Discussion

Although 20% of hospitalized patients experience an antibiotic-associated ADE, there is a gap in tracking and reporting the direct harms of antibiotics to ASPs and clinical providers. ^{Reference Tamma, Avdic, Li, Dzintars and Cosgrove1} In this study, we obtained antibiotic stewards’ perceptions on the utility, feasibility, and possible structure of an antibiotic ADE surveillance system to fill this information gap. Prior work shows that prescribers prioritized immediate patient risks over long-term population risks such as AMR, which were perceived by frontline clinicians as more abstract and a less imminent threat. ^{Reference Pandolfo, Horne and Jani5,Reference Krockow, Colman and Chattoe-Brown6} Focusing antimicrobial discontinuation efforts on patient-level harms may support stewardship efforts by aligning the long-term goals of ASP with those of frontline clinicians.

Antibiotic ADEs constitute a wide spectrum of toxicities with varying incidence and severity and therefore could be measured and structured in several ways. For example, ADEs could be grouped by antibiotic type or by organ system affected or both. Respondents’ preference for organization of ADE by specific drug likely reflects a desire for simplicity over complexity. Major challenges in operationalizing a drug-based surveillance system include the diversity of drugs involved, the sheer number of potential toxicities, challenges with electronic measurement, and difficulties attributing specific events to specific drugs, particularly in the setting of comorbidities and polypharmacy. Despite these barriers, a drug-based system may be perceived to be more practical as it could utilize existing data infrastructure, which frequently tracks use by type.

The respondents’ emphasis on incorporating ADE severity was also reflected in the free-text results, although there were clear tensions between implementation feasibility and clinical importance and significance. Among the three proposed definitions, two of which were laboratory-based, the dermatological reactions definition (which included SJS) had the lowest median feasibility score, despite other responses indicating the importance of identifying severe and life-threatening ADE. How information will be used is an important consideration in designing surveillance tools. ICD-10 codes could be combined with laboratory or other measures to create standardized variables. However, these systems are inherently delayed and thus would be unlikely to be available for supporting point-of-care decisions. Additionally using a general adverse event identification system such as the Institute for Healthcare Improvement Trigger tool would reduce the need to develop large numbers of individual definitions, however, the trade-off of the general ADE surveillance approach is that manual review would be necessary to determine the type and severity of the ADE.

While not statistically significant, the median score for local AMR was higher, compared to the three other ADEs when it came to utility, feasibility, and patient-level impact. This may be because rates of AMR are felt to be more directly attributable to antimicrobial exposure than drug toxicities. However, AMR is primarily a population-level risk, rather than a patient-level risk. The perceived greater importance of local AMR rates in a harm metric conflicts with the implied emphasis of the ADE metric on direct patient outcomes. Interestingly, it also contrasts with how the majority of respondents chose “direct communication with clinician” in daily stewardship activities as the objective of the surveillance tool when prior work indicated that AMR is not a considerable priority in day-to-day clinician decision-making. ^{Reference Broom, Broom, Kirby, Gibson and Post7} This preference for local AMR rates may reflect the pervasiveness of population-level AMR as the traditional focus of ASPs.

To our knowledge, this is the first study to capture the perceptions of antimicrobial stewardship practitioners on establishing an antibiotic ADE surveillance system. The respondents represent an expert panel that would be the expected to adapt and implement ADE surveillance tools. Limitations include small sample size and a survey-based format that might lack the depth of focus group discussions and introduce the possibility of response bias. The respondents were limited to U.S. institutions, predominantly those with an academic background and some data analytics infrastructure, and thus perceptions may not be reflective of hospitals with less IT support and more limited access to Electronic Health Records. An additional limitation is that the scope of the study did not encompass surveying frontline prescribers who are key stakeholders in stewardship initiatives.

Additional research is needed to develop and implement an antibiotic ADE metric. Some of the key challenges include formulating standardized definitions for ADEs that acknowledge differences in event timing. Furthermore, it is important to devise a practical system for identifying ADE and for appropriately attributing ADEs to antibiotic use. Next steps could involve using the valuable insights provided by the respondents in our study to develop a model of an antimicrobial ADE surveillance system and solicit feedback from both antimicrobial stewards and frontline prescribers.

In conclusion, this study provides important pre-implementation data to inform the development and testing of surveillance tools within antimicrobial stewardship that directly measure patient-level ADE. A successful ADE measurement system should feature standardized definitions that allow for accurate attribution of ADEs to antimicrobials while considering the severity of the events. Additionally, it is essential to balance this accuracy with feasibility and equity, ensuring operationalization of the tool minimizes the need for additional resources and manual chart review that may not be universally available or accessible.