Two Major Trials Identify Effective Antibiotic Selection Method for Hospitalized Infection Patients
In a significant advancement for infectious disease care and antibiotic stewardship, two large-scale clinical trials funded by the National Institutes of Health (NIH) have demonstrated that integrating real-time, patient-specific decision support into hospital workflows can greatly enhance the accuracy of antibiotic prescribing practices. Conducted by a team of researchers from the University of California, Irvine, Harvard Pilgrim Health Care Institute, and HCA Healthcare, the studies offer compelling evidence that personalized electronic alerts embedded within hospital systems can help clinicians select the most appropriate antibiotics for patients suffering from abdominal or skin and soft tissue infections (SSTIs).
The results of the trials — known collectively as the INSPIRE Abdominal and Skin & Soft Tissue Trials — were published in JAMA Surgery and JAMA Internal Medicine, two of the most respected journals in their respective fields. The findings were also highlighted at the prestigious Congress of the European Society of Clinical Microbiology and Infectious Diseases, underscoring their global relevance and potential for impact.
Addressing a Global Public Health Threat
Antibiotic resistance remains one of the most pressing public health crises worldwide. Infections caused by drug-resistant bacteria are more difficult to treat, often necessitating longer hospital stays, additional medical interventions, and more expensive or toxic medications. These infections also increase the risk of severe complications and death. According to the Centers for Disease Control and Prevention (CDC), over 2.8 million cases of antibiotic-resistant infections occur annually in the United States alone. On a global scale, the World Health Organization (WHO) reported that bacterial resistance was responsible for approximately 1.27 million deaths in 2019 — a figure expected to rise dramatically if current prescribing trends continue.
One of the key drivers of this crisis is the overuse and misuse of broad-spectrum antibiotics, which are designed to target a wide array of bacterial species but also indiscriminately disrupt the body’s natural microbiota. This not only reduces the effectiveness of treatment for the patient but also increases the likelihood of resistance developing within the hospital and broader community. Over time, these resistant strains can become dominant, rendering common antibiotics ineffective and making even routine medical procedures increasingly risky.
Study Design: Harnessing the Power of Electronic Health Data
Recognizing the need for innovative solutions to combat this trend, the research team implemented a sophisticated alert system across 92 community hospitals operated by HCA Healthcare, a leading U.S. provider of inpatient medical care. The hospitals, located in 15 states, represent a diverse and extensive patient population, ensuring that the study findings are highly generalizable.
The trials enrolled more than 316,000 patients hospitalized with abdominal or skin and soft tissue infections. These are among the most common infections treated in inpatient settings and are major contributors to the overprescription of broad-spectrum antibiotics.
In half of the participating hospitals, physicians received real-time computerized alerts as they ordered antibiotics for these conditions. These alerts were generated using advanced algorithms that assessed each patient’s risk of harboring antibiotic-resistant bacteria. The system used a combination of data points, including individual patient medical histories, local antibiotic resistance patterns, and broader hospital-specific epidemiological trends, all extracted from electronic medical records (EMRs).
When the alert system determined that a patient had a low risk of resistant infection but was being prescribed a broad-spectrum antibiotic, it prompted the prescribing physician to consider switching to a narrower-spectrum, standard antibiotic. In this way, the system encouraged a more targeted approach to treatment — matching the antibiotic’s spectrum to the patient’s actual clinical need rather than defaulting to a one-size-fits-all, overly aggressive regimen.
Impactful Results: Improved Prescribing Without Compromising Care
The intervention yielded substantial improvements in prescribing behavior. In patients with abdominal infections, appropriate antibiotic selection improved by 35% in the intervention group compared to the control group. Similarly, among those with skin and soft tissue infections, correct antibiotic selection improved by 28%. These are remarkable gains given the complexity of diagnosing and treating bacterial infections, especially in time-sensitive hospital settings.
Notably, these improvements did not require major changes to hospital infrastructure or clinical workflows. Instead, the success stemmed from giving physicians access to highly relevant information exactly when they needed it — at the point of care. By leveraging data already available in the hospital system and applying it through intelligent alerting mechanisms, the researchers demonstrated a scalable, low-barrier solution that can be replicated in other health systems across the country and potentially around the world.
This trial builds on the success of two earlier studies by the same research team that focused on pneumonia and urinary tract infections (UTIs) — two other leading causes of hospitalization and broad-spectrum antibiotic use. Taken together, the four INSPIRE trials now encompass the most common infection types responsible for hospital admissions and collectively form one of the most comprehensive efforts to modernize antibiotic stewardship using real-world evidence and digital innovation.
Clinical and Policy Implications
The implications of these findings extend far beyond the walls of the hospitals that participated in the studies. With the increasing integration of EMRs and decision-support tools in hospitals worldwide, the INSPIRE model offers a practical roadmap for health systems looking to enhance patient safety, reduce costs, and tackle the growing threat of antimicrobial resistance.
“This is a powerful example of how the right information at the right time can significantly improve care,” said Dr. Shruti Gohil, MD, MPH, an associate professor in the Division of Infectious Diseases at the UC Irvine School of Medicine and one of the principal investigators of the study. “Abdominal and soft tissue infections can be caused by a variety of bacteria, making it difficult to select the right antibiotic. These studies show that using patient-specific data to inform prescribing decisions helps reduce unnecessary use of extended-spectrum antibiotics, which in turn lowers the risk of adverse events and antibiotic resistance.”
Indeed, the risks of overprescribing broad-spectrum antibiotics are not merely theoretical. Such practices have been directly linked to increased rates of Clostridioides difficile (C. difficile) infections, as well as liver and kidney toxicity — all of which can result in longer hospital stays, readmissions, or even death. By promoting more judicious use of antibiotics, the INSPIRE alert system supports both individual patient safety and broader public health goals.
Scaling Up: A Nationwide Model
HCA Healthcare has already begun rolling out the alert system based on earlier INSPIRE studies across its 190 hospitals, signaling a strong commitment to transforming antibiotic stewardship across its network. “HCA Healthcare is committed to using our scale and data ecosystem to answer important clinical questions that benefit patients,” said Dr. Kenneth Sands, MD, MPH, Chief Epidemiologist at HCA Healthcare. “The ability to identify patients at low risk for antibiotic resistance and adjust prescribing accordingly can help hospitals meet stewardship goals and ultimately reduce the national burden of antimicrobial resistance.”
Moreover, the collaboration between academic institutions and a large healthcare provider demonstrates the power of public-private partnerships in generating high-quality, practice-changing clinical research. The studies were the product of a long-standing partnership among HCA Healthcare, Harvard Pilgrim Health Care Institute, and the University of California, Irvine — a model that can be emulated in other areas of healthcare innovation.
As antibiotic resistance continues to challenge healthcare systems globally, the INSPIRE studies offer a hopeful path forward. By harnessing the power of data-driven decision support and embedding it into routine clinical practice, health systems can make measurable progress in preserving the efficacy of existing antibiotics — a finite and invaluable resource.
The stakes could not be higher. Without such innovations, the world faces a future in which simple infections once again become life-threatening, and routine surgeries carry unacceptable levels of risk. With the publication of these groundbreaking findings, a new standard for infection management may be on the horizon — one that is smarter, safer, and better tailored to the individual patient.
