By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Synopsis: A cluster randomized clinical trial assessed the effect of an antibiotic stewardship bundle that included computerized provider order entry (CPOE) prompts vs. routine stewardship on antibiotic selection during the first three hospital days in noncritically ill adults hospitalized with skin and soft tissue infections. CPOE prompts significantly reduced use of extended-spectrum antibiotics without increasing admissions to intensive care units or hospital length of stay.
Source: Gohil SK, Septimus E, Kleinman K, et al. Improving empiric antibiotic selection for patients hospitalized with skin and soft tissue infection: The INSPIRE 3 skin and soft tissue randomized clinical trial. JAMA Intern Med. 2025;185:680-691.
Broad-spectrum antibiotics exert selective pressure on bacteria and are one of the main drivers of antimicrobial resistance (AMR). Unfortunately, these drugs frequently are prescribed for noncritically ill adults hospitalized with skin and soft tissue infections (SSTIs). Computerized provider order entry (CPOE) prompts have emerged as an important tool for antibiotic stewardship programs, providing real-time guidance to clinicians when they order antibiotics. Gohil and colleagues sought to determine whether CPOE prompts presenting patient-specific and pathogen-specific multidrug-resistant organism (MDRO) infection risk estimates could decrease empiric broad-spectrum antibiotics for noncritically ill hospitalized patients with SSTIs.
The study was a cluster randomized clinical trial (INSPIRE 3, Intelligent Stewardship Prompts to Improve Real-Time Empiric Antibiotic Selection) comparing the effect of routine antibiotic stewardship to a CPOE stewardship bundle on empiric broad-spectrum antibiotic selection. Patients were included who were at least 18 years of age and hospitalized for an SSTI at HCA Healthcare, the largest private community hospital system in the United States. Patients were excluded who transferred to the intensive care unit (ICU) within two calendar days of admission.
For the study, researchers randomly assigned hospitals 1:1 to the routine stewardship group or the CPOE bundle group. The routine stewardship group hospitals received educational materials and quarterly coaching calls to maintain stewardship activities according to national guidance. The CPOE bundle group hospitals also received all of the education and activities for the routine stewardship group and monthly coaching calls. In addition, they received CPOE prompts recommending standard-spectrum antibiotics instead of broad-spectrum antibiotics during the first three hospital days for patients with an absolute risk less than 10% of Pseudomonas aeruginosa or MDRO SSTI; clinician education about risk estimate calculations and local P. aeruginosa or MDRO SSTI prevalence, investigator site visits to each hospital during the phase-in period, and webinars; and clinician SSTI antibiotic prescribing reports.
The study’s primary outcome was broad-spectrum antibiotics days of therapy in the first three calendar days of hospitalization, calculated as the total number of different broad-spectrum antibiotics targeting P. aeruginosa and/or MDR gram-negative bacteria received per patient each calendar day beginning at admission. The secondary outcome was antipseudomonal days of therapy. The safety outcomes were days to ICU transfer and hospital length of stay.
There were 118,562 patients admitted with an SSTI during the study period. Of these, 67,033 (56.7%) were male and the mean (standard deviation, SD) age was 58.0 (17.5) years. Hospitals assigned to the CPOE bundle reported a 27.5% reduction in broad-spectrum antibiotic days of therapy (rate ratio, 0.72; 95% confidence interval [CI], 0.67-0.79; P < 0.001) compared to the routine antibiotic stewardship group. Of the 6,886 clinicians in the CPOE bundle hospitals, 657 (9.5%) changed their orders from broad-spectrum to narrow-spectrum antibiotic therapy after receiving a real-time prompt during antibiotic ordering. Antipseudomonal days of therapy also were reduced in the CPOE bundle group compared to the routine antibiotic stewardship group.
The percentage of patients transferred to the ICU was similar in both groups, with 3.0% (835 of 27,837) in the routine stewardship group and 3.0% (784 of 26,174) in the CPOE bundle group. For the safety outcomes, there was no evidence of inferiority for the CPOE bundle group regarding days to ICU transfer (hazard ratio [HR], 1.14; 90% CI, 1.00-1.31) or hospital length of stay (HR, 0.99; 90% CI, 0.95-1.04).
Commentary
The study found that CPOE prompts recommending narrow-spectrum empiric antibiotics for low-risk patients hospitalized with SSTIs along with education and feedback significantly reduced the use of broad-spectrum antibiotics without increasing admissions to the ICU or hospital length of stay. Thus, CPOE can be a valuable method for reducing unnecessary broad-spectrum antibiotic prescribing. Although the electronic prompts were a main feature of the CPOE bundle, the actual number of clinicians who changed from a broad-spectrum to a narrow-spectrum antibiotic was fairly small (i.e., 657 out of 6,886; 9.5%). Therefore, it is likely that other aspects of the bundle, or implementation of the bundle itself, were just as important in changing antibiotic prescribing as the real-time prompts. For example, explaining the rationale for the alerts may have addressed knowledge deficits and thereby promoted the change in behavior.
There are a few limitations to the study worth noting. First, the facilities were all community hospitals, which may limit the generalizability of the results to other settings. Second, positive skin cultures were included regardless of specimen quality, so it was not possible to differentiate colonization from infection. Finally, the investigators were not able to separate the effects of the prompts from education and feedback; thus, the true effect of the CPOE prompts remains uncertain.
This study is an important advancement for antibiotic stewardship. Combining CPOE with artificial intelligence could further aid clinicians in making informed and rational decisions about appropriate antibiotic prescribing, thereby leading to a reduction in antimicrobial resistance and improving patient safety. Further studies that investigate CPOE prompts for other common infections for which overly broad antibiotics frequently are prescribed (e.g., community-acquired pneumonia and urinary tract infections) are warranted.
Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC, is Professor of Medicine, Division of Infectious Diseases, Northeast Ohio Medical University, Rootstown, OH.
A cluster randomized clinical trial assessed the effect of an antibiotic stewardship bundle that included computerized provider order entry (CPOE) prompts vs. routine stewardship on antibiotic selection during the first three hospital days in noncritically ill adults hospitalized with skin and soft tissue infections. CPOE prompts significantly reduced use of extended-spectrum antibiotics without increasing admissions to intensive care units or hospital length of stay.
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