Jan-Willem H. Dik

Financial evaluations of antibiotic stewardship programs—a systematic review

Introduction: There is an increasing awareness to counteract problems due to incorrect antimicrobial use. Interventions that are implemented are often part of an Antimicrobial Stewardship Program (ASPs). Studies publishing results from these interventions are increasing, including reports on the economical effects of ASPs. This review will look at the economical sections of these studies and the methods that were used. Methods: A systematic review was performed of articles found in the PubMed and EMBASE databases published from 2000 until November 2014. Included studies found were scored for various aspects and the quality of the papers was assessed following an appropriate check list (CHEC criteria list). Results: 1233 studies were found, of which 149 were read completely. Ninety-nine were included in the final review. Of these studies, 57 only mentioned the costs associated with the antimicrobial medication. Others also included operational costs (n = 23), costs for hospital stay (n = 18), and/or other costs (n = 19). Nine studies were further assessed for their quality. These studies scored between 2 and 14 out of a potential total score of 19. Conclusions: This review gives an extensive overview of the current financial evaluation of ASPs and the quality of these economical studies. We show that there is still major potential to improve financial evaluations of ASPs. Studies do not use similar nor consistent methods or outcome measures, making it impossible draw sound conclusions and compare different studies. Finally, we make some recommendations for the future.

Measuring the impact of antimicrobial stewardship programs.

ABSTRACT Antimicrobial Stewardship Programs (ASPs) are being implemented worldwide to optimize antimicrobial therapy, and thereby improve patient safety and quality of care. Additionally, this should counteract resistance development. It is, however, vital that correct and timely diagnostics are performed in parallel, and that an institution runs a well-organized infection prevention program. Currently, there is no clear consensus on which interventions an ASP should comprise. Indeed this depends on the institution, the region, and the patient population that is served. Different interventions will lead to different effects. Therefore, adequate evaluations, both clinically and financially, are crucial. Here, we provide a general overview of, and perspective on different intervention strategies and methods to evaluate these ASP programs, covering before mentioned topics. This should lead to a more consistent approach in evaluating these programs, making it easier to compare different interventions and studies with each other and ultimately improve infection and patient management.

Cost-minimization model of a multidisciplinary antibiotic stewardship team based on a successful implementation on a urology ward of an academic hospital.

Background In order to stimulate appropriate antimicrobial use and thereby lower the chances of resistance development, an Antibiotic Stewardship Team (A-Team) has been implemented at the University Medical Center Groningen, the Netherlands. Focus of the A-Team was a pro-active day 2 case-audit, which was financially evaluated here to calculate the return on investment from a hospital perspective. Methods Effects were evaluated by comparing audited patients with a historic cohort with the same diagnosis-related groups. Based upon this evaluation a cost-minimization model was created that can be used to predict the financial effects of a day 2 case-audit. Sensitivity analyses were performed to deal with uncertainties. Finally, the model was used to financially evaluate the A-Team. Results One whole year including 114 patients was evaluated. Implementation costs were calculated to be €17,732, which represent total costs spent to implement this A-Team. For this specific patient group admitted to a urology ward and consulted on day 2 by the A-Team, the model estimated total savings of €60,306 after one year for this single department, leading to a return on investment of 5.9. Conclusions The implemented multi-disciplinary A-Team performing a day 2 case-audit in the hospital had a positive return on investment caused by a reduced length of stay due to a more appropriate antibiotic therapy. Based on the extensive data analysis, a model of this intervention could be constructed. This model could be used by other institutions, using their own data to estimate the effects of a day 2 case-audit in their hospital.

Cost-analysis of seven nosocomial outbreaks in an academic hospital

Objectives Nosocomial outbreaks, especially with (multi-)resistant microorganisms, are a major problem for health care institutions. They can cause morbidity and mortality for patients and controlling these costs substantial amounts of funds and resources. However, how much is unclear. This study sets out to provide a comparable overview of the costs of multiple outbreaks in a single academic hospital in the Netherlands. Methods Based on interviews with the involved staff, multiple databases and stored records from the Infection Prevention Division all actions undertaken, extra staff employment, use of resources, bed-occupancy rates, and other miscellaneous cost drivers during different outbreaks were scored and quantified into Euros. This led to total costs per outbreak and an estimated average cost per positive patient per outbreak day. Results Seven outbreaks that occurred between 2012 and 2014 in the hospital were evaluated. Total costs for the hospital ranged between €10,778 and €356,754. Costs per positive patient per outbreak day, ranged between €10 and €1,369 (95% CI: €49-€1,042), with a mean of €546 and a median of €519. Majority of the costs (50%) were made because of closed beds. Conclusions This analysis is the first to give a comparable overview of various outbreaks, caused by different microorganisms, in the same hospital and all analyzed with the same method. It shows a large variation within the average costs due to different factors (e.g. closure of wards, type of ward). All outbreaks however cost considerable amounts of efforts and money (up to €356,754), including missed revenue and control measures.

Automatic day-2 intervention by a multidisciplinary antimicrobial stewardship-team leads to multiple positive effects

Background: Antimicrobial resistance rates are increasing. This is, among others, caused by incorrect or inappropriate use of antimicrobials. To target this, a multidisciplinary antimicrobial stewardship-team (A-Team) was implemented at the University Medical Center Groningen on a urology ward. Goal of this study is to evaluate the clinical effects of the case-audits done by this team, looking at length of stay (LOS) and antimicrobial use. Methods: Automatic e-mail alerts were sent after 48 h of consecutive antimicrobial use triggering the case-audits, consisting of an A-Team member visiting the ward, discussing the patient’s therapy with the bed-side physician and together deciding on further treatment based on available diagnostics and guidelines. Clinical effects of the audits were evaluated through an Interrupted Time Series analysis and a retrospective historic cohort. Results: A significant systemic reduction of antimicrobial consumption for all patients on the ward, both with and without case-audits was observed. Furthermore, LOS for patients with case-audits who were admitted primarily due to infections decreased to 6.20 days (95% CI: 5.59–6.81) compared to the historic cohort (7.57 days; 95% CI: 6.92–8.21; p = 0.012). Antimicrobial consumption decreased for these patients from 8.17 DDD/patient (95% CI: 7.10–9.24) to 5.93 DDD/patient (95% CI: 5.02–6.83; p = 0.008). For patients with severe underlying diseases (e.g., cancer) these outcome measures remained unchanged. Conclusion: The evaluation showed a considerable positive impact. Antibiotic use of the whole ward was reduced, transcending the intervened patients. Furthermore, LOS and mean antimicrobial consumption for a subgroup was reduced, thereby improving patient care and potentially lowering resistance rates.

Integrated Stewardship Model Comprising Antimicrobial, Infection Prevention, and Diagnostic Stewardship (AID Stewardship)

We wholeheartedly agree with Dik et al. ([1][1]) that a combined approach is the future of stewardship and commend the authors for their innovative model. Incorporating infection control and epidemiology into an integrated diagnostic and antimicrobial stewardship model further capitalizes upon the

Challenges for a sustainable financial foundation for antimicrobial stewardship

Antimicrobial resistance is a worldwide threat and a problem with large clinical and economic impact. Antimicrobial Stewardship Programs are a solution to curb resistance development. A problem of resistance is a separation of actions and consequences, financial and clinical. Such a separation makes it difficult to create support among stakeholders leading to a lack of sense of responsibility. To counteract the resistance development it is important to perform diagnostics and know how to interpret the results. One should see diagnostics, therapy and resistance as one single process. Within this process all involved stakeholders need to work together on a more institutional level. We suggest therefore a solution: combining diagnostics and therapy into one single financial product. Such a product should act as an incentive to perform correct diagnostics. It also makes it easier to cover the costs of an antimicrobial stewardship program, which is often overlooked. Finally, such a product involves all stakeholders in the process and does not lay the costs at one stakeholder and the benefits somewhere else, solving the misbalance that is present nowadays.

Combating the complex global challenge of antimicrobial resistance: what can Antimicrobial Stewardship contribute?

Antimicrobial resistance is a major health issue and a worldwide problem. The O’Neill report published in 2016 analyses different aspects and provides an extrapolation of the consequences.1 An increasing number of stakeholders are recognizing the fact that such a large and complex problem requires multiple approaches tackling it from different angles and perspectives – the One Health approach.2 It is not just a problem in hospitals for medical professionals to solve. Antibiotic resistance is much more complex. It is also about over-use of antibiotics in livestock, about general over use in general practice, about unregulated access, about long-term care facilities, about frequent and easy travelling across the globe, about the pharmaceutical industry and financial incentives, both in general economy as well as in health care insurance. So many factors have a wide economic impact across all different sectors.3 This has drawn political attention and action so as to stimulate all parties to work together towards a sustainable future from a One Health perspective. Patients’ safety against healthcare associated infections (HAI) is a key indicator of the quality of healthcare. This has been underlined recently by the first report on communicable diseases of the European Centres for Disease Prevention and Control stating that HAI without or with antimicrobial resistance [e.g. Methicillin-resistant Staphylococcus aureus [MRSA], and carbapenem-resistant Enterobacteriaceae (CRE)] are the most important infectious disease threat in the European Union, ranking higher than HIV, pneumococcal infections and influenza.4 This is furthermore underlined by the recent publication of the WHO list of Top-12 organisms wherein the most critical microorganisms all are most frequent causes of healthcare-associated and less frequently community-associated infections [e.g. carbapenem-resistant Acinetobacter baumanii (CRAB)]. Within a given healthcare system, the spread of antimicrobial resistant microorganisms (AMR) is largely determined by the flux of patients through referral networks.5 With those patients AMR are transferred, as well. It is thus crucial to take these referral networks into account when organizing measures for Antimicrobial Stewardship and prevention of AMR. This concept has led to the most recent Dutch approach of creating ten regional health care regions.6 This concept has been also adopted on a supranational level, e.g. in the EU. The importance of antimicrobial resistance as a factor which increases mortality and morbidity of communicable disease for patients in European member states has been expressed by the Council Resolution (1999/C195/01) on antimicrobial resistance claiming a strategy against the threat of antimicrobial resistance. Different healthcare systems, such as the Dutch and the German are strongly divided by two totally different prevalences of healthcare-associated infections (HAI). This is difference is especially caused by AMR, such as MRSA, Vancomycin-resistant Enterococcus faecium or carbapenemresistant Pseudomonas aeruginonsa. The EUREGIO networks MRSA-net and EurSafety Health-net (www.eursafety.eu) have shown that infections with MRSA occur up to 32 times more frequently in Germany than in the Netherlands.7 On the other side it made clear that in the Netherlands there are up to 3 times fewer hospital-beds per 1000 inhabitants and up to 4 times fewer doctors in outpatient service, making access to health care and possibly to most antibiotics also difficult. Higher rates of death due to pneumonia in the Netherlands might be an indicator for lower accessibility to healthcare services, leading to a late diagnosis. A proper (tentative) diagnosis in turn is needed for a prudent use of antibiotic treatment, as has been also underlined by the Council recommendation (2002/77/EC). Whilst we recognise that the link between use in livestock and agriculture on the one side and resistance in humans is still not completely understood, antimicrobial use in the livestock and agricultural sectors is several times more than is used for humans.8 Estimates range from roughly 63,000 tons globally in 2010, rising to roughly 105,000 tons in 20309 to several hundred thousand tons.10 This issue of Infectious Disease Reports addresses the challenge of antimicrobial resistance from different perspectives and provides examples of different solutions that people are actively pursuing with a focus on the health care sector and sustainable use of antimicrobials. This issue focuses on the clinical (inpatient) setting where the impact of resistant infections is current greatest leading to use of last resort antimicrobials. It is this setting that also most urgently identifies the need for a balanced approach to antimicrobial resistancesupporting innovation through developing new antibiotics and preservation of existing antimicrobialsantimicrobial stewardship. Antimicrobial stewardship programmes (ASP) immersed in a model that integrates appropriate and timely diagnostics and an optimal infection prevention and control programme perhaps is an effective model for optimising the clinical response to drug resistant infection in this setting.11 Adaption of such a model is clearly important and dependent on local resources, geography, cultures and healthcare systems. ASPs usually comprise bundles of interventions designed to increase prudent use of antimicrobials by a range of restrictive and persuasive methods including guidelines, pre-authorisation, review, audit and feedback, supported by education and incentives.12 Core stewardship interventions are local guidelines and education. The importance of educating the multi-professional healthcare team in delivering antibiotics effectively and safely is critical. RochaInfectious Disease Reports 2017; volume 9:7158

Development of an interactive open source software application (RadaR) for infection management / antimicrobial stewardship

Objectives Analysing process and outcome measures for patients suspected of or having an infection in an entire hospital requires processing large datasets and accounting for numerous patient parameters and treatment guidelines. Rapid, reproducible and adaptable analyses usually need substantial technical expertise but can yield valuable insight for infection management and antimicrobial stewardship (AMS) teams. We describe a software application (RadaR - Rapid analysis of diagnostic and antimicrobial patterns in R) for infection management allowing user-friendly, intuitive and interactive analysis of large datasets without prior in-depth statistical or software knowledge. Methods and Results RadaR was built in R, an open source programming language, making it free to use and adaptable to different settings. Shiny, an additional open source package to implement web-application frameworks in R, was used to develop the application. RadaR was developed in the context of a 1339-bed academic tertiary referral hospital to handle data of more than 180,000 admissions. RadaR visualizes analytical graphs and statistical summaries in an interactive manner within seconds. Users can filter large patient groups by 17 different criteria and investigate antimicrobial use, microbiological diagnostic use and results, and outcome in length of stay. Results can easily be stratified and grouped to compare individually defined patient groups. Finally, datasets of identified patients / groups can be downloaded for further analyses. Conclusion RadaR facilitates understanding and communication of trends in antimicrobial use, diagnostic use and patient outcome by linking and aggregating individual patient data in one user-friendly application. RadaR can produce aggregated data analysis while preserving patients’ features in the data to adjust and stratify results in detail. AMS teams can use RadaR to identify areas, both for diagnostic and therapeutic procedures, within their institutions that might benefit from increased support and to target their interventions.

Prevention of Surgical Site Infections: A Systematic Review of Cost Analyses in the Use of Prophylactic Antibiotics

Introduction: The preoperative phase is an important period in which to prevent surgical site infections (SSIs). Prophylactic antibiotic use helps to reduce SSI rates, leading to reductions in hospitalization time and cost. In clinical practice, besides effectiveness and safety, the selection of prophylactic antibiotic agents should also consider the evidence with regard to costs and microbiological results. This review assessed the current research related to the use of antibiotics for SSI prophylaxis from an economic perspective and the underlying epidemiology of microbiological findings. Methods: A literature search was carried out through PubMed and Embase databases from 1 January 2006 to 31 August 2017. The relevant studies which reported the use of prophylactic antibiotics, SSI rates, and costs were included for analysis. The causing pathogens for SSIs were categorized by sites of the surgery. The quality of reporting on each included study was assessed with the “Consensus on Health Economic Criteria” (CHEC). Results: We identified 20 eligible full-text studies that met our inclusion criteria, which were subsequently assessed, studies had in a reporting quality scored on the CHEC list averaging 13.03 (8–18.5). Of the included studies, 14 were trial-based studies, and the others were model-based studies. The SSI rates ranged from 0 to 71.1% with costs amounting to US