Evidence of SARS-CoV-2 convergent evolution in immunosuppressed patients treated with antiviral therapies.

BACKGROUND: The factors contributing to the accelerated convergent evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not fully understood. Unraveling the contribution of viral replication in immunocompromised patients is important for the early detection of novel mutations and developing approaches to limit COVID-19. METHODS: We deep sequenced SARS-CoV-2 RNA from 192 patients (64% hospitalized, 39% immunosuppressed) and compared the viral genetic diversity within the patient groups of different immunity and hospitalization status. Serial sampling of 14 patients was evaluated for viral evolution in response to antiviral treatments. RESULTS: We identified hospitalized and immunosuppressed patients with significantly higher levels of viral genetic diversity and variability. Further evaluation of serial samples revealed accumulated mutations associated with escape from neutralizing antibodies in a subset of the immunosuppressed patients treated with antiviral therapies. Interestingly, the accumulated viral mutations that arose in this early Omicron wave, which were not common in the patient viral lineages, represent convergent mutations that are prevalent in the later Omicron sublineages, including the XBB, BA.2.86.1 and its descendent JN sublineages. CONCLUSIONS: Our results illustrate the importance of identifying convergent mutations generated during antiviral therapy in immunosuppressed patients, as they may contribute to the future evolutionary landscape of SARS-CoV-2. Our study also provides evidence of a correlation between SARS-CoV-2 convergent mutations and specific antiviral treatments. Evaluating high-confidence genomes from distinct waves in the pandemic with detailed patient metadata allows for discerning of convergent mutations that contribute to the ongoing evolution of SARS-CoV-2.

A qualitative study to explore the burden of disease in activated phosphoinositide 3-kinase delta syndrome (APDS).

BACKGROUND: Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare primary immunodeficiency, with only 256 cases reported globally. This study aimed to explore the disease burden of APDS from the perspective of individuals with APDS and their caregivers. METHODS: Qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers, to explore the symptoms and health-related quality of life (HRQoL) impact of APDS. Some individuals and caregivers also completed a narrative account exercise. All interviews were audio recorded and transcribed. Data were analysed using thematic analysis and saturation was recorded. RESULTS: Semi-structured qualitative interviews were conducted with healthcare providers (HCPs), individuals with APDS and caregivers. Individuals and caregivers had the option of completing a narrative account exercise. Six HCPs participated in an interview. Seven participants completed the narrative account exercise (N = 5 caregivers and N = 2 individuals with APDS) and 12 took part in an interview (N = 4 caregivers and N = 8 individuals with APDS). Themes identified from HCPs interviews included symptoms, clinical manifestations, HRQoL impacts and treatments/management of APDS. The narrative account exercise identified similar themes, but with the addition to the journey to diagnosis. These themes were explored during the individual/caregiver interviews. Reported clinical manifestations and symptoms of APDS included susceptibility to infections, lymphoproliferation, gastrointestinal (GI) disorders, fatigue, bodily pain, and breathing difficulties. HRQoL impacts of living with APDS included negative impacts to daily activities, including work, education and social and leisure activities, physical functioning, as well as emotional well-being, such as concern for the future, and interpersonal relationships. Impacts to caregiver HRQoL included negative impacts to physical health, work, emotional well-being, interpersonal relationships and family life and holidays. The management of APDS included the use of healthcare services and medications including immunoglobulin replacement therapy (IRT), rapamycin, prophylactic antibiotics, leniolisib, as well as medical procedures due to complications. CONCLUSIONS: APDS has a high disease burden and there is an unmet need for licensed, more targeted treatments which modify disease progression. This study was the first to describe the day-to-day experience and HRQoL impact of APDS from the perspective of individuals living with the condition, caregivers and treating physicians.

Guide to Utilization of the Microbiology Laboratory for Diagnosis of Infectious Diseases: 2024 Update by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM).

The critical nature of the microbiology laboratory in infectious disease diagnosis calls for a close, positive working relationship between the physician and the microbiologists who provide enormous value to the health care team. This document, developed by experts in both adult and pediatric laboratory and clinical medicine, provides information on which tests are valuable and in which contexts, and on tests that add little or no value for diagnostic decisions. Sections are divided into anatomic systems, including Bloodstream Infections and Infections of the Cardiovascular System, Central Nervous System Infections, Ocular Infections, Soft Tissue Infections of the Head and Neck, Upper Respiratory Infections, Lower Respiratory Tract infections, Infections of the Gastrointestinal Tract, Intraabdominal Infections, Bone and Joint Infections, Urinary Tract Infections, Genital Infections, and Skin and Soft Tissue Infections; or into etiologic agent groups, including arboviral Infections, Viral Syndromes, and Blood and Tissue Parasite Infections. Each section contains introductory concepts, a summary of key points, and detailed tables that list suspected agents; the most reliable tests to order; the samples (and volumes) to collect in order of preference; specimen transport devices, procedures, times, and temperatures; and detailed notes on specific issues regarding the test methods, such as when tests are likely to require a specialized laboratory or have prolonged turnaround times. In addition, the pediatric needs of specimen management are also addressed. There is redundancy among the tables and sections, as many agents and assay choices overlap. The document is intended to serve as a reference to guide physicians in choosing tests that will aid them to diagnose infectious diseases in their patients.

Multicenter evaluation of the Selux Next-Generation Phenotyping antimicrobial susceptibility testing system.

The Selux Next-Generation Phenotyping (NGP) system (Charlestown, MA) is a new antimicrobial susceptibility testing system that utilizes two sequential assays performed on all wells of doubling dilution series to determine MICs. A multicenter evaluation of the performance of the Selux NGP system compared with reference broth microdilution was conducted following FDA recommendations and using FDA-defined breakpoints. A total of 2,488 clinical and challenge isolates were included; gram-negative isolates were tested against 24 antimicrobials, and gram-positive isolates were tested against 15 antimicrobials. Data is provided for all organism-antimicrobial combinations evaluated, including those that did and did not meet FDA performance requirements. Overall very major error and major error rates were less than 1% (31/3,805 and 107/15,606, respectively), essential agreement and categorical agreement were >95%, reproducibility was ≥95%, and the average time-to-result (from time of assay start to time of MIC result) was 5.65 hours.

Estimating Changes in Weight and Metabolic Parameters Before and After Treatment With Cariprazine: A Retrospective Study of Electronic Health Records.

PURPOSE: Weight gain and associated negative cardiometabolic effects can occur as a result of mental illness or treatment with second-generation antipsychotics (SGAs), leading to increased rates of morbidity and mortality. In this analysis, we evaluated the effect of the SGA cariprazine on weight and metabolic parameters in a real-world, retrospective, observational dataset. METHODS: Electronic health records from the Optum Humedica database (October 1, 2014-December 31, 2020) were analyzed during the 12-month period before starting cariprazine (baseline) and for up to 12 months following cariprazine initiation; approved and off-label indications were included. Body weight trajectories were estimated in the overall patient cohort and at 3-, 6-, and 12-month timepoints (primary objective). Changes in hemoglobin A1c (HbA1c), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were also evaluated (secondary objectives). Percentages of patients with clinically relevant shifts in body weight, total cholesterol, and fasting triglycerides were also determined. Discontinuation rates for metabolic regulating medications were calculated. Average predicted values were estimated by linear mixed-effects regression models. FINDINGS: A total of 2,301 patients were included; average duration of follow-up was 133.7 days. Average predicted weight change for patients during the cariprazine overall follow-up period was +2.4 kg, with predicted weight changes of +0.8 kg (n = 811), +1.1 kg (n = 350), and +1.4 kg (n = 107) at months 3, 6, and 12, respectively. Overall, the majority of patients did not experience clinically significant (≥7%) weight gain (82.8%) or loss (90.5%) after starting cariprazine. Average predicted HbA1c levels (n = 189) increased during baseline (0.15%/year) and decreased during cariprazine treatment (-0.2%/year). Average predicted triglyceride levels (n = 257) increased during baseline (15.0 mg/dL/year) and decreased during cariprazine treatment (-0.7 mg/dL/year). Predicted LDL (n = 247) and HDL (n = 255) values decreased during baseline (-7.3 and -1.1 mg/dL/year, respectively); during cariprazine treatment, LDL increased by 5.6 mg/dL/year and HDL decreased by -0.6 mg/dL/year. During follow-up, most patients did not shift from normal/borderline to high total cholesterol (<240 to ≥240 mg/dL; 522 [90.2%]) or fasting triglyceride (<200 to ≥200 mg/dL; 143 [88.8%] patients) levels; shifts from high to normal/borderline levels occurred in 44 (61.1%) patients for total cholesterol and 38 (57.6%) patients for fasting triglycerides. After starting cariprazine, the discontinuation rate per 100 patient-years was 60.4 for antihyperglycemic medication and 87.4 for hyperlipidemia medication. IMPLICATIONS: These real-world results support short-term clinical trial findings describing a neutral weight and metabolic profile associated with cariprazine treatment and they expand the dataset to include long-term follow-up.

A conceptual framework for nomenclatural stability and validity of medically important fungi: a proposed global consensus guideline for fungal name changes supported by ABP, ASM, CLSI, ECMM, ESCMID-EFISG, EUCAST-AFST, FDLC, IDSA, ISHAM, MMSA, and MSGERC.

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the overarching species and that of the molecular sibling, often cryptic species. Because the use of different names for the same species will be unavoidable for many years to come, an open access online database of the names of all medically important fungi, with proper nomenclatural designation and synonymy, is essential. We further recommend that while taxonomic discovery continues, the adaptation of new name changes by clinical laboratories and clinicians be reviewed routinely by a standing committee for validation and stability over time, with reference to an open access database, wherein reasons for changes are listed in a transparent way.

Filling the gaps: A community case study in using an interprofessional approach and community-academic partnerships to address COVID-19-related inequities.

Public health challenges rapidly escalated during the COVID-19 pandemic. In response to a severe lack of resources and support in the near western suburbs of Chicago, the COVID Equity Response Collaborative: Loyola (CERCL) was established by an interprofessional team of Loyola University Chicago students, staff, and faculty. CERCL sought to minimize the negative impact of COVID-19 on vulnerable communities, those that are largely Black, Hispanic, or low-income. From April 2020 to the present, the collaborative utilized community-academic partnerships and interdisciplinary collaborations to conduct programming. CERCL's programming included free community-based testing, screening for and assistance with social determinants of health, dissemination of relevant and reliable COVID-related information, provision of personal protective equipment, and facilitation of access to vaccines. With partners, the collaborative conducted 1,500 COVID-19 tests, trained 80 individuals in contact tracing, provided over 100 individuals with specifically tailored resources to address social and legal needs, distributed 5,000 resource bags, held 20 community conversations, canvassed 3,735 homes, and hosted 19 vaccine clinics. Community-academic partnerships with the health system, community and governmental agencies, and the local public health department have been critical to CERCL efforts. The interdisciplinary and interprofessional successes demonstrated in this case study lends the example of a relevant, sustainable, and practical intervention to address nuanced public health issues.

Treatment patterns, health care resource utilization, and costs associated with use of atypical antipsychotics as first vs subsequent adjunctive treatment in major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a highly prevalent mental health condition associated with substantial economic burden. Inadequate response to first-line antidepressant monotherapy is common, with most patients requiring 1 or more changes in their treatment regimen. Adjunctive treatment with atypical antipsychotics (AAs) is a guideline-recommended treatment option in patients with inadequate response. However, patients often cycle through multiple treatments before receiving adjunctive AAs, and the economic impact of this delay is unknown. OBJECTIVE: To describe adjunctive treatment patterns among patients with MDD and compare health care resource utilization (HCRU) and costs between patients whose first adjunctive therapy included an AA and those who received an AA after other adjunctive treatments. METHODS: The Merative MarketScan Commercial Database (January 1, 2014, to June 30, 2019) was used to identify patients with administrative claims meeting the following inclusion criteria: adults with newly diagnosed MDD (first observed MDD diagnosis = index diagnosis date); continuous health insurance for at least 6 months pre-index and at least 3 months post-index; and initiation of MDD treatment within 60 days post-index. Lines of therapy (LOTs), HCRU, and costs were analyzed in patients who received AA adjunctive therapy, including those who initiated AAs as the first adjunctive treatment and those who initiated AAs as subsequent adjunctive treatment. RESULTS: Of 508,830 patients meeting inclusion criteria, 121,060 (24%) received adjunctive treatment and 20,797 (4%) received an AA as adjunctive therapy. Mean time to adjunctive therapy initiation was approximately 7.3 months for AA adjunctive therapy. Patients who initiated an AA as their first adjunctive therapy compared with patients who initiated an AA as their subsequent adjunctive therapy had fewer LOTs on average (0.9 LOTs vs 3.9 LOTs) and shorter time between index diagnosis date and initiation of an AA (5 months vs 12 months). Subsequent AA initiators had significantly greater HCRU than first AA initiators (driven primarily by outpatient visits) and incurred significantly higher total health care costs, with mean all-cause and mental health-related health care cost differences per patient per year of $2,441 and $1,762, respectively (both P < 0.05). CONCLUSIONS: Less than 5% of patients in this study received an adjunctive AA as part of their MDD treatment regimen, suggesting underutilization of this recommended therapeutic approach. Patients who received an AA as their first adjunctive treatment regimen had lower HCRU and health care costs than subsequent AA initiators. Along with published evidence of clinical benefits, this potential impact on economic burden should be considered when making treatment choices for patients with inadequate response to antidepressants.

Multicenter Evaluation of the BIOFIRE Blood Culture Identification 2 Panel for Detection of Bacteria, Yeasts, and Antimicrobial Resistance Genes in Positive Blood Culture Samples.

Diagnostic tools that can rapidly identify and characterize microbes growing in blood cultures are important components of clinical microbiology practice because they help to provide timely information that can be used to optimize patient management. This publication describes the bioMérieux BIOFIRE Blood Culture Identification 2 (BCID2) Panel clinical study that was submitted to the U.S. Food & Drug Administration. Results obtained with the BIOFIRE BCID2 Panel were compared to standard-of-care (SoC) results, sequencing results, PCR results, and reference laboratory antimicrobial susceptibility testing results to evaluate the accuracy of its performance. Results for 1,093 retrospectively and prospectively collected positive blood culture samples were initially enrolled, and 1,074 samples met the study criteria and were included in the final analyses. The BIOFIRE BCID2 Panel demonstrated an overall sensitivity of 98.9% (1,712/1,731) and an overall specificity of 99.6% (33,592/33,711) for Gram-positive bacteria, Gram-negative bacteria and yeast targets which the panel is designed to detect. One hundred eighteen off-panel organisms, which the BIOFIRE BCID2 Panel is not designed to detect, were identified by SoC in 10.6% (114/1,074) of samples. The BIOFIRE BCID2 Panel also demonstrated an overall positive percent agreement (PPA) of 97.9% (325/332) and an overall negative percent agreement (NPA) of 99.9% (2,465/2,767) for antimicrobial resistance determinants which the panel is designed to detect. The presence or absence of resistance markers in Enterobacterales correlated closely with phenotypic susceptibility and resistance. We conclude that the BIOFIRE BCID2 Panel produced accurate results in this clinical trial.

Place of care and costs associated with acute episodes and remission in schizophrenia.

BACKGROUND: Schizophrenia imposes significant economic burden on patients, families, caregivers, and society. To our knowledge, place of care and associated costs of acute schizophrenia episodes have not been well characterized. OBJECTIVE: To describe the care settings and costs associated with likely acute episodes and untreated remission periods among patients with schizophrenia. METHODS: Adults with schizophrenia were identified using the IBM MarketScan Commercial and Medicare Supplemental databases (2009-2018); claims for capitated benefits plans were excluded. Acute episode index date was defined as at least 1 inpatient schizophrenia claim or outpatient schizophrenia claim (frequency of claim dependent on visit type, such as hospitalization, emergency department, private practice, clinic, urgent care, or laboratory). Mental health-related medical costs (health plan+patient) associated with acute episodes were collected over a 2-month follow-up period and stratified by setting (inpatient vs outpatient); acute episode data were reported in subgroups of patients without or with prior clozapine use, as an indication of disease severity. Remission index date was defined as at least 1 outpatient claim with a schizophrenia diagnosis with no acute episode and no oral or injectable antipsychotic therapy. Remission costs were assessed over a 3-month period. All data were analyzed descriptively. RESULTS: A total of 14,824 patients with schizophrenia met criteria for an acute episode (12,896 [87.0%] without prior clozapine use; 1,427 [9.6%] with prior clozapine use). Most acute episodes were treated in an outpatient setting (all patients, 76.3%; without prior clozapine use, 74.5%; with prior clozapine use, 87.1%). When treated inpatient, mean (SD) episode medical costs were $17,045 ($28,101) for all patients, $16,060 ($22,786) for those without prior clozapine use, and $22,827 ($55,860) for those with prior clozapine use. When treated outpatient, mean (SD) medical costs for acute episodes were $2,478 ($6,961) for all patients, $2,609 ($7,068) for those without prior clozapine use, and $1,770 ($6,560) for those with prior clozapine use. For all patients with acute episodes, regardless of clozapine use, patient-incurred out-of-pocket costs were approximately 30% of total medical costs. For an untreated period of remission, 6,950 patients with schizophrenia met criteria. Total medical costs were $2,399 for these patients over a 3-month period. CONCLUSIONS: The majority of acute schizophrenia episodes were treated in the outpatient setting. For episodes that required inpatient care, inpatient episodes were approximately 7 times more costly than episodes treated in outpatient-only settings. For acute episodes and remission periods, health plans covered most costs; however, there were additional patient-incurred out-of-pocket costs. DISCLOSURES: All authors met the International Committee of Medical Journal Editors authorship criteria. Neither honoraria nor payments were made for authorship. Dr McIntyre has received research grant support from CIHR/GACD/National Natural Science Foundation of China (NSFC) and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular, NewBridge Pharmaceuticals, Viatris, AbbVie, Atai Life Sciences. Dr McIntyre is a CEO of Braxia Scientific Corp. Mr Doan, Dr Amari, and Mr Mercer are employees of Genesis Research, which was funded to perform the study. Ms Higa, Dr Gillard, and Dr Harrington were employees of AbbVie at the time of the study and may hold stock. This study was sponsored by AbbVie.

Screening for Bipolar I Disorder and the Rapid Mood Screener: Results of a Nationwide Health Care Provider Survey.

Objective: Effective screening for bipolar I disorder can lead to enhanced assessment, improved diagnosis, and better patient outcomes. The Rapid Mood Screener (RMS), a new bipolar I disorder screening tool, was evaluated in a nationwide survey of health care providers (HCPs).Methods: Eligible HCPs were asked to describe their opinions/current use of screening tools, assess the RMS, and evaluate the RMS versus the Mood Disorder Questionnaire (MDQ). Results were stratified by primary care and psychiatric specialty. Findings were reported using descriptive statistics; statistical significance was reported at the 95% confidence level.Results: Among respondents (N = 200), 82% used a tool to screen for major depressive disorder (MDD), while 32% used a tool for bipolar disorder. Most HCPs were aware of the MDQ (85%), but only 29% reported current use. According to HCPs, the RMS was significantly better than the MDQ on all screening tool attributes (eg, sensitivity/specificity, brevity, practicality, easy scoring; P < .05 for all). Significantly more HCPs reported that they would use the RMS versus the MDQ (81% vs 19%, P < .05); 76% reported that they would screen new patients with depressive symptoms, and 68% indicated they would rescreen patients with a depression diagnosis. Most HCPs (84%) said the RMS would have a positive impact on their practice, with 46% saying they would screen more patients for bipolar disorder.Discussion: In our survey, the RMS was favorably evaluated by HCPs. A large percentage of respondents preferred the RMS over the MDQ and indicated that it would likely have a positive impact on clinicians' screening behavior.

Total healthcare cost savings through improved bipolar I disorder identification using the Rapid Mood Screener in patients diagnosed with major depressive disorder.

INTRODUCTION: Misdiagnosis of bipolar I disorder (BP-I) as major depressive disorder (MDD) leads to increased healthcare resource utilization and costs. The cost-effectiveness of the Rapid Mood Screener (RMS), a tool to identify BP-I in patients with depressive symptoms, was assessed in patients diagnosed with MDD presenting with depressive episodes. METHODS: A decision-tree model of a hypothetical cohort of 1000 patients in a US health plan was used to estimate the number of correct diagnoses and overall total, direct healthcare costs over a 3-year timeframe for RMS-screened versus unscreened patients. Model inputs included the prevalence of BP-I in patients diagnosed with MDD, RMS sensitivity/specificity, and the cost of misdiagnosing BP-I as MDD. RESULTS: Screening with the RMS resulted in 171, 159, and 143 additional correct BP-I or MDD diagnoses at Years 1, 2, and 3, respectively. Total healthcare plan cost savings were $1279 per patient in Year 1. Cumulative cost savings per patient for RMS screening versus no RMS screening were $2307 over 2 years and $3011 over 3 years. Scenario analyses showed that the RMS would remain cost-saving assuming a lower prevalence of BP-I (20% or 10%) versus the base case (24.3%). CONCLUSION: The RMS is a cost-effective tool to identify BP-I in patients who would otherwise be misdiagnosed with MDD. Screening with the RMS resulted in cost-savings over 3 years, with model results remaining robust even with lower prevalence of BP-I and reduced RMS sensitivity assumptions.

In vitro susceptibility of carbapenem resistant Enterobacterales to meropenem-vaborbactam and ceftazidime-avibactam at a single academic medical centre.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are considered an urgent threat. Ceftazidime-avibactam and meropenem-vaborbactam contain ß-lactamase inhibitors active against CRE isolates including those that produce Klebsiella pneumoniae carbapenemases (KPC). METHODS: Retrospective chart review of CRE isolates from 1 January 2016 to 1 November 2018. Collected data includes a descriptive overview of measured MIC values, resistance mechanism via a polymerase chain reaction test (Xpert Carba-R, Cepheid, Sunnyvale CA), as well as clinical outcomes. RESULTS: Of 106 isolates reviewed, 86 isolates met the inclusion criteria from 85 individual subjects. The breakpoint:MIC ratio for ceftazidime-avibactam overall was 4, while for meropenem-vaborbactam this ratio was 32 (p < 0.0001). For KPC isolates, ceftazidime-avibactam MIC50/MIC90 in 2016, 2017, and 2018 were 2/4 mg/L (n = 32), 2/4 mg/L (n = 17), and 2/8 mg/L (n = 30), respectively. The meropenem-vaborbactam MIC50/MIC90, for KPC isolates in 2016, 2017, and 2018 were 0.06/0.125 mg/L (n = 32), 0.06/0.1 mg/L (n = 17), and 0.06/0.5 mg/L (n = 30), respectively. Microbiologic cure was 75% (n = 16) in ceftazidime-avibactam subjects and 58.3% (n = 12) in subjects treated with alternative agents (p = 0.43). The 14- and 30-day mortality was numerically higher in subjects treated with alternate agents when compared ceftazidime-avibactam 2/9 (22.2%) vs 3/17 (17.6%) (p = 1.00) and 4/9 (44.4%) vs 4/17 (28.6%) (p = 0.38), respectively. For ceftazidime-avibactam, 30-day mortality in 2016, 2017, and 2018 was 0/5 (0%), 0/2 (0%), and 4/10 (40%). CONCLUSION: Selective pressure from the use of ceftazidime-avibactam at our institution may be decreasing its utility as a first-line agent for CRE infections. Meropenem-vaborbactam maintained low MIC values and may be a promising treatment option for CRE.

Disseminated Protothecosis Due to Prototheca zopfii and Literature Review.

ABSTRACT: Prototheca species are achlorophyllic algae that are a rare cause of infection in humans. It most commonly causes localized cutaneous disease and rarely disseminated infection. Immunocompromised patients have the highest risk of disseminated protothecosis, with a higher mortality rate than localized cutaneous infections. At the species level, infections caused by Prototheca zopfii are reported less frequently than those caused by Prototheca wickerhamii. The diagnosis can be made using histopathology, culture, and molecular testing. There is no definitive evidence for an effective treatment, which currently consists of antifungals (primarily amphotericin B). With only a handful of cases of disseminated protothecosis reported worldwide that are caused by P. zopfii , we herein present an additional case of a postbone marrow transplant patient in the Midwest of the United States.

Effect of Torsemide vs Furosemide After Discharge on All-Cause Mortality in Patients Hospitalized With Heart Failure: The TRANSFORM-HF Randomized Clinical Trial.

Importance: Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. Objective: To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. Design, Setting, and Participants: TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Interventions: Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. Main Outcomes and Measures: The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. Results: TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Conclusions and Relevance: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Trial Registration: ClinicalTrials.gov Identifier: NCT03296813.

Evaluation of Piperacillin-Tazobactam Testing against Enterobacterales by the Phoenix, MicroScan, and Vitek2 Tests Using Updated Clinical and Laboratory Standards Institute Breakpoints.

In 2022, the Clinical and Laboratory Standards Institute (CLSI) updated piperacillin-tazobactam (TZP) breakpoints for Enterobacterales, based on substantial data suggesting that historical breakpoints did not predict treatment outcomes for TZP. The U.S. Food and Drug Administration (FDA) has not yet adopted these breakpoints, meaning commercial manufacturers of antimicrobial susceptibility testing devices cannot obtain FDA clearance for the revised breakpoints. We evaluated the Phoenix (BD, Sparks, MD), MicroScan (Beckman Coulter, Sacramento, CA), and Vitek2 (bioMérieux, Durham, NC) TZP MICs compared to reference broth microdilution for a collection of 284 Enterobacterales isolates. Phoenix (n = 167 isolates) demonstrated 84.4% categorical agreement (CA), with 4.2% very major errors (VMEs) and 1.8% major errors (MEs) by CLSI breakpoints. In contrast, CA was 85.0% with 4.3% VMEs and 0.8% MEs for the Phoenix with FDA breakpoints. MicroScan (n = 55 isolates) demonstrated 80.0% CA, 36.4% VMEs, and 4.8% MEs by CLSI breakpoints and 81.8% CA, 44.4% VMEs, and 0.0% MEs by FDA breakpoints. Vitek2 (n = 62 isolates) demonstrated 95.2% CA, 6.3% VMEs, and 0.0% MEs by CLSI and 96.8% CA, 0.0% VMEs, and 2.2% MEs by FDA breakpoints. Overall, the performance of the test systems was not substantially different using CLSI breakpoints off-label than using on-label FDA breakpoints. However, limitations were noted with higher-than-desired VME rates (all three systems) and lower-than-desired CA (MicroScan and Phoenix). Laboratories should consider adoption of the revised CLSI breakpoints with automated test systems but be aware that some performance challenges exist for testing TZP on automated systems, regardless of breakpoints applied.