A randomized clinical trial conducted in Canada found that a core strategy of antimicrobial stewardship programs can help safely reduce antibiotic use in patients admitted to the hospital with COVID-19, researchers reported late last week in The Lancet Infectious Diseases.
The investigators say the trial, which was conducted at three hospitals in Edmonton, is the first known study to evaluate the use of prospective audit and feedback for optimizing antibiotic therapy in COVID-19 patients.
No negative effect on patient outcomes
For the prospective, cluster-randomized clinical trial, a team led by investigators with the University of Alberta enrolled adults who were admitted to one of three acute care hospitals for the treatment of COVID-19 pneumonia from Mar 1, 2021 to Oct 29, 2021. COVID-19 unit and critical care unit beds were stratified and randomly assigned on a 1:1 basis to a prospective audit and feedback plus standard of care group (the intervention group) or the standard of care group (the control group).
In the intervention group, physicians and pharmacists on each hospital's antimicrobial stewardship team reviewed eligible patients on the day they were enrolled, if and when they were prescribed an antibiotic, then conducted weekly audits thereafter. Appropriateness of antibiotic prescribing was assessed against local clinical guidelines.
The primary outcome was clinical status on post-admission day 15, measured using a 7-point ordinal scale (with 1 defined as not hospitalized and able to resume normal activities and 7 defined as death). The non-inferiority margin was 0.5.
A total of 429 patients in the intervention group and 404 in the control group completed the study. The overall mean age in both groups was 56.7 years, 56% were men, and the median baseline ordinal scale score was 4 (hospitalized and on supplemental oxygen). Antibiotics were prescribed for 438 (53%) of 833 patients at enrollment, and the rate of culture-positive bacterial co-infection was 4%.
Among patients hospitalised with COVID-19 pneumonia, rationalising antibiotic therapy with antimicrobial stewardship prospective audit and feedback interventions did not negatively affect patient outcomes despite an overall reduction in antibiotic use
In the intervention group, 301 prospective audit and feedback events were recorded, 119 antibiotic prescriptions were deemed guideline-discordant, and 215 recommendations were made to optimize care, with an acceptance rate of 84%. The most common recommendation was discontinuation of antibiotic therapy (57%), followed by a change in duration of therapy (21%) and a change in antibiotic agent (8%).
Despite lower antibiotic use in the intervention group than in the control group (length of therapy 364.9 vs 384.2 days per 1,000 patient days), the clinical status at post-admission day 15 was the same in both groups—2 (not hospitalized and unable to resume normal daily activities). The secondary outcomes of in-hospital mortality (11% vs 13%), 30-day mortality (11% vs 12%), acute length of hospital stay (9.59 vs 11.03 days), and 30-day readmission rates (4% vs 5%) were also similar in both groups.
"Among patients hospitalised with COVID-19 pneumonia, rationalising antibiotic therapy with antimicrobial stewardship prospective audit and feedback interventions did not negatively affect patient outcomes despite an overall reduction in antibiotic use," the study authors wrote. "Despite many competing priorities during the COVID-19 pandemic, antimicrobial stewardship should remain a priority to mitigate the pervasive overuse of antibiotics in patients with the disease."
Antibiotic use in COVID-19 patients remains high
The findings are noteworthy, because high rates of antibiotic use in COVID-19 patients has been observed throughout the pandemic, despite the increasing availability of vaccines, antiviral agents, and other treatments and the fact that multiple studies have found low incidence of bacterial coinfections similar to this study's findings. Many fear that the overuse of antibiotics during the pandemic has increased the rates of antibiotic resistance.
A review and meta-analysis published in January 2021 found that the prevalence of antibiotic prescribing in COVID-19 patients in the first year of the pandemic, when there were fewer treatment option and clinicians were still learning how to manage COVID-19, was 74.6%. Subsequent studies have found that fewer antibiotics have been used since then, but empiric antibiotic use in COVID-19 patients remains high, while the incidence of bacterial co-infections is low.
In an accompanying commentary, infectious disease specialists from the University of Genoa say that even though the rate of antibiotic use observed in the trial (53%) was lower than other studies have found, it still remains "uncomfortably high from an antimicrobial stewardship perspective."
"Although some encouraging steps forward have been made, a lot of ground is still left to cover," they wrote.