An Evaluation of the Impact of an OPEN Stewardship Generated Feedback Intervention on Antibiotic Prescribing among Primary Care Veterinarians in Canada and Israel.

An interrupted time-series study design was implemented to evaluate the impact of antibiotic stewardship interventions on antibiotic prescribing among veterinarians. A total of 41 veterinarians were enrolled in Canada and Israel and their prescribing data between 2019 and 2021 were obtained. As an intervention, veterinarians periodically received three feedback reports comprising feedback on the participants' antibiotic prescribing and prescribing guidelines. A change in the level and trend of antibiotic prescribing after the administration of the intervention was compared using a multi-level generalized linear mixed-effect negative-binomial model. After the receipt of the first (incidence rate ratios [IRR] = 0.88; 95% confidence interval (CI): 0.79, 0.98), and second (IRR = 0.85; 95% CI: 0.75, 0.97) feedback reports, there was a reduced prescribing rate of total antibiotic when other parameters were held constant. This decline was more pronounced among Israeli veterinarians compared to Canadian veterinarians. When other parameters were held constant, the prescribing of critical antibiotics by Canadian veterinarians decreased by a factor of 0.39 compared to that of Israeli veterinarians. Evidently, antibiotic stewardship interventions can improve antibiotic prescribing in a veterinary setting. The strategy to sustain the effect of feedback reports and the determinants of differences between the two cohorts should be further explored.

Evaluation of an automated feedback intervention to improve antibiotic prescribing among primary care physicians (OPEN Stewardship): a multinational controlled interrupted time-series study.

Tools to advance antimicrobial stewardship in the primary health care setting, where most antimicrobials are prescribed, are urgently needed. The aim of this study was to evaluate OPEN Stewarship (Online Platform for Expanding aNtibiotic Stewardship), an automated feedback intervention, among a cohort of primary care physicians. We performed a controlled, interrupted time-series study of 32 intervention and 725 control participants, consisting of primary care physicians from Ontario, Canada and Southern Israel, from October 2020 to December 2021. Intervention participants received three personalized feedback reports targeting several aspects of antibiotic prescribing. Study outcomes (overall prescribing rate, prescribing rate for viral respiratory conditions, prescribing rate for acute sinusitis, and mean duration of therapy) were evaluated using multilevel regression models. We observed a decrease in the mean duration of antibiotic therapy (IRR = 0.94; 95% CI: 0.90, 0.99) in intervention participants during the intervention period. We did not observe a significant decline in overall antibiotic prescribing (OR = 1.01; 95% CI: 0.94, 1.07), prescribing for viral respiratory conditions (OR = 0.87; 95% CI: 0.73, 1.03), or prescribing for acute sinusitis (OR = 0.85; 95% CI: 0.67, 1.07). In this antimicrobial stewardship intervention among primary care physicians, we observed shorter durations of therapy per antibiotic prescription during the intervention period. The COVID-19 pandemic may have hampered recruitment; a dramatic reduction in antibiotic prescribing rates in the months before our intervention may have made physicians less amenable to further reductions in prescribing, limiting the generalizability of the estimates obtained.IMPORTANCEAntibiotic overprescribing contributes to antibiotic resistance, a major threat to our ability to treat infections. We developed the OPEN Stewardship (Online Platform for Expanding aNtibiotic Stewardship) platform to provide automated feedback on antibiotic prescribing in primary care, where most antibiotics for human use are prescribed but where the resources to improve antibiotic prescribing are limited. We evaluated the platform among a cohort of primary care physicians from Ontario, Canada and Southern Israel from October 2020 to December 2021. The results showed that physicians who received personalized feedback reports prescribed shorter courses of antibiotics compared to controls, although they did not write fewer antibiotic prescriptions. While the COVID-19 pandemic presented logistical and analytical challenges, our study suggests that our intervention meaningfully improved an important aspect of antibiotic prescribing. The OPEN Stewardship platform stands as an automated, scalable intervention for improving antibiotic prescribing in primary care, where needs are diverse and technical capacity is limited.

Australian Veterinarians' Perceptions Regarding the Zoonotic Potential of Mycobacterium avium Subspecies Paratuberculosis.

Public concerns over exposure to Mycobacterium avium subspecies paratuberculosis (MAP) or MAP components via foods of animal origin could have negative trade consequences, despite the absence of conclusive scientific evidence of a causal association between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease (CD). This study was conducted among Australian veterinarians to understand (a) their perceptions regarding the role of MAP in the causation of CD (an ordinal outcome), and (b) their consideration of the adoption of the precautionary principle against Johne's disease (JD; a binary outcome). Ordinal and binary logistic regression analyses were performed to evaluate the association of explanatory variables with the above outcomes, respectively. Almost one-third of the respondents (32.2%) considered that MAP was likely to be involved in the causation of CD whereas more than two-thirds (69.8%) agreed with the adoption of the precautionary principle against JD. Veterinarians who were concerned about exposure to and/or getting infected with MAP were more likely to consider MAP as a causative agent of CD (odds ratio: 7.63; 95% CI: 1.55, 37.63) and favor the adoption of the precautionary principle against JD (odds ratio: 6.20; 95% CI: 1.90, 20.25). Those perceiving MAP as a causative agent of CD were also more likely to favor the adoption of the precautionary principle against JD (odds ratio: 13.2; 95% CI: 1.26, 138.90). The results suggest that Australian veterinarians, particularly those who consider MAP as a causative agent of CD are concerned about exposure to MAP and favor the adoption of the precautionary principle against JD. These findings can be useful for animal health authorities for designing JD control programs and policies.

Detection of Mycobacterium avium subspecies paratuberculosis in powdered infant formula using IS900 quantitative PCR and liquid culture media.

Mycobacterium avium subspecies paratuberculosis (MAP) has been implicated in Crohn's disease in humans resulting in public concern over the presence of MAP in powdered infant formula, which could contribute towards early human exposure to MAP or MAP components. Testing of representative powdered infant formula samples using effective tests is required to provide information on contamination of infant formula with MAP, so that consumers can make informed decisions. This study aimed to test representative powdered infant formula samples for the presence of MAP using a quantitative PCR and liquid culture method. For this purpose, an efficient DNA extraction method was developed and an optimum decontamination protocol for culture method was identified. A total of 122 powdered infant formula samples were tested, comprising 72 brands produced by 12 manufacturers from 9 countries. Powdered infant formula samples were reconstituted and centrifuged to separate the casein pellet, cream layer and whey fraction. A sensitive qPCR test was performed on DNA extracted from the casein pellet. In addition, the cream layer and casein pellet were cultured in liquid media, following decontamination with the optimum protocol. Of the 122 samples tested, 6 were positive for MAP DNA but none were positive for growth in culture at 12 and 20 weeks. The limit of detection of the quantitative PCR was less than 5 MAP organisms per 1.5g milk powder. The methods developed in the study could be used for quality assurance testing for infant formula and calf milk replacers. The low contamination level of MAP and absence of viable forms in our study suggests a relatively low risk of exposure of infants to MAP components.

PCR Inhibition of a Quantitative PCR for Detection of Mycobacterium avium Subspecies Paratuberculosis DNA in Feces: Diagnostic Implications and Potential Solutions.

Molecular tests such as polymerase chain reaction (PCR) are increasingly being applied for the diagnosis of Johne's disease, a chronic intestinal infection of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Feces, as the primary test sample, presents challenges in terms of effective DNA isolation, with potential for PCR inhibition and ultimately for reduced analytical and diagnostic sensitivity. However, limited evidence is available regarding the magnitude and diagnostic implications of PCR inhibition for the detection of MAP in feces. This study aimed to investigate the presence and diagnostic implications of PCR inhibition in a quantitative PCR assay for MAP (High-throughput Johne's test) to investigate the characteristics of samples prone to inhibition and to identify measures that can be taken to overcome this. In a study of fecal samples derived from a high prevalence, endemically infected cattle herd, 19.94% of fecal DNA extracts showed some evidence of inhibition. Relief of inhibition by a five-fold dilution of the DNA extract led to an average increase in quantification of DNA by 3.3-fold that consequently increased test sensitivity of the qPCR from 55 to 80% compared to fecal culture. DNA extracts with higher DNA and protein content had 19.33 and 10.94 times higher odds of showing inhibition, respectively. The results suggest that the current test protocol is sensitive for herd level diagnosis of Johne's disease but that test sensitivity and individual level diagnosis could be enhanced by relief of PCR inhibition, achieved by five-fold dilution of the DNA extract. Furthermore, qualitative and quantitative parameters derived from absorbance measures of DNA extracts could be useful for prediction of inhibitory fecal samples.

Culture-Independent Identification of Mycobacterium avium Subspecies paratuberculosis in Ovine Tissues: Comparison with Bacterial Culture and Histopathological Lesions.

Johne's disease is a chronic debilitating enteropathy of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Current abattoir surveillance programs detect disease via examination of gross lesions and confirmation by histopathological and/or tissue culture, which is time-consuming and has relatively low sensitivity. This study aimed to investigate whether a high-throughput quantitative PCR (qPCR) test is a viable alternative for tissue testing. Intestine and mesenteric lymph nodes were sourced from sheep experimentally infected with MAP and the DNA extracted using a protocol developed for tissues, comprised enzymatic digestion of the tissue homogenate, chemical and mechanical lysis, and magnetic bead-based DNA purification. The extracted DNA was tested by adapting a previously validated qPCR for fecal samples, and the results were compared with culture and histopathology results of the corresponding tissues. The MAP tissue qPCR confirmed infection in the majority of sheep with gross lesions on postmortem (37/38). Likewise, almost all tissue culture (61/64) or histopathology (52/58) positives were detected with good to moderate agreement (Cohen's kappa statistic) and no significant difference to the reference tests (McNemar's Chi-square test). Higher MAP DNA quantities corresponded to animals with more severe histopathology (odds ratio: 1.82; 95% confidence interval: 1.60, 2.07). Culture-independent strain typing on tissue DNA was successfully performed. This MAP tissue qPCR method had a sensitivity equivalent to the reference tests and is thus a viable replacement for gross- and histopathological examination of tissue samples in abattoirs. In addition, the test could be validated for testing tissue samples intended for human consumption.