Can't keep it SECRET: system evaluation of carbapenem restriction against empirical therapy.

Objectives: Carbapenems are appealing agents for empirical use given their broad spectrum of activity; however, selective use is vital in minimizing the risk for development of carbapenem-resistant pathogens. We aimed to examine the impact of carbapenem restriction criteria and a pre-authorization process on utilization and cost savings across a health system. Methods: This retrospective study was conducted across five adult hospitals. The pre-implementation period was 8 February 2020 to 30 April 2020 and the post-implementation period was 8 February 2022 to 30 April 2022. The primary outcome was to compare the number of orders for carbapenems between the study periods for both the intervention and non-intervention hospitals. Secondary outcomes included projected annual cost and an estimated cost-savings evaluation using a stratified analysis for the intervention and non-intervention facilities to account for more resource-limited settings. Results: The total number of carbapenem orders decreased between study periods at the intervention hospital (246 versus 61, P < 0.01). At the non-intervention hospitals, orders decreased, although not significantly (333 versus 279, P = 0.58). Meropenem orders decreased by 66% compared with 12% for the intervention and the non-intervention hospitals, respectively (P < 0.001). Annual estimated cost for all facilities was $255 561 in the pre-implementation period compared with $29 593 in the post-implementation period (P < 0.001). Using a stratified analysis to account for available resources, the estimated annual cost saving was $225 968 for the system. Conclusions: Implementation of carbapenem restriction at the intervention hospital decreased utilization and provided significant cost savings. Furthermore, resource-limited facilities can still experience significant cost savings using a stratified antimicrobial stewardship intervention approach.

A plant-based mutant huntingtin model-driven discovery of impaired expression of GTPCH and DHFR.

Pathophysiology associated with Huntington's disease (HD) has been studied extensively in various cell and animal models since the 1993 discovery of the mutant huntingtin (mHtt) with abnormally expanded polyglutamine (polyQ) tracts as the causative factor. However, the sequence of early pathophysiological events leading to HD still remains elusive. To gain new insights into the early polyQ-induced pathogenic events, we expressed Htt exon1 (Httex1) with a normal (21), or an extended (42 or 63) number of polyQ in tobacco plants. Here, we show that transgenic plants accumulated Httex1 proteins with corresponding polyQ tracts, and mHttex1 induced protein aggregation and affected plant growth, especially root and root hair development, in a polyQ length-dependent manner. Quantitative proteomic analysis of young roots from severely affected Httex1Q63 and unaffected Httex1Q21 plants showed that the most reduced protein by polyQ63 is a GTP cyclohydrolase I (GTPCH) along with many of its related one-carbon (C1) metabolic pathway enzymes. GTPCH is a key enzyme involved in folate biosynthesis in plants and tetrahydrobiopterin (BH4) biosynthesis in mammals. Validating studies in 4-week-old R6/2 HD mice expressing a mHttex1 showed reduced levels of GTPCH and dihydrofolate reductase (DHFR, a key folate utilization/alternate BH4 biosynthesis enzyme), and impaired C1 and BH4 metabolism. Our findings from mHttex1 plants and mice reveal impaired expressions of GTPCH and DHFR and may contribute to a better understanding of mHtt-altered C1 and BH4 metabolism, and their roles in the pathogenesis of HD.

From Start to Finish: Examining Factors Associated With Higher Likelihood of Publication Among Abstracts Presented at an International Infectious Diseases Scientific Meeting.

Background: The landscape of infectious diseases research by interprofessional teams continues to change in both scope and engagement. Limited information exists regarding publication metrics and factors associated with publication of abstracts presented at professional infectious diseases meetings. Methods: This was a retrospective, observational study evaluating abstracts presented at IDWeek in 2017 and 2018. The primary endpoint was the proportion of abstracts that were subsequently published in peer-reviewed journals. Factors associated with publication were evaluated, and a description of publication metrics was reported. Results: Of the 887 abstracts analyzed from the IDWeek meetings, 236 (26.6%) were published. Significantly more abstracts were published if they were presented as a platform presentation versus poster presentation (35% vs 21%, P < .001). Inclusion of a PhD author significantly increased the likelihood of publication (P = .0014). Prospective studies, greater number of authors, and greater number of study subjects were more common among published abstracts. Median time to publication was 10.9 months, and the majority were published in infectious diseases journals, with an overall average impact factor of 7.7 across all journals. Conclusions: Abstracts from IDWeek presented as oral platforms and those including a PhD author were more likely to be published. Large, diverse authorship teams were common among published abstracts. The high quality of resulting manuscripts is evident by the destination journals and their respective impact factors. These data may be used to inform and motivate clinicians and trainees engaging in infectious diseases-related research.

Criteria Restricting Inappropriate Meropenem Empiricism (CRIME): a quasi-experimental carbapenem restriction pilot at a large academic medical centre.

The broad-spectrum activity of carbapenems makes them appealing for empirical use; however, they are associated with development of Clostridioides difficile infection (CDI) and multidrug resistance. Selective carbapenem use is vital in maintaining their effectiveness. We examined the impact of meropenem restriction criteria on utilisation and patient outcomes. This quasi-experimental study was conducted at a single academic medical centre after medication use evaluation found frequent inappropriate meropenem utilisation. Antimicrobial stewardship-led restriction criteria were developed and implemented in February 2022. Investigators aimed to determine how restriction criteria affected meropenem utilisation across 8 weeks in the pre- (February-April 2020) versus post-implementation period (February-April 2022). The primary outcome was inappropriateness of meropenem utilisation. Secondary outcomes included days of therapy per 1000 patient-days (DOT/1000 PD), hospital length of stay (LOS), CDI Standardized Infection Ratio (SIR), and acquisition cost. Across the 8-week timeframes, reductions in inappropriate meropenem use (64.5% vs. 12.8%; P < 0.001), duration of therapy [5.8 (3.2-7.3) vs. 2.4 (1.0-5.5) days; P < 0.001] and utilisation (30.5 vs. 8.3 DOT/1000 PD; P < 0.001) pre- versus post-implementation were observed. Total meropenem orders decreased by 65% (P < 0.001). Median hospital LOS also decreased between periods [11.9 (7.8-20.4) vs. 9.2 (5.4-15.2) days], although not statistically significant (P = 0.051). There was no difference in CDI SIR (0.1 vs. 0.1; P = 0.99). Projected annual cost savings were ∼US$57 300. Implementation of antimicrobial stewardship-initiated restriction criteria can reduce inappropriate meropenem utilisation, overall number of orders, and total duration of therapy.