maximal drug concentration in the large intestine was 0.3 μg/mL; during disease control it was 1.7 μg/mL; and during treatment it was 31.5 μg/mL. The estimated CTC concentrations in the central circulation and the steer's manure agreed reasonably well with published data.

Background: The objective of this study was to identify associations between the concentration of Mycobacterium avium subsp. paratuberculosis (MAP) antibodies in bulk milk and potential risk factors in herd management and herd characteristics, explaining high MAP antibody titers in milk. An extensive questionnaire was administered to 292 organic and conventional dairy farms from New York, Wisconsin and Oregon. Bulk milk samples were taken from each farm for MAP enzyme-linked immunosorbent assay (ELISA). A general linear model was constructed with MAP ELISA value as the outcome variable and the management factors and herd characteristics as independent variables, while at the same time controlling for the study design variables of state, herd size, and production system (organic or conventional). High bulk tank MAP ELISA value may be due to either a high prevalence of MAP in a herd with many cows contributing to the antibody titer or due to a few infected cows that produce large quantities of antibodies. Results: Results of the regression models indicated that bulk milk ELISA value was associated with season of sampling and the presence or absence of protocols for managing MAP-positive cows. The concentration of MAP antibodies in bulk milk varied seasonally with a peak in the summer and low concentrations in the winter months. When compared to farms that had never observed clinical Johne’s disease, keeping MAP-positive cows or only culling them after a period of delay was associated with an increase in optical density. Conclusions: The seasonal variation in MAP antibody titers, with a peak in the summer, may be due to a seasonal increase in MAP-bacterial load. Additionally, seasonal calving practices may contribute to seasonal fluctuations in MAP antibody titers in bulk tank milk. Keeping MAP-positive cows increases the antibody titer in bulk milk, likely due to direct antibody production in the infected cow and indirect triggering of antibody production in herdmates.