Trials Identify Better Way to Select Antibiotics for UTIs, Pneumonia in Inpatients

Algorithm-driven prompts with patient-specific estimates about their risk of having a multidrug-resistant infection significantly reduced the use of empiric extended-spectrum antibiotics in adults hospitalized for urinary tract infections (UTIs) or pneumonia, according to results from two cluster randomized trials.

In the INSPIRE UTI trial, use of the computerized provider order entry (CPOE) stewardship bundle -- including education, feedback, and real-time and risk-based CPOE prompts -- resulted in a 17.4% reduction in the empiric use of these antibiotics compared with routine antibiotic stewardship. And the CPOE bundle in the INSPIRE Pneumonia trial resulted in a 28.4% reduction, reported Shruti K. Gohil, MD, MPH, of the University of California Irvine School of Medicine, and colleagues in JAMA.

Use of these drugs was reduced without significantly affecting the safety outcomes of days to intensive care unit (ICU) transfer and hospital length of stay.

"The right information at the right time can improve physician antibiotic selection," Gohil said in a press release. "Many different bacteria can cause pneumonia or UTI, and picking the best matched antibiotic can be a challenge. Results from these trials show that giving physicians an alert informing them of their patient's actual risk for antibiotic resistance can help them choose the best antibiotic and reduce extended-spectrum antibiotic use."

In an editorial accompanying the study, Anurag N. Malani, MD, of Trinity Health Michigan in Ann Arbor, and Preeti N. Malani, MD, of the University of Michigan in Ann Arbor, who is a JAMA deputy editor, said the INSPIRE trials "do just that -- provide inspiration and imagination, along with a powerful paradigm to harness the EHR [electronic health record] to optimize antibiotic prescribing and improve human health."

According to Gohil and colleagues, as many as 40% of patients hospitalized for UTIs and half of those hospitalized for pneumonia unnecessarily receive extended-spectrum antibiotics. In the case of UTIs, even brief antibiotic exposures can alter gut and urinary microbiomes, predisposing patients to UTI recurrence, while both patients with UTIs and pneumonia risk future multidrug-resistant organism infections, Clostridioides difficile infection, and other adverse effects.

Thus, additional safe strategies are needed to limit extended-spectrum antibiotics in these patients, they argued.

The study authors compared routine stewardship -- such as education on national standards for empiric antibiotic treatment and feedback -- with the CPOE bundle composed of routine stewardship plus CPOE prompts that recommended standard-spectrum instead of extended-spectrum antibiotics during the first 3 hospital days (empiric period) for patients with a low absolute risk (<10%) of multidrug-resistant organism infection.

The studies were conducted at a network of 59 geographically diverse community hospitals across the U.S. that were randomized to routine antibiotic stewardship or use of the CPOE bundle, and included an 18-month baseline period (April 2017 through September 2018), a 6-month phase-in period (October 2018 through March 2019), and a 15-month intervention period (April 2019 through June 2020).

Malani and Malani called the decision to focus on empiric antibiotic use in the first few days of hospitalization noteworthy, since hospital-based stewardship efforts usually emphasize de-escalation after microbiologic test results are returned, "and few focus on initial empiric prescribing."

The editorialists also cautioned that while the intervention used in the INSPIRE trials seems simple, integrating it into existing clinical workflows could be challenging, since this would require strong support from leadership, as well as collaboration among different groups of frontline clinicians. In addition, the fact that hospitals and health systems use different EHRs could be a hurdle to widespread implementation.

"Potential barriers highlight the need for additional studies that focus on the implementation of an intervention using CPOE prompts, especially in settings with a more limited stewardship footprint," wrote Malani and Malani.

INSPIRE UTI

The INSPIRE UTI trial included 127,403 adults (71,991 during the baseline period and 55,412 during the intervention period) who were hospitalized with UTIs. Mean age was 69.4 years, 30.5% were men, and the median Elixhauser Comorbidity Index count was 4.

Receipt of any empiric extended-spectrum antibiotics was 40.9% during the baseline period and 42.6% during the intervention period for the routine stewardship group compared with 37.3% and 33.5%, respectively, for the CPOE bundle group.

For the primary outcome, empiric extended-spectrum days of therapy per 1,000 empiric days was 431.1 during the baseline period and 446 during the intervention period for the routine stewardship group. For the CPOE bundle group, extended-spectrum days of therapy per 1,000 empiric days decreased from 392.2 during the baseline period to 326 during the intervention period.

When clustering by hospital and period, this resulted in an overall rate ratio of 0.83 (95% CI 0.77-0.89, P<0.001) for the primary outcome.

The percentage of patients transferred to the ICU was 4% for the routine group versus 3.7% for the intervention group, and the percentage requiring antibiotic escalation was 10.2% versus 10%, respectively.

The safety outcomes of mean days to ICU transfer (6.6 vs 7 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups.

INSPIRE Pneumonia

This trial included 96,451 patients (51,671 in the baseline period and 44,780 in the intervention period) hospitalized with pneumonia. Mean age of patients was 68.1 years, 48.1% were men, and the median Elixhauser Comorbidity Index was 4.

Receipt of any empiric extended-spectrum antibiotics was 51.5% during the baseline period and 50.1% during the intervention period for the routine stewardship group, and 50% and 38.1%, respectively, for the CPOE bundle group.

For the primary outcome, empiric extended-spectrum days of therapy per 1,000 empiric days was 633 during the baseline period and 615.2 during the intervention period for the routine stewardship group. For the CPOE bundle group, extended-spectrum days of therapy per 1,000 empiric days decreased from 613.9 during the baseline period to 428.5 during the intervention period.

The overall rate ratio when clustering by hospital and period was 0.72 (95% CI 0.66-0.78, P<0.001).

The percentage of patients transferred to the ICU was 6.9% in the routine group versus 6.7% in the CPOE bundle group, while the percentage requiring antibiotic escalation was 11.9% versus 10.8%, respectively.

As with the UTI study, the safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and intervention groups.