Key features of hospitals antibiotic stewardship software solutions needed for successfully optimizing patient outcomes while fighting antibiotic resistance on a global scale – a shared experience

Antimicrobial resistance threatens the very core of modern medicine and currently costs the EU more than 11.7 billion euro per year. In 2050 it is projected that 10 million people will die from infections with the so called “superbugs”. In the past few decades, no entirely new antibiotic groups are being discovered which makes of crucial importance to preserve the effectiveness of the antibiotics we have today for future generations


Introduction
Effective antimicrobial drugs are necessary for treatment of potentially fatal diseases and ensure that complex interventions like surgeries can be performed at low risk for the patient.The global consumption of antibiotics is projected to drastically increase with the increasing population and duration of life with advanced age being a risk factor for acquiring an infection (Klein et al. 2018).Antimicrobial resistance (AMR) threatens the very core of modern medicine and currently costs the EU more than 1.1 billion euro per year (Anderson et al. (2023).In 2050 it is projected that 10 million people will die from infections with the so called "superbugs" (Tang et al. 2023).After the golden era of finding of new antibiotic molecules , in the past few decades no entirely new antibiotic groups are being discovered with notable decrease of investments from pharmaceutical companies for R&D projects in this field with the remaining clinical pipeline being insufficient to tackle AMR (WHO 2019).That's why it is of crucial importance to preserve the effectiveness of the antibiotics we have today for future generations by optimizing antibiotic consumption and by implementing digital solutions to fight antimicrobial resistance.
During the period 2013-2022 Bulgaria shows a significantly increasing trend in consumption of antibacterials for systemic use (ATC group J01) in the hospital sector compared to overall decrease in EU/EEA level.Bulgaria has the highest proportion of hospital consumptions of cephalosporins -61%, compared to the lowest in EU/EEA in Denmark and Malta -11% (ECDC 2023).The Final joint report in respect of a one health country visit to Bulgaria from ECDC and the European Commission in 2018 concluded there are numerous gaps and weaknesses in the approach towards tackling AMR (ECDC country visit Bulgaria 2018).
Around 80-90% of antibiotics in humanitarian medicine is used in primary care -with 50-80% of them not being prescribed or used rationally (ECDC 2022(ECDC , 2023)).In 2024, a new national law was accepted in Bulgaria which states that antibiotics in primary care can only be prescribed via electronic prescriptions, which is expected to drastically improve the usage of antimicrobials in the community.Not many measures have been taken yet on a national level to improve antibiotic usage in hospitals, which accounts for 6-10% of antibiotic usage in Bulgaria (ECDC 2023).
Even though smaller percentage of antibiotic usage in Bulgaria is attributed to hospital consumption, hospitals are critical places with high risk for spreading of hospital acquired infections with multidrug-resistant pathogens and where reserved antibiotics are often used.A meta-analysis from 2016 shows that of all antibiotics prescribed in acute-care hospitals, 20-50% are inappropriately prescribed (Schuts et al. 2016).Irrational or inappropriate antibiotic usage is an umbrella term, which includes unnecessary use -when the antimicrobial agent is not indicated and has no benefit its application to the patient's health, for example antibiotic treatment of upper respiratory infections caused by viruses, and improper use -when the choice of antibiotic, the time for initiation of therapy, dose, route of administration, frequency of administration or duration of treatment are not optimal.
Antimicrobial stewardship programs worldwide aim to optimize the use of antimicrobials to improve patient outcomes and prevent occurrence of antibiotic resistance.The concept of ASPs is to provide the right antibiotic for the right patient, at the right time, with the right dose, via the right route, causing the best possible outcome and least harm to the patient and future patients.There are many studies (Zay Ya et al. 2023) proving the benefits of already implemented local antibiotic stewardships in hospitals around the world, but not many explaining the key features needed and steps required for implementation of software solutions for digital antibiotic stewardship programs for decision support and monitoring of antibiotic usage.In this article we are sharing our experience for building a software for digital antibiotic stewardship program -what are the key functions needed for successful implementation of the digital antibiotic stewardship and who are the stakeholders in a project of this nature.

Materials and methods
For the duration of 3 years the climate of antibiotic consumption in Bulgarian hospitals was thoroughly studied via one-to-one personal interviews with open questions conducted with healthcare workers.An audit of the antibiotic usage in a department of abdominal surgery with pre-existing local antibiotic stewardship policy was performed by a team of clinical pharmacologists.Based on the gaps and problems found a software solution was created for implementing the local antibiotic stewardship policies and improving the effectiveness, safety, and economic feasibility of antibiotics.To build the software solution the programming language Java was used and for the user interface the free and opensource JavaScript library React.js was implemented.To store the software, Google Cloud Platform was used, which is compliant with HIPPA (Health Insurance Portability and Accountability Act).A hospital lawyer approved the project regarding GDPR safety regulations.
Personal one-on-one interviews were held with 43 healthcare practitioners in six big hospitals (with > than 100 beds) in Bulgaria, including 26 surgeons (general and abdominal surgery), 6 clinical microbiologists, 3 anaesthesiologists, 3 pulmonologists, 3 clinical pharmacologists, and 2 hospital pharmacists.Open questions were asked regarding: 1.The level of awareness regarding the problem with increasing rates of AMR; 2. The availability and access to local and/or national antibiotic stewardship policies; 3. The availability and access of data regarding local antimicrobial resistance rates; 4. How decisions regarding empirical, targeted and/or prophylactic usage of antibiotics are made in their department/hospital; 5.The collaboration between different hospital departments regarding AMR; 6.The level of monitoring and control of antibiotic usage on local and national level; After evaluation of the gathered information, the following observations and conclusions were made for the general climate of antibiotic usage in hospitals in Bulgaria: • Lack of easily accessible and/or regularly updated national and local (hospital) guidelines for preventing and treating infections • Lack of easily accessible information regarding local antimicrobial resistance • Lack of awareness among doctors about comparative effectiveness and safety of available antibiotics or modern approaches for optimal application of antibiotics based on established pharmacokinetic and pharmacodynamic (Pk/Pd) parameters • Lack of optimal collaboration of the attending physicians with the specialists in antibiotic therapy such as microbiologists and clinical pharmacologists • Lack of or ineffective hospital drug policy commissions • Lack of systemic monitoring and control of antibiotic usage from head of hospital departments and responsible authorities • Lack of software solutions for digitalizing local antibiotic stewardship policies After identifying the departments with the worst indicators for irrational antibiotic usage and highest resistance rates in the researched hospitals (mainly the surgical departments and the intensive care units), an abdominal surgery department was chosen, and an official audit was carried out regarding the quality of preoperative antibiotic prophylaxis performed for а 2-month period.Different criteria were evaluated like presence of an indication for prophylaxis and was the prophylaxis administered respectively, which antibiotics were chosen, the dosage and method of administration, the time of administration (should be before, not during or after surgery), duration of administration (should be less than 24 hours), and the diligence of the patient documentation.The evaluation criteria for the conducted antibacterial surgical prophylaxis were based on pre-existing local antibiotic stewardship policy (Petrov et al. 2014).
Based on the identified gaps in the antibiotic stewardship policy implementation, the data regarding the most frequently isolated bacteria and the AMR data for this department provided by the microbiological department a consensus was reached between the chief surgeon, the microbiological department, the clinical pharmacology department, and the hospital pharmacy how to update the local antibiotic stewardship policy.A round table was organized with the full surgical team where the results of the audit were shared, the updated antibiotic stewardship policy was presented, and a software solution for decision support and monitoring regarding antibiotic usage was decided to be created and implemented.In the next 7 months the software solution was built to serve the predefined purpose to be a tool to optimize effectiveness and safety of antibiotics, decrease costs of antibiotic usage and allow the control of the implementation of the updated antibiotic stewardship policy.
For the software solution the programming language Java was used and for the user interface the free and opensource JavaScript library React.js was implemented.To store the software, Google Cloud Platform is chosen, which is compliant with HIPPA (Health Insurance Portability and Accountability Act).The software solution created is web-based and could be accessed through any device with internet access, in this case -smartphones and tablets of doctors and hospital computers.
The following main tools of the software were created: 1. Information tool (IT) with quick access to the updated Antibiotic stewardship policy of the department (PDF), the AMR data for the surgical department and the hospital (in Excell) provided by the microbiological team and the SmPCs (Summary of Product Characteristics, PDF) of the available antibiotics in the hospital pharmacy.2. Tool for decision support (TDS) with treatment recommendations given to the practitioner for first choice antibiotic and at least one alternative for empirical treatment and surgical prophylaxis with full drug information based on local antimicrobial resistance rates and personal characteristics of the patient.When the indication for antibiotic usage (in this case the surgery to be performed) is selected by the doctor a few key questions are asked regarding patient characteristics (allergies, weight, comorbidities, etc).After answering with an easyto-use interface, the doctor receives advice for the recommended first-line antibiotic for prophylaxis (or combination) with information regarding dose, method of administration, when and why the dose ought to be repeated, adverse drug reactions to be expected and potential clinically important drug interactions.The recommendations were pre-approved by the antibiotic stewardship committee, clinical microbiology department, hospitals drug

Results and discussion
A digital software solution for implementation of hospitals local antibiotic stewardship policy was created and successfully implemented in the everyday clinical practice.We recommend the process of creation and implementation of local digital antibiotic stewardship policy to be done one department at a time, starting with the departments with the worst indicators for irrational antibiotic usage.The approach of digitalization needs to be personalized to deeply understand and successfully target the gaps and prejudices regarding antibiotic usage in any certain department.Instructions regarding antibiotic usage need to be short, clear, and easily followed.The necessity of interdisciplinary collaboration between departments should be well understood by the management of the hospital and is a good idea to be given as responsibility to a team formed by the microbiological department, the clinical pharmacology department, and the hospital pharmacy with a representative from each of the remaining departments.Regular support to the departments and monitoring and control of the implementation of the policies are necessary to tackle clinical inertia, alongside with funding and accountability to the antibiotic stewardship committees themselves.

Conclusion
In conclusion, we created a useful software tool for improving the implementation of antibiotic stewardship policies which is currently being used in a regional hospital in Bulgaria.The project won several Intel AI&ML potential awards and currently is collecting data to implement these technologies for a better impact in the global fight with AMR.
policy commission and the head of the department.A representation of the Tool for decision support is shown on Fig. 1. 3. Patient management tool (PMT) for continued tracking of the patients currently receiving antibiotic treatment in the department with alerts and tips as time passes.After the recommendation for treatment is accepted from the doctor, the patient and his prescription appear as active in a list of active patients.At any time, the doctors in the department can see how many patients currently are on antibiotic treatment in the department, when was the treatment initiated, and what ADR and DR can be expected in case of a newly presented symptom.A very useful feature of the Patient Management Tool turned out to be the notification system in certain points of time during the antibiotic treatment.The first alert is received by doctors on day 3 of treatment to recall the need for reassessment of the empirical treatment and to check for the results from the microbiological department if such are expected.Another alert is given through the software to doctors on day 5, 7 or 10 (depending on the diagnosis) to remind the doctor to evaluate the need to terminate or continue the antibiotic treatment.When the treatment is terminated the patient is archived and no longer in the list of active patients with the option to check the history and revisit the previous antibiotic treatment if he is admitted again in the same department (useful for patients with resistant and/or recurring infections).4. Decision Tree Builder Tool (DTB) allows for the algorithm to be visualized like a tree with the branches being the different treatment or prophylaxis options based on personal characteristics of the patient.This allows any microbiological department or antibiotic stewardship committee with basic computer skills to independently build and regularly update their digital antibiotic stewardship program based on changes in AMR rates.This is especially useful if the hospital currently cannot afford expensive software companies to provide this service.A representation of the tool is shown on Fig. 2. 5. Monitoring and Statistics Tool (MST) to provide live data and periodical statistics regarding the antibiotic usage in the hospital and the success rate of the implementation of the local antibio tic stewardship policy to the antibiotic stewardship committee, the microbiological department, clinical pharmacology department and the hospital.This tool also allows doctors to give feedback regarding the effectiveness and safety of the antibiotic usage, which combined with the data from the microbiological department regarding the rates of AMR has great potential for implementation of Artificial Intelligence and Machine Learning technologies for further understanding the connection between AMR and prescription behaviours and to take more appropriate measures for combating AMR.

Figure 1 .
Figure 1.Visualization of the Tool for decision support of the software for digital antibiotic stewardship policy created for surgical prophylaxis.

Figure 2 .
Figure 2. Visualization of the Decision Tree Builder tool, which allows independent and easy access to the algorithm of decision support for updates based on changes of AMR by the antibiotic stewardship committee.

Figure 3 .
Figure 3. Visualization of the Monitoring and Statistics tool for live data and periodical statistics regarding the antibiotic usage in the hospital and the success rate of the implementation of the local antibiotic stewardship policy.