Impact of real-time antimicrobial stewardship team intervention versus conventional microbiology reporting on time to appropriate antimicrobial therapy in patients with Enterobacterales bacteremia

Scott C. King Alyssa B. Christensen, Brent W. Footer, Timothy G. Shan, Kim Health, Ivor Thomas, and Margret Oethinger Impact of real-time antimicrobial stewardship team intervention versus conventional microbiology reporting on time to appropriate antimicrobial therapy in patients with Enterobacterales bacteremia. Introduction: The benefit of rapid laboratory speciation combined with real time antimicrobial stewardship team (AMT) interventions has been shown to improve patient outcomes and decrease hospital costs. The Providence Oregon region conducts direct from blood culture matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) identification, which results in decreased time to organism identification. The MALDI-TOF identification has allowed the AMT to intervene earlier than a health system using standard MALDI identification or comparable methods. The purpose of this study is to assess the impact of real time notification plus AMT intervention on clinical outcomes in patients with Enterobacterales blood stream infections (BSI). Methods: This was an IRB approved, retrospective, multi-center, pre- and post- quasi-experimental study conducted at eight acute care hospitals in the Providence Health & Services Oregon region. Adult patients (\u3e18 years old) with a diagnosed BSI caused by an Enterobacterales species were included. The control group was from August 2018 to January 2019 and the intervention group was from February 2019 to June 2019. Patients were matched based on age, gender, and admission to the ICU. Exclusion criteria included polymicrobial infection, Pitt bacteremia score \u3e1, unable to take PO therapy, and patients discharged to hospice care. During the intervention period the AMT members received real-time alerts for all blood culture speciation via a paging system. These cases where then reviewed and recommendations were made to the primary care team based off an approved protocol. The primary outcome for the study was time to de-escalation of therapy. Secondary outcomes include hospital length of stay and total duration of therapy. Results: A total of 60 patients were include in this study: 30 patients in the pre-intervention group and 30 patients in the post-intervention group. The most common age group was patients 60-69 years of age (43% vs 43%). The most common causative organism for the BSI was found to be Escherichia coli (76.7% vs 50%). During the intervention period a decrease was noted in median time to de-escalation of therapy (2.7 days vs 1.8 days, p=0.0061) and length of stay (5.3 days vs 4.3 days, p=0.0475). There was no statistical difference in the total length of therapy (combined inpatient and outpatient duration) noted between the two groups (9 days vs 9.5 days, p=1). Conclusion: The results show a statistically significant decrease in both time to de-escalation and length of stay within the intervention group due to AMT recommendations. This is in line with previous studies and also highlights the benefit de-escalation could have on length of stay in the hospital. Studies with larger samples sizes should be considered to further explore these results. IRB Status: Approvedhttps://digitalcommons.psjhealth.org/pharmacy_PGY1/1009/thumbnail.jp

Stoichiometrically driven disorder and local diffusion in NMC cathodes

Major structural differences in lithium nickel manganese cobalt oxides (NMC) prepared under identical conditions have been uncovered using neutron powder diffraction. Sample NMC-622 was obtained as a single R[3 with combining macron]m crystal structure with little defects, whereas NMC-811 showed significant Li deficiency and NMC-433 formed three distinct phases; ordered R[3 with combining macron]m, disordered R[3 with combining macron]m and a C2/m phase. Local diffusion behaviour was also studied by muon spin relaxation (μSR). It was observed that single phase R[3 with combining macron]m NMC-622 showed a higher lithium diffusion coefficient (4.4 × 10−11 cm2 s−1) compared to lithium deficient NMC-811 (2.9 × 10−11 cm2 s−1), or the highly disordered NMC-433 (3.4 × 10−11 cm2 s−1). Furthermore, activation energies for the Li diffusion process were estimated to be 58 meV, 61 meV and 28 meV for NMC-811, NMC-622 and NMC-433, respectively

Quaternary ferrites by batch and continuous flow hydrothermal synthesis: a comparison

Crystalline spinel quaternary ferrites MxZn1−xFe2O4 (M = Co, Ni; x = 0.2, 0.35, 0.5, 0.65, 0.8) were synthesised through conventional batch hydrothermal synthesis (HT) at 135 °C as well as via continuous flow hydrothermal synthesis (CHFS). The as prepared compounds were thoroughly characterised from a compositional (ICP-MS, XPS) and structural (XRD) point of view in order to compare the synthetic approaches and achieve a greater understanding of how the chosen approach influences the characteristics of the resulting spinel

Interplay of Magnetic Interactions and Active Movements in the Formation of Magnetosome Chains

Magnetotactic bacteria assemble chains of magnetosomes, organelles that contain magnetic nano-crystals. A number of genetic factors involved in the controlled biomineralization of these crystals and the assembly of magnetosome chains have been identified in recent years, but how the specific biological regulation is coordinated with general physical processes such as diffusion and magnetic interactions remains unresolved. Here, these questions are addressed by simulations of different scenarios for magnetosome chain formation, in which various physical processes and interactions are either switched on or off. The simulation results indicate that purely physical processes of magnetosome diffusion, guided by their magnetic interactions, are not sufficient for the robust chain formation observed experimentally and suggest that biologically encoded active movements of magnetosomes may be required. Not surprisingly, the chain pattern is most resembling experimental results when both magnetic interactions and active movement are coordinated. We estimate that the force such active transport has to generate is compatible with forces generated by the polymerization or depolymerization of cytoskeletal filaments. The simulations suggest that the pleiotropic phenotypes of mamK deletion strains may be due to a defect in active motility of magnetosomes and that crystal formation in magneteosome vesicles is coupled to the activation of their active motility in M. gryphiswaldense, but not in M. magneticum

Force-Velocity Measurements of a Few Growing Actin Filaments

The authors propose a new mechanism for actin-based force generation based on results using chains of actin-grafted magnetic colloids

An Experimental and Computational Study of the Effect of ActA Polarity on the Speed of Listeria monocytogenes Actin-based Motility

Listeria monocytogenes is a pathogenic bacterium that moves within infected cells and spreads directly between cells by harnessing the cell's dendritic actin machinery. This motility is dependent on expression of a single bacterial surface protein, ActA, a constitutively active Arp2,3 activator, and has been widely studied as a biochemical and biophysical model system for actin-based motility. Dendritic actin network dynamics are important for cell processes including eukaryotic cell motility, cytokinesis, and endocytosis. Here we experimentally altered the degree of ActA polarity on a population of bacteria and made use of an ActA-RFP fusion to determine the relationship between ActA distribution and speed of bacterial motion. We found a positive linear relationship for both ActA intensity and polarity with speed. We explored the underlying mechanisms of this dependence with two distinctly different quantitative models: a detailed agent-based model in which each actin filament and branched network is explicitly simulated, and a three-state continuum model that describes a simplified relationship between bacterial speed and barbed-end actin populations. In silico bacterial motility required a cooperative restraining mechanism to reconstitute our observed speed-polarity relationship, suggesting that kinetic friction between actin filaments and the bacterial surface, a restraining force previously neglected in motility models, is important in determining the effect of ActA polarity on bacterial motility. The continuum model was less restrictive, requiring only a filament number-dependent restraining mechanism to reproduce our experimental observations. However, seemingly rational assumptions in the continuum model, e.g. an average propulsive force per filament, were invalidated by further analysis with the agent-based model. We found that the average contribution to motility from side-interacting filaments was actually a function of the ActA distribution. This ActA-dependence would be difficult to intuit but emerges naturally from the nanoscale interactions in the agent-based representation

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

IMPORTANCE Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. OBJECTIVE To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. EVIDENCE REVIEW This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. FINDINGS A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. CONCLUSIONS AND RELEVANCE In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed