Antibiotics

Grand Rounds September 25, 2026: Research During Active War in Ukraine: Experiences From the PACT-ARROW Study (The Prevention and Treatment Clinical Trials for Antimicrobial Resistance Research to Improve Outcomes of Traumatic Wounds in Ukraine) (Corey Bills, MD, MPH, FACEP)

Posted on by Sophia Ramirez

Speaker

Corey Bills, MD, MPH, FACEP
Department of Emergency Medicine
Associate Professor | Emergency Medicine
Director | Global Emergency Care Initiative
Director | CU-WHO Collaborating Centre for Acute Care
Fellowship Director | Global Emergency Medicine and Public Health
Co-Principal Investigator | ATLAS Research Program
Colorado School of Public Health
Senior Investigator | Center for Global Health

Keywords

Conflict; War; Wounds; Wound Care; Antibiotics; Antimicrobial Resistance; Master Protocol; Ukraine

Key Points

  • Armed conflict has been shown to contribute to the development of antimicrobial resistance, which poses a major threat to human health. In the war in Ukraine, prolonged casualty-care in facilities with high circulation of resistant organisms, weak stewardship, and limited infection control increase the risk of infection.
  • There is little trial evidence for wound care in active conflict. Factors like data completeness, clinical priorities, logistics, layered approvals, an unstable environment, and attacks on healthcare make it difficult to conduct research. Without trials, treatment must rely on extrapolation and caution.
  • A master protocol facilitates research conducted during an armed conflict by pre-positioning ethics approvals, infrastructure, and standard outcomes. The PACT-ARROW master protocol applies a platform model to acute wound care in Ukraine, providing a framework for testing the safety, efficacy, and effectiveness of wound care interventions.
  • The research team began with an observational cohort, collecting longitudinal data from 905 adults with acute traumatic wounds: wound biospecimens, standardized photographs, clinical care data, and clinical outcomes. This showed which data were feasible before any intervention was tested. They found that many isolated bacteria had at least 1 concerning resistance gene to known commonly used antibiotics.

Discussion Themes

Dr. Bills shared lessons learned from implementation in an active war zone. He recommended keeping the data burden small with a minimum necessary dataset and limited follow-up; solving logistics locally; and working with partners for the sake of regulatory speed.

The trial developed from a confluence of U.S. Department of Defense funding opportunities, global acute care research expertise, and established pre-war trial partnerships with Ukrainian clinician-researchers.

The team partnered with Ukraine's Ministry of Health and Ministry of Defense to select 5 civilian hospital sites along active evacuation routes, where the median time from frontline injury to hospital study enrollment is approximately 6 days.

Grand Rounds May 31, 2024: INSPIRE Abdominal & Skin/Soft Tissue Infection Trials: INtelligent Stewardship Prompts to Improve Real-time Empiric Antibiotic Selection for Patients (Shruti K. Gohil, MD, MPH)

Posted on by Sophia Ramirez

Speaker

Shruti K. Gohil, MD, MPH
Assistant Professor, Infectious Diseases
Associate Medical Director, Epidemiology & Infection Prevention
University of California, Irvine School of Medicine

Keywords

Antibiotics; Antibiotic Resistance; Infection; Prompts; Clinical Decision-Making

Key Points

  • Multidrug-resistant organisms are a major public health threat, with more than 2.8 million antibiotic-resistant infections occurring annually in the U.S. This leads to increased readmissions, healthcare costs, and thousands of attributable deaths. Overprescribing is a major contributor to antibiotic resistance.
  • The culture of empiric antibiotic selection currently reflects a “start broad, narrow later” approach: an effort to avoid missing resistant infections at the cost of unnecessary broad spectrum antibiotics. The INSPIRE trials aim to encourage a new practice: “start narrow, broaden if needed,” in which physicians use data on resistance risk to spare broad spectrum antibiotic use. This delay in broadening is not high-risk for the vast majority of patients.
  • The 4 most commonly treated infections in U.S. hospitals (pneumonia, urinary tract infections (UTI), abdominal infections, and skin/soft tissue infections) do not reflect the multi-drug resistant organisms that physicians most worry about, but comprise the bulk of what physicians prescribe extended spectrum antibiotics for.
  • Risk factor research typically reports relative risk, AKA odds. This can exaggerate physician perception of risk. The INSPIRE trials sought to reframe risk perceptions by using absolute risk, based on a series of models for every extended-spectrum antibiotic and multidrug-resistant organism pair.
  • The research team developed a computerized provider order entry (CPOE) smart prompt, activated when a physician in a non-ICU location selected extended-spectrum antibiotics to treat abdominal or skin/soft tissue infections. These real-time prompts provided the absolute risk of infection due to multidrug-resistant organisms, in a manner that was patient-specific, infection syndrome-specific, and pathogen-specific.
  • The INSPIRE Abdominal and Skin/Soft Tissue Trials consisted of 2 cluster-randomized, 92-hospital trials. Arm 1 received routine care, and Arm 2 received the INSPIRE CPOE bundle intervention, in which physicians received the CPOE smart prompts recommending appropriate antibiotic choice.
  • The INSPIRE trials demonstrated the effectiveness of real-time, individualized smart prompts. In both the abdominal infection trial and the skin and soft tissue infection trial, the group that received the CPOE prompts saw a 35% and 28% reduction in extended-spectrum days of therapy, respectively. There was no difference in safety outcomes for either trial.
  • The intervention was rolled out as a bundle; this makes it difficult to know the impact of the individual components. One limitation of this intervention is that activating it requires CPOE capability and a live link to the EHR.
  • The research team took some proactive steps, including actively extracting and cleaning data starting in the CPOE prompt development stage. That allowed them to identify issues early in the process, adjust accordingly, and ultimately speed the analysis.
  • Precision medicine trials for antibiotic stewardship can work; physicians are willing to make different choices when they’re given the right kind of information. If you thoughtfully construct a prompt-based intervention and populate it with useful and applicable information, these interventions could help lead to new best practices for empiric treatment in the U.S.

Discussion Themes

The trial defined the threshold for acceptable risk – i.e., differentiated between high and low risk – at 10%. This was based on precedence set by the Infectious Diseases Society of America (IDSA) guidelines and vetted by the INSPIRE steering committee and national experts. Each patient had their own risk profile – comprised of a series of risk factors, pulled from the EHR – that the algorithm drew upon to place the patient on either side of the risk threshold.

Patient rates of ICU transfer and length of stay were equal between the intervention and control groups. This addresses a significant concern amongst physicians when it comes to reducing broad-spectrum antibiotic prescription, as many worry about incurring any unnecessary risk for their patients.

The prompts were intensely vetted. One important consideration making sure they appeared only for low-risk patients. This was an important step in getting local physicians on board with the prompts as a clinical decision support tool. Stewardship teams played an important role in this provider education.

Nurse practitioners, physician assistants, and residents were another key audience, as they often play a significant role in ordering antibiotics.