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The Centers for Medicare & Medicaid Services' Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) measure has appropriately established sepsis as a national priority. However, the Infectious Diseases Society of America (IDSA and five additional endorsing societies) is concerned about SEP-1's potential to drive antibiotic overuse because it does not account for the high rate of sepsis overdiagnosis and encourages aggressive antibiotics for all patients with possible sepsis, regardless of the certainty of diagnosis or severity of illness. IDSA is also concerned that SEP-1's complex "time zero" definition is not evidence-based and is prone to inter-observer variation. In this position paper, IDSA outlines several recommendations aimed at reducing the risk of unintended consequences of SEP-1 while maintaining focus on its evidence-based elements. IDSA's core recommendation is to limit SEP-1 to septic shock, for which the evidence supporting the benefit of immediate antibiotics is greatest. Prompt empiric antibiotics are often appropriate for suspected sepsis without shock, but IDSA believes there is too much heterogeneity and difficulty defining this population, uncertainty about the presence of infection, and insufficient data on the necessity of immediate antibiotics to support a mandatory treatment standard for all patients in this category. IDSA believes guidance on managing possible sepsis without shock is more appropriate for guidelines that can delineate the strengths and limitations of supporting evidence and allow clinicians discretion in applying specific recommendations to individual patients. Removing sepsis without shock from SEP-1 will mitigate the risk of unnecessary antibiotic prescribing for noninfectious syndromes, simplify data abstraction, increase measure reliability, and focus attention on the population most likely to benefit from immediate empiric broad-spectrum antibiotics. [ABSTRACT FROM AUTHOR]

We performed a concurrent comparison between solid organ transplant recipients and nontransplant patients with blood culture–proven sepsis; after adjustments for clinical presentation, severity of illness, and infection types, transplant patients had a significantly lower risk of death.Background. Sepsis is a serious complication of solid organ transplant (SOT). Evidence on survival differences between SOT recipients and non-SOT patients with sepsis is lacking.Methods. This was a matched, case-control propensity-adjusted study. Conditional logistic regression was performed for risk factor analysis, and Cox proportional hazards regression for survival analysis.Results. Three hundred sixty-nine patients (123 cases; 246 controls) diagnosed with blood culture–proven sepsis were matched 1:2 by age, sex, and hospital location. The distribution of allografts was 36.6% kidney, 34.1% liver, 13% kidney-pancreas, 7.3% small bowel/liver, 5.7% heart/lung, and 3.3% multivisceral. The conditional logistic regression showed that the following factors were significantly more frequently associated with SOT compared to non-SOT: higher number of comorbidities (odds ratio [OR] = 8.2 [95% confidence interval {CI}, 1.48–45.44], P = .016); higher Sepsis-related Organ Failure Assessment score (OR = 1.2 [95% CI, 1.07–1.32], P = .001); presence of nosocomial infection (OR = 36.3 [95% CI, 9.71–135.96], P < .0001); appropriate initial antibiotics (OR = 0.04 [95% CI, .006–.23], P < .0001); and lower white blood cell count (OR = 0.93 [95% CI, .89–.97], P < .0001). Cox proportional hazards regression showed that after all adjustments for clinical presentation, severity of illness, and types of infection, SOT recipients with sepsis had a significantly lower risk of death at 28 days (hazard ratio [HR] = 0.22 [95% CI, .09–.54], P = .001) and at 90 days (HR = 0.43 [95% CI, .20–.89], P = .025).Conclusions. The 28-day and 90-day mortality were significantly decreased for transplant recipients compared with nontransplant patients. These findings suggest that the immunosuppression associated with transplantation may provide a survival advantage to transplant recipients with sepsis through modulation of the inflammatory response. [ABSTRACT FROM PUBLISHER]

Objective: This report describes three patients with Ebola virus disease who were treated in the United States and developed for severe critical illness and multiple organ failure secondary to Ebola virus infection. The patients received mechanical ventilation, renal replacement therapy, invasive monitoring, vasopressor support, and investigational therapies for Ebola virus disease.Data Sources: Patient medical records from three tertiary care centers (Emory University Hospital, University of Nebraska Medical Center, and Texas Health Presbyterian Dallas Hospital).Study Selection: Not applicable.Data Extraction: Not applicable.Data Synthesis: Not applicable.Conclusion: In the severe form, patients with Ebola virus disease may require life-sustaining therapy, including mechanical ventilation and renal replacement therapy. In conjunction with other reported cases, this series suggests that respiratory and renal failure may occur in severe Ebola virus disease, especially in patients burdened with high viral loads. Ebola virus disease complicated by multiple organ failure can be survivable with the application of advanced life support measures. This collective, multicenter experience is presented with the hope that it may inform future treatment of patients with Ebola virus disease requiring critical care treatment. [ABSTRACT FROM AUTHOR]

Objective: This report will describe the preparations for and the provision of care of two patients with Ebola virus disease in the biocontainment unit at the University of Nebraska Medical Center. Data Sources: Patient medical records. Study Selection: Not applicable. Data Extraction: Not applicable. Data Synthesis: Not applicable. Conclusions: Safe and effective care of patients with Ebola virus disease requires significant communication and planning. Adherence to a predetermined isolation protocol is essential, including proper donning and doffing of personal protective equipment. Location of the patient care area and the logistics of laboratory testing, diagnostic imaging, and the removal of waste must be considered. Patients with Ebola virus disease are often dehydrated and need adequate vascular access for fluid resuscitation, nutrition, and phlebotomy for laboratory sampling. Advanced planning for acute life-threatening events and code status must be considered. Intensivist scheduling should account for the significant amount of time required for the care of patients with Ebola virus disease. With appropriate precautions and resources, designated hospitals in the United States can safely provide care for patients with Ebola virus disease. [ABSTRACT FROM AUTHOR]

The Centers for Medicare & Medicaid Services (CMS) introduced the Severe Sepsis/Septic Shock Management Bundle (SEP-1) as a pay-for-reporting measure in 2015 and is now planning to make it a pay-for-performance measure by incorporating it into the Hospital Value-Based Purchasing Program. This joint IDSA/ACEP/PIDS/SHEA/SHM/SIPD position paper highlights concerns with this change. Multiple studies indicate that SEP-1 implementation was associated with increased broad-spectrum antibiotic use, lactate measurements, and aggressive fluid resuscitation for patients with suspected sepsis but not with decreased mortality rates. Increased focus on SEP-1 risks further diverting attention and resources from more effective measures and comprehensive sepsis care. We recommend retiring SEP-1 rather than using it in a payment model and shifting instead to new sepsis metrics that focus on patient outcomes. CMS is developing a community-onset sepsis 30-day mortality electronic clinical quality measure (eCQM) that is an important step in this direction. The eCQM preliminarily identifies sepsis using systemic inflammatory response syndrome (SIRS) criteria, antibiotic administrations or diagnosis codes for infection or sepsis, and clinical indicators of acute organ dysfunction. We support the eCQM but recommend removing SIRS criteria and diagnosis codes to streamline implementation, decrease variability between hospitals, maintain vigilance for patients with sepsis but without SIRS, and avoid promoting antibiotic use in uninfected patients with SIRS. We further advocate for CMS to harmonize the eCQM with the Centers for Disease Control and Prevention's (CDC) Adult Sepsis Event surveillance metric to promote unity in federal measures, decrease reporting burden for hospitals, and facilitate shared prevention initiatives. These steps will result in a more robust measure that will encourage hospitals to pay more attention to the full breadth of sepsis care, stimulate new innovations in diagnosis and treatment, and ultimately bring us closer to our shared goal of improving outcomes for patients., Competing Interests: Potential conflicts of interest. K. C. discloses grants or contracts from the CDC and AHRQ to my institution and serves as the IDSA and PIDS representative to the SCCM Pediatric Sepsis Definitions Taskforce. D. C. C. reports payment for expert testimony. S. E. C. reports grants or contracts from Patient-Centered Outcomes Research Institute (PCORI), National Institutes of Health (NIH), Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), Agency for Healthcare Research and Quality (AHRQ); consulting fees from Duke Clinical Research Institute; participation on a Data Safety Monitoring Board or Advisory Board for Debiopharm; roles as a Board Member for National Foundation for Infectious Diseases and for Global Antibiotic Research & Development Partnership North America (GARDP-NA). R. G. reports support for attending meetings and/or travel for his government relations work from Society of Hospital Medicine; participation as an advisor on a Data Safety Monitoring Board or Advisory Board for Honor Technologies, Clinical Language Engineering Workbench (CLEW), Sitka; volunteer position as Sr. Advisor for Government Affairs SHM; stock from Sitka, Honor Technologies, CLEW. E. L. H. reports consulting fees paid to author for peer review of drug monographs from Wolters Kluwer (Lexi-Comp); honoraria for continuing education presentations from Clinical Care Options. A. C. K. reports grants or contracts as Investigator for the National Institutes of Health Adaptive COVID-19 Treatment Trial. M. K. reports grants to institution from CDC and AHRQ; royalties to author from UpToDate; Honorarium for lecture on sepsis metrics, paid to author, from Burns & Trauma Journal. H. M. reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Infectious Disease Board Review and International AIDS Society USA; patents planned, issued or pending for Immunofluorescent antibody for pneumocystis; leadership or fiduciary role with Society of Critical Care Medicine, Critical Care Medicine (Senior Editor) and is an IDSA representative to Surviving Sepsis Guideline; and other financial or non-financial interests in Infectious Disease Board Review LLC. C. R. reports grants to institution from CDC and AHRQ; royalties to author from UpToDate; payment to author for consulting related to sepsis diagnostics from Cytovale; leadership or fiduciary role with IDSA as Associate Editor for Clinical Infectious Diseases. D. A. S. reports grants or contracts as investigator for the National Institutes of Health Adaptive COVID-19 Treatment Trial. A. T. reports consulting fees from Vapotherm (no payments made related to this manuscript; Vapotherm is a medical device that can be used to treat sepsis); a role as President-elect for the American College of Emergency Physicians (no direct payment related to this manuscript). D. M. Y. reports grants or contracts to institution from National Heart, Lung, and Blood Institute (NHLBI); royalties or licenses from UpToDate (pneumonia chapter) and Lippincott Inc (EM text editor); payment or honoraria as journal editor for American College of Emergency Physicians; payment for expert testimony from University of Pennsylvania and Pennsylvania State University. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Functional impairment of interferon, a natural antiviral component of the immune system, is associated with the pathogenesis and severity of COVID-19. We aimed to compare the efficacy of interferon beta-1a in combination with remdesivir compared with remdesivir alone in hospitalised patients with COVID-19., Methods: We did a double-blind, randomised, placebo-controlled trial at 63 hospitals across five countries (Japan, Mexico, Singapore, South Korea, and the USA). Eligible patients were hospitalised adults (aged ≥18 years) with SARS-CoV-2 infection, as confirmed by a positive RT-PCR test, and who met one of the following criteria suggestive of lower respiratory tract infection: the presence of radiographic infiltrates on imaging, a peripheral oxygen saturation on room air of 94% or less, or requiring supplemental oxygen. Patients were excluded if they had either an alanine aminotransferase or an aspartate aminotransferase concentration more than five times the upper limit of normal; had impaired renal function; were allergic to the study product; were pregnant or breast feeding; were already on mechanical ventilation; or were anticipating discharge from the hospital or transfer to another hospital within 72 h of enrolment. Patients were randomly assigned (1:1) to receive intravenous remdesivir as a 200 mg loading dose on day 1 followed by a 100 mg maintenance dose administered daily for up to 9 days and up to four doses of either 44 μg interferon beta-1a (interferon beta-1a group plus remdesivir group) or placebo (placebo plus remdesivir group) administered subcutaneously every other day. Randomisation was stratified by study site and disease severity at enrolment. Patients, investigators, and site staff were masked to interferon beta-1a and placebo treatment; remdesivir treatment was given to all patients without masking. The primary outcome was time to recovery, defined as the first day that a patient attained a category 1, 2, or 3 score on the eight-category ordinal scale within 28 days, assessed in the modified intention-to-treat population, defined as all randomised patients who were classified according to actual clinical severity. Safety was assessed in the as-treated population, defined as all patients who received at least one dose of the assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04492475., Findings: Between Aug 5, 2020, and Nov 11, 2020, 969 patients were enrolled and randomly assigned to the interferon beta-1a plus remdesivir group (n=487) or to the placebo plus remdesivir group (n=482). The mean duration of symptoms before enrolment was 8·7 days (SD 4·4) in the interferon beta-1a plus remdesivir group and 8·5 days (SD 4·3) days in the placebo plus remdesivir group. Patients in both groups had a time to recovery of 5 days (95% CI not estimable) (rate ratio of interferon beta-1a plus remdesivir group vs placebo plus remdesivir 0·99 [95% CI 0·87-1·13]; p=0·88). The Kaplan-Meier estimate of mortality at 28 days was 5% (95% CI 3-7%) in the interferon beta-1a plus remdesivir group and 3% (2-6%) in the placebo plus remdesivir group (hazard ratio 1·33 [95% CI 0·69-2·55]; p=0·39). Patients who did not require high-flow oxygen at baseline were more likely to have at least one related adverse event in the interferon beta-1a plus remdesivir group (33 [7%] of 442 patients) than in the placebo plus remdesivir group (15 [3%] of 435). In patients who required high-flow oxygen at baseline, 24 (69%) of 35 had an adverse event and 21 (60%) had a serious adverse event in the interferon beta-1a plus remdesivir group compared with 13 (39%) of 33 who had an adverse event and eight (24%) who had a serious adverse event in the placebo plus remdesivir group., Interpretation: Interferon beta-1a plus remdesivir was not superior to remdesivir alone in hospitalised patients with COVID-19 pneumonia. Patients who required high-flow oxygen at baseline had worse outcomes after treatment with interferon beta-1a compared with those given placebo., Funding: The National Institute of Allergy and Infectious Diseases (USA)., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To provide guidance to rheumatology providers on the management of adult rheumatic disease in the context of the coronavirus disease 2019 (COVID-19) pandemic., Methods: A task force, including 10 rheumatologists and 4 infectious disease specialists from North America, was convened. Clinical questions were collated, and an evidence report was rapidly generated and disseminated. Questions and drafted statements were reviewed and assessed using a modified Delphi process. This included asynchronous anonymous voting by e-mail and webinars with the entire panel. Task force members voted on agreement with draft statements using a 1-9-point numerical scoring system, and consensus was determined to be low, moderate, or high based on the dispersion of votes. For approval, median votes were required to meet predefined levels of agreement (median values of 7-9, 4-6, and 1-3 defined as agreement, uncertainty, or disagreement, respectively) with either moderate or high levels of consensus., Results: To date, the task force has approved 80 guidance statements: 36 with moderate and 44 with high consensus. These were combined, resulting in 27 final guidance statements., Conclusion: These guidance statements are provided to promote optimal care during the current pandemic. However, given the low level of available evidence and the rapidly evolving literature, this guidance is presented as a "living document," and future updates are anticipated., (© 2020, American College of Rheumatology.)

Purpose: Low-dose steroids have shown contradictory results in trials and three recent meta-analyses. We aimed to assess the efficacy and safety of low-dose steroids for severe sepsis and septic shock by Bayesian methodology., Methods: Randomized trials from three published meta-analyses were reviewed and entered in both classic and Bayesian databases to estimate relative risk reduction (RRR) for 28-day mortality, and relative risk increase (RRI) for shock reversal and side effects., Results: In septic shock trials only (Marik meta-analysis; N = 965), the probability that low-dose steroids decrease mortality by more than 15% (i.e., RRR > 15%) was 0.41 (0.24 for RRR > 20% and 0.14 for RRR > 25%). For severe sepsis and septic shock trials combined, the results were as follows: (1) for the Annane meta-analysis (N = 1,228), the probabilities were 0.57 (RRR > 15%), 0.32 (RRR > 20%), and 0.13 (RRR > 25%); (2) for the Minneci meta-analysis (N = 1,171), the probability was 0.57 to achieve mortality RRR > 15%, 0.32 (RRR > 20%), and 0.14 (RRR > 25%). The removal of the Sprung trial from each analysis did not change the overall results. The probability of achieving shock reversal ranged from 65 to 92%. The probability of developing steroid-induced side effects was as follows: for gastrointestinal bleeding (N = 924), there was a 0.73 probability of steroids causing an RRI > 1%, 0.70 for RRI > 2%, and 0.67 for RRI > 5%; for superinfections (N = 964), probabilities were 0.81 (RRI > 1%), 0.76 (RRI > 2%), and 0.70 (RRI > 5%); and for hyperglycemia (N = 540), 0.99 (RRI > 1%), 0.97 (RRI > 2%), and 0.94 (RRI > 5%)., Conclusions: Based on clinically meaningful thresholds (RRR > 15-25%) for mortality reduction in severe sepsis or septic shock, the Bayesian approach to all three meta-analyses consistently showed that low-dose steroids were not associated with survival benefits. The probabilities of developing steroid-induced side effects (superinfections, bleeding, and hyperglycemia) were high for all analyses.

Background: Whether there are geographic differences in clinical presentation of cryptococcosis in solid organ transplant (SOT) recipients in the United States (US) is not known., Material/methods: Patients comprised a cohort of 120 SOT recipients from US transplant centers who fulfilled the EORTC/MSG criteria for cryptococcal disease., Results: Central nervous system, pulmonary, and cutaneous cryptococcal disease were observed in 51% (61/120), 64% (77/120), and 15% (18/120) of the patients, respectively. Cutaneous disease was documented in 9% (3/32) of the patients from South Atlantic region, 19% (6/32) from Mid Atlantic, 26% (6/23) from Southern, 7% (2/29) from Midwestern, and in 1 of 4 patients from the Northwestern region of the US. When controlled for age, immunosuppressive regimen, type of transplant, and renal failure at baseline, patients from the Southern compared with other regions of the US were significantly more likely to have cutaneous cryptococcal disease (OR 3.8, 95% CI 1.1-14, P=0.045)., Conclusions: Post-transplant cryptococcosis is more likely to present with cutaneous disease in the Southern region compared with other regions in the US. This predilection for cutaneous cryptococcosis could not be explained on the basis of differences in immunosuppression or the type of transplant. Whether our findings are related to strain-related variations in characteristics of the yeast or other transplant variables remains to be determined.

Objective: To update the practice parameters for the evaluation of adult patients who develop a new fever in the intensive care unit, for the purpose of guiding clinical practice., Participants: A task force of 11 experts in the disciplines related to critical care medicine and infectious diseases was convened from the membership of the Society of Critical Care Medicine and the Infectious Diseases Society of America. Specialties represented included critical care medicine, surgery, internal medicine, infectious diseases, neurology, and laboratory medicine/microbiology., Evidence: The task force members provided personal experience and determined the published literature (MEDLINE articles, textbooks, etc.) from which consensus was obtained. Published literature was reviewed and classified into one of four categories, according to study design and scientific value., Consensus Process: The task force met twice in person, several times by teleconference, and held multiple e-mail discussions during a 2-yr period to identify the pertinent literature and arrive at consensus recommendations. Consideration was given to the relationship between the weight of scientific evidence and the strength of the recommendation. Draft documents were composed and debated by the task force until consensus was reached by nominal group process., Conclusions: The panel concluded that, because fever can have many infectious and noninfectious etiologies, a new fever in a patient in the intensive care unit should trigger a careful clinical assessment rather than automatic orders for laboratory and radiologic tests. A cost-conscious approach to obtaining cultures and imaging studies should be undertaken if indicated after a clinical evaluation. The goal of such an approach is to determine, in a directed manner, whether infection is present so that additional testing can be avoided and therapeutic decisions can be made.