A multi-species outbreak of VIM-producing carbapenem-resistant bacteria in a burn unit and subsequent investigation of rapid development of cefiderocol resistance.

Carbapenem resistance due to metallo-ß-lactamases (MBLs) such as the Verona integron-encoded metallo-ß-lactamase (VIM) is particularly problematic due to the limited treatment options. We describe a case series of bacterial infections in a tertiary care hospital due to multi-species acquisition of a VIM gene along with our experience using novel ß-lactam antibiotics and antibiotic combinations to treat these infections. Four patients were treated with the combination of ceftazidime-avibactam and aztreonam, with no resistance to the combination detected. However, cefiderocol-resistant Klebsiella pneumoniae isolates were detected in two out of the five patients who received cefiderocol within 3 weeks of having started the antibiotic. Strain pairs of sequential susceptible and resistant isolates from both patients were analyzed using whole-genome sequencing. This analysis revealed that the pairs of isolates independently acquired point mutations in both the cirA and fiu genes, which encode siderophore receptors. These point mutations were remade in a laboratory strain of K. pneumoniae and resulted in a significant increase in the MIC of cefiderocol, even in the absence of a beta-lactamase enzyme or a penicillin-binding protein 3 (PBP3) mutation. While newer ß-lactam antibiotics remain an exciting addition to the antibiotic armamentarium, their use must be accompanied by diligent monitoring for the rapid development of resistance.

Cefepime vs Piperacillin-Tazobactam in Adults Hospitalized With Acute Infection: The ACORN Randomized Clinical Trial.

Importance: Cefepime and piperacillin-tazobactam are commonly administered to hospitalized adults for empirical treatment of infection. Although piperacillin-tazobactam has been hypothesized to cause acute kidney injury and cefepime has been hypothesized to cause neurological dysfunction, their comparative safety has not been evaluated in a randomized clinical trial. Objective: To determine whether the choice between cefepime and piperacillin-tazobactam affects the risks of acute kidney injury or neurological dysfunction. Design, Setting, and Participants: The Antibiotic Choice on Renal Outcomes (ACORN) randomized clinical trial compared cefepime vs piperacillin-tazobactam in adults for whom a clinician initiated an order for antipseudomonal antibiotics within 12 hours of presentation to the hospital in the emergency department or medical intensive care unit at an academic medical center in the US between November 10, 2021, and October 7, 2022. The final date of follow-up was November 4, 2022. Interventions: Patients were randomized in a 1:1 ratio to cefepime or piperacillin-tazobactam. Main Outcomes and Measures: The primary outcome was the highest stage of acute kidney injury or death by day 14, measured on a 5-level ordinal scale ranging from no acute kidney injury to death. The 2 secondary outcomes were the incidence of major adverse kidney events at day 14 and the number of days alive and free of delirium and coma within 14 days. Results: There were 2511 patients included in the primary analysis (median age, 58 years [IQR, 43-69 years]; 42.7% were female; 16.3% were Non-Hispanic Black; 5.4% were Hispanic; 94.7% were enrolled in the emergency department; and 77.2% were receiving vancomycin at enrollment). The highest stage of acute kidney injury or death was not significantly different between the cefepime group and the piperacillin-tazobactam group; there were 85 patients (n = 1214; 7.0%) in the cefepime group with stage 3 acute kidney injury and 92 (7.6%) who died vs 97 patients (n = 1297; 7.5%) in the piperacillin-tazobactam group with stage 3 acute kidney injury and 78 (6.0%) who died (odds ratio, 0.95 [95% CI, 0.80 to 1.13], P = .56). The incidence of major adverse kidney events at day 14 did not differ between groups (124 patients [10.2%] in the cefepime group vs 114 patients [8.8%] in the piperacillin-tazobactam group; absolute difference, 1.4% [95% CI, -1.0% to 3.8%]). Patients in the cefepime group experienced fewer days alive and free of delirium and coma within 14 days (mean [SD], 11.9 [4.6] days vs 12.2 [4.3] days in the piperacillin-tazobactam group; odds ratio, 0.79 [95% CI, 0.65 to 0.95]). Conclusions and Relevance: Among hospitalized adults in this randomized clinical trial, treatment with piperacillin-tazobactam did not increase the incidence of acute kidney injury or death. Treatment with cefepime resulted in more neurological dysfunction. Trial Registration: ClinicalTrials.gov Identifier: NCT05094154.

Principles and Practice of Antimicrobial Stewardship Program Resource Allocation.

Antimicrobial Stewardship Programs (ASP) improve individual patient outcomes and clinical care processes while reducing antimicrobial-associated adverse events, optimizing operational priorities, and providing institutional cost savings. ASP composition, resources required, and priority focuses are influenced by myriad factors. Despite robust evidence and broad national support, individual ASPs still face challenges in obtaining appropriate resources. Though understanding the current landscape of ASP resource allocation, factors influencing staffing needs, and strategies required to obtain desired resources is important, acceptance of recommended staffing levels and appropriate ASP resource allocation are much needed to facilitate ASP sustainability and growth across the complex and diverse health care continuum.

The Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D) at the Spallation Neutron Source (invited).

The Oak Ridge National Laboratory is planning to build the Second Target Station (STS) at the Spallation Neutron Source (SNS). STS will host a suite of novel instruments that complement the First Target Station's beamline capabilities by offering an increased flux for cold neutrons and a broader wavelength bandwidth. A novel neutron imaging beamline, named the Complex, Unique, and Powerful Imaging Instrument for Dynamics (CUPI2D), is among the first eight instruments that will be commissioned at STS as part of the construction project. CUPI2D is designed for a broad range of neutron imaging scientific applications, such as energy storage and conversion (batteries and fuel cells), materials science and engineering (additive manufacturing, superalloys, and archaeometry), nuclear materials (novel cladding materials, nuclear fuel, and moderators), cementitious materials, biology/medical/dental applications (regenerative medicine and cancer), and life sciences (plant-soil interactions and nutrient dynamics). The innovation of this instrument lies in the utilization of a high flux of wavelength-separated cold neutrons to perform real time in situ neutron grating interferometry and Bragg edge imaging-with a wavelength resolution of δλ/λ ≈ 0.3%-simultaneously when required, across a broad range of length and time scales. This manuscript briefly describes the science enabled at CUPI2D based on its unique capabilities. The preliminary beamline performance, a design concept, and future development requirements are also presented.

An app a day: Results of pre- and post-surveys of knowledge, attitudes, and practices (KAP) regarding antimicrobial stewardship principles among nurses who utilized a novel learning platform.

Background: Nurses perform several functions that are integral for antimicrobial stewardship (AMS). However, nurses are underrepresented in research and underutilized in implementation of AMS interventions. The objective of this pilot study was to assess the effect of asynchronous microlearning on inpatient nursing staff knowledge, attitudes, and practices (KAP) regarding AMS principles. Methods: A team of pharmacists, physicians, and nurses developed 9 case-based, multiple-choice questions with accompanying educational explanations on associated AMS principles. One case was delivered to participants daily via an institutional web-based application (QuizTime). A KAP survey with 20 questions on a 5-point Likert scale was administered before and after the intervention. Survey results were compared using a Wilcoxon signed-rank test. Results: Participants' mean survey score after the intervention demonstrated statistically significant improvement for 18 (90%) of 20 items compared to before the intervention. Participants' confidence improved in key AMS activities: (1) differentiating between colonization and infection (mean difference, 0.63; P < .001), (2) identifying unnecessary urine cultures and inappropriate treatment of urinary tract infections (mean difference, 0.94; P < .001), (3) recognizing opportunities for intravenous to oral therapy conversion (mean difference, 1.07; P < .001), and (4) assessing for antibiotic-associated adverse effects (mean difference, 0.54; P < .001). Conclusions: Nursing education provided through an asynchronous, microlearning format via a mobile platform resulted in statistically significant improvement in most KAP topics. Nurses are integral members of a multidisciplinary AMS team, and novel education methods can help equip them with the necessary AMS tools. This pilot study forms the basis for expanded AMS educational efforts in all healthcare professionals.

Protocol and statistical analysis plan for the Antibiotic Choice On ReNal outcomes (ACORN) randomised clinical trial.

INTRODUCTION: Antibiotics are time-critical in the management of sepsis. When infectious organisms are unknown, patients are treated with empiric antibiotics to include coverage for gram-negative organisms, such as antipseudomonal cephalosporins and penicillins. However, in observational studies, some antipseudomonal cephalosporins (eg, cefepime) are associated with neurologic dysfunction while the most common antipseudomonal penicillin (piperacillin-tazobactam) is associated with acute kidney injury (AKI). No randomised control trials have compared these regimens. This manuscript describes the protocol and analysis plan for a trial designed to compare the effects of antipseudomonal cephalosporins and antipseudomonal penicillins among acutely ill patients receiving empiric antibiotics. METHODS AND ANALYSIS: The Antibiotic Choice On ReNal outcomes trial is a prospective, single-centre, non-blinded randomised trial being conducted at Vanderbilt University Medical Center. The trial will enrol 2500 acutely ill adults receiving gram-negative coverage for treatment of infection. Eligible patients are randomised 1:1 to receive cefepime or piperacillin-tazobactam on first order entry of a broad-spectrum antibiotic covering gram-negative organisms. The primary outcome is the highest stage of AKI and death occurring between enrolment and 14 days after enrolment. This will be compared between patients randomised to cefepime and randomised to piperacillin-tazobactam using an unadjusted proportional odds regression model. The secondary outcomes are major adverse kidney events through day 14 and number of days alive and free of delirium and coma in 14 days after enrolment. Enrolment began on 10 November 2021 and is expected to be completed in December 2022. ETHICS AND DISSEMINATION: The trial was approved by the Vanderbilt University Medical Center institutional review board (IRB#210591) with a waiver of informed consent. Results will be submitted to a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: NCT05094154.

HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.

The development of an effective vaccine to protect against HIV acquisition will be greatly bolstered by in-depth understanding of the innate and adaptive responses to vaccination. We report here that the efficacy of DNA/ALVAC/gp120/alum vaccines, based on V2-specific antibodies mediating apoptosis of infected cells (V2-ADCC), is complemented by efferocytosis, a cyclic AMP (cAMP)-dependent antiphlogistic engulfment of apoptotic cells by CD14+ monocytes. Central to vaccine efficacy is the engagement of the CCL2/CCR2 axis and tolerogenic dendritic cells producing IL-10 (DC-10). Epigenetic reprogramming in CD14+ cells of the cyclic AMP/CREB pathway and increased systemic levels of miRNA-139-5p, a negative regulator of expression of the cAMP-specific phosphodiesterase PDE4D, correlated with vaccine efficacy. These data posit that efferocytosis, through the prompt and effective removal of apoptotic infected cells, contributes to vaccine efficacy by decreasing inflammation and maintaining tissue homeostasis.

Causal and putative pathogenic mutations identified in 39% of children with primary steroid-resistant nephrotic syndrome in South Africa.

There is a paucity of data identifying genetic mutations that account for the high rate of steroid-resistant nephrotic syndrome (SRNS) in a South African paediatric population. The aim was to identify causal mutations in genes implicated in SRNS within a South African paediatric population. We enrolled 118 children with primary nephrotic syndrome (NS), 70 SRNS and 48 steroid-sensitive NS. All children with SRNS underwent kidney biopsy. We first genotyped the NPHS2 gene for the p.V260E variant in all NS cases (n = 118) and controls (n = 219). To further identify additional variants, we performed whole-exome sequencing and interrogated ten genes (NPHS1, NPHS2, WT1, LAMB2, ACTN4, TRPC6, INF2, CD2AP, PLCE1, MYO1E) implicated in SRNS with histopathological features of focal segmental glomerulosclerosis (FSGS) in 56 SRNS cases and 29 controls; we also performed exome sequencing on two patients carrying the NPHS2 p.V260E mutation as positive controls. The overall detection rate of causal and putative pathogenic mutations in children with SRNS was 27/70 (39%): 15 (21%) carried the NPHS2 p.V260E causal mutation in the homozygous state, and 12 (17%) SRNS cases carried a putative pathogenic mutation in the heterozygous state in genes (INF2 (n = 8), CD2AP (n = 3) and TRPC6 (n = 1)) known to have autosomal dominant inheritance mode. NPHS2 p.V260E homozygosity was specifically associated with biopsy-proven FSGS, accounting for 24% of children of Black ethnicity (15 of 63) with steroid-resistant FSGS. No causal or putative pathogenic mutations were identified in NPHS1, WT1, LAMB2, PLCE1, MYO1E and ACTN4. We report four novel variants in INF2, PLCE1, ACTN4 and TRPC6.   Conclusion: We report putative missense variants predicted to be pathogenic in INF2, CD2AP and TRPC6 among steroid-resistant-FSGS children. However, the NPHS2 p.V260E mutation is a prevalent cause of steroid-resistant FSGS among Black South African children occurring in 24% of children with SRNS. Screening all Black African children presenting with NS for NPHS2 p.V260E will provide a precision diagnosis of steroid-resistant FSGS and inform clinical management. What is Known: • Limited data is available on the genetic disparity of SNRS in a South African paediatric setting. • The high rate of steroid resistance in Black South African children with FSGS compared to other racial groups is partially explained by the founder variant NPHS2 p.V260E. What is New: • We report putative missense variants predicted to be pathogenic in INF2, CD2AP and TRPC6 among steroid-resistant FSGS children. • NPHS2 p.V260E mutation remains a prevalent cause of steroid-resistant FSGS among Black South African children, demonstrating precision diagnostic utility.

Multiscale Electrochemomechanics Interaction and Degradation Analytics of Sn Electrodes for Sodium-Ion Batteries.

Sodium-ion batteries have emerged as a strong contender among the beyond lithium-ion chemistries due to elemental abundance and the low cost of sodium. Tin (Sn) is a promising alloying electrode with high capacity, redox reversibility, and earth abundance. Tin electrodes, however, undergo a series of intermediate reactions exhibiting multiple voltage plateaus upon sodiation/desodiation. Phase transformations related to incomplete sodiation in tin during cycling, in the presence of a frail solid electrolyte interphase layer, can quickly weaken the structural stability. The structural dynamics and reactivity of the electrode/electrolyte interface, being further dependent on the size and morphology of the active material particle in the presence of different electrolytes, dictate the electrode degradation and survivability during cycling. In this study, we paint a comprehensive picture of the underpinnings of the electrochemical and mechanics coupling and electrode/electrolyte interfacial interactions in alloying Sn electrodes. We elicit the fundamental role of electrode/electrolyte complexations in the Sn electrode structure-property-performance relationship based on multimodal analytics, including electrochemical, microscopy, and tomography analyses.

Modeling free-carrier absorption in ultrathin III-V solar cells with light management.

Ultrathin III-V solar cells with proper light management have become more attractive than their optically thick counterparts as they are less expensive and lightweight, can maintain photon absorption, and have high radiation tolerance for space-related applications. Comprehensive optical modeling efforts have provided pathways to improve device efficiency in ultrathin GaAs solar cells with light trapping structures. Usually, the absorption mechanism known as free-carrier absorption (FCA) is ignored in these models due to the ultrathin layers and the direct bandgap of GaAs. This manuscript reports the significance of considering FCA as a parasitic loss caused by the optical enhancement in highly doped non-active layers between the ultrathin solar cell and backside light trapping structures. We model FCA based on Drude theory in a p-type AlGaAs layer behind ultrathin GaAs solar cells with a planar mirror and cylindrical gratings. Our results show that, depending on the AlGaAs thickness and doping concentration, free carriers will absorb transmitted photons and reduce the backside reflectance, degrading the current and voltage output from ideal conditions. One example shows that for a 300 nm-thick GaAs solar cell, the Ag mirror's peak reflectance decreases nearly 12% when the AlGaAs back layer is 800 nm-thick at a doping concentration of 4x1019 cm-3. Notably, the cylindrical grating designs with 38.5%, 46.5%, and 64.9% AlGaAs coverage resulted in an absolute efficiency reduction of 0.6%, 1.8%, and 2.9% at a doping concentration of 4x1019 cm-3, respectively. This novel study demonstrates that FCA in non-active layers must be properly addressed in the device design to progress the efficiency of ultrathin III-V solar cells with light trapping structures.

Urine Single-Cell RNA Sequencing in Focal Segmental Glomerulosclerosis Reveals Inflammatory Signatures.

INTRODUCTION: Individuals with focal segmental glomerular sclerosis (FSGS) typically undergo kidney biopsy only once, which limits the ability to characterize kidney cell gene expression over time. METHODS: We used single-cell RNA sequencing (scRNA-seq) to explore disease-related molecular signatures in urine cells from subjects with FSGS. We collected 17 urine samples from 12 FSGS subjects and captured these as 23 urine cell samples. The inflammatory signatures from renal epithelial and immune cells were evaluated in bulk gene expression data sets of FSGS and minimal change disease (MCD) (The Nephrotic Syndrome Study Network [NEPTUNE] study) and an immune single-cell data set from lupus nephritis (Accelerating Medicines Partnership). RESULTS: We identified immune cells, predominantly monocytes, and renal epithelial cells in the urine. Further analysis revealed 2 monocyte subtypes consistent with M1 and M2 monocytes. Shed podocytes in the urine had high expression of marker genes for epithelial-to-mesenchymal transition (EMT). We selected the 16 most highly expressed genes from urine immune cells and 10 most highly expressed EMT genes from urine podocytes as immune signatures and EMT signatures, respectively. Using kidney biopsy transcriptomic data from NEPTUNE, we found that urine cell immune signature and EMT signature genes were more highly expressed in FSGS biopsies compared with MCD biopsies. CONCLUSION: The identification of monocyte subsets and podocyte expression signatures in the urine samples of subjects with FSGS suggests that urine cell profiling might serve as a diagnostic and prognostic tool in nephrotic syndrome. Furthermore, this approach may aid in the development of novel biomarkers and identifying personalized therapies targeting particular molecular pathways in immune cells and podocytes.

Identification and Antibiotic Susceptibility Patterns of Clinical Blood Culture Isolates Not Identified by a Rapid Microarray Diagnostic System.

The use of molecular-based diagnostic testing, such as the Luminex Verigene system, to rapidly identify the most common bacterial isolates from blood cultures is an important tool that reduces the duration of inappropriate antibiotics and decreases mortality. However, 5 to 15% of microorganisms recovered from blood culture are unable to be identified by the Verigene Gram-negative (BC-GN) or Gram-positive (BC-GP) assays. In this retrospective, observational study, we evaluate the identities and antimicrobial susceptibility patterns of 229 isolates that were not identified by either the Verigene BC-GN or BC-GP assay. The results presented here suggest that important, clinically relevant information about antimicrobial susceptibility patterns can still be inferred even when isolates are not identified by Verigene. We also examined changes in antibiotic use for patients with "unidentified" Verigene results at our institution and found that this subgroup represents an opportunity to optimize empirical antibiotic therapy. IMPORTANCE Rapid diagnostic testing to identify bloodstream pathogens has arisen as an important tool both to ensure adequate antimicrobial therapy is given early and to aid in antimicrobial stewardship by allowing for more rapid deescalation of inappropriate antimicrobial therapy. However, there is a paucity of data regarding the significance of isolates that are not able to be identified by rapid diagnostic testing. In this study, we report the identification to the species level and antimicrobial susceptibilities among isolates that were not identified by one such rapid diagnostic platform, the Verigene system. This study provides important insight into how a strong understanding of the strengths and limitations of a given rapid diagnostic platform, coupled with insight into local antibiotic susceptibility patterns, can allow for more nuanced and thoughtful empirical antibiotic selection.

Development of the Three Antimicrobial Stewardship E's (TASE) Framework and Association Between Stewardship Interventions and Intended Results Analysis to Identify Key Facility-Specific Interventions and Strategies for Successful Antimicrobial Stewardship.

BACKGROUND: Successful antimicrobial stewardship (AS) interventions have been described previously. Currently, a uniform operational approach to planning and implementing successful AS interventions does not exist. From 2015 to 2019, concomitant vancomycin and piperacillin-tazobactam use (CVPTU) for >48 hours at Vanderbilt University Medical Center (VUMC) significantly decreased through AS efforts. We analyzed the interventions that led to this change and created a model to inform future intervention planning and development. METHODS: Adult admissions at VUMC from January 2015 to August 2019 were evaluated for CVPTU. The percentage of admissions receiving CVPTU for >48 hours, the primary outcome, was evaluated using statistical process control charts. We created the Three Antimicrobial Stewardship E's (TASE) framework and Association between Stewardship Interventions and Intended Results (ASIR) analysis to assess potential intensity and impact of interventions associated with successful change during this time period and to identify guiding principles for development of future initiatives. RESULTS: The mean percentage of admissions receiving CVPTU per month declined from 4.2% to 0.7%. Over 8 time periods, we identified 4 periods with high, 3 with moderate, and 1 with low intervention intensity. Continuous provider-level AS education was present throughout. Creation and dissemination of division and department algorithms and reinforcement via computerized provider order entry sets preceded the largest reduction in CVPTU and sustained prescribing practice changes. CONCLUSIONS: The TASE framework and ASIR analysis successfully identified pivotal interventions and strategies needed to effect and sustain change at VUMC. Further research is needed to validate the effectiveness of this framework as a stewardship intervention planning tool at our institution and others.

HLA Alleles B*53:01 and C*06:02 Are Associated With Higher Risk of P. falciparum Parasitemia in a Cohort in Uganda.

Variation within the HLA locus been shown to play an important role in the susceptibility to and outcomes of numerous infections, but its influence on immunity to P. falciparum malaria is unclear. Increasing evidence indicates that acquired immunity to P. falciparum is mediated in part by the cellular immune response, including NK cells, CD4 and CD8 T cells, and semi-invariant γδ T cells. HLA molecules expressed by these lymphocytes influence the epitopes recognized by P. falciparum-specific T cells, and class I HLA molecules also serve as ligands for inhibitory receptors including KIR. Here we assessed the relationship of HLA class I and II alleles to the risk of P. falciparum infection and symptomatic malaria in a cohort of 892 Ugandan children and adults followed prospectively via both active and passive surveillance. We identified two HLA class I alleles, HLA-B*53:01 and HLA-C*06:02, that were associated with a higher prevalence of P. falciparum infection. Notably, no class I or II HLA alleles were found to be associated with protection from P. falciparum parasitemia or symptomatic malaria. These findings suggest that class I HLA plays a role in the ability to restrict parasitemia, supporting an essential role for the cellular immune response in P. falciparum immunity. Our findings underscore the need for better tools to enable mechanistic studies of the T cell response to P. falciparum at the epitope level and suggest that further study of the role of HLA in regulating pre-erythrocytic stages of the P. falciparum life cycle is warranted.

APOL1 variant alleles associate with reduced risk for opportunistic infections in HIV infection.

Apolipoprotein L1 (APOL1), an innate immune factor against African trypanosoma brucei, inhibits HIV-1 in vitro. The impact of APOL1 G1-G2 variants on HIV-1-associated opportunistic infections (OIs) is unknown. Here, we report findings from a metaanalysis of four HIV/AIDS prospective cohorts (ALIVE, LSOCA, MACS, and WIHS) including 2066 African American participants. Using a global test combining all four cohorts, carriage of two APOL1 variant alleles is associated with a 50% reduction in odds of OI (combined OR 0.50, 95% CI 0.33-0.76). Subgroup analysis of OI etiological categories (viral, parasitic, fungal and Mycobacterial) suggests the possibility of specific protection from fungal infections (OR 0.54. 95% CI 0.32-0.93; PBonferroni corrected = 0.08). We observe an association of APOL1 variant alleles with host protection against OI in HIV-positive individuals. The study suggests a broader role of APOL1 variant alleles in innate immunity in vivo.

Risk factors for mortality and progression to severe COVID-19 disease in the Southeast region in the United States: A report from the SEUS Study Group.

OBJECTIVE: Identify risk factors that could increase progression to severe disease and mortality in hospitalized SARS-CoV-2 patients in the Southeast region of the United States. DESIGN, SETTING, AND PARTICIPANTS: Multicenter, retrospective cohort including 502 adults hospitalized with laboratory-confirmed COVID-19 between March 1, 2020, and May 8, 2020 within 1 of 15 participating hospitals in 5 health systems across 5 states in the Southeast United States. METHODS: The study objectives were to identify risk factors that could increase progression to hospital mortality and severe disease (defined as a composite of intensive care unit admission or requirement of mechanical ventilation) in hospitalized SARS-CoV-2 patients in the Southeast United States. RESULTS: In total, 502 patients were included, and 476 of 502 (95%) had clinically evaluable outcomes. The hospital mortality rate was 16% (76 of 476); 35% (177 of 502) required ICU admission and 18% (91 of 502) required mechanical ventilation. By both univariate and adjusted multivariate analyses, hospital mortality was independently associated with age (adjusted odds ratio [aOR], 2.03 for each decade increase; 95% confidence interval [CI], 1.56--2.69), male sex (aOR, 2.44; 95% CI, 1.34-4.59), and cardiovascular disease (aOR, 2.16; 95% CI, 1.15-4.09). As with mortality, risk of severe disease was independently associated with age (aOR, 1.17 for each decade increase; 95% CI, 1.00-1.37), male sex (aOR, 2.34; 95% CI, 1.54-3.60), and cardiovascular disease (aOR, 1.77; 95% CI, 1.09-2.85). CONCLUSIONS: In an adjusted multivariate analysis, advanced age, male sex, and cardiovascular disease increased risk of severe disease and mortality in patients with COVID-19 in the Southeast United States. In-hospital mortality risk doubled with each subsequent decade of life.

Antimicrobial de-escalation in patients with high-risk febrile neutropenia: Attitudes and practices of adult hospital care providers.

In a survey of adult hospital providers regarding antibiotic use in the treatment of febrile neutropenia, clinical fellows, and pharmacists showed higher comfort levels with early antimicrobial de-escalation compared to hematology-oncology and transplant infectious diseases physicians. These frontline team members are ideal partners to champion antimicrobial stewardship interventions in febrile neutropenia.

Changes in antimicrobial utilization during the coronavirus disease 2019 (COVID-19) pandemic after implementation of a multispecialty clinical guidance team.

OBJECTIVE: Evaluate changes in antimicrobial use during COVID-19 and after implementation of a multispecialty COVID-19 clinical guidance team compared to pre-COVID-19 antimicrobial use. DESIGN: Retrospective observational study. SETTING: Tertiary-care academic medical center. PARTICIPANTS: Internal medicine and medical intensive care unit (MICU) provider teams and hospitalized COVID-19 patients. METHODS: Difference-in-differences analyses of antibiotic days of therapy per 1,000 patient days present (DOT) for internal medicine and MICU teams treating COVID-19 patients versus teams that did not were performed for 3 periods: before COVID-19, initial COVID-19 period, and after implementation of a multispecialty COVID-19 clinical guidance team which included daily, patient-specific antimicrobial stewardship recommendations. Patient characteristics associated with antibiotic DOT were evaluated using multivariable Poisson regression. RESULTS: In the initial COVID-19 period, compared to the pre-COVID-19 period, internal medicine and MICU teams increased weekly antimicrobial use by 145.3 DOT (95% CI, 35.1-255.5) and 204.0 DOT (95% CI, -16.9 to 424.8), respectively, compared to non-COVID-19 teams. In the intervention period, internal medicine and MICU COVID-19 teams both had significant weekly decreases of 362.3 DOT (95% CI, -443.3 to -281.2) and 226.3 DOT (95% CI, -381.2 to -71.3). Of 131 patients hospitalized with COVID-19, 86 (65.6%) received antibiotics; no specific patient factors were significantly associated with an expected change in antibiotic days. CONCLUSIONS: Antimicrobial use initially increased for COVID-19 patient care teams compared to pre-COVID-19 levels but significantly decreased after implementation of a multispecialty clinical guidance team, which may be an effective strategy to reduce unnecessary antimicrobial use.