Following the implementation of a guideline outlining antibiotic use for bacterial pneumonia among COVID-19 inpatients, we observed a 32.5% absolute reduction in antibiotic prescribing and a 1.3-day shorter duration of therapy. The reduction in duration of therapy was most pronounced with antibiotics targeted at atypical pathogens (e.g. azithromycin, doxycycline, levofloxacin) likely due to guideline recommendations to utilize the RBVP panel and Legionella urinary antigen results to aid in de-escalation decisions. Of note, at no point was the use of azithromycin recommended as part of the institution’s COVID-19 treatment guideline (in the absence of possible bacterial pneumonia). As every patient received an ID consultation, we were able to monitor this practice directly. Similar to previous reports1-4, we observed a high rate of antibiotic prescribing (49%, 246/505) among patients admitted with COVID-19 despite available data suggesting that bacterial co-infection is uncommon among patients with the disease. Our data similarly reflects low rates (4.5%) of co-infection with bacterial pathogens which further supports a need for stewardship interventions to reduce antimicrobial prescribing in this patient population. We found that guideline implementation reinforced by ID COVID-19 Consultation Service recommendations was able to fill this need and increase appropriate antibiotic initiation and de-escalation for CABP in this population.
We observed a higher percentage (non-statistically significant) of patients being re-initiated on antibiotics in the post-intervention group for the indications of hospital-acquired or ventilator-associated pneumonia. Whether the continuation of empiric antibiotics initiated within 48hours of admission for CABP would have prevented the need to reinitiate antibiotics in these patients is unclear, though unlikely as antibiotics initiated for CABP would have likely been narrower in spectrum than what would be necessary to treat nosocomial pathogens.
Other targets for antimicrobial stewardship interventions include duration of therapy, guideline concordant selection of antibiotics, and intravenous to oral conversion of antibiotics.8-19 Stewardship interventions targeting these aspects of antibiotics for the indication of CABP have been found to be associated with reduced length of stay,12,18 improved concordance with guideline recommended management (antibiotic selection and duration),13-16,19 reduced duration of IV antibiotics,10,17,18 and fewer adverse drug reactions.12 While the benefits of stewardship interventions for patients with CABP in general has been shown in these previous studies, this is the first study to evaluate the impact of ASP on antibiotic use for CABP among patients with COVID-19.
To our knowledge, this is the first report of an antimicrobial stewardship intervention to reduce the prescribing of empiric antibiotics for CABP in COVID-19 patients. Reductions in antibiotic use have important implications and can potentially reduce antimicrobial resistance and antibiotic-related toxicities.2 Several previous studies have evaluated the impact of stewardship interventions on CABP therapy among the general population. Similar to our findings, most of these studies found no difference in clinical outcomes, suggesting a lack of harm with reduced antibiotic use.8-10 Furthermore, two previous studies have identified a mortality benefit with antibiotic de-escalation in the setting of CABP (15.1% vs. 25%, p=0.04 and 1.8% vs. 5.5%, p=0.04), and one found a significantly reduced length of stay (5 vs. 9 days, p<0.001).10-11 Additional findings that support the safety of reduced antibiotic prescribing in our study include similar rates of antibiotic re-initiation and readmission between groups.
There are a few pertinent limitations to outline. Given the quasi-experimental study design, there are several confounders that may have contributed to the study results. First, the higher rate of mechanical ventilation in the pre-intervention group suggests the disease severity at baseline may have differed between groups. However, this difference may be attributed to changes in critical care practice in utilization of non-invasive ventilatory interventions such as proning, high flow nasal cannula, and helmet ventilation.20 Additionally, more patients in the post-intervention group had fever and leukocytosis, which also speaks to impact of the intervention in terms of facilitating appropriate initiation of empiric antibiotics based on the presence of fever and/or leukocytosis. Second, after several weeks of managing COVID-19 inpatients, there was likely improved clinician comfort with COVID-19 management as well as more data suggesting low concern for bacterial co-infection during the post-intervention period. Third, changes in SARS-CoV-2 testing may have resulted in a reduced turnaround time in the post-intervention period. Although the timeliness of the SARS-CoV-2 test result may not have had a direct impact on prescribing empiric antibiotics, this may have contributed to a longer duration of antibiotics in the pre-intervention period. Lastly, this study was underpowered and not designed to investigate clinical outcomes such as adverse drug effects, mortality, and length of stay.
In conclusion, a targeted clinical guideline implemented by an ASP/ID COVID-19 consult service was an effective tool to reduce inappropriate prescribing of antibiotics for CABP in patients with COVID-19 pneumonia. Additional studies are needed to further explore the potential clinical impact of stewardship interventions targeting prescribing of antibiotics for CABP among patients with COVID-19.