A survey on define daily dose of watch- and access-category antibiotics in two Indonesian hospitals following the implementation of digital antimicrobial stewardship tool.

The World Health Organization (WHO) in 2023 began to set the target of prescribing Access antibiotics at 60 % of reach.1, 2 It certainly must be followed by supporting efforts in various sectors such as the hospital management sectors, human resources, knowledge of antibiotics and various other supporting devices. Some studies suggest that the use of antimicrobial stewardship tools can provide good results in terms of antimicrobial use and reducing antibiotic DDD; however, it may not be possible to determine what kind of digital model is good to use.3, 4.

WHO has categorized antibiotics into Access, Watch and Reserve (AWARE).⁵ The Access category includes antibiotics that are considered to have a lower potential for resistance compared to the Watch category.² While Reserve category antibiotics are types of antibiotics that are only used if there are suspected infections caused by Multi-Drug Resistant (MDR) pathogens.² Therefore, Reserve category antibiotics are antibiotics that the use must be restricted in accordance to the necessity.⁵ The WHO AWaRe became a reminder to stakeholders for promoting antimicrobial appropriate use and antimicrobial stewardship with consideration of local epidemiology and antimicrobial sensitivity data.⁶.

RASPRO Indonesia Study Group has tried to develop a digital device by integrating the AWARE antibiotic category based on what has been launched by WHO. The use of this tool is intended to guide clinicians in administering prophylactic, empiric and definitive antibiotics. Moreover, it also facilitates consultation with the hospital’s Antimicrobial Stewardship Team (PGA) in coordinating the approval of administering antibiotics of Watch and Reserve categories, helping hospitals to monitor, evaluate report and create action plans related to antibiotic use.

This survey was the initial result of a review on the implementation of e-RASPRO tool prior to its wider use in future hospitals. The socialization on implementation of e-RASPRO tool along with a guideline on digital antimicrobial use was carried out at two hospitals in Indonesia. The e-RASPRO tool in Hospital 1 was an initial device (blueprint); while in Hospital 2 it was a full-version device. However, both of them had the same flow, only different on the screen display. These two hospitals were chosen because they have different status in service. Hospital 1, a primary hospital with 134 beds, 9 pharmacists, 115 nurses, and 37 specialist doctors. Hospital 2, a referral hospital with 254 beds, 39 pharmacists, 368 nurses, and 102 specialist doctors.

Digital antimicrobial usage guideline was made based on literature synthesis and observation of local microorganism pattern (in hospitals that already hold data on microorganism patterns) by entering antibiotic categories in accordance with the AWARE-WHO. The guideline on digital antimicrobial usage was then agreed by hospital management and the hospital’s Antimicrobial Resistance Control Committee / Komite Pengendalian Resistensi Antimikroba (KPRA), which was then included in the e-RASPRO tool.

The e-RASPRO was then implemented in both hospitals and used to guide clinicians in prescribing prophylactic, empiric and definitive antibiotics. At 9 months and 3 months following the implementation of e-RASPRO, the define daily dose (DDD) of antibiotics was calculated and evaluated whether there was a change in the pattern of antimicrobial use before and after the implementation of the e-RASPRO tool from the Watch category to the Access category.

Type I Risk Stratification Group was a group of patients that could receive empiric antibiotics for multi-sensitive microorganism coverage. This group was a group of immunocompetent patients or could also be a group of immunocompromised patients with the severity of bacterial infections that were not threatening or at risk of MDR and they were not included in Type II and III Risk Stratification Groups.⁷.

Type II Risk Stratification Group for non-severe infectious condition with ((Immunocompromised AND/OR uncontrolled diabetes mellitus) with (History of antibiotic administration within ≤ 90 days ago AND / OR History of having treatment in healthcare facilities of ≥ 48 h, ≤ 90 days ago, AND / OR History of medical instrument use of ≤ 90 days ago)). Type II Risk Stratification group was a group which was at risk of infection with Multi Drug Resistant (MDR) microorganisms − Extended Spectrum Beta-Lactamases (ESBLs).7, 8, 9, 10, 11, 12, 13, 14, 15.

Type III Risk Stratification Group was a group with threatening infectious condition AND / OR ((Immunocompromised AND / OR uncontrolled diabetes mellitus) with (History of antibiotic administration ≤ 30 days ago AND / OR History of having treatment in healthcare facilities of ≥ 48 h ≤ 30 days ago, AND / OR History of medical instrument use ≤ 30 days ago)). This group is at risk of infections by ESBLs and other Multi-Drug Resistant (MDR) microorganisms including MDR Pseudomonas sp and others.7, 16, 17, 18, 19, 20, 21.

The group of patients with Healthcare Associated Infections (HAIs) was also included in the Type III Risk Stratification group. The group categorized as HAIs was a group with a period of infection occurrence at ≥ 48 h treatment in a healthcare facility, even at 90 days following a surgery.22, 23, 24, 25 Moreover, a research with a limited scope of study demonstrated that patients included in the Type III Risk Stratification in the RASPRO system were also the group that was at risk for sepsis.²⁶.

The digital guidelines on the use of empiric antimicrobial agents in both hospitals were developed similiarly. Patients who were digitally categorized as those with Type I Risk Stratification on the e-RASPRO tool, were given a choice of antibiotics listed in the digital guidelines on Access-categorized Single or Combination antimicrobial agents (e.g. Ampicillin, Ampicillin Sulbactam, Amikacin dan Gentamycin).⁵ Meanwhile, for the group of patients with Type II Risk Stratification on the e-RASPRO tool, the choice of empiric antibiotics was anti-ESBL antibiotics with a choice of antibiotics included in the Access-Watch category on the digital guidelines of antimicrobial agents or also with a consideration on the use of Carbapenem Sparing Regimen (e.g. Piperacillin Tazobactam or Amoxicillin Clavulanate / Ampicillin Sulbactam + Aminoglycosides combination). The use of Quinolone only for patients who were allergic to Penicillin or with other considerations).⁵ The group of patients with Type III Risk Stratificationon the e-RASPRO tool had a choice of antibiotics of those that were able to eradicate ESBLs or other MDR bacteria with the majority of antibiotic choices listed on the digital guidelines of antimicrobial agents including those of Access, Watch to Reserve category (e.g. Meropenem with or without combination with Aminoglycosides to Polymixin and Tygecycline).⁵ The digital guidelines on empiric antimicrobial use, which had been developed on the device, included a guideline on using antimicrobial agents, particularly using the third generation of Cephalosporin as minimum as possible. It was correlated to the developing issues in both hospitals on the high incidence of using the third generation of Cephalosporin. Escalation and de-escalation, as well as step up and step down empiric antibiotics were also carried out by filling out the digital form of digital guidelines on antibiotics that could provide guidance for clinicians. In addition, the dose of antibiotics that had been administered, the presence or absence of adjustment dose would also be documented on the device.

By implementing the e-RASPRO tool, initial data was retrieved within the first 3 months of using e-RASPRO device to evaluate the suitability on the type of prophylactic antibiotics. The survey was then continued with data collection on DDD of antibiotics at 9 months before and after the use of e-RASPRO in Hospital 1 and 3 months before and after the use of e-RASPRO tool in Hospital 2. Data was collected when Hospital 2 had only been using the e-RASPRO tool for 3 months.

After data collection had been completed, the data were presented descriptively and changes in antibiotic use patterns before and after the implementation of e-RASPRO tool were observed. Survey data was calculated and submitted to a pharmacist of each hospital and the data had been verified by the KPRA of each surveyed hospital. Data was presented as it was in accordance with those that had been submitted by each hospital.

Within the first 3 months of using the e-RASPRO tool, data on DDD prophylactic antibiotic were retrieved. Efforts that had been made through e-RASPRO tool were to increase the use of Cefazolin as the main prophylactic antibiotic in accordance with the applicable regulations in Indonesia.

There was an increase in DDD of Cefazolin by 167.18 % with a decrease in DDD of Ceftriaxone and Cefotaxime by 9.98 % and 7.84 % respectively that served as prophylactic antibiotics in Hospital 1 at three months after implementing the e-RASPRO tool. Meanwhile, in Hospital 2 there was no use of Ceftriaxone and Cefotaxime as well as other antibiotics as prophylactic antibiotics. Cefazolin had been used since the socialization of the manual (non-electronic) RASPRO concept had been carried out in Hospital 2.

The survey on DDD of Watch-category antibiotics at 9 months and 3 months following the implementation of e-RASPRO tool in Hospital 1 and Hospital 2 was as followed: there was a decrease in DDD of Cephalosporin antibiotics by 51.25 % and 7.63 %, respectively. Meanwhile, there was also a sharp decrease in the DDD of Quinolone antibiotics in Hospital 1 by 46.71 %; however, a significant increase was still observed on the use of Quinolone antibiotics by 69.15 % in Hospital 2. The DDD of Carbapenem antibiotics in Hospital 1 seemed to decrease by 22.81 %; however, it increased in Hospital 2 by 12.28 %. There was a decrease in total DDD of Watch antibiotics in Hospital 1 by 49.01 % and an increase of 20.18 % in Hospital 2.

The survey on DDD of Access category antibiotics at 9 months and 3 months following the implementation of e-RASPRO tool in Hospital 1 and Hospital 2 was as followed: there was an increase in DDD of Ampicillin and Amoxicillin Clavulanate in Hospital 1 by 100 % respectively. Meanwhile, in Hospital 2 there was also a significant increase on the DDD of 1.5 g and 0.75 g Ampicillin Sulbactam by 126.25 % and 54.35 %. It had been documented that there was a decrease in DDD of Gentamycin in Hospital 1 by 80.90 %. A decrease in DDD of Metronidazole in Hospital 1 and Hospital 2 were recorded at 8.47 % and 11.60 %, respectively. There was a decrease in total DDD of Access-category antibiotics by 3.64 % in Hospital 1 and an increase of 8.14 % in Hospital 2. No exact data about number of difficult case or automatic stop order event, both hospitals have not implemented this policy strictly.

Surveys related to Antimicrobial Resistance (AMR) and Antimicrobial Use (AMU) should be carried out to evaluate the effectiveness of policies, evidence and implementation of PGA.27, 28 In addition, specific intervention strategies are also needed in order to improve the wise use of antibiotics in Indonesia.²⁹ RASPRO Indonesia Study Group initially had tried to write a manual concept so that hospitals could carry out antimicrobial stewardship in a more targeted manner. In 2022, the manual concept was then developed into e-RASPRO digital tool, a digital device that could be used in integration or parallel with the hospital information system.

The digital tool is then used as a model that is expected to assist hospitals in guiding clinicians in the wise use of antibiotics based on WHO AWARE. It also considers local microorganism patterns (if the hospital has already had any representative microorganism patterns). The guideline on empirical antimicrobial use is digitized by considering patient risk stratification.

In addition, this digital device is able to record the suitability of empiric antibiotic use in accordance with the risk stratification of each patient, the suitability of changing empiric antibiotics based on local guidelines, antibiotics de-escalation time (administering antibiotics according to culture findings), the duration of antibiotic use until reaching the antibiotic-time-out period. The e-RASPRO tool also facilitates faster consultation with the pharmacists and clinician electronically via What’s App, What’s App Call, Video Call even using mobile phone with the hospital PGA team. The device can also assist the hospital in conducting integrative monitoring, retrieving data, performing reporting that are necessary to determine the next action plan related to the implementation of PGA.

On the e-RASPRO tool, clinicians who want to perform clean surgeries with prostheses or clean-contaminated surgeries or other surgeries with a high risk of infection can fill out an electronic form and they will be guided to use 2 g of Cefazolin. In a study conducted in Thailand, it has been found that 70 % of prophylactic antibiotic use is continued for more than a day.³⁰ The e-RASPRO tool can detect whether there is further use of antibiotics that should not be given if the status of initial antibiotic given is prophylactic antibiotic. The use of prophylactic antibiotics listed on the e-RASPRO tool is Cefazolin, which is in accordance with the applicable regulations in Indonesia.

DDD of antibiotics of Quinolone group in Hospital 1 had a significant decrease of 46.71 %; while it still shows a striking increase of 69.15 % in Hospital 2. There is no certainty on why there is a stark difference between the two hospitals regarding the use of Quinolone. In the digital guideline on the use of antimicrobial agents in both hospitals, Quinolones have only been placed as an alternative treatment for Penicillin-allergic patients, who are also not recommended to be treated with Cephalosporin group, even Carbapenem group. The high use of Quinolones in Hospital 2 may be related to various issues such as: the subjective doctor’s confidence on Access-category antibiotics in the management of mild infection cases (Type I and II Risk Stratification), drug availability, managerial strength on the compliance with antimicrobial use guidelines and others.

DDD of Carbapenem antibiotics has decreased by 22.81 % in Hospital 1, but it increased by 12.28 % in Hospital 2. Meanwhile, the DDD of Glycopeptide class in Hospital 2 has also decreased by 49.20 %. There has been no specific research on the causal correlation regarding the increased and decreased use of both antibiotic groups following the implementation of e-RASPRO tool. It may occur since the number of patients classified as Type III Risk Stratification could fluctuate.

In Hospital 2, it can be seen that there is still an increase in total DDD of Watch-category antibiotics by 20.18 %; however, the increased DDD of Access-category is expected to be the beginning of a new culture of using Access-category antibiotics that one day may shift the dominance on the use of Watch-category antibiotics in accordance with its indication. The difference in the length of use of the e-RASPRO tool of 9 months and 3 months may still the one of causes of different results found in both hospitals. When there is a shift in prescribing from Watch to Access category antibiotics and decrease in antibiotic prescribing, hopefully, there will be a decrease in the risk of selective pressure events which will reduce the risk of the emergence of MDR bacteria. However, it certainly needs further studies to come to such conclusion.

e-RASPRO able to record conditions where there is no agreement between the clinician, pharmacist and the hospital’s antimicrobial stewardship team in administering antibiotics, while rapid drug administration is needed (in patients with sepsis who fall into the type III risk stratification category). In this condition, antibiotic can be dispensed as is recommended by the clinician. However, through the e-RASPRO device, pharmacist can create notes on the device for this situation. The administration of antibiotics with pharmacist notes can be reviewed in the following days. All of these notes can be traced by e-RASPRO device when evaluation is carried out next day. All of these data can be used as evaluation material to develop action plan for better future improvements.

The survey may indicate that there are saving endeavors in antibiotic use as well as an early change in antibiotic DDD from the Watch category to the Access category following the implementation of e-RASPRO tool in both hospitals. The period of time of using the digital device may still affect the results. However, the survey certainly does not illustrate a strong cause-and-effect relationship between the use of e-RASPRO tool and antibiotic DDD.

Ronald Irwanto Natadidjaja: Writing – original draft, Supervision, Project administration, Methodology, Investigation, Formal analysis, Conceptualization. Aziza Ariyani: Writing – review & editing, Supervision, Resources, Methodology, Investigation, Formal analysis, Data curation. Hadianti Adlani: Writing – review & editing, Supervision, Investigation, Formal analysis, Data curation. Raymond Adianto: Software, Data curation. Iin Indah Pertiwi: Resources, Investigation, Data curation. Grace Nerry Legoh: Resources, Investigation, Data curation. Alvin Lekonardo Rantung: Resources, Investigation, Data curation. Hadi Sumarsono: Writing – review & editing, Supervision.