Cathy A Petti’s research while affiliated with Duke University Medical Center and other places

To the editor—We appreciate the thoughtful questions posed by our colleagues. Our responses to each are provided below. Our aim is to pursue a “living document” concept for the 2023 Duke/ISCVID Criteria in the ISCVID Website (http://iscvid.org/) and all advances and changes will be updated periodically. Financial support. Work contained in this manuscript was made possible by grant 1R01-AI165671 (V. G. F.) from the National Institutes of Health. J. M. M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–2023.

Introduction The COVID-19 pandemic focused attention on healthcare disparities and inequities faced by individuals within marginalized and structurally disadvantaged groups in the United States. These individuals bore the heaviest burden across this pandemic as they faced increased risk of infection and difficulty in accessing testing and medical care. Individuals experiencing housing insecurity are a particularly vulnerable population given the additional barriers they face. In this scoping review, we identify some of the barriers this high-risk group experienced during the early days of the pandemic and assess novel solutions to overcome these barriers. Methods A scoping review was performed following PRISMA-Sc guidelines looking for studies focusing on COVID-19 testing among individuals experiencing housing insecurity. Barriers as well as solutions to barriers were identified as applicable and summarized using qualitative methods, highlighting particular ways that proved effective in facilitating access to testing access and delivery. Results Ultimately, 42 studies were included in the scoping review, with 143 barriers grouped into four categories: lack of cultural understanding, systemic racism, and stigma; medical care cost, insurance, and logistics; immigration policies, language, and fear of deportation; and other. Out of these 42 studies, 30 of these studies also suggested solutions to address them. Conclusion A paucity of studies have analyzed COVID-19 testing barriers among those experiencing housing insecurity, and this is even more pronounced in terms of solutions to address those barriers. Expanding resources and supporting investigators within this space is necessary to ensure equitable healthcare delivery.

Research on the COVID-19 pandemic revealed a disproportionate burden of COVID-19 infection and death among underserved populations and exposed low rates of SARS-CoV-2 testing in these communities. A landmark National Institutes of Health (NIH) funding initiative, the Rapid Acceleration of Diagnostics-Underserved Populations (RADx-UP) program, was developed to address the research gap in understanding the adoption of COVID-19 testing in underserved populations. This program is the single largest investment in health disparities and community-engaged research in the history of the NIH. The RADx-UP Testing Core (TC) provides community-based investigators with essential scientific expertise and guidance on COVID-19 diagnostics. This commentary describes the first 2 years of the TC's experience, highlighting the challenges faced and insights gained to safely and effectively deploy large-scale diagnostics for community-initiated research in underserved populations during a pandemic. The success of RADx-UP shows that community-based research to increase access and uptake of testing among underserved populations can be accomplished during a pandemic with tools, resources, and multidisciplinary expertise provided by a centralized testing-specific coordinating center. We developed adaptive tools to support individual testing strategies and frameworks for these diverse studies and ensured continuous monitoring of testing strategies and use of study data. In a rapidly evolving setting of tremendous uncertainty, the TC provided essential and real-time technical expertise to support safe, effective, and adaptive testing. The lessons learned go beyond this pandemic and can serve as a framework for rapid deployment of testing in response to future crises, especially when populations are affected inequitably.

The microbiology, epidemiology, diagnostics, and treatment of infective endocarditis (IE) have changed significantly since the Duke Criteria were published in 1994 and modified in 2000. The International Society for Cardiovascular Infectious Diseases (ISCVID) convened a multidisciplinary Working Group to update the diagnostic criteria for IE. The resulting 2023 Duke-ISCVID IE Criteria propose significant changes, including new microbiology diagnostics (enzyme immunoassay for Bartonella species, PCR, amplicon/metagenomic sequencing, in situ hybridization), imaging ([18F]FDG PET/CT, Cardiac Computed Tomography), and inclusion of intraoperative inspection as a new Major Clinical Criterion. The list of "typical" microorganisms causing IE was expanded and includes pathogens to be considered as typical only in the presence of intracardiac prostheses. The requirements for timing and separate venipunctures for blood cultures were removed. Last, additional predisposing conditions (transcatheter valve implants, endovascular cardiac implantable electronic devices, prior IE) were clarified. These diagnostic criteria should be updated periodically by making the ISCVID-Duke Criteria available online as a "Living Document".

We evaluated the performance of an early prototype core molecular mirroring nuclear magnetic resonance detection platform (Mentor-100) to detect toxigenic Clostridium difficile from stool. This technology uses customized nanoparticles bound to target specific oligonucleotide probes that form binaries in the presence of nucleic acid from the target microorganism. Liquid patient stool specimens were seeded with C. difficile or other Clostridium species to determine the analytical sensitivity and specificity. Samples underwent nucleic acid extraction and target amplification with probes conjugated with iron nanoparticles. Signal from nuclear magnetic resonance spin-spin relaxation time was measured to detect the presence or absence of toxigenic C. difficile. The limit of detection was <180 colony forming units per reaction of toxigenic C. difficile. No cross-reactivity was observed with nontoxigenic C. difficile, Clostridium sordellii, Clostridium perfringens, Bacillus subtilis, or Paenibacillus polymyxa at 10(8) colony forming units/mL. Correlation studies using frozen stool samples yielded a sensitivity of 88.4% (61 of 69) and a specificity of 87.0% (40 of 46) as compared with the Xpert C. difficile/Epi PCR assay. The area under the curve in the receiver operating characteristic curve analysis was 0.922. The prototype molecular mirroring platform showed promising performance for pathogen detection from clinical specimens. The platform design has the potential to offer a novel, low-cost alternative to currently available nucleic acid-based tests.

BACKGROUND The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of presence of the mecA gene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with anti-staphylococcal β-lactams (ASB) vs. vancomycin (VAN). METHODS Multicenter cohort study based on the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. ICE-PCS contains prospective data on 5,568 patients with IE between 2000 and 2006, while ICE-Plus contains prospective data on 2,019 patients with IE between 2008 and 2012. Primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. RESULTS Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available in 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% vs.11.1%; p=0.27), 6-month mortality (31.6% vs. 25.9%; p=0.58), and survival time after discharge (p=0.26) did not significantly differ in the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (HR 1.7; p=0.22); this result was not affected by adjusting for confounders. CONCLUSIONS This study provides no evidence for a difference in outcome with the use of VAN vs. ASB for methicillin-susceptible CoNS IE.

Consensus definitions have emerged for the discrimination between infected and uninfected prosthetic joints but diagnostic uncertainty often occurs. We examined the accuracy of orthopaedic surgeons' assessments to diagnose the infected prosthetic hip or knee and elucidated the added value of laboratory parameters. A prospective cohort study of patients undergoing revision arthroplasty of hip or knee was conducted over a one-year period. Orthopaedic surgeons' determinations prior to arthroplasty were recorded. A reference diagnostic standard was determined retrospectively by independent review from 3 infectious diseases physicians. Patients were followed up to 12 months. For 198 patients enrolled, 228 surgical encounters (110 knee, 118 hip) were classified by independent reviewers as 176 uninfected and 52 infected. Orthopaedic surgeons' preoperative diagnoses of infection had high diagnostic accuracy (sensitivity 89%, specificity 99%, PPV 98%, NPV 97%). Addition of intraoperative findings and histopathology improved their diagnostic accuracy. Addition of culture and PCR results improved sensitivity of diagnostic determinations but not specificity. We provide evidence that clinical acumen has high diagnostic accuracy using routine preoperative parameters. Histopathology from intraoperative specimens would improve surgeons' diagnostic accuracy but culture and PCR from intraoperative specimens could create greater diagnostic uncertainty. This study is critical to further our understanding of the added value, if any, of laboratory testing to support clinical decision making for the suspected infected joint and allow us to identify diagnostic gaps for emerging technologies to fill that will improve our ability to diagnose the infected prosthetic joint.