Introduction

I. Why is this important ?

Since the discovery and development of the first antimicrobial drugs in the 1940s, the scientific community has also discovered that pathogens can develop immunities against these drugs. This ability to become resistant to one or several antimicrobial drugs is commonly referred to as antimicrobial resistance (AMR). Its prevalence has increased steadily since then, reaching critical points in some parts of the globe. The World Health Organization (WHO) estimates that AMR will lead to prolonged hospitalizations and loss of productivity, translating into billions of dollars in economic loss. Additionally, it will make treating trivial infections, such as skin and soft tissue infections, more challenging for physicians. One way to prevent or reverse this situation is through the appropriate use of antimicrobial drugs, a program known as antimicrobial stewardship (AMS). Antimicrobial stewards, typically physicians trained in infectious diseases with a focus on infection control and prevention, play a crucial role in ensuring the appropriate utilization of antimicrobial drugs in hospitals and clinics. They collaborate with medical teams to assess the suitability of antimicrobial drugs chosen for patient treatment. Whenever possible, they recommend replacing broad-spectrum drugs with narrow-spectrum drugs (i.e., targeted therapy), which can be equally or even more effective while reducing the patient’s exposure to broad-spectrum antimicrobial drugs. This practice, known as antimicrobial de-escalation (ADE), helps minimize prolonged exposure to broad-spectrum antimicrobial drugs, which are often administered as first-line treatment when an infection is suspected but the pathogen has not been identified. Despite its potential benefits, current literature suggests that ADE has not shown a significant effect on patient care or the incidence of adverse effects of broad-spectrum antimicrobial drugs. This may be attributed to the lack of standardization and high heterogeneity in the definitions and ranking of antimicrobial drugs based on their spectra of activity, often derived from expert opinions rather than objective and verifiable sources.

II. Why was this app developed ?

The S³ (Simplified Spectrum Score) was developed to harmonize and standardize the ranking of antimicrobial drugs according to their spectrum of activity using evidence-based medicine, rather than relying solely on expert opinions. The variability in expert assessments contributes to the high heterogeneity observed in current literature. For example, one antimicrobial stewardship (AMS) expert may consider amoxicillin-clavulanate to have a broader spectrum of activity compared to ceftriaxone, while another expert may hold the opposite view. Such discrepancies make it challenging to use antimicrobial de-escalation (ADE) as an outcome in clinical studies, as the definition of ADE events depends on the ranking of antimicrobial spectra of activity against pathogens. The S3 app addresses this challenge by utilizing publicly available antimicrobial susceptibility testing (AST) data from the European Committee on Antimicrobial Susceptibility Testing (EUCAST), which follows ISO guidance documents (ISO 20776-1 and ISO 20776-2) to ensure reproducibility and quality control. By standardizing assessments based on these guidelines, the S3 app aims to mitigate uncertainty associated with scientific testing and provide a reliable tool for antimicrobial stewardship.

III. How does it work ?

While I highly recommend reading our publication for a comprehensive understanding of the app, I’ll provide a brief overview of how it works hereafter. The cornerstone of S³ app is its database built on a dichotomy (inactive/active) score for each bacterium-antimicrobial drug pair. The app utilizes this database to determine the number of bacteria known to be susceptible to the input drug or combination of drugs selected by the user, based on published evidence from EUCAST clinical breakpoints. It generates an initial therapy (S³) score for the currently administered antimicrobial drug(s) and another score for the desired final therapy. The app then calculates the difference between these scores, known as the delta S³ score (ΔS³: S³_final – S³_initial). A negative ΔS³ (ΔS³ < 0) indicates a de-escalation event (i.e., switching from broad-spectrum antimicrobial drugs toward narrow-spectrum antimicrobial drugs), while a positive or null ΔS³ indicates no-de-escalation (ΔS³ ≥ 0). This approach provides a practical tool for clinicians to optimize antimicrobial therapy and combat antimicrobial resistance effectively.

IV. Who is it for ?

The S³ app was developed for infectious diseases clinicians and researchers working in the field of antimicrobial resistance. Hopefully, this tool would be able to help researchers performing clinical studies in this field to improve de-escalation events detection and to assess its efficacy on patient care circumventing the need of expert opinions on antimicrobial spectra ranking. However, any person is welcome to use it whether it is for research or entertaining purposes.

User Interface

Here is an illustration of the general UI of the S³ app. The left screenshot displays the main menu with links were the user can navigate to by clicking on it. Clicking on “S³ score calculator” will take the user to the page where antimicrobial de-escalation can be assessed (1). The next step is choosing which antimicrobial drug, either alone or in combination with others, is part of the initial antimicrobial therapy (2,3) and the ones included in the final antimicrobial therapy (3,4). Once these steps are performed, clicking on the “S3score” button will compute the scores, calculate the delta score and informs the user if the therapy changes account as an ADE (6).

Here are two examples to illustrate the use of the S³ app. In the first example below, the user wants to assess the delta S³ score of a switch in antimicrobial therapy from piperacillin-tazobactam and vancomycin (a common antimicrobial drug combination for empirical therapy) to amoxicillin-clavulanate (a supposedly more targeted therapy). After clicking on the “S3score” button (5), the user is able to see that this change is recorded as an ADE event since the delta S³ score is negative (6).

The second example below shows a case where de-escalation was assumed based on the switch from an intravenous antimicrobial drug (piperacillin-tazobactam) to a drug that can be taken orally (levofloxacin), however the calculations show that no de-escalation occurred (6).

Thank you for following this brief tutorial, do not hesitate to contact me if needed, your feedback is always welcome!