Faculty Bibliography

Tigecycline serves as one of the last-resort antibiotics to treat multidrug-resistant (including carbapenem-resistant) pathogens. However, the recently emerged plasmid-mediated tigecycline resistance mechanisms, Tet(X), challenge the clinical efficacy of this class of antibiotics. In this study, we detected one hundred and eighty tet(X)-harboring Acinetobacter isolates (8.9%, n=180) from 2018 samples collected from the avian farms and adjacent environment in China. Eighteen tet(X)-harboring isolates (10.0%) were found to co-carry the carbapenemase gene bla_NDM-1, mostly from waterfowls samples (94.4%, 17/18). Interestingly, among six Acinetobacter strains, the tet(X) and bla_NDM-1 were found to co-localize on the same plasmids. Moreover, WGS revealed a novel orthologue of tet(X) in the six tet(X)- and bla_NDM-1-co-harboring isolates. Inverse PCR suggested that the two tet(X) genes form a single transposable unit and may be co-transferred. Sequence comparison between six tet(X) and bla_NDM-1-co-harboring plasmids showed they shared a highly homologous plasmid backbone, even though they were isolated from different Acinetobacter species (3 A. indicus, 2 A. schindleri, and 1 A. lwoffii) in various sources and from different geological regions, suggesting the horizontal genetic transfer of a common tet(X) and bla_NDM-1-co-harboring plasmid among Acinetobacter species in China. Emergence and spread of such plasmids and strains are of great clinical concern, and measures must be implemented to avoid their dissemination.

Patients living with end stage renal disease (ESRD) who are undergoing hemodialysis experience frequent hospitalizations associated with complications of care and exacerbations of illness. Efforts to reduce hospitalizations have had limited success. The purpose of this study was to explore why hospitalizations occur from the perspectives of patients undergoing hemodialysis treatment, their caregivers, and health care providers. Semi-structured interviews and focus groups were conducted with 21 patients living with ESRD, 10 caregivers, and three focus groups with health care professionals. Findings are discussed under four main themes: Graft site/Catheter/Access issues, "My resistance is low," "I could not breathe," and "The perfect storm." Results highlight the complexity of care and vulnerability of patients with ESRD. Further interprofessional research is needed to improve transitional care and care delivery for patient populations receiving hemodialysis.

Whole genome sequencing (WGS) is replacing traditional microbiological typing methods for investigation of outbreaks in clinical settings. Here, we used a clinical microbiology laboratory core genome multilocus sequence typing (cgMLST) workflow to analyze 40 isolates of K. pneumoniae which are part of the Antimicrobial Resistance Leadership Group (ARLG) isolate collection, alongside 10 Mayo Clinic K. pneumoniae isolates, comparing results to those of pulsed-field gel electrophoresis (PFGE). Additionally, we used the WGS data to predict phenotypic antimicrobial susceptibility (AST). Thirty-one of 40 ARLG K. pneumoniae isolates belonged to the same PFGE type, all of which, alongside 3 isolates of different PFGE types, formed a large cluster by cgMLST. PFGE and cgMLST were completely concordant for the 10 Mayo Clinic K. pneumoniae isolates. For AST prediction, the overall agreement between phenotypic AST and genotypic prediction was 95.6%.

The most widely discussed antibiotic-resistant tuberculosis strains ("W" and "B0/W148", "CAO") belong to L2/Beijing Lineage and are characterized by IS6110 insertion sequences at the NTF locus. We present a high-throughput, microbead-based method, called NTF-RINT for detection of IS in NTF and Rifampicin and Isoniazid Typing. This method provides tuberculosis diagnostic confirmation, screens for the so-called modern L2/Beijing sublineage and detects mutations involved in resistance to Rifampicin (RIF) and Isoniazid (INH).

BACKGROUND:To ensure a next generation of female leaders in academia, we need to understand challenges they face and factors that enable fellowship-prepared women to thrive. We surveyed woman graduates of the Robert Wood Johnson Clinical Scholars Program (CSP) from 1976 to 2011 regarding their experiences, insights, and advice to women entering the field. METHODS:We surveyed every CSP woman graduate through 2012 (n = 360) by email and post. The survey, 12 prompts requiring open text responses, explored current work situation, personal definitions of success, job negotiations, career regrets, feelings about work, and advice for others. Four independent reviewers read overlapping subsets of the de-identified data, iteratively created coding categories, and defined and refined emergent themes. RESULTS:Of the 360 cohort, 108 (30%) responded. The mean age of respondents was 45 (range 32 to 65), 85% are partnered, and 87% have children (average number of children 2.15, range 1 to 5). We identified 11 major code categories and conducted a thematic analysis. Factors common to very satisfied respondents include personally meaningful work, schedule flexibility, spousal support, and collaborative team research. Managing professional-personal balance depended on career stage, clinical specialty, and children's age. Unique to women who completed the CSP prior to 1995 were descriptions of "atypical" paths with career transitions motivated by discord between work and personal ambitions and the emphasis on the importance of maintaining relevance and remaining open to opportunities in later life. CONCLUSIONS:Women CSP graduates who stayed in academic medicine are proud to have pursued meaningful work despite challenges and uncertain futures. They thrived by remaining flexible and managing change while remaining true to their values. We likely captured the voices of long-term survivors in academic medicine. Although transferability of these findings is uncertain, these voices add to the national discussion about retaining clinical researchers and keeping women academics productive and engaged.

OBJECTIVE:People with HIV (PWH) who are well treated on antiretroviral therapy remain at increased risk for body composition changes, including increased visceral adipose tissue (VAT) and reduced subcutaneous adipose tissue (SAT), as well as increased cardiovascular disease (CVD). The relationship between adipose compartments and coronary disease is not well understood among PWH. METHODS:A total of 148 PWH and 68 uninfected individuals without CVD were well phenotyped for VAT and SAT via single-section abdominal computed tomography (CT) at L4. Coronary artery calcium (CAC) score was assessed by noncontrast cardiac CT and coronary plaque composition by coronary CT angiography. RESULTS:, P = 0.007) among PWH. The VAT to SAT ratio showed a strong relationship to overall presence of calcified plaque (OR, 3.30; P = 0.03) and CAC > 0 (OR, 3.57; P < 0.001) in the HIV group. VAT and waist to hip ratio, but not SAT, were strong predictors of plaque in the uninfected group. BMI did not relate in either group. CONCLUSIONS:Fat redistribution phenotyping by simultaneous quantification of VAT and SAT as independent measures could help identify those PWH at higher risk for CVD.

Members of the lesbian, gay, bisexual, transgender, and queer (LGBTQ) community experience marginalization, bias, and discrimination, including in the world of academic medicine. People who are transgender and gender non-binary (TGNB) experience further marginalization compared to individuals who are lesbian, gay, bisexual, and queer. According to a recent survey, more than half of medical students who are TGNB chose not to disclose their gender identities during training due to fears of discrimination, feeling a lack of support, and concerns about future career options. Academic medicine has historically pathologized TGNB individuals, perpetuating discrimination structurally and reinforcing discriminatory behaviors in peers and faculty. In this Perspective, the authors provide a comprehensive overview of the challenges that administrators and educators face in creating a learning environment that is inclusive of TGNB trainees. They outline opportunities for change and provide strategies to address administrative and educational challenges, including those related to institutional climate, policies, data collection, physical spaces, health care, the curriculum, mentoring, and the evaluation of TGNB trainees. Finally, the authors issue a call to action for medical educators and administrators to create environments in which trainees who are TGNB can fulfill their primary mission: to learn the practice of medicine.