The use of antimicrobials in the pig sector in the Netherlands has been reduced by more than 70% over the last decade. However, there is still a considerable number of pig farms that have not been able to lower their antimicrobial usage (AMU) to a sufficiently low level, comparable to the majority of the other pig farms. Therefore, an intervention study was initiated to lower on-farm antimicrobial use in which 45 pig farms with high AMU were recruited. These farms were coached over a period of 2 years whereby different management interventions were introduced. During the 2-year study period a significant reduction of 13 and 17% in total AMU was seen in weaned piglets and fattening pigs respectively. The introduction of coaching as well as multiple management interventions were (univariably) associated with the decrease in AMU. After mutual adjustment of coaching and individual interventions, the association between coaching and AMU became substantially weaker, indicating that coaching and interventions were interrelated and specific interventions explained the reduction in AMU. In conclusion, a coaching effect was observed in this study, with an effect on AMU through specific interventions. More insights are needed regarding the role and effects of coaching on the influence on the management team comprising the farmer, veterinarian and (feed) advisor, and interventions implemented.

BACKGROUND: In Japan, the supply of one generic meropenem product was restricted from August 2022 to March 2023.
OBJECTIVE: To determine the effects of meropenem (MEPM) restriction.
METHODS: We conducted a multicenter retrospective study comparing antimicrobial use, bacteremia mortality, and drug-resistant bacteria detected before the restriction of MEPM (control period), from September 2021 to February 2022, and after the restriction of MEPM (MEPM supply restriction period), from September 2022 to February 2023, in five institutions.
RESULTS: The number of carbapenem days of therapy (DOTs) were decreased in all five institutions. Fourth-generation cephalosporin DOTs increased in all facilities, and piperacillin/tazobactam DOTs increased in four facilities. The 30-day and 90-day mortality rates were significantly higher during the MEPM supply restriction period than those during the control period. Moreover, survival time was significantly shorter during the MEPM supply restriction period than that during the control period. Multivariable analysis revealed that MEPM supply restriction, age >80 years, Pitt Bacteremia Score ≥4, platelet count <10 × 104/μL, serum albumin level <2.5 g/dL, and methicillin-resistant Staphylococcus aureus bloodstream infection were independent risk factors for 30-day mortality. The detection rates of carbapenem-resistant Pseudomonas aeruginosa and Enterobacteriaceae did not differ significantly between the two periods.
CONCLUSIONS: MEPM supply restriction decreased the use of carbapenems and increased the use of other broad-spectrum antimicrobial agents, which worsened the prognosis of bacteremia. Overall, carbapenems are important drugs for the treatment of infectious diseases and are difficult to replace in unforeseen situations such as drug supply outages.

BACKGROUND: Antimicrobial stewardship programmes are a critical tool for addressing the rising threat of antimicrobial resistance.
OBJECTIVE: To determine changes in patterns of antimicrobial use in Queensland public hospitals following introduction of the National Safety and Quality Health Service antimicrobial stewardship standard.
METHODS: A retrospective pre/post intervention study was conducted across Queensland public hospitals at the ecological level using Queensland Health\'s MedTRx database. An interrupted time-series analysis was performed using linear regression models to determine rates of antimicrobial use by quarterly aggregated defined daily dose per 1000 patient-days, for groups of hospitals stratified by peer group classification. Pre-defined time-periods for antimicrobial stewardship programme implementation in response to the introduction of the standard were analysed.
RESULTS: In the post-intervention period, there was a decrease in overall use of systemic antimicrobials, glycopeptides, carbapenems and fluoroquinolones in principal referral and public acute group A hospitals. A decrease in overall use was also observed for smaller regional and remote public acute group C and D hospitals; however, increases in glycopeptide and fluoroquinolone use were observed. Third-generation cephalosporin use was unchanged for all hospital peer groups. The proportion of overall use that was accounted for by narrow-spectrum penicillin was low for all facilities, with modest improvements in the post-intervention period observed in principal referral facilities only.
CONCLUSIONS: These findings add to current knowledge on the effectiveness of legislative quality standards on antimicrobial stewardship at the macro level and highlight gaps to target for future programmes.

BACKGROUND: We aimed to analyze the effects of an antimicrobial stewardship program (ASP) on the proportion of antimicrobial-resistant pathogens in bacteremia, antimicrobial use, and mortality in pediatric patients.
METHODS: A retrospective single-center study was performed on pediatric inpatients under 19 years old who received systemic antimicrobial treatment from 2001 to 2019. A pediatric infectious disease attending physician started ASP in January 2008. The study period was divided into the pre-intervention (2001-2008) and the post-intervention (2009-2019) periods. The amount of antimicrobial use was defined as days of therapy per 1,000 patient-days, and the differences were compared using delta slope (= changes in slopes) between the two study periods by an interrupted time-series analysis. The proportion of resistant pathogens and the 30-day overall mortality rate were analyzed by the χ².
RESULTS: The proportion of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae bacteremia increased from 17% (39 of 235) in the pre-intervention period to 35% (189 of 533) in the post-intervention period (P < 0.001). The total amount of antimicrobial use significantly decreased after the introduction of ASP (delta slope value = -16.5; 95% confidence interval [CI], -30.6 to -2.3; P = 0.049). The 30-day overall mortality rate in patients with bacteremia did not increase, being 10% (55 of 564) in the pre-intervention and 10% (94 of 941) in the post-intervention period (P = 0.881).
CONCLUSIONS: The introduction of ASP for pediatric patients reduced the delta slope of the total antimicrobial use without increasing the mortality rate despite an increased incidence of ESBL-producing gram-negative bacteremia.

Antimicrobial resistance (AMR) poses a significant threat in veterinary medicine due to the excessive and inappropriate use of antimicrobial agents, compromising the effectiveness of these drugs. To combat AMR, the collection of data on the consumption of antibiotics is paramount, as there is a well-established connection between antibiotic use and AMR in both humans and food-producing animals. Hence, the current study aimed to generate measurable data concerning the sales patterns of antimicrobial drugs used in animal treatment in Montenegro over a five-year period (from 2017 to 2021). Furthermore, the study aimed to compare these sales figures with the overall sales of antimicrobial veterinary medicine products (AMVMPs) during the same period, with particular emphasis on the utilization of critically important antimicrobials (CIAs) for human use. Data on AMVMPs consumption from 2017 to 2021 were expressed in euros and were sourced from the Institute for Medicines and Medical Devices of Montenegro (CInMED) annual reports, complying with the regulatory framework of the Law on Medicines in this country. Research results indicate that the sales of AMVMPs increased from 2017 to peak in 2019, followed by a stable decline of 21.79% in 2021. However, the portion of selected CIAs AMVMPs in total sales experienced a minor decline from 2017 to 2019, followed by a noticeable 6.11% increase from 2019 to 2021. In order to address AMR challenges, these findings emphasize the importance of enhancing surveillance and monitoring of veterinary antimicrobial use, as well as CIAs for human use.

Voriconazole (VRCZ) is an antifungal drug that necessitates therapeutic monitoring (TDM). Typically, TDM is recommended for patients undergoing long-term outpatient treatment. However, in Japan, insurance reimbursement for TDM is only permitted for inpatients. There is a concern that VRCZ use is growing among outpatients, although information regarding this issue remains unavailable. Therefore, we aimed to clarify the use of VRCZ by utilizing data from the National Database of Health Insurance Claims and Specific Health Checkups in Japan. The use of branded and generic oral VRCZ from 2013 to 2019 was calculated using the defined daily doses/1000 inhabitants/d (DID) for each receipt type. Oral VRCZ was used more frequently in the outpatient setting than that in the inpatient setting, with use increasing over time. The use of generic drugs began in 2016 and accounted for 52.5% of the use in 2019 among outpatients. Considering outpatient prescriptions, 76.4-81.0% were dispensed at insurance pharmacies, indicating the need for community pharmacist involvement. Accordingly, the appropriate use of VRCZ in ambulatory care should be promoted in collaboration with community pharmacists, and a reimbursement system should be established to implement TDM in ambulatory care.

Campylobacteriosis is one of the most common zoonotic diseases in North America. As opposed to humans, animal infections caused by Campylobacter spp. are often asymptomatic. In this study, data collected through the Canadian Dairy Network for Antimicrobial Stewardship surveillance system were used to determine the proportion of Campylobacter spp. and antimicrobial resistant isolates recovered from dairy cattle herds. Additionally, the association of antimicrobial use (AMU) with fecal carriage and antimicrobial resistance (AMR) of Campylobacter spp. were investigated. Pooled fecal samples from 5 animals from each production phase (pre-weaned calves, post-weaned heifers, lactating cows), and a manure storage sample were collected from 140 dairy herds across Canada. Samples were cultured using selective media, and Campylobacter isolates were speciated using matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Antimicrobial susceptibilities were determined using the minimum inhibitory concentration test, and interpretation was made according to the Clinical and Laboratory Standards Institute. Two multilevel logistic regression models were used to investigate the association between the AMU with the isolation and antimicrobial resistance in Campylobacter spp. Of 560 samples, 63.8% were positive for Campylobacter spp., and 96% of the participating farms had at least one sample source (i.e., calves, heifers, lactating cows, or manure storage) positive for Campylobacter spp. Overall, 54.3% of the Campylobacter spp. isolates were resistant to at least one antimicrobial. Resistance to tetracycline was observed in 49.7% of the Campylobacter spp. isolates, followed by ciprofloxacin (19.9%) and nalidixic acid (19.3%). The proportion of multi-drug resistant (≥3 antimicrobial classes) Campylobacter spp. isolates was low (0.3%); however, 15.6% were resistant to two different classes of antimicrobials. Samples collected from lactating cows, heifers, and manure storage were more likely to be positive for Campylobacter spp. compared to calves. Total AMU was associated with a decreased probability of recovering Campylobacter spp. In addition, AMR to either tetracycline or ciprofloxacin had an interaction with antimicrobial use. The probability of resistance to tetracycline increased for each unit increase in the total AMU (Defined Course Dose/100 animal-years), while the probability of resistance to ciprofloxacin decreased. Campylobacter coli isolates were more likely to be resistant to ciprofloxacin and tetracycline when compared to C. jejuni. Our study demonstrated that Campylobacter spp. is widespread among Canadian dairy farms, and a higher proportion of resistance to tetracycline was identified. The total AMU was associated with increased resistance to tetracycline in Campylobacter spp. isolates; however, for ciprofloxacin the AMU was associated with decreased resistance.

The objectives were to evaluate the effects of metaphylaxis (META) and pull-and-treat (PT) programs on health, antimicrobial use, beef production, economics, and greenhouse gas emissions in cattle at medium risk for bovine respiratory disease (BRD). A randomized complete block design was used at two US commercial feedlots. Steers and heifers [2366 total; 261 (±11.0) kg initial weight] were blocked by sex and feedlot arrival, and allocated to one of two pens within a block (16 pens total, eight blocks). Pens were randomly assigned to treatment: META, tulathromycin injection at initial processing; or PT, tulathromycin injection only for first clinical BRD treatment. Data were analyzed with linear and generalized linear mixed models. There was greater BRD morbidity in PT than META cattle (17.2% vs. 7.3% respectively; p < 0.01), and greater total mortality (2.5% vs. 1.1% respectively; p = 0.03). Per animal enrolled, 1.1 antimicrobial doses were used for META compared to 0.2 for PT (p < 0.01). Per animal enrolled, final live (p = 0.04) and carcass (p = 0.08) weights were greater for META than PT; however, net returns ($/animal) were not significantly different (p = 0.71). Compared to PT, total lifetime estimated CO2 equivalent emissions from production were reduced by 2% per unit of live weight for META (p = 0.09). While antimicrobial use was reduced with PT, there may be substantial negative impacts on other outcomes if META was not used in this type of cattle population.

The Netherlands has been very successful in the last decade in reducing antimicrobial use in animals. On about a quarter of farms, antimicrobial use in weaned pigs remains relatively high. As Streptococcus suis (S. suis) infections are responsible for a high consumption of antimicrobials, a specific veterinary guideline to control S. suis was developed, but seemed to be poorly adopted by veterinarians. Guided by the theoretical domains framework, the aim of this study was to identify determinants influencing veterinarians\' adherence to this guideline. We interviewed 13 pig veterinarians. Interviewees described multiple approaches to managing S. suis problems and adherence to the guideline. Mentioned determinants could be categorized into 12 theoretical domains. The following six domains were mentioned in all interviews: knowledge, skills, beliefs about capabilities, beliefs about consequences, social influences, and environmental context and resources. The insights derived from this study are relevant for understanding factors influencing veterinarians\' adoption of scientific evidence and guidelines and can be used to develop evidence-based implementation strategies for veterinary guidelines.

UNASSIGNED: With AMU projected to increase, South East Asia (SEA) is at high risk of experiencing disproportionate health, social, and economic burdens due to antimicrobial resistance (AMR). Our objective was to identify factors influencing AMR in SEA\'s food system and places for intervention by integrating the perspectives of experts from the region to inform policy and management decisions.
UNASSIGNED: We conducted two 6.5 h workshops and two 90-min interviews involving 18 AMR and other disciplinary experts from human, animal, and environment sectors who brainstormed the factors influencing AMR and identified leverage points (places) for intervention. Transcripts and workshop materials were coded for factors and their connections and transcribed into a causal loop diagram (CLD). Thematic analysis described AMR dynamics in SEA\'s food system and leverage points for intervention. The CLD and themes were confirmed via participant feedback.
UNASSIGNED: Participants constructed a CLD of AMR in the SEA food system that contained 98 factors interlinked by 362 connections. CLD factors reflected eight sub-areas of the SEA food system (e.g., government). Seven themes [e.g., antimicrobial and pesticide use and AMR spread (n = 40 quotes)], six \"overarching factors\" that impact the entire AMR system [e.g., the drive to survive (n = 12 quotes)], and 10 places for intervention that target CLD factors (n = 5) and overarching factors (n = 2) emerged from workshop discussions.
UNASSIGNED: The participant derived CLD of factors influencing AMR in the SEA food system demonstrates that AMR is a product of numerous interlinked actions taken across the One Health spectrum and that finding solutions is no simple task. Developing the model enabled the identification of potentially promising leverage points across human, animal, and environment sectors that, if comprehensively targeted using multi-pronged interventions, could evoke system wide changes that mitigate AMR. Even targeting some leverage points for intervention, such as increasing investments in research and capacity building, and setting and enforcing regulations to control antimicrobial supply, demand, and use could, in turn, shift mindsets that lead to changes in more difficult to alter leverage points, such as redefining the profit-driven intent that drives system behavior in ways that transform AMU and sustainably mitigate AMR.