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Over the past 10 years, there has been a rapid expansion in the use of extracorporeal membrane oxygenation (ECMO) in the care of patients with refractory cardiac or respiratory failure. Infectious diseases clinicians must reconcile conflicting evidence from limited studies as they develop practices at their own institutions, which has resulted in considerably different practices globally. This review describes infection control and prevention as well as antimicrobial prophylaxis strategies in this population. Data on diagnostics and treatment for patients receiving ECMO with a focus on diagnostic and antimicrobial stewardship is then examined. This review summarizes gaps in the current ECMO literature and proposes future needs, including developing clear definitions for infections and encouraging transparent reporting of practices at individual facilities in future clinical trials. [ABSTRACT FROM AUTHOR]

Introduction: Extracorporeal membrane oxygenation (ECMO) is an increasingly used modality of life support with high risk for nosocomial infections. The accuracy of sepsis prediction tools in identifying blood stream infections (BSI) in this population is unknown as measurement of multiple variables commonly associated with infection are altered by the circuit. Methods: This study compares all blood stream infections for patients receiving ECMO between January 2012 and December 2020 to timepoints when blood cultures were negative using the Sequential Organ Failure Assessment (SOFA), Logistic Organ Dysfunction Score (LODS), American Burn Association Sepsis Criteria (ABA), Systemic Inflammatory Response Syndrome (SIRS) scores. Results: Of the 220 patients who received ECMO during the study period, 40 (18%) had 51 blood stream infections and were included in this study. Gram-positive infections composed 57% (n = 29) of infections with E. faecalis (n = 12, 24%) being the most common organism isolated. There were no significant differences in sepsis prediction scores at the time of infection compared to infection-free time points for SOFA (median (IQR) 7 (5–9) vs. 6 (5–8), p = 0.22), LODS (median (IQR) 12 (10–14) vs. 12 (10–13), p = 0.28), ABA (median (IQR) 2 (1–3) vs. 2 (1–3) p = 0.75), or SIRS (median (IQR) 3 (2–3) vs. 3 (2–3), p = 0.20). Conclusions: Our data shows that previously published sepsis scores are elevated throughout a patient's ECMO course, and do not correlate with bacteremia. Better predictive tools are needed to determine the appropriate timing for blood cultures in this population. [ABSTRACT FROM AUTHOR]

Background For persons entering congregate settings, optimal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) arrival surveillance screening method, nucleic acid amplification test (NAAT) versus rapid antigen detection test (RADT), is debated. To aid this, we sought to determine the risk of secondary symptomatic coronavirus disease 19 (COVID-19) among military trainees with negative arrival NAAT or RADT screening. Methods Individuals who arrived for US Air Force basic military training from 1 January–31 August 2021 were placed into training groups and screened for SARS-CoV-2 via NAAT or RADT. Secondary symptomatic COVID-19 cases within 2 weeks of training were then measured. A case cluster was defined as ≥5 individual symptomatic COVID-19 cases. Results 406 (1.6%) of 24 601 trainees screened positive upon arrival. The rate of positive screen was greater for those tested with NAAT versus RADT (2.5% vs 0.4%; RR: 5.4; 95% CI: 4.0–7.3; P <.001). The proportion of training groups with ≥1 positive individual screen was greater in groups screened via NAAT (57.5% vs 10.8%; RR: 5.31; 95% CI: 3.65–7.72; P <.001). However, NAAT versus RADT screening was not associated with a difference in number of training groups to develop a secondary symptomatic case (20.3% vs 22.5%; RR:.9; 95% CI:.66–1.23; P =.53) or case cluster of COVID-19 (4% vs 6.6%; RR:.61; 95% CI:.3–1.22; P =.16). Conclusions NAAT versus RADT arrival surveillance screening method impacted individual transmission of COVID-19 but had no effect on number of training groups developing a secondary symptomatic case or case cluster. This study provides consideration for RADT arrival screening in congregate settings. [ABSTRACT FROM AUTHOR]

Background Fever and leukocytosis are 2 parameters commonly cited in clinical practice as indications to perform an infectious workup in patients receiving extracorporeal membrane oxygenation (ECMO), but their utility is unknown. Methods All patients who received ECMO between December 2014 and December 2020 with influenza or COVID-19 were included in this retrospective cohort study. Cultures were included if they were drawn from patients without signs of decompensation. Maximum temperature and white blood cell count were recorded on the day of culture collection. Workups with infections were compared with those that were negative. Results Of the 137 infectious workups in this 45-patient cohort, 86 (63%) were performed in patients with no signs of decompensation, totaling 165 cultures. These workups yielded 10 (12%) true infections. There were no differences in median (IQR) temperature (100.4 °F [100.2–100.8] vs 100.4 °F [99.3–100.9], P =.90) or white blood cell count (18.6 cells/mL [16.8–20.1] vs 16.7 cells/mL [12.8–22.3], P =.90) between those with and without infections. Conclusions In patients with influenza or COVID-19 who require ECMO, fever and leukocytosis were common indications for infectious workups, yet results were frequently negative. Despite their use in clinical practice, fever and leukocytosis are not reliable indicators of infection in patients who are hemodynamically stable and receiving ECMO. [ABSTRACT FROM AUTHOR]

RNA interference (RNAi) is a powerful tool whose efficacy against a broad range of targets enables functional genetic tests individually or systematically. However, the RNAi pathway has been lost in evolution by a variety of eukaryotes including most Leishmania sp. RNAi was retained in species of the Leishmania subgenus Viannia, and here we describe the development, optimization, and application of RNAi tools to the study of L. (Viannia) braziliensis (Lbr). We developed vectors facilitating generation of long-hairpin or "stem-loop" (StL) RNAi knockdown constructs, using GatewayTM site-specific recombinase technology. A survey of applications of RNAi in L. braziliensis included genes interspersed within multigene tandem arrays such as quinonoid dihydropteridine reductase (QDPR), a potential target or modulator of antifolate sensitivity. Other tests include genes involved in cell differentiation and amastigote proliferation (A600), and essential genes of the intraflagellar transport (IFT) pathway. We tested a range of stem lengths targeting the L. braziliensis hypoxanthine-guanine phosphoribosyl transferase (HGPRT) and reporter firefly luciferase (LUC) genes and found that the efficacy of RNAi increased with stem length, and fell off greatly below about 128 nt. We used the StL length dependency to establish a useful 'hypomorphic' approach not possible with other gene ablation strategies, with shorter IFT140 stems yielding viable cells with compromised flagellar morphology. We showed that co-selection for RNAi against adenine phosphoryl transferase (APRT1) using 4-aminopyrazolpyrimidine (APP) could increase the efficacy of RNAi against reporter constructs, a finding that may facilitate improvements in future work. Thus, for many genes, RNAi provides a useful tool for studying Leishmania gene function with some unique advantages. [ABSTRACT FROM AUTHOR]

In this retrospective cohort study of military trainees, symptomatic-only coronavirus disease 2019 (COVID-19) arrival antigen testing decreased isolation requirements without increasing secondary cases compared to universal antigen testing. Symptomatic-only arrival antigen testing is a feasible alternative for individuals entering a congregant setting with a high risk of COVID-19 transmission., (© Cambridge University Press 2024.)

Introduction: Nosocomial infections are frequent in patients receiving extracorporeal membrane oxygenation (ECMO). Leukemoid reaction, defined as >50,000 white blood cells (WBCs) per microliter, has been associated with infections in some populations. As ECMO is associated with significant inflammation activation between the patient's immune system and the circuit components, it is hypothesized that leukemoid reactions may have low specificity for identifying new infections in patients receiving ECMO., Materials and Methods: A retrospective cohort study was performed on all adult patients admitted to the Brooke Army Medical Center who received ECMO for greater than 72 hours between 2018 and 2022. Maximum WBCs were obtained for all charts. For those with leukemoid reaction, demographic information and clinical management was obtained. This study was determined to be exempt by Brooke Army Medical Center Institutional Review Board., Results: Among 182 patients receiving ECMO for greater than 72 hours, 15 (8%) developed a leukemoid reaction while on ECMO. The median (Interquartile range, IQR) WBC was 53.94 (50.98 to 62.55). Fourteen (93%) patients underwent an infectious evaluation. Patients had a median of 2 (IQR: 2 to 3) etiologies contributing to their leukemoid reaction. At the time of leukemoid reaction, 11 (73%) patients were receiving treatment for a known infection, 6 (40%) were found to have a new thrombus, and 4 (27%) were receiving glucocorticoids. Only 1 (7%) patient was found to have a new infection, an Acinetobacter baumannii bacteremia., Conclusions: Leukemoid reactions occur infrequently in patients receiving ECMO and are generally multifactorial. In this cohort, leukemoid reactions rarely occurred in the setting of a new infection and suggest low utility to starting or broadening antimicrobials for these patients. Future studies identifying useful infectious markers are needed for patients receiving ECMO., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Introduction: Infectious diseases physicians invest significant time mentoring medical students and internal medicine residents through research projects as well as case reports. While having an infectious diseases mentor has been shown to be associated with subsequent infectious diseases fellowship application, the impact of specific scholarly activities on future application to infectious diseases fellowship is unknown., Methods: All research and case reports published or presented from Brooke Army Medical Center between 2014-2022 with an infectious diseases senior author and a medical student or internal medicine resident first author were evaluated. The presentations and publications that resulted from each project as well as whether the trainee applied to infectious diseases were recorded., Results: During the study period, 16 faculty mentored 35 medical student and resident research projects and 26 case reports. Research and case reports were primarily performed by residents (88% and 96% respectively). Compared to case reports, research projects were more likely to be presented at national meetings (77% vs 32%, p=0.0009). Of the 55 projects performed by trainees who completed training, research was associated with greater rates of infectious disease fellowship application as compared to case reports (41% vs. 4%, p=0.0012)., Conclusion: Internal medicine resident and medical student involvement in research mentored by an infectious disease physician was associated with a greater infectious diseases fellowship application rate as compared to those who were mentored for case reports. Investment in trainee research may be a strategy for recruiting the next generation of infectious diseases physicians., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Background: Identifying secondary infections in patients receiving extracorporeal membrane oxygenation (ECMO) presents challenges due to the ECMO circuit's influence on traditional signs of infection., Objectives: This study evaluates procalcitonin as a diagnostic marker for secondary infections in patients receiving ECMO with influenza or COVID-19 infection., Design: Single-center retrospective cohort study., Methods: All adult patients receiving veno-venous ECMO with underlying influenza or COVID-19 from November 2017 to October 2021 were included. Patient demographics, time receiving ECMO, culture data, and procalcitonin levels were examined. The first procalcitonin within 3 days of infection was compared to negative workups that were collected at least 10 days from the last positive culture. Furthermore, we compared procalcitonin levels by the type of pathogen and site of infection., Results: In this study, 84 patients with influenza or COVID-19 who received ECMO were included. A total of 276 procalcitonin labs were ordered in this cohort, with 33/92 (36%) of the secondary infections having an associated procalcitonin value. When comparing procalcitonin levels, there was no significant difference between the infection and negative workup groups [1 ng/mL (interquartile ranges, IQR: 0.4-1.2) versus 1.3 (0.5-4.3), p  = 0.19]. Using 0.5 ng/mL as the cut-off, the sensitivity of procalcitonin was 67% and the specificity was 30%. In our cohort, the positive predictive value of procalcitonin was 14.5% and the negative predictive value was 84%. There was no difference in procalcitonin by type of organism or site of infection. Procalcitonin levels did not routinely decline even after an infection was identified., Conclusion: While procalcitonin is a proposed potential diagnostic marker for secondary infections in patients receiving ECMO, this single-center study demonstrated low sensitivity and specificity of procalcitonin in identifying secondary infections. Furthermore, there was no association of procalcitonin levels with etiology of infection when one was present. Procalcitonin should be used cautiously in identifying infections in veno-venous ECMO., (© The Author(s), 2024.)

The coronavirus disease 2019 (COVID-19) pandemic has resulted in substantial morbidity and mortality since it was first described in December 2019 (1). Based on epidemiologic data showing spread in congregate settings (2-4), national, state, and local governments instituted significant restrictions on large gatherings to prevent transmission of disease in early March 2020. This and other nonpharmaceutical interventions (NPIs) have shown initial success in slowing the pandemic across the country (5). This report examines the first 7 weeks (March 1-April 18) of implementation of NPIs in Basic Military Training (BMT) at a U.S. Air Force base. In a population of 10,579 trainees, COVID-19 incidence was limited to five cases (47 per 100,000 persons), three of which were in persons who were contacts of the first patient. Transmission of symptomatic COVID-19 was successfully limited using strategies of quarantine, social distancing, early screening of trainees, rapid isolation of persons with suspected cases, and monitored reentry into training for trainees with positive test results after resolution of symptoms., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.