title: From Hospital-Level to Patient-Level Antibiotic Consumption Data: How Can We Improve Surveillance of Antibiotic Use in the Frame of Antibiotic Stewardship Programmes?
Creators: name: Renggli, Luzia
Publisher: name: Universität Bern
Year: 2023
Subjects: subject: 360 Social problems &amp; social services
subject: 570 Life sciences; biology
subject: 610 Medicine &amp; health

description: Infections with antimicrobial-resistant bacteria caused approximately 4.95 million deaths worldwide in 2019 and are, thus, one of the major threats to public health [1, 2]. Antimicrobial resistance is the ability of a microorganism to withstand antimicrobial treatment and occurs naturally [3]. However, its spread has been driven by the extensive use of antibiotics in agriculture, and human and veterinary medicine during recent decades [4]. Improving the adequate use of antibiotics in order to slow antimicrobial resistance, treat patients effectively and enhance patient safety is referred to as antibiotic stewardship [5]. Surveillance of antibiotic consumption is a crucial element in antibiotic stewardship programmes in defining interventions to optimise antibiotic use [6, 7].
The quantity of antibiotic consumption is analysed routinely in Switzerland. The Swiss Centre for Antibiotic Resistance (ANRESIS) has collected and analysed antimicrobial resistance data and antibiotic consumption data from an increasing number of microbiology laboratories and hospital pharmacies throughout Switzerland since 2006 [8]. Antimicrobial resistance data are provided at the patient-level while antibiotic consumption data are aggregated at the department or hospital-level per year or month. The results of the analyses are sent back to individual hospitals in the form of feedback and benchmark reports. The purpose of these reports is to support local antibiotic stewardship teams when defining interventions.
The quality of antibiotic use has been analysed only sporadically in Switzerland [9, 10]. Recently, a consensus on quality indicators for antibiotic use was published [11]. This consensus includes antibiotic stewardship indicators that assess antibiotic treatment decisions. In recent years, most of the larger Swiss hospitals have implemented electronic medical record systems. Hence, patient-level antibiotic prescription data are increasingly available that could improve the monitoring of antibiotic use and provide better support for antibiotic stewardship programmes.
Aims: The overall aims of this PhD thesis were, first, to evaluate the benefits of extracting patient-level antibiotic prescription data compared to hospital-level data and, second, to propose a method for incorporating these data into future surveillance of antibiotic use.
The purpose of the first part was to assess whether associations between AMR and antibiotic consumption can be investigated using hospital-level data generated for routine surveillance. Three epidemiological projects aimed to investigate the temporal trends including explanatory variables of 1) consumption of antibiotics active against methicillin-resistant Staphylococcus aureus (MRSA), 2) the incidence of Staphylococcus aureus bloodstream infections and 3) extended-spectrum cephalosporin-resistant Klebsiella pneumoniae (ESCR-KP). The objective of the fourth project was to develop an interactive dashboard to improve data visualisation for routine surveillance. 
In the second part, we aimed to assess 5) the feasibility of converting patient-level antibiotic prescription data of the electronic medical record into antibiotic stewardship indicators. The last project (6) aimed to identify risk factors for the occurrence of extended-spectrum cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae.
Methods: Data from the ANRESIS database were used to analyse trends and risk factors for 1) consumption of anti-MRSA antibiotics (glycopeptides, daptomycin, linezolid) and 2) incidence of ESCR-KP in 21 hospitals between 2009 and 2019. The same data source was used for analysing 3) the incidence of Staphylococcus aureus bloodstream infections in 70 hospitals over time (2008-2021). Trends and risk factors were analysed by applying multiple linear regression models. 4) A dashboard visualising antibiotic consumption of hospitals participating in the ANRESIS surveillance system was developed using the R software environment and packages such as Shiny and Plotly.
For projects 5 and 6, patients hospitalised between 1 October 2019 and 30 September 2021 at Lucerne cantonal hospital and who received at least one dose of a systemic antibiotic were included. Antibiotic prescription data were obtained from the electronic medical record Epic software® and linked with microbiological data from the ANRESIS database. Antibiotic stewardship indicators proposed by the literature were collected and, if needed, rephrased or specified to be calculable (project 5). Algorithms were programmed in R to convert electronic medical record data into antibiotic stewardship indicators. These were calculated, and the validity of each output value was assessed and categorised as either good quality data, missing data due to incomplete documentation or data processing issues or not computable.
For the resistance models with patient-level data, the dataset was restricted to patients with possibly nosocomial Escherichia coli and Klebsiella pneumoniae (project 6). A multiple logistic regression model was applied to investigate risk factors for the occurrence of extend-spectrum cephalosporin resistance in Escherichia coli and Klebsiella pneumoniae.
Results: Analysis of hospital-level antibiotic consumption data revealed an increase in the consumption of anti-MRSA antibiotics in Switzerland between 2009 and 2019 (project 1). Hospitals with lower levels of consumption of anti-MRSA antibiotics were associated with having an antibiotic stewardship group and restrictions for prescriptions of anti-MRSA antibiotics.
The MRSA incidence decreased significantly in the French-speaking region while increasing significantly in the German-speaking region, although at a low incidence level (project 2). The incidence of Staphylococcus aureus bloodstream infections increased in Switzerland between 2008 and 2021, mainly due to the increasing incidence of methicillin-susceptible Staphylococcus aureus bloodstream infections in elderly males. The increase was more pronounced in the German-speaking than in the French-speaking region.
Project 3 described a significant increase in the incidence of invasive ESCR-KP infections in Switzerland between 2009 and 2019. The incidence was higher in university than in non-university hospitals and in the French-speaking compared to the German-speaking region. However, the incidence was not associated with antibiotic consumption. Analysing the overall ESCR-KP incidence (all sample sites) revealed high variability between university hospitals, mainly due to a high proportion of patients with screening isolates at Geneva University Hospital (50% of patients with ESCR-KP).
A dashboard was developed that visualised antibiotic consumption of the user's hospital (project 4). The hospital-specific login provides free access to interactive graphics and interactive tables for the 71 hospitals that are part of the ANRESIS surveillance system. Antibiotic consumption is depicted graphically over ten years and the graphics can be adjusted according to selection criteria. A benchmark boxplot enables users to compare antibiotic consumption of their hospital with other hospitals of comparable size or in the same linguistic region.
Project 5 demonstrated the feasibility of converting electronic medical records data into antibiotic stewardship indicators. In total, data from 25,338 hospitalisations from 20,723 individual patients were analysed and visualised in an interactive dashboard. Data extraction allowed us to program algorithms for 89% (25/28) of the indicators assessing treatment decisions, and data quality was classified as good in 46% (13/28). According to the data quality observed, the most important issues were A) missing (58% of hospitalisations) or meaningless (37% of hospitalisations) information on indication (e.g. general indication, infection) and B) data processing issues such as insufficiently categorised metadata. 
The result of the resistance model with patient-level data was not meaningful since the number of patients with ESCR isolates was too low (project 6).
Conclusion: Our studies revealed that several national trends in antibiotic consumption and resistance were mainly caused by subpopulations. This demonstrates the need for stratifying surveillance analyses to formulate appropriate target measures at the right intervention level. Higher resolution data on antibiotic use are essential to provide better decision support to policy makers in hospitals and on regional and national committees. To improve surveillance analysis for hospitals, we developed a procedure that converts electronic medical record data into antibiotic stewardship indicators. The routine monitoring of these indicators would be very useful for local antibiotic stewardship teams when defining and measuring the effectiveness of interventions. This PhD project has demonstrated the benefit of patient-level antibiotic data and is therefore the first step towards integrating patient-level antibiotic prescription data into routine surveillance.