Providers need to be aware of the potential causes of false positive Xpert TB test results, this letter provides a practical approach to confirm and differentiate between a true positive by reviewing that all probes are positive and the Ct values have reached a certain threshold.

Metagenomics has enabled the comprehensive study of microbiomes. However, many applications would benefit from a method that sequences specific bacterial taxa of interest, but not most background taxa. We developed mEnrich-seq (in which ‘m’ stands for methylation and seq for sequencing) for enriching taxa of interest from metagenomic DNA before sequencing. The core idea is to exploit the self versus nonself differentiation by natural bacterial DNA methylation and rationally choose methylation-sensitive restriction enzymes, individually or in combination, to deplete host and background taxa while enriching targeted taxa. This idea is integrated with library preparation procedures and applied in several applications to enrich (up to 117-fold) pathogenic or beneficial bacteria from human urine and fecal samples, including species that are hard to culture or of low abundance. We assessed 4,601 bacterial strains with mapped methylomes so far and showed broad applicability of mEnrich-seq. mEnrich-seq provides microbiome researchers with a versatile and cost-effective approach for selective sequencing of diverse taxa of interest.

In an era of head and neck oncology where HPV status will soon dictate patient management, reliable HPV detection is critical. P16 immunohistochemistry (IHC) is currently recommended as the test of choice for oropharyngeal squamous cell carcinomas (OPSCCs). The purpose of this study was to determine the performance characteristics of p16 IHC based on a large clinical experience of squamous cell carcinomas (SCC) arising from HPV hot-spot regions of the head and neck. Consecutive OPSCCs, sinonasal SCCs, and metastatic SCCs of unknown primary sites were evaluated for the presence of HPV by p16 IHC and PCR-based HPV DNA testing as part of clinical care. For discrepant cases, high-risk HPV E6/E7 mRNA in situ hybridization (ISH) and, when possible, matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MassArray) genotyping were performed. 746 cancers underwent HPV testing by p16 IHC and DNA PCR genotyping. There was a 95.6% concordance between the 2 assays. Of the 33 discrepant cases, 32 cases (4.3%) were p16 positive but HPV DNA negative. In these cases, 68% were positive for mRNA ISH, invariably related to a non-16 HPV genotype. P16 IHC had an overall accuracy of 98.8%, a sensitivity of 99.8%, and a specificity of 92.1%. P16 IHC is a sensitive and specific assay for determining HPV status. HPV DNA PCR appears vulnerable to HPV genotype diversity and is prone to missing rare non-16 genotypes. HPV mRNA ISH is a practical and reliable direct measure of HPV that may help eliminate the small number of false-positive p16 cases and avoid potential patient harm related to erroneous HPV classification.

Medical microbiologists, defined as doctoral-level laboratory directors with subspecialty training in medical microbiology, lead the clinical laboratory operations through activities such as clinical consultations, oversight of diagnostic testing menu, institutional leadership, education, and scholastic activities. However, unlike their clinical colleagues, medical microbiologists are largely unable to bill for clinical consultations performed within the hospital and, therefore, unable to generate relative value units or a similar quantifiable metric. As hospital budgets tighten and justification of staffing becomes a necessity, this may present a challenge to the medical microbiologist attempting to prove their value to the organization. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. Consults were generated equally from internal (laboratory-based) and external (hospital-based) parties, with the majority directly impacting patient management. Near universal acceptance of the medical microbiologist's recommendation highlights the worth derived from their expertise. External consults required more time commitment from the medical microbiologist than internal consults, although both presented ample opportunity for secondary value, including impact through stewardship, education, clinical guidance, and cost reduction. This study is a description of the content and impact of consultations that underscore the importance of the medical microbiologist as a key member of the healthcare team. IMPORTANCE:Medical microbiologists are invaluable to the clinical microbiology laboratory and the healthcare system as a whole. However, as medical microbiologists do not regularly generate relative value units, capturing and quantifying the value provided is challenging. As hospital budgets tighten, justification of staffing becomes a necessity. To aid in providing tangible data, the Personnel Standards and Workforce subcommittee of the American Society for Microbiology conducted a multi-center study across seven medical centers to document clinical consultations and their impact. To our knowledge, this is the first study to provide detailed evaluation of the consultative value provided by medical microbiologists.

AbstractBackgroundCytomegalovirus‐specific T‐cell‐mediated immunity (CMV‐CMI) protects from CMV infection in allogeneic hematopoietic cell transplantation (allo‐HCT), but to date, there is no validated measure of CMV immunity for this population.MethodsIn this prospective, observational, pilot study, CMV T‐cell responses were evaluated monthly and at onset of graft‐versus‐host disease (GVHD) or CMV infection in CMV‐seropositive allo‐HCT recipients using a commercial flow cytometry assay, the CMV inSIGHT T‐Cell Immunity Panel (CMV‐TCIP). The primary endpoint was the time to first positive CMV‐TCIP, defined as percentage of interferon‐γ‐producing CD4+ or CD8+ CMV‐specific T cells >0.2%. Letermovir was prescribed from day +10 to ≥100.ResultsTwenty‐eight allo‐HCT recipients were enrolled. The median time to first positive CMV‐TCIP result was earlier for CD4+ (60 days [interquartile range, IQR 33‒148]) than for CD8+ T cells (96 days [IQR 33‒155]) and longer for haploidentical and mismatched transplant recipients (77 and 96 days, respectively) than for matched donors (45 and 33 days, respectively). CD4+ and CD8+ CMV‐CMI recovery was sustained in 10/10 (100%) and 10/11 (91%) patients, respectively, without GVHD, whereas CD4+ and/or CD8+ CMV‐CMI was lost in 4/6 and 2/6 patients, respectively, with GVHD requiring steroids. As a predictor of clinically significant CMV infection in patients with low‐level CMV reactivation, the sensitivity and negative predictive value of CMV‐TCIP were 90% and 87.5%, respectively, for CD4+ CMV‐TCIP and 66.7% and 62.5%, respectively, for CD8+ CMV‐TCIP.ConclusionsThere was significant variability in time to CMV‐CMI recovery post‐HCT, with slower recovery after haploidentical and mismatched HCT. CD4+ CMV‐CMI may protect against CS‐CMVi, but immunity may be lost with GVHD diagnosis and treatment. image

Abstract Background Enterococcus faecalis isolates with an elevated penicillin minimum inhibitory concentration (MIC) ≥ 4 mg/L have decreased in vitro ampicillin plus ceftriaxone bactericidal and synergistic activity, despite ampicillin susceptibility. This phenotype’s implication on patient outcomes and prevalence in the US is unknown due to limited penicillin susceptibility reporting. Methods This was a retrospective cohort study of adult patients with E. faecalis bacteremia between August 20, 2018 and May 13, 2021 from the Mount Sinai Health System in New York City. Patients were excluded if they were discharged or deceased within 48 hours of index blood culture, did not receive active definitive therapy, or the blood culture was determined to be contamination. The primary outcome was differences in 30-day and 90-day mortality based on the penicillin MIC and the secondary outcome was microbiological relapse. Multivariable logistic regression was used to identify risk factors for 90-day mortality. Corresponding blood isolates were tested for penicillin susceptibility by broth microdilution in accordance with CLSI. Results A total of 124 patients were included, with 27% having an elevated penicillin MIC ≥ 4 mg/L. Differences in baseline characteristics (Table 1) as well as source of infection and treatments received (Table 2) were similar between groups. Endocarditis infected 18.5% of patients and was less common in cases with an elevated penicillin MIC. Thirty-day and 90-day mortality, and microbiological relapse were higher in cases with an elevated penicillin MIC (14.4% vs. 20.6%, p=0.58; 20% vs. 26.5%, p=0.59; and 4.4% vs. 8.8%, p=0.39, respectively). Pitt bacteremia score and prior ceftriaxone usage had a higher odds of 90-day mortality (OR 1.2 [95% CI 1.03-1.4], p=0.02; OR 2.8 [95% CI 1.02-7.9], p=0.04, respectively), whereas definitive treatment with an aminopenicillin compared to piperacillin/tazobactam was protective of 90-day mortality (OR 0.21 [95% CI 0.05-0.93], p=0.04). Conclusion E. faecalis with an elevated penicillin MIC ≥ 4 mg/L is present in over a quarter of patients across New York City. Larger studies are warranted to determine the impact on patient outcomes. E. faecalis bacteremia treatment with piperacillin/tazobactam may be associated higher mortality. Disclosures Jaclyn A. Cusumano, PharmD, BCIDP, Shionogi: Advisor/Consultant

Abstract Background GenMark ePlex BCID panels detect common gram-positive resistance genes, allowing for earlier optimization of empiric therapy. Data regarding genotypic and phenotypic concordance of isolates remains limited. Our primary objective was to study the prevalence of mecA and mecC among Staphylococcus aureus isolates and of vanA and vanB among Enterococcus spp. and determine the concordance with phenotypic susceptibility profiles. Methods The study was conducted at the clinical microbiology laboratory of Mount Sinai Health System (NY, NY). Samples were collected between March 2019 and April 2021. Presumptive identification and molecular data were obtained from ePlex BCID Panels and compared to phenotypic susceptibility testing performed on Vitek or Microscan systems. Results Data were obtained from 1493 isolates tested on the GenMark ePlex BCID gram positive panels. The total prevalence of mecA in Staphylococcus aureus isolates was 460/989 = 46.5%. There was no mecC detected. Of the 460 mecA positive S. aureus isolates, 99% were oxacillin resistant and 1.0% were oxacillin susceptible. Of the 529 mecA negative S. aureus isolates, 98.5% were oxacillin susceptible and 1.5% were oxacillin resistant. The total prevalence of vanA in enterococcus isolates was 38% (193/504), 81% were detected in E. fecium sp, 17% in E. fecalis sp, 0.5% in E. gallinarium sp and 1.5% in E. raffinosus sp. The total prevalence of vanB was 1.1% (6/504). E. faecium accounted for 83% and E. faecalis for 16% of the isolates. Of the vanA positive isolates, 7/193 (3.6%) were vancomycin susceptible, 2 were e. fecalis and 5 were e. fecium species. None of the isolates in which vanB detected were vancomycin susceptible. No van gene was detected in 305 of enterococcus isolates. Of these, 250/305 (81%) were E. faecalis sp and 36/305 (11%) were E. faecium sp. 290/305 total isolates were vancomycin susceptible and 15 were vancomycin resistant, of which 12/15 were E. gallinarum and E. avium (which are intrinsically resistant), 1 was E. faecium and 2 were E. faecalis. Conclusion Our data shows overall that the susceptibility profile and resistance gene detection by ePlex correlated well with overall minimal discordance. Further studies are needed to determine the optimal management when phenotypic genotypic discordance occurs. Disclosures Meenakshi M. Rana, MD, Eli Lilly: advisory board

Abstract Background This is a systematic review and meta-analysis of diagnostic test accuracy studies to assess the predictive value of both tuberculin skin test (TST) and interferon-gamma release assays (IGRA) for active tuberculosis (TB) among solid organ transplantation (SOT) recipients. Methods Medline, Embase, and the CENTRAL databases were searched from 1946 until June 30, 2022. Two independent assessors extracted data from studies. Sensitivity analyses were performed to investigate the effect of studies with high or low risk of bias. Methodological quality of each publication was assessed using QUADAS-2. Results A total of 43 studies (36 403 patients) with patients who were screened for latent TB infection (LTBI) and who underwent SOT were included: 18 were comparative and 25 noncomparative (19 TST, 6 QuantiFERON-TB Gold In-Tube [QFT-GIT]). For IGRA tests taken together, positive predictive value (PPV) and negative predictive value (NPV) were 1.2% and 99.6%, respectively. For TST, PPV was 2.13% and NPV was 95.5%. Overall, PPV is higher when TB burden is higher, regardless of test type, although still low in absolute terms. Incidence of active TB was similar between studies using LTBI prophylaxis (mean incidence 1.22%; 95% confidence interval [CI], .2179–2.221) and those not using prophylaxis (mean incidence 1.045%; 95% CI, 0.2731–1.817; P = .7717). Strengths of this study include the large number of studies available from multiple different countries; limitations include absence of gold standard for diagnosis of latent TB and low incidence of active TB. Conclusions We found both TST and IGRA had a low PPV and high NPV for the development of active TB posttransplant. Further studies are needed to better understand how to prevent active TB in the SOT population.

Abstract This case–control study of 25 cases with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with vancomycin minimum inhibitory concentration (MIC) ≥ 2 µg/mL and 391 controls (MIC < 2 µg/mL) characterized the clinical characteristics, treatments, and outcomes associated with elevated vancomycin MIC. Elevated vancomycin MIC was associated with baseline hemodialysis, prior MRSA colonization, and metastatic infection.

Objective:Dual carbapenemase-producing organisms (DCPOs) are an emerging threat that expands the spectrum of antimicrobial resistance. There is limited literature on the clinical and genetic epidemiology of DCPOs. Methods:DCPO isolates were identified by Xpert® Carba-R PCR testing of routine diagnostic cultures performed from 2018 to 2021 at a New York City health system. WGS was performed by Illumina and/or PacBio. Medical records of patients were reviewed for clinical and epidemiological data. Results:Twenty-six DCPO isolates were obtained from 13 patients. Klebsiella pneumoniae (n = 22) was most frequent, followed by Pseudomonas aeruginosa (n = 2), Escherichia coli (n = 1) and Enterobacter cloacae (n = 1). The most common DCPO combination was blaNDM/blaOXA-48-like (n = 16). Notably, 1.05% (24/2290) of carbapenem-resistant Enterobacterales isolates were identified as DCPOs. The susceptibility profiles matched the identified resistance genes, except for a K. pneumoniae (blaKPC/blaOXA-48-like) isolate that was phenotypically susceptible to meropenem. Eleven patients were hospitalized within the year prior to admission, and received antibiotic(s) 1 month prior. Seven patients were originally from outside the USA. Hypertension, kidney disease and diabetes were frequent comorbidities. Death in two cases was attributed to DCPO infection. WGS of eight isolates showed that carbapenemases were located on distinct plasmids, except for one K. pneumoniae isolate where NDM and KPC carbapenemases were located on a single IncC-type plasmid backbone. Conclusions:Here we characterized a series of DCPOs from New York City. Foreign travel, prior hospitalization, antibiotic usage and comorbidities were common among DCPO cases. All carbapenemases were encoded on plasmids, which may facilitate horizontal transfer.

Abstract Background: Febrile neutropenia (FN) is a medical emergency with significant morbidity and mortality for oncology patients, requiring comprehensive workup and timely antibiotic administration. We evaluated concordance with locally developed FN guidelines and outcomes of cancer patients admitted to general internal medicine at an academic teaching hospital. Methods: We conducted a retrospective observational cohort study of patients admitted between July 1, 2016, and June 30, 2017, for FN. Patients were classified as having low-risk or high-risk FN according to their malignancy and chemotherapy. Primary outcome was the proportion of patients receiving guideline-concordant antibiotics within 48 hours of admission to general internal medicine. Secondary outcomes were the proportion of patients in whom empirical antibiotics were active against pathogens isolated, rate of antibiotic-associated adverse events, and in-hospital mortality. We used logistic regression to model relationship between FN risk and guideline-concordant antibiotics. Results: Among 100 patients included, 34 (34%) were low-risk FN and 66 (66%) were high-risk. Proportion of guideline-concordant empirical antibiotics was significantly lower among low-risk FN patients than high-risk patients: 12 (35%) of 34 versus 47 (71%) of 66 (P = .001). Empirical antibiotics were active against 17 (94%) of 18 isolated pathogens. The mortality rate was 3%, and 16% of patients experienced antibiotic-associated adverse events. Hematological malignancy and infectious diseases–trained physician involvement were associated with guideline-concordant prescribing, with adjusted odds ratios of 3.76 (95% CI, 1.46–9.70; P = .006) and 3.71 (95% CI, 1.49–9.23; P = .005), respectively. Conclusions: Guideline concordance was low compared to published reports. Factors influencing appropriate antimicrobial prescribing in patients with FN warrant further exploration.

Abstract Background Plasma cell-free metagenomic next-generation sequencing (cf-mNGS) offers potential for rapid, noninvasive diagnosis of complex infections, though clinical impact remains incompletely characterized. Here, we describe impacts on diagnosis and antimicrobial management among patients evaluated with plasma cf-mNGS. Methods Patients evaluated with plasma cf-mNGS (Karius®) in the Mount Sinai Health System from January 1, 2019 to December 23, 2022 were included. Cases were each reviewed independently in the medical record by two investigators using a standardized data collection form with discrepancies adjudicated collectively. Data were analyzed descriptively. Results Plasma cf-mNGS was sent for 37 patients of whom 29 (78%) were immunocompromised. 26 (70%) had prior invasive diagnostics. Median time from admission to NGS was 15 days. NGS was positive in 24 cases (65%), with results reflecting 20 bacterial infections, 9 viral, and 4 fungal (14 monomicrobial, 10 polymicrobial). Results were deemed clinically relevant in 18 cases (49%) including 12 positive and 6 negative tests. Testing led to antimicrobial changes in 11 cases (30%), discontinuation in 3 cases (8%), and no change in 23 cases (62%). After plasma cf-mNGS (compared with prior), fewer patients received 3 or 4 antimicrobials, while more received 0, 1, or 2 antimicrobials (Fig. 1A); fewer patients received combined antibiotic/antifungal therapy, while more received no antimicrobials or antifungal therapy alone; there was no change in use of antibiotic therapy alone (Fig. 1B). Final diagnoses included 15 bacterial infections (41%), 9 fungal (24%), 0 viral, and 7 noninfectious conditions (19%). Final diagnoses were attributed to NGS in 6 cases (16%), other diagnostics in 9 cases (24%), and both NGS and other diagnostics in 6 cases (16%); in the latter group, NGS provided a diagnosis prior to another study in 3 cases by intervals of 13, 19, and 72 days, respectively. A. Changes in number of antimicrobials, B. Changes in classes of antimicrobials Conclusion Plasma cf-mNGS, as an adjunct to traditional methods, may provide unique or expedited diagnosis of bacterial or fungal infections, accelerate diagnosis of noninfectious conditions, or inform changes in broad-spectrum antimicrobial regimens. Continued study is warranted to delineate clinical impact and optimal use of plasma cf-mNGS. Disclosures All Authors: No reported disclosures

There is limited literature on corresponding results obtained from rapid molecular diagnostics with the antibiotic susceptibility profile. We reported a correlation between the results obtained from ePlex and the antibiograms against a large collection of Gram-negative bacteria. We reported that there can be a discrepancy in a small number of cases, but the clinical significance of that is unknown.

Background Healthcare-associated infections pose a potentially fatal threat to patients worldwide and Staphylococcus aureus is one of the most common causes of healthcare-associated infections. S. aureus is a common commensal pathogen and a frequent cause of bacteremia, with studies demonstrating that nasal and blood isolates from single patients match more than 80% of the time. Here we report on a contemporary collection of colonizing isolates from those with methicillin-resistant S. aureus (MRSA) bloodstream infections to evaluate the diversity within hosts, and detail the clinical features associated with concomitant nasal colonization. Methods Swabs of the bilateral anterior nares were obtained from patients diagnosed with MRSA bacteremia. A single colony culture from the blood and an average of 6 colonies from the nares were evaluated for MRSA growth. For the nares cultures, we typed multiple isolates for staphylococcal protein A ( spa ) and derived the clonal complexes. Demographic and clinical data were obtained retrospectively from the electronic medical record system and analysed using univariate and multivariable regression models. Results Over an 11-month period, 68 patients were diagnosed with MRSA bloodstream infection, 53 were swabbed, and 37 (70%) were colonized with MRSA in the anterior nares. We performed molecular typing on 213 nasal colonies. Spa types and clonal complexes found in the blood were also detected in the nares in 95% of the cases. We also found that 11% of patients carried more than one clone of MRSA in the nares. Male sex and history of prior hospitalization within the past 90 days increased odds for MRSA colonization. Conclusion The molecular epidemiological landscape of colonization in the setting of invasive disease is diverse and defining the interplay between colonization and invasive disease is critical to combating invasive MRSA disease.

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern have emerged. New variants pose challenges for diagnostic platforms because sequence diversity can alter primer/probe-binding sites (PBSs), causing false-negative results. The MassARRAY SARS-CoV-2 Panel (Agena Bioscience) uses RT-PCR and mass spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we use a data set of 256 SARS-CoV-2-positive specimens collected between April 11, 2021, and August 28, 2021, to evaluate target performance with paired sequencing data. During this time frame, two targets in the N gene (N2 and N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3'-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk, 20.02; 95% CI, 11.36 to 35.72; P < 0.0001). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3'-mismatch to the N2 probe PBS and increases target dropout risk (relative risk, 11.92; 95% CI, 8.17 to 14.06; P < 0.0001). These findings highlight the robust capability of MassARRAY SARS-CoV-2 Panel target results to reveal circulating virus diversity, and they underscore the power of multitarget design to capture variants of concern.

Candida auris is an urgent antimicrobial resistance threat due to its global emergence, high mortality, and persistent transmissions. Nearly half of C. auris clinical and surveillance cases in the United States are from the New York and New Jersey Metropolitan area. We performed genome, and drug-resistance analysis of C. auris isolates from a patient who underwent multi-visceral transplantation. Whole-genome comparisons of 19 isolates, collected over 72 days, revealed closed similarity (Average Nucleotide Identity. 0.9996; Aligned Percentage. 0.9764) and a distinct subcluster of NY C. auris South Asia Clade I. All isolates had azole-linked resistance in ERG11(K143R) and CDR1(V704L). Echinocandin resistance first appeared with FKS1(S639Y) mutation and then a unique FKS1(F635C) mutation. Flucytosine-resistant isolates had mutations in FCY1, FUR1, and ADE17. Two pan-drug-resistant C. auris isolates had uracil phosphoribosyltransferase deletion (FUR1[1 Delta 33]) and the elimination of FUR1 expression, confirmed by a qPCR test developed in this study. Besides ERG11 mutations, four amphotericin B-resistant isolates showed no distinct nonsynonymous variants suggesting unknown genetic elements driving the resistance. Pan-drug-resistant C. auris isolates were not susceptible to two-drug antifungal combinations tested by checker-board, Etest, and time-kill methods. The fungal population pattern, discerned from SNP phylogenetic analysis, was consistent with in-hospital or inpatient evolution of C. auris isolates circulating locally and not indicative of a recent introduction from elsewhere. The emergence of pan-drug-resistance to four major classes of antifungals in C. auris is alarming. Patients at high risk for drug-resistant C. auris might require novel therapeutic strategies and targeted pre-and/or posttransplant surveillance.

Background: Pandemics are unpredictable and can rapidly spread. Proper planning and preparation for managing the impact of outbreaks is only achievable through continuous and systematic collection and analysis of health-related data. We describe our experience on how to comply with required reporting and develop a robust platform for surveillance data during an outbreak. Materials and Methods: At Mount Sinai Health System, New York City, we applied Visiun, a laboratory analytics dashboard, to support main response activities. Epic System Inc.’s SlicerDicer application was used to develop clinical and research reports. We followed World Health Organization (WHO); federal and state guidelines; departmental policies; and expert consultation to create the framework. Results: The developed dashboard integrated data from scattered sources are used to seamlessly distribute reports to key stakeholders. The main report categories included federal, state, laboratory, clinical, and research. The first two groups were created to meet government and state reporting requirements. The laboratory group was the most comprehensive category and included operational reports such as performance metrics, technician performance assessment, and analyzer metrics. The close monitoring of testing volumes and lab operational efficiency was essential to manage increasing demands and provide timely and accurate results. The clinical data reports were valuable for proper managing of medical surge requirements, such as healthcare workforce and medical supplies. The reports included in the research category were highly variable and depended on healthcare setting, research priorities, and available funding. We share a few examples of queries that were included in the designed framework for research projects. Conclusion: We reviewed here the key components of a conceptual surveillance framework required for a robust response to COVID-19 pandemics. We demonstrated leveraging a lab analytics dashboard, Visiun, combined with Epic reporting tools to function as a surveillance system. The framework could be used as a generic template for possible future outbreak events.

The continued circulation of SARS-CoV-2 amid limited surveillance efforts and inconsistent vaccination of populations has resulted in the emergence of variants that uniquely impact public health systems. Thus, in conjunction with functional and clinical studies, continuous detection and identification are quintessential to informing diagnostic and public health measures.

The last decade has seen an explosion of advanced assays for the diagnosis of infectious diseases, yet evidence-based recommendations to inform their optimal use in the care of transplant recipients are lacking. A consensus conference sponsored by the American Society of Transplantation (AST) was convened on December 7, 2021, to define the utility of novel infectious disease diagnostics in organ transplant recipients. The conference represented a collaborative effort by experts in transplant infectious diseases, diagnostic stewardship, and clinical microbiology from centers across North America to evaluate current uses, unmet needs, and future directions for assays in 5 categories including (1) multiplex molecular assays, (2) rapid antimicrobial resistance detection methods, (3) pathogen-specific T-cell reactivity assays, (4) next-generation sequencing assays, and (5) mass spectrometry-based assays. Participants reviewed and appraised available literature, determined assay advantages and limitations, developed best practice guidance largely based on expert opinion for clinical use, and identified areas of future investigation in the setting of transplantation. In addition, attendees emphasized the need for well-designed studies to generate high-quality evidence needed to guide care, identified regulatory and financial barriers, and discussed the role of regulatory agencies in facilitating research and implementation of these assays. Findings and consensus statements are presented.

Background: Screening for latent tuberculosis infection (LTBI) in patients with hematological malignancy is recommended because of their increased risk of tuberculosis (TB). We assessed the utility of tuberculin skin test (TST) screening in patients with acute leukemia and subsequent outcomes of LTBI treatment. Methods: We retrospectively evaluated patients ≥16 years of age with acute leukemia from 2013–2014 with a TST planted and read prior to the initiation of antineoplastic chemotherapy treatment. Demographics, clinical information and treatment outcomes of LTBI therapy were compared between patients with positive TST (≥10 mm induration) and negative TST. Results: A total of 389 patients with acute leukemia were included in the cohort. Of them, 37/389 (9.5%) had a positive TST. Only 3.4% (8/235) of individuals originating from North and South America as well as the Caribbean were TST positive, while 21% (20/95) of individuals from Asia were TST positive. Diagnostic imaging findings consistent with prior tuberculosis infection were higher in TST positive patients compared to TST negative ones (29.7% versus 9.4%, p < 0.0001). Furthermore, 31/38 patients (81.6%) who were TST positive received LTBI therapy, which was well tolerated. There was no significant difference in overall survival among those who received LTBI therapy compared to those who did not. No patients developed active TB. Conclusions: Universal screening with TST may be of low yield in individuals with acute leukemia unless patients originate from a TB endemic country. When therapy for LTBI is prescribed, patients with acute leukemia do not experience drug-induced liver toxicity and are likely to complete the intended duration of therapy, thus preventing the development of active tuberculosis.