A Systematic Review of Health-Related Quality-of-Life Measurement in Patients With Complicated Intraabdominal Infections.

Background: In this systematic review, we assessed health-related quality-of-life (HRQoL) measures in patients with complicated intraabdominal infections (cIAIs) commonly associated with sepsis and evaluated the impact of cIAIs on HRQoL.

Methods: Following a prospectively registered protocol in PROSPERO (CRD42021255827), we searched electronic databases, including MEDLINE (PubMed), EMBASE (Elsevier), and CINAHL (EBSCO), from database inception through September 2022 to identify studies that measured HRQoL in patients with cIAIs.

Results: We identified 93 articles that included 45 HRQoL measures: 32 generic, 5 condition-specific, and 8 symptom-specific.

A Systematic Review of Health-Related Quality-of-Life Measurement in Patients With Acute Bacterial Skin and Skin Structure Infections.

Background: Acute bacterial skin and skin structure infections (ABSSSIs) can diminish patients' health-related quality of life (HRQoL). We performed a systematic review to determine how HRQoL has been measured in patients with ABSSSIs.

Methods: We searched MEDLINE (PubMed), Embase (Elsevier), and CINAHL (EBSCO) for articles published between database inception and 14 October 2022, following a prospectively registered protocol in PROSPERO (CRD42021225414).

A Qualitative Secondary Analysis of Patient Health-Related Quality of Life in Bloodstream Infections by Source: Intra-abdominal, Urinary Tract, and Acute Bacterial Skin and Skin Structure Infection.

Background: Despite the prevalence of intra-abdominal infections, urinary tract infections, and skin/skin structure infections, the relative impact of these syndromes on patient health-related quality of life (HRQoL) is unclear. This qualitative secondary analysis used data from an interview-based HRQoL qualitative study of bloodstream infections by source of infection to inform the potential development, adaptation, and use of HRQoL measures.

Methods: Interview transcripts from eligible participants (aged ≥18 years) with intra-abdominal, urinary tract, and skin/skin structure infections as the source of bloodstream infection were selected from parent study data collected between May 2017 and September 2018.

A Systematic Review of Health-Related Quality-of-Life Measurement in Patients With Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia.

Background: We conducted a systematic review to gain insight into how health-related quality of life (HRQoL) is measured and reported in hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP), common causes of disease and death in hospitalized patients.

Methods: Following a prospectively registered protocol in PROSPERO (CRD42021253579), we searched electronic databases, including MEDLINE (PubMed), EMBASE (Elsevier), and CINAHL (EBSCO) from database inception through October 2022 to identify studies measuring HRQoL in patients with HABP and/or VABP.

Results: Of 2633 studies identified, 5 articles met our inclusion criteria.

A Systematic Review of Health-Related Quality-of-Life Measurement in Patients With Complicated Urinary Tract Infections.

Background: Complicated urinary tract infections (cUTIs) significantly affect patients' health-related quality of life (HRQoL), yet current end points defined by the United States Food and Drug Administration for antibiotic registrational trials fail to capture important elements of the patient experience with cUTI. In this systematic review, we aimed to identify measurement tools for HRQoL that have been studied in patients with cUTIs.

Methods: Following a prospectively registered protocol in PROSPERO (CRD42020215641), English-language articles were queried using MEDLINE (via PubMed), Embase (Elsevier), and CINAHL (EBSCO) from database inception to 12 October 2022.

Interagency Collaboration for Patient-Centered Antibacterial Drug Development.

This manuscript presents key advances of the Antibacterial Resistance Leadership Group (ARLG) Innovations Task Force, a collaboration focused on improving endpoints for registrational trials of antibacterial drugs, including health-related quality-of-life measures, for common acute infections. This group includes members from the United States Food and Drug Administration, National Institutes of Health, academia, industry, and patient representatives to amplify patient voices and ensure that the endpoints are meaningful to how patients feel, function, and survive.

Epidemiology, Treatment, and Outcomes of Gram-Negative Bacteremia in a Multicenter Cohort of Solid Organ Transplant Recipients.

Introduction: Little is known about the epidemiology and management of gram-negative bloodstream infections (GN-BSIs) in patients after solid organ transplant (SOT). We describe epidemiology, treatment approaches, and outcomes in a subset of patients with SOT from a larger cohort with GN-BSI.

Methods: This was a multicenter, retrospective cohort study that enrolled unique, consecutive adults with GN-BSI hospitalized at any of 24 participating hospitals between January and December 2019.

Intention-to-diagnose and distinct research foci in diagnostic accuracy studies.

The intention-to-diagnose principle, an analogue to the intention-to-treat principle in clinical trials, protects the foundation for inference in diagnostic test accuracy studies. This foundation provides for robust control of error rates during hypothesis testing and correct coverage probability during confidence interval estimation of accuracy parameters, in well defined populations for transparent generalisability. The intention-to-diagnose principle requires distinguishing between various non-positive non-negative (NPNN) test results, such as equivocal and invalid results, and appropriate handling of these distinct results during statistical analyses.

Impact of rapid antibiotic susceptibility testing for Gram-negative bacteremia varies by pathogen type and resistance: a secondary analysis of the RAPIDS GN trial.

In this secondary analysis of 386 subjects with Gram-negative bacteremia enrolled in the RAPIDS GN trial, rapid antibiotic susceptibility testing had a greater benefit on the management of bacteremia caused by antibiotic-resistant compared to antibiotic-susceptible isolates, especially for species and species.IMPORTANCERapid blood culture diagnostics are costly, and their use has not demonstrated clear clinical benefit for patients with Gram-negative sepsis, possibly because prior trials did not enroll sufficient numbers of patients with antibiotic-resistant infections. This analysis of patients with sepsis previously enrolled in a randomized controlled clinical trial demonstrates that rapid susceptibility testing of bacteria from blood cultures had the greatest impact for patients with antibiotic-resistant infections.

Exploration of a Potential DOOR Endpoint for Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia Using Six Registrational Trials for Antibacterial Drugs.

Background: Desirability of outcome ranking (DOOR) is an innovative approach to clinical trial design and analysis that uses an ordinal ranking system to incorporate the overall risks and benefits of a therapeutic intervention into a single measurement. Here we derived and evaluated a disease-specific DOOR endpoint for registrational trials for hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP).

Methods: Through comprehensive examination of data from nearly 4000 participants enrolled in six registrational trials for HABP/VABP submitted to the Food and Drug Administration (FDA) between 2005 and 2022, we derived and applied a HABP/VABP specific endpoint.

Predictive Modeling of Drug-Related Adverse Events with Real-World Data: A Case Study of Linezolid Hematologic Outcomes.

Electronic health records (EHRs) provide meaningful knowledge of drug-related adverse events (AEs) that are not captured in standard drug development and postmarketing surveillance. Using variables obtained from EHR data in the University of California San Francisco de-identified Clinical Data Warehouse, we aimed to evaluate the potential of machine learning to predict two hematological AEs, thrombocytopenia and anemia, in a cohort of patients treated with linezolid for 3 or more days. Features for model input were extracted at linezolid initiation (index), and outcomes were characterized from index to 14 days post-treatment.

Contemporary Management of Staphylococcus aureus Bacteremia-Controversies in Clinical Practice.

Staphylococcus aureus bacteremia (SAB) carries a high risk for excess morbidity and mortality. Despite its prevalence, significant practice variation continues to permeate clinical management of this syndrome. Since the publication of the 2011 Infectious Diseases Society of America (IDSA) guidelines on management of methicillin-resistant Staphylococcus aureus infections, the field of SAB has evolved with the emergence of newer diagnostic strategies and therapeutic options.

Priorities and Progress in Diagnostic Research by the Antibacterial Resistance Leadership Group.

The advancement of infectious disease diagnostics, along with studies devoted to infections caused by gram-negative and gram-positive bacteria, is a top scientific priority of the Antibacterial Resistance Leadership Group (ARLG). Diagnostic tests for infectious diseases are rapidly evolving and improving. However, the availability of rapid tests designed to determine antibacterial resistance or susceptibility directly in clinical specimens remains limited, especially for gram-negative organisms.

Priorities and Progress in Gram-positive Bacterial Infection Research by the Antibacterial Resistance Leadership Group: A Narrative Review.

The Antibacterial Resistance Leadership Group (ARLG) has prioritized infections caused by gram-positive bacteria as one of its core areas of emphasis. The ARLG Gram-positive Committee has focused on studies responding to 3 main identified research priorities: (1) investigation of strategies or therapies for infections predominantly caused by gram-positive bacteria, (2) evaluation of the efficacy of novel agents for infections caused by methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci, and (3) optimization of dosing and duration of antimicrobial agents for gram-positive infections. Herein, we summarize ARLG accomplishments in gram-positive bacterial infection research, including studies aiming to (1) inform optimal vancomycin dosing, (2) determine the role of dalbavancin in MRSA bloodstream infection, (3) characterize enterococcal bloodstream infections, (4) demonstrate the benefits of short-course therapy for pediatric community-acquired pneumonia, (5) develop quality of life measures for use in clinical trials, and (6) advance understanding of the microbiome.

Ceftobiprole for Treatment of Complicated Bacteremia.

Background: Ceftobiprole is a cephalosporin that may be effective for treating complicated bacteremia, including methicillin-resistant .

Methods: In this phase 3, double-blind, double-dummy, noninferiority trial, adults with complicated bacteremia were randomly assigned in a 1:1 ratio to receive ceftobiprole at a dose of 500 mg intravenously every 6 hours for 8 days and every 8 hours thereafter, or daptomycin at a dose of 6 to 10 mg per kilogram of body weight intravenously every 24 hours plus optional aztreonam (at the discretion of the trial-site investigators). The primary outcome, overall treatment success 70 days after randomization (defined as survival, bacteremia clearance, symptom improvement, no new bacteremia-related complications, and no receipt of other potentially effective antibiotics), with a noninferiority margin of 15%, was adjudicated by a data review committee whose members were unaware of the trial-group assignments.

Moving Beyond Mortality: Development and Application of a Desirability of Outcome Ranking (DOOR) Endpoint for Hospital-Acquired Bacterial Pneumonia and Ventilator-Associated Bacterial Pneumonia.

Background: Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are frequently caused by multidrug-resistant organisms. Patient-centered endpoints in clinical trials are needed to develop new antibiotics for HABP/VABP. Desirability of outcome ranking (DOOR) is a paradigm for the design, analysis, and interpretation of clinical trials based on a patient-centered, benefit-risk evaluation.

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.

A Retrospective, Observational Study of 12 Cases of Expanded-Access Customized Phage Therapy: Production, Characteristics, and Clinical Outcomes.

Background: Antimicrobial resistance (AMR) is undermining modern medicine, a problem compounded by bacterial adaptation to antibiotic pressures. Phages are viruses that infect bacteria. Their diversity and evolvability offer the prospect of their use as a therapeutic solution.

Impact of an Inpatient Allergy Guideline on β-Lactam and Alternative Antibiotic Use.

Background: A guideline identifying when inpatients with penicillin or cephalosporin antibiotic allergy labels (PCAAL) can receive β-lactam antibiotics increased β-lactam receipt at a large northeastern US health care system.

Objective: To report outcomes of implementing a similar guideline and electronic order set (OS) at an independent academic health care system.

Methods: Penicillin/cephalosporin receipt (percentage of inpatients receiving full doses) and alternative antibiotic use (days of therapy per 1000 patient-days [DOT/1000PD]) were compared over 3 periods before (February 1, 2017, to January 31, 2018) and after guideline implementation (February 1, 2018, to January 31, 2019), and after OS implementation (February 1, 2019, to January 31, 2020) among inpatients with PCAAL admitted on medical services with access to guideline/OS and education (Medical-PCAAL, n = 8721), surgical services with access to guideline/OS without education (Surgical-PCAAL, n = 5069), and obstetrics/gynecology services without interventions (Ob/Gyn-PCAAL, n = 798) and inpatients without PCAAL admitted on the same services (Medical-No-PCAAL, n = 50,840; Surgical-No-PCAAL, n = 29,845; Ob/Gyn-No-PCAAL, n = 6109).