Jessica Howard-Anderson

Background: Prevalence surveys in U.S. hospitals in 2011 and 2015 showed that half of inpatients received antimicrobials on the survey day or day before. We repeated the survey in 2023 to assess changes in antimicrobial use (AU). Methods: Ten Emerging Infections Program (EIP) sites recruited up to 25 hospitals each, prioritizing prior participants. EIP staff reviewed medical records of randomly selected inpatients from the survey day morning census and documented AU on the survey day or day before. We compared AU and stewardship characteristics between 2023 and 2015 and used multivariable log-binomial regression to identify factors associated with AU in 2023. Results: Antimicrobial stewardship programs were present in 215/218 hospitals in 2023 (98.6%) compared with 158/199 (79.4%) in 2015. Of 13 653 patients in 2023, 6785 (49.7%) received ≥1 antimicrobial on the survey day or day before. Among 151 hospitals participating in both surveys, overall AU prevalence was similar in 2015 and 2023 (49.2% vs 49.1%), with decreases in neonatal critical care (23.4% to 17.1%) and increases in mother–baby units (24.4% to 32.8%). Fluoroquinolone use declined (9.2% to 2.8%), while third- or fourth-generation cephalosporin use increased (12.3% to 18.6%). In 2023, higher AU was associated with patient factors (medical devices, inpatient location, obesity, 4–17 day hospital stays, and suburban residence) and hospital factors (Northeast and South regions, AU audits). Conclusions: One in two inpatients received an antimicrobial in 2023, similar to 2015. However, changes in AU by inpatient location and antimicrobial class suggest evolving prescribing practices and may inform targeted surveillance and stewardship efforts.

Objective: Use the electronic health record (EHR) to prospectively validate a risk prediction tool identifying patients at high-risk for carbapenem-resistant Enterobacterales (CRE). Design: Prospective, cross-sectional analysis. Participants: Adults admitted to two hospitals in Atlanta, Georgia. Methods: An EHR report calculated a CRE risk score on all admissions from 6/2024–3/2025. The risk score was determined from a prior model incorporating data from current and prior hospitalizations. Stool or perianal samples were cultured from a convenience sample of patients with the highest risk scores. A receiver operating curve analysis calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) of various risk scores that could be used as a “threshold” for CRE admission testing. Using the threshold with the greatest Youden’s index, we estimated the cost of implementing a CRE screening program. Results: Of the 853 patients approached, 342 (40%) consented. Eleven (3.2%) tested positive for CRE. Patients with CRE had a higher median CRE risk score (0.19% vs 0.04%) than those who tested negative. The AUC of the model was 0.66. Using a testing threshold of 0.16% yielded a 55% sensitivity, 84% specificity, 10% PPV, and 98% NPV. The number needed to screen to diagnose 1 patient with CRE was 12 patients, and the screening program approximately costs $8,015/month. Conclusions: An EHR-based risk prediction tool can detect patients likely to be colonized with CRE. In facilities with a low CRE prevalence, identifying a high-risk subset of patients to test could be a cost-effective infection prevention initiative.

Background: Desirability of outcome ranking (DOOR), a paradigm for the design, analysis, and interpretation of clinical trials based on patient-centered benefit-risk evaluation, could help inform drug development for acute bacterial skin and skin structure infections (ABSSSIs). Method: A multidisciplinary committee created an infectious diseases DOOR endpoint, incorporating clinical response, infectious complications, serious adverse events, and mortality, and adapted this for ABSSSI. We retrospectively applied DOOR to 2 previous ABSSSI randomized controlled registrational trials (OASIS-1 and OASIS-2), both comparing omadacycline with linezolid. We evaluated the DOOR distribution and estimated the probability of having a more desirable outcome with omadacycline compared with linezolid. For OASIS-2, we used the 36-Item Short Form Health Survey Version 2 (SF-36v2) scores as a “tiebreaker” for participants who would otherwise have the same DOOR outcome. We performed DOOR component, partial credit, and subgroup analyses. Results: The ABSSSI DOOR demonstrated similar overall clinical outcomes between treatment arms for OASIS-1 and OASIS-2. The probability of a more desirable outcome for a participant treated with omadacycline, compared with linezolid, was 50.6% (95% confidence interval [CI], 47.4%–53.7%) and 52.1% (95% CI, 49.2%–55.0%) in OASIS-1 and OASIS-2, respectively. In OASIS-2, applying a health-related quality-of-life score as a tiebreaker did not significantly change the DOOR probability. Partial credit and subgroup analyses demonstrated similar overall results. Conclusions: DOOR may provide additional perspective on benefit versus risk in individual patients in ABSSSI trials. Future trials using DOOR prospectively will continue inform how to incorporate patient-centered outcomes in ABSSSI trials.

Background: Group A Streptococcus (GAS) infections are common in children, ranging from mild to life-threatening invasive disease. Large-scale descriptions of changes in pediatric invasive GAS infections in the United States, particularly during the COVID-19 pandemic, are limited. Methods: We used CDC’s Active Bacterial Core surveillance (ABCs), a multistate, population- and laboratory-based surveillance system, to assess changes in pediatric (<18 years old) invasive GAS incidence, clinical presentation, and bacterial strain characteristics from 2004–2023. Interrupted time series analysis was used to compare observed versus expected GAS incidence during 2020–2023, informed by trends before the COVID-19 pandemic (2004–2019). Results: During 2004–2023, 2,856 invasive GAS cases were identified. Incidence remained stable from 2004–2019 (mean incidence 1.9 per 100,000), decreased in 2020 (1.0) and 2021 (0.6), and rebounded in 2022 (1.5) and 2023 (4.4). ICU admission increased from 2011 to 2023; case fatality remained stable. Penicillin resistance was not detected. Clindamycin non-susceptibility doubled from 2011 (3.8%) to 2022 (7.5%), before slightly decreasing in 2023 (6.4%). Infections due to emm1, the most frequently identified emm type in children with severe disease, almost disappeared in 2021 but surged in late 2022. Conclusions: After remaining stable for more than a decade, pediatric invasive GAS incidence declined during the COVID-19 pandemic and rebounded in 2022, more than doubling 2004–2019 incidence in 2023. While case fatality remained low, ICU admissions increased over time, highlighting the need for effective preventive measures such as vaccines. Increasing clindamycin non-susceptibility bears continued monitoring.

Randomized clinical trials are the gold standard for evaluating the benefits and harms of interventions and yet may not provide the evidence needed to inform medical decision-making, an ultimate goal for clinical research. Commonly used design and analysis approaches are often not suited to answer the most important questions to inform clinical practice, specifically how do resulting patient experiences, when comprehensively considering benefits and harms, compare between therapeutic alternatives? The standard approach of siloed analysis of one outcome at a time: (i) does not incorporate associations between multiple outcomes; (ii) does not recognize the cumulative nature of multiple outcomes in individual patients or recognize important gradations of global patient response; (iii) suffers from competing risk complexities during interpretation of individual outcomes; (iv) provides for ambiguous generalizability with respect to benefit:risk since efficacy and safety analyses are often conducted on different populations. Evaluation of treatment effect heterogeneity to identify subgroups for treatment or avoidance of treatment is typically evaluated based on a single efficacy or safety endpoint and rarely evaluated based on the overall benefit:risk. Methods that quantify and compare the patient experience are needed. The desirability of outcome ranking (DOOR) is a paradigm for the design, monitoring, analysis, interpretation, and reporting of clinical trials and other research studies based on patient-centric benefit:risk evaluation, developed to address these issues and advance clinical trial science. Aligning the clinical research strategy with the relevant question for clinical practice will enhance research applicability. Careful design and comprehensive analyses are critical for DOOR paradigm application. We provide a recommended statistical analysis plan for research studies implementing DOOR, describe its elements, and illustrate analysis application using examples. A freely available online tool for the recommended analyses and the design of studies implementing the DOOR paradigm is provided.

We surveyed physicians and patients to create a novel Desirability of outcome ranking (DOOR) for non-severe community-acquired pneumonia (CAP). Patients generally ranked uncomfortable but non-life-threatening symptoms as less desirable, while physicians focused on traditional medical outcomes. When developing DOORs, both patient and clinician perspectives should be considered.

We explored the impact of infectious disease (ID) consultations on hospitalists’ prescribing of broad-spectrum, hospital-onset (BSHO) antibiotics. Periods with more ID consults had increased BSHO-DOT; however, this relationship was nonlinear, and ID consult frequency did not explain variability in prescribing. ID consultation should be considered when creating prescriber performance metrics.

Background and objectives: New antibiotics effective against carbapenem-resistant Enterobacterales (CRE) provide additional treatment options, but data on clinician decision-making are limited. We sought to understand treatment preferences, factors influencing antibiotic selection for CRE infections and barriers to prescribing newer agents. Methods: We surveyed infectious disease clinicians through the Infectious Diseases Society of America (IDSA) Emerging Infections Network (EIN) about their experience treating CRE infections, availability of resistance mechanism testing, antibiotic choices in four CRE infection scenarios and barriers to using newer antibiotics. We used the 2023 IDSA Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections to classify antibiotic selections for the scenario-based questions as preferred approach, alternative option or not in guidance. Results: Overall, 441 EIN members responded. Among these, 337 (76%) reported treating a CRE infection in the last year. For the clinical scenarios, 851 (63%) of 1356 selections were IDSA-preferred approaches; of these, 653 (77%) were for ceftazidime-avibactam, either alone (n = 456) or in combination with aztreonam (n = 197), more than for other β-lactam/β-lactamase inhibitor combination agents active against CRE. For an uncomplicated urinary tract infection caused by carbapenem-resistant Klebsiella pneumoniae, where no preferred approaches were available, the most common antibiotic selected was oral fosfomycin (169/343 (49%)). Conclusions: Most clinicians selected antibiotics aligned with the IDSA guidance for serious CRE infections, although the frequent selection of an agent not in the guidance for uncomplicated cystitis suggests that treatment selection is complex and may depend on infection severity, among other factors. The preference for ceftazidime-avibactam among similar agents is notable and may reflect its longer market availability.

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.