Antimicrobial Stewardship Training for Infectious Diseases Fellows: Program Directors Identify a Curriculum Need

A needs assessment survey of infectious diseases (ID) training program directors identified gaps in educational resources for training and evaluating ID fellows in antimicrobial stewardship. An Infectious Diseases Society of America-sponsored core curriculum was developed to address that need

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

Successful Treatment of Clostridium difficile Bacteremia with Aortic Mycotic Aneurysm in a Patient with Prior Endovascular Aortic Aneurysm Repair

The clinical spectrum of Clostridium difficile infection can range from benign gastrointestinal colonization to mild diarrhea and life threatening conditions such as pseudomembranous colitis and toxic megacolon. Extraintestinal manifestations of C. difficile are rare. Here, we report a patient with a history of an endovascular aortic aneurysm repair (EVAR) presenting with an endovascular leak complicated by C. difficile bacteremia and a mycotic aneurysm. He was successfully treated with an explant of the EVAR, an aorto-left renal bypass, and aorto-bi-iliac bypass graft placement along with a six-week duration of intravenous vancomycin and oral metronidazole

Vaccine Enthusiasm and Hesitancy in Cancer Patients and the Impact of a Webinar

(1) Background: Vaccine hesitancy and rejection are major threats to controlling coronavirus disease 2019 (COVID-19). There is a paucity of information about the attitudes of cancer patients towards vaccinations and the role of clinical oncologists in influencing vaccination acceptance. (2) Methods: Cancer patients and caregivers were invited to participate in a webinar and two surveys (pre- and post-webinar) assessing intention and thought processes associated with receiving COVID-19 vaccines. (3) Results: Two hundred and sixty-four participants participated in the webinar and registered to take at least one survey. Participants reported receiving most of their COVID-19 vaccine information from their doctor, clinic, or hospital. Before the webinar, 71% of participants reported the intention to receive a COVID-19 vaccine, 24% were unsure, and 5% had no intention of receiving a vaccine. The strongest predictors of vaccine enthusiasm were (a) planning to encourage the vaccination of family, friends, co-workers, and community, and (b) physician recommendation. The chief reason for vaccine hesitancy was a fear of side effects. After the webinar, 82.5% reported the intention to receive a vaccine, 15.4% were still unsure, and 2% stated that they had no intention of receiving a vaccine. The webinar shifted the attitude towards vaccine enthusiasm, despite an already vaccine-enthusiastic population. Communicating about vaccines using positive framing is associated with greater vaccine enthusiasm. (4) Conclusions: Patient education programs co-hosted by multiple stakeholders and delivered by oncologists can increase cancer patient enthusiasm for COVID-19 vaccination

Antifungal Potential of Host Defense Peptide Mimetics in a Mouse Model of Disseminated Candidiasis

Invasive candidiasis caused by Candida albicans and non-albicans Candida (NAC) present a serious disease threat. Although the echinocandins are recommended as the first line of antifungal drug class, resistance to these agents is beginning to emerge, demonstrating the need for new antifungal agents. Host defense peptides (HDP) exhibit potent antifungal activity, but as drugs they are difficult to manufacture efficiently, and they are often inactivated by serum proteins. HDP mimetics are low molecular weight non-peptide compounds that can alleviate these problems and were shown to be membrane-active against C. albicans and NAC. Here, we expand upon our previous works to describe the in vitro and in vivo activity of 11 new HDP mimetics that are active against C. albicans and NAC that are both sensitive and resistant to standard antifungal drugs. These compounds exhibit minimum inhibitory/fungicidal concentration (MIC/MFC) in the µg/mL range in the presence of serum and are inhibited by divalent cations. Rapid propidium iodide influx into the yeast cells following in vitro exposure suggested that these HDP mimetics were also membrane active. The lead compounds were able to kill C. albicans in an invasive candidiasis CD-1 mouse model with some mimetic candidates decreasing kidney burden by 3–4 logs after 24 h in a dose-dependent manner. The data encouraged further development of this new anti-fungal drug class for invasive candidiasis

Viable SARS-CoV-2 in the air of a hospital room with COVID-19 patients

OBJECTIVES: Because the detection of SARS-CoV-2 RNA in aerosols but failure to isolate viable (infectious) virus are commonly reported, there is substantial controversy whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be transmitted through aerosols. This conundrum occurs because common air samplers can inactivate virions through their harsh collection processes. We sought to resolve the question whether viable SARS-CoV-2 can occur in aerosols using VIVAS air samplers that operate on a gentle water vapor condensation principle. METHODS: Air samples collected in the hospital room of two coronavirus disease-2019 (COVID-19) patients, one ready for discharge and the other newly admitted, were subjected to RT-qPCR and virus culture. The genomes of the SARS-CoV-2 collected from the air and isolated in cell culture were sequenced. RESULTS: Viable SARS-CoV-2 was isolated from air samples collected 2 to 4.8 m away from the patients. The genome sequence of the SARS-CoV-2 strain isolated from the material collected by the air samplers was identical to that isolated from the newly admitted patient. Estimates of viable viral concentrations ranged from 6 to 74 TCID50 units/L of air. CONCLUSIONS: Patients with respiratory manifestations of COVID-19 produce aerosols in the absence of aerosol-generating procedures that contain viable SARS-CoV-2, and these aerosols may serve as a source of transmission of the virus

1111. #BeASteward: Transforming Infectious Diseases Fellows Into Antimicrobial Stewards Using the IDSA Antimicrobial Stewardship Curriculum

Abstract Background The Infectious Diseases Society of America (IDSA) has supported the development of the Core and Advanced Antimicrobial Stewardship (AS) Curricula for fellows to ensure the future ID workforce is effectively prepared to practice, participate in and lead AS efforts in health care institutions. The Core AS Curriculum is currently available; the Advanced AS Curriculum pilot will begin July, 2020. Methods IDSA formed the AS Curriculum Workgroup, comprised of leaders in AS and medical education from institutions across the country, to lead the AS Curricula development process. The workgroup conducted two surveys of ID Fellowship Program Directors, one in 2016 for the core curriculum and a second in 2018 for the advanced curriculum, to assess existing AS educational resources and determine needs for additional AS educational and evaluation resources. The workgroup used the evaluation data to inform the content, delivery methods, and assessment tools for the curricula. The Core AS Curriculum is designed to provide fellows foundational knowledge and skills in AS. The Advanced AS Curriculum is designed to provide fellows the knowledge and skills to become leaders in AS. The Core AS Curriculum was piloted by 56 ID Fellowship Programs in 2018 and then made broadly available via IDSA Academy in 2019. Pilot data will be used to improve future iterations of the curriculum. The Advanced AS Curriculum pilot will begin in 2020 and will be broadly available in 2021. Results The curricular packages contain a variety of training resources including eLearning modules, lectures slides, case-based questions, videos, reading materials, pocket cards, group-based learning, role play exercises and simulations. The modules can be taught by faculty to fellows or conducted as a self-directed learning experience. Program directors and fellows who participated in the Core AS Curriculum pilot reported that their fellowship program was significantly more effective in teaching multiple key stewardship content areas (Table). Table. Conclusion Evaluation data from programs who piloted the Core AS Curriculum indicate that this blended learning experience is an effective method for teaching AS and in providing educational and assessment tools for ID fellowship programs. The Advanced AS Curriculum will be similarly evaluated. Disclosures Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)TRC Healthcare (Speaker’s Bureau

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\u27s 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\u27s 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

Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients : a randomised controlled trial

Background: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. Methods: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Results: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: − 23.7%; 80% confidence interval [CI] − 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) μg/mL, with 80.6% (n = 58/72) subjects achieving concentration