Mohammadreza Heydari
email: mohammadreza.heydari@polimi.it

Christian Zanetti
email: christian.zanetti@polimi.it

Marco Taisch
email: marco.taisch@polimi.it

Margherita Peruzzini
email: margherita.peruzzini@consultants.indesit.com

PI Toolset Methodology for Virtual Enterprise Performance Assessment and Governance

Keywords: Virtual Enterprise, Service governance support toolset, Performance Indicators

This paper aims at describing a proposed Performance Indicators (PIs) Toolset, which has been developed to provide useful methodologies and tools to enterprises, especially Virtual Manufacturing Enterprises (VMEs), in order to support the management and evaluation of their service systems. Particularly, the identified PI Toolset helps VMEs to understand how well they are performing and contributing to their strategic goals and objectives. Indeed, determining which activities should be monitored, controlled and measured through proper PIs is essential for a VME. In this context the proposed PI Toolset helps to select the significant activities, to manage governance processes, and to support the design and implement the specific PIs related to the precise use case objectives. Finally, the proposed Toolset defined a set of PIs that can be used to evaluate business processes related to governance issues.

Introduction

Global industrial competition, current economic crisis and market turbulences have opened up more threats and also opportunities to enterprises both in manufacturing and service environment; furthermore, threats and opportunities generate exceeding pressure on enterprises to improve their capabilities. This paper investigates a key topic in management area based on the mutual interests of individual managers, decision makers, and also the capabilities of a network or supply chain: process evaluation through Performance Indicators (PIs). Therefore, enterprises need to employ different strategies with different context and circumstances in order to achieve a differentiated competitive advantage [START_REF] Donaldson | The contingency theory of organizations[END_REF]. The competitive advantage will help enterprises to survive in an increasingly competitive context [START_REF] Heydari | Service performance monitoring and control Toolset[END_REF].

Despite the facts that individual enterprises gain the opportunities through its own internal Tangible and Intangible (T/I) assets such as knowledge management and progressive R&D process; nevertheless, individual enterprises need to get closer to their partners in supply chain network and optimize their relations through the outsourcing process. Therefore, in order to be able to provide outsourcing process, individual enterprises need to participate in a collaborative network that has nowadays become crucial for any manufacturers and service providers.

With respect to the above mentioned context, individual enterprises need to shift from autonomous work toward collaborative network that can be defined as a common way by which all enterprises in supply chain are actively working together toward shared objectives. Consequently, collaborative networks are characterized by sharing T/I assets such as information, knowledge, risk and profits [2, 3 & 4].

Undeniably, enterprises need to provide some requirements in collaborative network environment such as restructuring their internal and external operating process; reengineering the production and service system; redefine the roles and rules of members in network; employed multi skilled and flexible people and at last, but not at least preparing the proper IT tool in order to coordinate the relationship among the members. Therefore, collaborative networks need significantly to improve competencies in terms of dealing with new business models, strategies, organizational and governance principles, processes and technological capabilities [START_REF]European Collaborative Networked Organizations Leadership Initiative IST IP 506958 project[END_REF] in order to be successful in a very competitive and rapid changing environment.

In this context, this paper aims to define and develop an overall Toolset to monitor VE based on Product-Service solution, through PIs and Product-Service oriented methods. Therefore, the proposed method should be applied to VE in order to efficiently control the product-service system within a Manufacturing Service Ecosystem. Meanwhile, in order to be able to produce significant results, an industrial case study is presented where the proposed PI Toolset is validated and adopted on it.

Research Background

A collaborative network can be defined as composed by various entities such as organizations, people and machines, and is characterized by geographical distribution, large autonomous and heterogeneity in terms of their operating environment and goals [START_REF] Camarinha-Matos | Collaborative networks: A new scientific discipline[END_REF]. For its mature it needs to be supported by IT tools in order to set the interaction among the participants.

A relevant stream of literature mainly rooted that a collaborative network structure classified in classical and dynamic format. In classical format network is relatively stable with well-defined roles in organizational forms; nevertheless, nowadays more dynamic structure are emerging in industries. One of the most important organizational forms, which will be analyzed in this paper, is the so-called Virtual Enterprises (VE). VE is a temporary organization of companies formed to exploit fast changing opportunities. In this case, companies come together to share costs, skills and core competencies in order to address the business opportunities that they could not undertake individually [START_REF] Gou | A framework for Virtual enterprise operation management[END_REF][START_REF] Cabale | Modelling and performance analysis of networking and collaborative systems-Simulation Modelling Practice and Theory[END_REF].

Although the combination of the core competencies of companies, the VE may become the best of everything enterprises and the key issue in order to fast reaction to market demands and business opportunities; Nevertheless, their practical implementation is still far from the expectations and also VE planning and creation, as well as several aspects of VE operation, are still difficult and need to be properly adapted even by advanced and competitive collaborative networks [START_REF] Gou | A framework for Virtual enterprise operation management[END_REF]. Some of the lacunae include the lack of common reference models and appropriate support tools following by below observed points [START_REF] Camarinha-Matos | -element of a base VE infrastructure[END_REF][START_REF] Camarinha-Matos | Collaborative networked organizations -Concepts and practice in manufacturing enterprisesǁ[END_REF][START_REF] Afsarmanesh | A framework for management of VO breeding environmentǁ[END_REF][START_REF] Goranson | The Agile Virtual Enterprise, Cases, Metrics, Tools[END_REF]:

-Partners search and selection; -Monitoring and coordination of task execution according to contracts; -Performance assessment.

In this context, understanding the VE formation process, modeling its processes and developing useful supporting tools are still open challenges [2, 9& 13]. In order to provide a meaningful analysis of the research background, the "Servitization" process is introduced. Indeed, it is accepted as one of the most successful structure which has been used to extend the after sale service activities. Meanwhile, it has been used frequently by manufacturing enterprises that would like to shift from a pure product sales structure towards after-sales services, and bundle their products with services to satisfy the customer needs [START_REF] Taisch | Manufacturing Service Innovation Ecosysetm-Advance Production Management System[END_REF]. In this context, Servitization process has been used to enhance the services that have been provided to support the manufactured products.

Use case plays an important role and leads the VE environment as a focal firm where it is responsible and allocates the manufacturing and service tasks among the partners (upstream level), and also sharing the costs and resources. Meanwhile, Use case (Focal firm) acts as a product integrator and also is responsible for the final product/service and relationship with the customer.

As far as the use of VE as an organizational form of a collaborative network is concerned, different Performance Measurement Systems (PMS) developed during the past decades in order to facilitate the generation and selection of most proper PIs. Consequently, PMS is used in order to be able to monitor the service performance effectiveness and efficiency through exploiting the suitable PIs. During the past decades, several PMS (Models, Tools, Methods and Frameworks) proposed and developed by various researchers and business managers. The most important are PMSs such as PRISM, ECOGRAI, Integrated Performance Measurement System (IPMS), Balanced Score Card (BSC), Six Sigma, European Foundation for Quality Management (EFQM), and Matrix and Brown's framework, which have been accepted and employed by various enterprises. [START_REF] Heydari | Service performance monitoring and control Toolset[END_REF][START_REF] Taisch | Service Performance Assessment and Governanceǁ International Conference 2013[END_REF][START_REF] Neely | Performance measurement system design: developing and testing a process-based approachǁ[END_REF][START_REF] Ghalayini | An integrated dynamic performance measurement system for improving manufacturing competitivenessǁ[END_REF][START_REF] Neely | The Performance Prism: The Scorecard for Measuring and Managing Business Success[END_REF][START_REF] Ducq | Definition and aggregation of a performance measurement system in three Aeronautical work shop using the ECOGARI Method[END_REF][START_REF] Bititci | Integrated Performance Measurement Systems: A Development Guideǁ[END_REF][START_REF] Kaplan | The Balanced Scorecard: Translating Strategy into Action[END_REF][START_REF] Ducq | Contribution to a method for analyzing the consistency of Production Systems in the GRAI modelǁ PhD thesis the University of Bordeaux I -France[END_REF][START_REF] Bourne | Why some performance measurement initiatives fail: lessons from the change management literature[END_REF]. The basic idea behind PMS exploitation is to encourage the enterprises to continue improvement and also to support appropriate activities through the proper PIs exploitation. Furthermore, PMS is used as a key process in the management of VE and traditionally, is defined as a systematic process of gathering, assessing and reporting the predefined tasks and objectives status. In order to be able to have meaningful analysis a set of quantitative and/or qualitative indicators can be used to help the enterprises and decision makers to evaluate the collaboration benefits in this environment such as activities performed resources employed, and outcomes obtained [START_REF]European Collaborative Networked Organizations Leadership Initiative IST IP 506958 project[END_REF].

Various authors expressed either positive or negative criticisms on the aforementioned PMS. For instance, EFQM and BSC highlighted in the literature as the most popular and employed by several enterprises today. Although, both models were initially designed for intra-organizational performance measurement in single companies and offer a measuring approach based on driver and outcome indicator to monitor and assess different perspectives in an enterprises; nevertheless, these models have a lack in terms of focusing on the strategy of collaborative network environment.

Additionally, BSC proposed a closer measure to predefined objectives and has a faster and more processed reporting especially based on financial measures. So, the relevant PIs make sometimes difficult in terms of comparison because indicators are contextual and need to be customized for each enterprises or objectives [START_REF]European Collaborative Networked Organizations Leadership Initiative IST IP 506958 project[END_REF][START_REF] Westphal | Managing collaboration performance to govern virtual organizations[END_REF][START_REF] Ducq | A contribution of system theory to sustainable enterprise interoperability science baseǁ[END_REF].

A relevant stream of the literature rooted some other criticism included: the nature of PIs used, dimensions retained, lack of procedures for the choice of PI's and procedure for the PIs connections, etc. Even the BSC, perhaps the most popular and used method, was deeply criticized about the reduced stakeholders [START_REF] Taisch | Service Performance Assessment and Governanceǁ International Conference 2013[END_REF].

In spite of these criticisms, it turns out that aforementioned PMS's present many similarities and differences, advantages and inconveniences. With respect to the mentioned methods, ECOGRAI method will be selected in this paper in order to design and to implement proper PIs in VE domains. The basic idea behind of ECOGRAI selection is that it has the opportunity to link with modelling tools such as Graph with reference Active Interrelated (GRAI) GRID and GRAI nets and also applied with the implication of the decision makers [START_REF] Heydari | Service performance monitoring and control Toolset[END_REF]. The selected method has a clear vision about the decomposition and the coherence of objectives in comparison to other most well known PMS such as BSC. Meanwhile, in ECOGRAI method is easy to have a very detailed view of the performance and also control of the performance [START_REF] Heydari | Service performance monitoring and control Toolset[END_REF][START_REF] Ducq | A contribution of system theory to sustainable enterprise interoperability science baseǁ[END_REF][START_REF] Ducq | -Interoperability in enterprise modelling: requirements and roadmapǁ[END_REF]. At last but not at least, the selected method covers the various functions and the various decision levels such as Strategic, Tactical and Operational in order to present a coherent distribution of PIs. Also, in order to manage the monitoring processes and to define the objectives, GRAI method will be used according to its proper integration between the focus on results and the consistency of the decision process [START_REF] Ducq | Coherence analysis methods for production systems by performance aggregation[END_REF]. Meanwhile, the selected method has a good possibility to analyze and to correct the coherence of an objective system in order to ensure that the operational objectives contribute to the strategic objectives.

In particular with regards to service performance, two research methodologies have been investigated and compared: Action Research Methodology (ARM) and Collaborative Management Research (CMR). CMR and ARM have some similarities as well as distinct features [START_REF] Shani | Action Research and Collaborative Management Research: More than Meets the Eye?[END_REF]. A comparative analysis revealed that both methodologies focus on developing a deeper level understanding and their main purpose is the identification, modification and transformation of the studied system [START_REF] Savall | The qualimetrics approach: Observing the complex object[END_REF]. Furthermore, both are concerned with system improvement and added value to the management realm. However, CMR is more oriented to capabilities' improvement and it can be adopted for both improving the capabilities of VE or even the capabilities of individual managers and decision makers by addressing specific aspects of management such as specific managerial actions or coordinating mechanisms among collaborative networks. In this way, CMR can be defined as an inquiry process that, through multiple studies, the accumulation of knowledge over time about different aspects of management, and across types of systems will clarify when and how managerial actions can make a difference [START_REF] Shani | Action Research and Collaborative Management Research: More than Meets the Eye?[END_REF]. The inquiry process of experiencing, understanding, judgment and action, as captured by Coghlan, is likely to confirm or disconfirm assumptions and is likely to result in general accumulation of managerial wisdom and scientific knowledge that eventually influence how management is taught and practiced [START_REF] Kuhn | The structure of scientific revolutions[END_REF][START_REF] Kaghlan | Action Research: Exploring Perspectives on a Philosophy of Practical Knowing[END_REF].

Research Questions and Methodology

This section presents the main research questions to satisfy the above-mentioned open challenges in VE realm, and indicates an overall method that combined a set of existing methodologies to achieve the research objectives. Therefore, the adopted research methodologies have been applied in an industrial case study to demonstrate its validity.

Research Questions and Objectives

In order to succeed in the modern turbulent and competitive climate, VEs require significantly improving competences in terms of business strategies, new governance principles and performance assessments. Moreover, in order to leverage the potential benefits, assessing the performance of the associated members in the VE through a proper set of PIs can usefully support the lifecycle of the designed and produced solutions, i.e. Product-Service.

In this context the authors identified the following research questions about performance assessment and governance in VE:

-Which specific performance assessments should be considered while monitoring VE (based on Product-Service) when numerous companies cooperate within a Manufacturing Service Ecosystem (MSE)?

-Which specific aspects related to performance indicators and methods should be applied to a VE in order to efficiently control the Product-Service system within a MSE? Such questions decline the overall research goal in two specific objectives; in particular, to answer the two research questions, the following three objectives have been defined:

-Development of a new methodology that helps enterprises selecting the activities to be monitored, controlled and measured through appropriate PIs;

-Definition of functions and actions at decisional levels (i.e. Strategic; Tactical and Operational);

-Preparation of a guideline to design, classify, implement and maintain effective PIs related to a specific VE with respect with its internal goals and objectives.

Moreover, the scope of research is focused on the analysis of the Service VE lifecycle by itself and the assessment of service performance for Service. As a consequence, the present research is based on the selection of a specific Use case focusing on a Service VE and the characteristics of the Service Lifecycle Management (SLM). Given the relative novelty of the subject, the literature lacunas in VE in which both manufacturing and service practices and performances can be considered according to the Use case objectives and strategies.

The proposed method starts from the investigation of existing methodologies about performance and service management lifecycle assessment. It includes a brief literature review based on major methodologies that have been used in research and short explanation of adoptable methodologies that can be used in order to develop the concepts/approaches proposed and methodologies adopted to validate that the concepts/approaches are applicable.

With respect to performance assessment requirements for Service in VEs, the research methodology is structured in the following steps:

-Monitoring Framework for Service Virtual Enterprises; -Generating a PIs model suitable for the specific purposes; -Defining a list of PIs for service VE; -Inserting this list in an ICT tool.

Furthermore, this paper considers that Use case seeking the transformation at all level of organizational life; consequently, Developmental Action Inquiry (DAI) also will be included. In the following table the research tools adopted in the proposed methodology to be used in on Use cases. In particular, it contains the list of tools for each step. With respect to the first step, the methodology has been developed starting from reference models available in the literature and using both selected tools from CIR and DAI approaches. The second step considers PMS tools for PIs generation models. The third step the list of PIs defined before will be shared with decision makers and study team in order to select the most proper PIs according to the use case objectives and main strategies. The fourth step will consist of insertion of PIs into an ICT tool according to Use case requirements according to the Process Modeling approach. Finally, a Use case is adopted to test the applicability of the model, as well as to refine the methodology itself.

Research Methodology Adopted

Approach Validation

Monitoring Framework for Service VE

PI Toolset

A PI Toolset has been created to support the managing and controlling issues of a VME. The stated Toolset includes various tools such as service governance framework, PI method and list of PIs that adopted together. By synthesizing the mentioned trio methods, PI Toolset will be able to create a coherent link between governance issues and the selection of specific PIs.

Service Governance Framework

The proposed service governance framework satisfies the first step fo the proposed methodology. It synthesized by GRAI model and Model Driven Service Engineering Architecture (MDSEA) within a VME environment in order to create a conceptual reference framework focusing on business objectives definition and governance issues.

Particularly, the GRAI model has been used to synthesize coherently various governance concepts (at detailed and global levels) into a unique generic model to facilitate integration between decisional levels and functions. On the other hand, MDSEA has been adopted with a conceptual framework in order to classify PIs into a different level of decomposition (i.e. decomposition by level of abstraction and decomposition by level of decision). The MDSEA has been used in order to facilitate the classification and implementation of PIs into a different level of decompositions; it means decomposition by level of abstraction (BSM, TIM and TSM) and decomposition by level of decision (Strategic, Tactical and Operational). In more details, BSM (Business Service Modeling) level has been used in order to elaborate high abstraction level model from users' point of view. TIM (Technology Independent Modeling) level gives detailed features of the service. TSM (Technology Specific Modeling) level insert a particular type of technology such as machine technology that is belongs to implementation options.

The conceptual framework has been used to lay down the foundations for governance framework which can be then linked with coherent monitoring and controlling activities; and to help the selection of highly exploitable PIs related to End User governance objectives. Table 2 provides an overview of the correlation between the stages considered for the Service Governance Framework and the MDSEA levels of decomposition.

PIs Generation Model

PIs Generation Model has been used to design, implement and classify the specific PIs related to the precise use case objectives. The (Fig. 1) Use case objective (i.e. Servitization) process has been modeled through the proposed framework and servitization characteristics have been specified such as functions and objectives at decisional levels. As described in Fig. 1 the following aspects can be observed: firstly, objectives at decisional level are defined through the proposed framework; secondly, a set of specific functions and actions have been defined through Value Reference Model (VRM) as decisional tools for supporting business processes; at the third level, an initial definition of specific PIs is carried out, and afterwards a personalized list of PIs is generated. At the end, the selected list of PIs is defined: they can be used to monitor and govern the service. VRM has been used deliberately in order to design and implement the related PIs. Indeed VRM provides a supporting tool to define and prioritize the PIs that are needed to govern business processes.

PI List and ICT tool creation

The PI list has been used to evaluate business processes related to governance issues. In the Table, 3 proposed methods developed a "Tree" structure file in order to filter the selection procedure of PIs. PI list classification in one side comes from VRM process categorization and on the other side comes from MDSEA. The PI List has been focused on VME creation with particular attention on BSM Level. Indeed the PI List is the results of service governance framework and PI Method. PI List is a supporting tool to assess service performances and manage the efficiency of enterprise resources. Meanwhile, a PI List structure has been created in order to facilitate the selection and the linkage of PIs to objectives and decision variables.

Finally, in order to support service design, management and evaluation within the manufacturing networks in an ICT environment PI Toolset has been implemented within the SLM Toolbox. By using the toolset the following points can be observed:

-Easy and coherent selection of highly exploitable PIs related to End User Governance objectives; -ICT implementation of the support control toolset through the SLM Toolbox; -End Users have the possibility to edit, change, save their PI List and share it with partners through the innovative ecosystem platform; -Adequate measures for effectiveness, efficiency and productivity can be assessed in order to offer a satisfactory service system; -The toolset can improve the efficiency of the service system by measuring the ability of a firm to reach its main governance goals within the VME perspectives.

MDSEA

The use case results

In order to produce meaningful results and optimize the proposed PI Toolset, the approach has been applied to an industrial Use case. The company is one of the largest European manufacturing industries in the white goods sector, aiming at providing its consumers with advanced services; therefore, the proposed PI Toolset has been developed and modified through industrial case study creating a real servitization process.

The current Servitization level in the selected company is rather low and limited to selling the physical product and only few basic services have been offered in a traditional way such as warranty, technical support and service center. The basic idea behind of Servitization process exploitation is to increase the product selling through differentiate the services according to the company profile. In particular, the company aims at realizing a new service focused on supporting the customers' usage by personalized services such as personalized best practice, machine monitoring and tailored commercial offers [START_REF] Taisch | Service Performance Assessment and Governanceǁ International Conference 2013[END_REF]. In order to provide the new services, Use case has been provided a new VE environment and selected the partners according to the preexisting suppliers profile and also new members from outside of its own ecosystem with respect to new VE defined activities and main objectives.

In particular, the company framework is actually characterized by the manufacturing company itself and a group of partners: it is actually organized in a vertical supplychain adopting a product-oriented development process. Collaboration between the manufacturer and its partners and suppliers is limited to design stages and components' supply. The leader company recently designs and produces a "Smart Washing Machine" enhanced with embedded items (e.g. sensors, Zigbee module, router Wi-Fi) and software components (e.g. web service, data repository, web/mobile application) as well as an infrastructure to connect the product to an external network. The Use case focuses on enabling new services for such Smart Washing Machines: it aims at realizing a new service, called "Carefree Washing Service", to provide the washing machine rent for free, a supply agreement comprising washing energy and detergent supply by paying an annual fee, and a web/mobile application for machine monitoring and customer training and coaching. Such Use case aims at enlarging the VEs by including also customers thanks to a direct relationship with them by facilitating the product use, educating the customers in a correct use and energy/cost saving practices, and collecting real-time feedback.

According to the Use case objectives, a set of functions has been defined and classified inside the framework of servitization (i.e. Customer decision, Customer ideation, Service product design, Service requirements). Then, according to the mentioned functions, main objectives have been defined at each stage (i.e. Strategic, Tactical and Operational). Table 4 represents the results related to the proposed framework. Finally, PI list has been represented in the Table 5.

Conclusions and future works

In this paper a methodology to define a PI Toolset for performance assessment in the VE has been proposed as an instrument to support service management and VME configuration. Indeed, it allows defining and representing an open structure (i.e. Service Governance Framework) to share knowledge and sources among the members inside the service ecosystem. Meanwhile, the PI Toolset is used as a decisional supporting tool to generate specific PIs related to end users' core activities. Particularly, the output of PI Toolset will provide a source of information to be used, visualized and shared among VME partners through ICT tools. PI Toolset can support VME to control and monitoring their performances in order to improve their level of service quality and, therefore, manage better the service governance. Indeed the PI Toolset is able to provide, collect and manage necessary information for helping the VMEs in identifying and understanding the needs and requirements of the service system and assessing current and future organizational and process capabilities of the service. The method is presented and tested on an industrial use case, whose preliminary results are shown and discussed. Obviously, this paper paves the way to a more detailed validation phase where the PI Toolset are improved through a huge number of use cases. Therefore, in order to generate additional positive results on use case servitization governance processes the following additional improvements such as visualization of performances, Internal audit and feedback on performances can be taken into account as further steps.

2 .

 2 Service governance framework

Fig. 1 .

 1 Fig. 1. PI Toolset: detail on PI Generation Model and PI List

Tab. 4 .

 4 Service Governance Framework Tab. 5. PI List

Acknowledgments.

This work has been partly funded from the European Union's Seventh Framework Programme for research; technological development and demonstration under grant agreement no [284860].


Elyes Lamine
email: elyes.lamine@mines-albi.fr

Abdel-Rahman H Tawil
email: a.r.tawil@uel.ac.uk

Rémi Bastide
email: remi.bastide@univ-jfc.fr

Hervé Pingaud
email: herve.pingaud@univ-jfc.fr

Ontology-based Workflow Design for the Coordination of Homecare Interventions

Keywords: Collaborative process, Homecare processes, Personalization, Workflow, Ontology, Model-Driven Engineering

ICT are recognized as key opportunity to improve healthcare practices ,in the homecare domain particularly in relation to care interventions. However, despite all the advances accomplished in this field, a problem of coordination and continuity of personalized care remains. Given these needs, workflow management systems appear to be an appropriate tool for supporting the communication between the different stakeholders involved in the homecare ecosystem. Nevertheless, the specific characteristics of homecare processes make the design of such workflows a real challenge. In order to help with the conception of these workflows, we propose in this paper an approach based on ontology matching between homecare domain models and semantic representation of Business Process Modeling Notations (BPMN). This approach leads to the design of custom workflow coordinated interventions for a given patient according to his profile.

Introduction

Homecare interventions are complex processes, which represents the chain of various activities achieved by several stakeholders trades (i.e., nurse, physician, professional caregivers, etc.) to follow patient's progression and needs at their homes. Interventions often represent collaborative or cooperative processes with strong human components involvement. Such processes are usually long termed, distributed among several participants and composed of heterogeneous elements with various levels of autonomy, but are subject to dynamic changes [START_REF] Lamine | A System Architecture Supporting the Agile Coordination of Homecare Services[END_REF]. As outlined in several research works [START_REF] Lamine | A System Architecture Supporting the Agile Coordination of Homecare Services[END_REF][START_REF] Riaño | An ontology-based personalization of health-care knowledge to support clinical decisions for chronically ill patients[END_REF][START_REF] Bastide | Plas'O'Soins: A software platform for modeling, planning and monitoring homecare activities[END_REF], the delivery of homecare interventions faces many challenges, mainly in terms of coordination and continuity of care. In both cases, the problem seems to be related to how care activities are distributed and managed among the different participants involved in such processes. As a result, there is a need to improve the efficiency of the way in which information is exchanged and shared among care providers. One approach to overcome these challenges is to employ workflow systems, which appear to be appropriate tools for supporting the communication and coordination between the different stakeholders through managing a sequence of care workflow (careflow) activities. Indeed, the role of a workflow management system could be to coordinate the work to be done by transmitting the necessary information and tasks among different stakeholders, according to patient's needs and roles of the participants. For example, sending information about patient conditions to the right participant in real-time or notifying when a planned care activity is actually performed (or canceled) by a specified nurse.

The design of such intervention workflows is facing hurdles due to the complex characteristics of homecare processes, and this issue represents the framework of our research work presented in this paper. We present a new approach to assist in the conception of workflows apt to dynamically improve the coordination in homecare. The remainder of the paper is structured as follows. In Section 2, we give in the next section an overview of the coordination concerns in homecare, show how workflows can be used to tackle these concerns and point out some challenges for their design. Based on the latter, in the third section, we focus our endeavor on the presentation of our proposed approach to facilitate the design of personalized workflows that can be enacted to improve the coordination of homecare interventions. Our main contribution concerning this approach is described in this section. In Section 4 we discuss related work. Finally, we provide concluding remarks and future outlook.

Workflows-based Coordination Challenges for Homecare Interventions

Homecare interventions occur in a mobile and dynamic environment that is continuously evolving during its execution, as new stakeholders can be integrated while others may leave depending on the outcomes of successive actions. The set of relationships and dependencies across intervention episodes requires for actors to share knowledge, expertise and experiences. Accordingly, care coordination is an essential component for quality healthcare delivery. A purposely-broad definition of care coordination has been proposed by [START_REF] Mcdonald | Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies (Vol. 7: Care Coordination)[END_REF], as "The deliberate organization of patient care activities between two or more participants (including the patient) involved in a patient's care to facilitate the appropriate delivery of health care services". The focus is on organizing care by systemizing personnel and other resources needed to carry out required patient activities through managing the exchange of carried interventions among the different actors responsible for the diverse aspects of care.

Within the homecare environment care coordination is considered as both crucial and timely for the efficient delivery of provided care services. Indeed, the homecare process represents a collaborative process which is a set of potentially interdependent services carried at patients' homes by different stakeholders in a cooperative way. For such process, the need for coordination stands at two levels:

• The interventions level: where different providers of social and healthcare participants have to organize the delivery of homecare activities and the exchange of information with regards to performed interventions. This information is necessary to facilitate the appropriate delivery of health care services. • The transitions over time level: where the stakeholders must ensure continuity and consistency of provided care during the transition of different episodes of care and across the full spectrum of patient's care. For instance when moving from one care institution to another arises the need for responsibility shifts.

As shown in Figure 1, the coordination of home-based interventions at the first level is generally focused on monitoring the proper enactment of patient care plans, which represents duly personalized statements of planned healthcare activities encompassing all health care provider activities to be performed by one or several healthcare professionals. The second level of coordination is mainly related the continuity of care over time through the integration, collaboration and sharing of information between different providers. Specifically, this level is focused on the anticipated care pathway, which is placed in an appropriate time frame, and agreed by a multidisciplinary team. In the home care domain, the coordination at this level simply consists of organizational shifting of care responsibilities and the transfer of current patient state condition and eventually the enactment of care history.

With regards to the above-mentioned levels we focus our endeavors on the first level of coordination since we consider it to be a fundamental step for homecare coordination. Given the needs at this level, workflow management systems appear to be an appropriate tool for supporting the communication and coordination between these different stakeholders through managing a sequence of care workflow activities.

Workflows Coordination for Homecare Process

Usually, workflow systems are process oriented, where a process represents a set of activities within a course-of-action that needs to be carried out in a prescribed sequence with the aim to achieve a determined outcome. In healthcare domain, such processes are known as care workflows (careflows), defined as the flow of carerelated tasks to be carried out together with the timing and sequence of these tasks and the disciplines involved in completing them. Careflows tasks can either be diagnostic, therapeutic, administrative, or decision-making [START_REF] Browne | Workflow modelling of coordinated inter-health-provider care plans[END_REF]. In the literature, there are several research works that have addressed the area of supporting healthcare process using workflow [START_REF] Gooch | Computerization of workflows, guidelines, and care pathways: a review of implementation challenges for process-oriented health information systems[END_REF], mainly for the hospital domain.

However, fewer papers explore the design of workflow within the homecare domain. The mainstream of careflows in homecare context typically involves the coordinated provision of service care at patients' homes through monitoring sequences of interventions. Hence, these careflows, namely workflow coordination should be setup regarding a structured multidisciplinary care plans that detail essential tasks in the care for patients requiring specifically timed home services and offers structured means for developing and implementing local protocols of care based on planned clinical guidelines.

Fig. 2 shows a BPMN model process that represent a simple example of such a careflow in the homecare domain. It represents a sequence of interventions performed within a one-day timeframe for a specific patient, with the distribution of interventions amongst stakeholders (nurse, cleaning agent, etc.). This BPMN Model shows one pool representing a coordinated workflow, containing three lanes representing three different categories of actors involved in the homecare of a specific patient. In this case a cleaning agent should perform the first intervention at 8 o'clock, followed by two tasks (help with dressing and bathing and preparation of pill box) performed by a care aid agent. Followed by a third intervention that should be performed by a nurse at 10:30, etc.

In accordance with the patients' care plan, this careflow could be used to coordinate care interventions in real-time, thus allowing for the timely checking of planned care activities as to whether they were correctly executed by a specified actor or reported as cancelled. Notifications can be launched automatically by the system to advise when intervention is required, including the date and time of actions needed or alternatively to alert coordinators for any delays or cancellations. In addition, stakeholders could rely on careflows for sharing information with regards to care progression and patients' conditions [START_REF] Lamine | An Ontology-Driven Approach for the Management of Home Healthcare Process[END_REF]. Accordingly, we have developed an ontology-based approach for the coordination of homecare interventions to fulfill the above-mentioned requirements. This approach is presented in the following section.

Ontology-based Careflow Design Approach

As noted in the previous section, a homecare plan can be considered as a rich temporal, process-centric, patient-specific representation of linked set of actions that need to be performed by several care providers at patient's home within agreed times. Based on the state-of-the-art, we have noticed that the knowledge management paradigm and more specifically the ontological approach are largely used in the field of medicine and health, especially to define careplans that are based on clinical guidelines. In addition they also seem to be a relevant means to cope with both flexibility and personalization needs.

Taking this into account and considering our goals, we propose to complement customized patient-centered workflows by using knowledge models. Specifically, according to the workflow architecture reference, ontologies are used to help in building workflow models in the design-time stage and to deal with the changing needs at run-time. In this work we have focused our endeavor on the design-time stage. Our approach consists of generating a "personalized care process" from a personalized careplan model. The resulting process model will be interpreted by a process definition tool in order to be enacted on a conventional workflow engine. This approach follows a Model-Driven Engineering approach, and is based on ontology matching between homecare domain conceptual models and a semantic representation of Business Process Modeling Notations. The result of the first step is an OWL model that conforms to a homecare ontology encompassing health objectives, subject of care profile, health and social conditions. Based on this intermediate personalized careplan model we generate a BPMN model by using the BPMN ontology [START_REF] Ghidini | Semantics-Based Aspect-Oriented Management of Exceptional Flows in Business Processes[END_REF] and SWRL (Semantic Web Rule Language) rules that define the mapping between the two ontologies. An important challenging step was to define a HomeCare Ontology (HCO).

Homecare Ontology: HCO

The use of ontologies has proven quite successful in the field of medicine and health in general, to describe diseases, their symptoms, and medical knowledge, e.g., CIM, UMLS and GALEN. A few ontologies have been built in the homecare area, however to our knowledge none is considered a standard in the field. Most ontologies of homecare remain at the stage of research projects, to address specific challenges of homecare [START_REF] Paganelli | An Ontology-Based Context Model for Home Health Monitoring and Alerting in Chronic Patient Care Networks[END_REF][START_REF] Lasierra | An ontology approach to manage individual patient profiles in home-based telemonitoring scenarios[END_REF][START_REF] Valls | Using ontologies for structuring organizational knowledge in Home Care assistance[END_REF].

In our work we adopted the APO (Actor Profile Ontology) and CPO (Case Profile Ontology) ontologies both implemented as part of the European K4Care project [START_REF] Riaño | An ontology-based personalization of health-care knowledge to support clinical decisions for chronically ill patients[END_REF][START_REF] Valls | Using ontologies for structuring organizational knowledge in Home Care assistance[END_REF]. APO deals with knowledge about actors and their skills involved in homecare domain and CPO is about illnesses and treatments. Though interesting, these ontologies on their own don't fit our needs Therefore we had to rebuild a new ontology that we called HCO. To build this ontology of homecare domain, we followed a synthesis of different methodologies in literature such as the ones proposed in [START_REF] Uschold | Ontologies: Principles, methods and applications[END_REF][START_REF] Corcho | Methodologies, Tools and Languages for Building Ontologies: Where is Their Meeting Point?[END_REF]. HCO focuses on the concepts of homecare coordination. This ontology contains global information about a structure and organization of homecare (actors, roles, etc.) as well as the knowledge for capturing the profile of patients, tasks required and actors needed for each disease. Our knowledge model is based on the reuse of some concepts from both APO and CPO such as Interventions, Actors and Actions. We also had to modify some other concepts such as patient and homecare semantic representation. We also introduced new concepts too, such as the duration and the frequency interventions This ontology could be queried to retrieve the elements that focus on which, when and by whom actions need to occur to treat a patient over a period of time.

With regard to the implementation of our approach, the software architecture is made of tree main components: a knowledge base, an inference engine that is able to query the knowledge base and the BPMN generator module that allows for generating BPMN files to be interpreted by a workflow modeler Tool.

Related Work

Numerous research efforts has focused on implementing computerized care pathway systems. Alexandrou et al. [START_REF] Alexandrou | SEMPATH Ontology: Modeling Multidisciplinary Treatment Schemes Utilizing Semantics[END_REF] proposed a semantic approach that supports the execution of treatment schemes based on clinical pathways to efficiently handle the application of healthcare business processes. The developed SEMantic PATHways (SEMPATH) system provisions for the constant monitoring of applied clinical pathways execution and automatically recognize any exceptional events. Abidi et al. [START_REF] Hurley | Ontology engineering to model clinical pathways: towards the computerization and execution of clinical pathways. Computer-Based Medical Systems[END_REF] propose a patient care planning system that can automatically and proactively generates adaptive patient-specific healthcare procedures based on a semantic framework. They developed a careplan system that tries to combine heterogeneous healthcare knowledge sources with available patient information into personalized healthcare plans while utilizing the technology of web-services for the composition of integrated pathways. Yao et al. [START_REF] Yao | CONFlexFlow: Integrating Flexible clinical pathways into clinical decision support systems using context and rules[END_REF] propose a novel approach for integrating clinical pathways into clinical decision support systems. There work acknowledges the frequent deviation that clinical pathways involves and the need for significant flexibility to build successful clinical decision applications. This is achieved based on a better understanding of clinical context through using ontologies, and associating with rules to provide the knowledge required to allow in deciding the correct activities execution.

Most of these research works develop electronic clones of existing paper-based care plan management methods with a focus that is mainly related to hospital care. Contrariwise, in homecare the collaboration is asynchronous where the interventions are distributed in space and time. Accordingly, these approaches gave little consideration for the explicit modeling of intervention outcomes and related temporal relationships when formally defining the coordination of homecare process models. In our work, we are interested in the design of customized patient profile careflow models and monitoring their execution to improve the coordination of homecare interventions. To our knowledge there are no other works with the same goals.

Conclusion

Homecare interventions give rise to coordination and continuity of care. To ensure such continuity and to improve its quality, we proposed an ontology-based workflow design approach for homecare coordination of interventions with focus on organizing tasks among the numerous involved stakeholders. Our work differs from classical workflow based methods in that we incorporate considerable domain in addition to organizational and temporal knowledge. The fundamental proposition of our approach is its ability to assess a patient case, evaluate and implement workflow models for personalized patients' care interventions. We rely on ontologies to overcome workflow flexibility as the major identified obstacle and allow for the dynamic construction of careflows. Next step in our work is to promote a human in the loop approach in our transformation process, as indeed all necessary knowledge is not present in our ontology and we still need to give the users the means to complete the missing items during the transformation process.

Fig. 1 .

 1 Fig. 1. Care coordination levels

Fig. 2 .

 2 Fig. 2. An example of daily Home-care coordination workflow of a specific patient

  . The proposed HCO is sketched in Fig 3. We use different colors, as specified in the figure legend, to clarify the origin of the concept: CPO, APO or others.

Fig. 3 .

 3 Fig. 3. Main classes and relations of HCO


MD Eric Dannaoui
email: eric.dannaoui@egp.aphp.fr

Keywords: Candida species, France, micafungin, EUCAST, Etest®

Multicenter comparison of the etest and EUCAST methods for antifungal susceptibility testing of Candida isolates to micafungin

1

Multicenter comparison of the Etest® and EUCAST for antifungal susceptibility testing of Candida isolates to micafungin M.E. Bougnoux 1 , E. Dannaoui 2* , I. Accoceberry 3 , A. Angoulvant 4 , E. Bailly 5 , F. Botterel 6 , S.

Chevrier 7 , T. Chouaki 8 , M. Cornet 9 , F. Dalle 10 , A. Datry 11 , A. Dupuis 1 , A. Fekkar 11, 12 , J.P.

Gangneux 7 , J. Guitard 13 , C. Hennequin 13 , Y.LeGovic 14 , P. Le Pape 15 , D. Maubon 9 , S.

Ranque 16 , M. Sautour 11 , B. Sendid 17 , J. Chandenier 5, 18 1: Université Paris-Descartes; Faculté de Médecine; Unité de Parasitologie-Mycologie, Service de Microbiologie, Hôpital Necker Enfants Malades, Assistance Publique -Hôpitaux de Paris, Paris, France. The echinocandin antifungal drug micafungin is highly effective in vitro against most Candida species (1-3). Micafungin is now widely used for prophylaxis and treatment of invasive candidiasis (IC) [START_REF] Cornely | ESCMID* guideline for the diagnosis and management of Candida diseases 2012: non-neutropenic adult patients[END_REF][START_REF] Groll | Micafungin: pharmacology, experimental therapeutics and clinical applications[END_REF]. During the last decade, acquired resistance of various Candida species to echinocandins has emerged worldwide, including France, and may become an important issue in the therapeutic management of IC [START_REF] Arendrup | Echinocandin resistance: an emerging clinical problem?[END_REF][START_REF] Dannaoui | Candida spp. with acquired echinocandin resistance, France, 2004-2010[END_REF][START_REF] Fekkar | Emergence of echinocandin-resistant Candida spp. in a hospital setting: a consequence of 10 years of increasing use of antifungal therapy?[END_REF][START_REF] Fekkar | Rapid emergence of echinocandin resistance during Candida kefyr fungemia treatment with caspofungin[END_REF][START_REF] Perlin | Echinocandin resistance, susceptibility testing and prophylaxis: implications for patient management[END_REF].

In vitro antifungal susceptibility testing is currently recommended to detect resistance in Candida species and to guide antifungal treatment [START_REF] Arendrup | Echinocandin resistance: an emerging clinical problem?[END_REF][START_REF] Cuenca-Estrella | ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures[END_REF]. Microdilution broth methods such as EUCAST and CLSI are the reference methods for antifungal susceptibility testing. andC. krusei) and four isolates belonging to other Candida species. Species identification was performed in each center according to the currently recommended phenotypic methods [START_REF] Howell | Candida, Cryptococcus, and other yeasts of medical importance[END_REF]. Micafungin susceptibility testing was performed using the Etest® (Biomérieux, Marcy l'Etoile, France), according to the manufacturer's instructions. Candida isolates were then centralized in a single center for MIC determination by the EUCAST reference method [START_REF] Eucast | EUCAST definitive document EDef 7.1: method for the determination of broth dilution MICs of antifungal agents for fermentative yeasts[END_REF].

C. krusei ATCC 6258 and C. parapsilosis ATCC 22019 were included as quality control strains [START_REF] Cuenca-Estrella | Multicentre determination of quality control strains and quality control ranges for antifungal susceptibility testing of yeasts and filamentous fungi using the methods of the Antifungal Susceptibility Testing Subcommittee of the European Committee on Antimicrobial Susceptibility Testing (AFST-EUCAST)[END_REF]. For comparison purposes, Etest® MICs were increased to the next higher corresponding EUCAST concentration [START_REF] Dannaoui | Comparison of antifungal MICs for yeasts obtained using the EUCAST method in a reference laboratory and the Etest in nine different hospital laboratories[END_REF]. Resistance was based on EUCAST clinical breakpoints. When clinical breakpoints were not available (i.e. for C. krusei and C. tropicalis), ECOFFs were used to categorize isolates as non-wild-type [START_REF] Arendrup | European Committee on Antimicrobial Susceptibility Testing -Subcommittee on Antifungal Susceptibility Testing[END_REF]. The same ECOFFs (defined by EUCAST) were used for analyzing results of Etest® as specific ECOFFs have not been determined yet. C.albicans, C. glabrata, and C. parapsilosis isolates were considered susceptible / resistant to micafungin when MICs were ≤0.016 / >0.016 µg/ml, ≤0.03 / >0.03 µg/ml, and ≤0.002 / >2 µg/ml, respectively. C. krusei and C. tropicalis isolates were considered wild-type / non-wild-type to micafungin when MICs were ≤0.25 / >0.25 µg/ml and ≤0.06 / >0.06 µg/ml, respectively. MIC results obtained by the two methods were considered to be in essential agreement when they were within ± 2 log 2 dilutions. Agreement at ± 1 log 2 dilution was also calculated. Categorical agreement was defined as the percentage of isolates classified in the same category (i.e. susceptible, intermediate, and resistant or wildtype and non-wild-type) by both techniques [START_REF] Dannaoui | Comparison of antifungal MICs for yeasts obtained using the EUCAST method in a reference laboratory and the Etest in nine different hospital laboratories[END_REF]. Discrepancies (very major, major, and minor errors) were defined as described previously [START_REF] Dannaoui | Comparison of antifungal MICs for yeasts obtained using the EUCAST method in a reference laboratory and the Etest in nine different hospital laboratories[END_REF].

Results from antifungal susceptibility testing were available for 933 Candida isolates, including 878 isolates of the six most medically important Candida species and 55 other Candida species. Table 1 shows the micafungin MICs for the 933 isolates determined by the EUCAST reference method. Micafungin MICs for C. parapsilosis isolates (modal MIC of 1 µg/ml) were several dilutions higher than for the other common species (modal MIC of 0.015 µg/ml for C. albicans, C. tropicalis, and C. glabrata and 0.03 and 0.06 µg/ml for C. kefyr and C. krusei, respectively). MICs for rare species were similar than those of the common species except for C. colliculosa and some isolates of C. guilliermondii and C. famata. According to the current clinical breakpoints [START_REF] Arendrup | European Committee on Antimicrobial Susceptibility Testing -Subcommittee on Antifungal Susceptibility Testing[END_REF], the micafungin resistance rate was <2% for C. albicans and C. parapsilosis, and 3.9% for C. glabrata. Based on ECOFFs, the non-wild-type rate was 0.7% for C. tropicalis and 0% for C. krusei. The overall essential agreement between EUCAST and Etest® results was high (98.5% at ± 2 log 2 dilutions and 90.2% at ± 1 log 2 dilution) (Figure 1) with minor differences between species (Table 2). The lowest essential agreement (96.7% at ± 2 log 2 dilutions) was observed for C. parapsilosis. An overall categorical agreement of 98.2% was observed for the 742 isolates belonging to the five species for which clinical breakpoints or ECOFFs are available (Table 3). The highest (100%) and lowest (96.7%) categorical agreements were found for C. krusei and C. glabrata, respectively. Major errors were observed in six cases (three C. albicans, two C. tropicalis, and one C. glabrata) and very major errors in six cases (two C. albicans and four C. glabrata). These 12 discrepancies were observed for strains isolated and tested in eight different centers.

The Etest® has been used in several studies for micafungin susceptibility testing of Candida spp. [START_REF] Arendrup | Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media[END_REF][START_REF] Axner-Elings | Echinocandin susceptibility testing of Candida isolates collected during a 1-year period in Sweden[END_REF][START_REF] Baixench | Acquired resistance to echinocandins in Candida albicans: case report and review[END_REF][START_REF] Espinel-Ingroff | Comparison of micafungin MICs as determined by the Clinical and Laboratory Standards Institute broth microdilution method (M27-A3 document) and Etest for Candida spp. isolates[END_REF][START_REF] Escribano | Comparison between the EUCAST procedure and the Etest for determination of the susceptibility of Candida species isolates to micafungin[END_REF][START_REF] Pfaller | Comparison of European Committee on Antimicrobial Susceptibility Testing[END_REF], but only a few comparative studies with a reference method have been performed [START_REF] Arendrup | Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media[END_REF][START_REF] Espinel-Ingroff | Comparison of micafungin MICs as determined by the Clinical and Laboratory Standards Institute broth microdilution method (M27-A3 document) and Etest for Candida spp. isolates[END_REF][START_REF] Escribano | Comparison between the EUCAST procedure and the Etest for determination of the susceptibility of Candida species isolates to micafungin[END_REF][START_REF] Pfaller | Comparison of European Committee on Antimicrobial Susceptibility Testing[END_REF]. In one of these previous studies, Marcos-Zambrano et al. [START_REF] Escribano | Comparison between the EUCAST procedure and the Etest for determination of the susceptibility of Candida species isolates to micafungin[END_REF] tested 160 yeast isolates with both the Etest® and EUCAST methods and reported an essential agreement of 90.3% at ± 2 log 2 dilutions (85.8% at ± 1 log 2 dilution) and a categorical agreement of >90%. Similarly, in another study, a comparison between Etest® and CLSI methods showed an overall essential agreement of 94.7% and a categorical agreement of 97.2% [START_REF] Espinel-Ingroff | Comparison of micafungin MICs as determined by the Clinical and Laboratory Standards Institute broth microdilution method (M27-A3 document) and Etest for Candida spp. isolates[END_REF]. The ability of the Etest® to detect micafungin resistance, for most of the species, has also been demonstrated previously by testing FKS mutant isolates [START_REF] Arendrup | Echinocandin susceptibility testing of Candida species: comparison of EUCAST EDef 7.1, CLSI M27-A3, Etest, disk diffusion, and agar dilution methods with RPMI and isosensitest media[END_REF][START_REF] Escribano | Comparison between the EUCAST procedure and the Etest for determination of the susceptibility of Candida species isolates to micafungin[END_REF][START_REF] Pfaller | Comparison of European Committee on Antimicrobial Susceptibility Testing[END_REF]. We enrolled 16 centers and demonstrated that under real-life conditions the Etest® gave very similar micafungin susceptibility results to the EUCAST reference method.

Altogether, our results show that the Etest® is a valuable and reliable method to routinely test the in vitro susceptibility of clinical Candida isolates to micafungin. In vitro micafungin resistance among the main Candida species isolated from clinical samples remains uncommon in France.

(EUCAST) and Etest methods with the CLSI broth microdilution method for echinocandin susceptibility testing of Candida species. J Clin Microbiol 48:1592-1599.

2 : 3 :France 7 :France 12 :

 23712 Université Paris-Descartes; Faculté de Médecine; Unité de Parasitologie-Mycologie, Service de Microbiologie, Hôpital Européen Georges Pompidou, Assistance Publique -Hôpitaux de Paris, Paris, France. Laboratoire de Parasitologie-Mycologie, Centre hospitalier Universitaire de Bordeaux, Bordeaux, France 4: Assistance Publique -Hôpitaux de Paris, Hôpital de Bicêtre, Laboratoire de Parasitologie-Mycologie; Université Paris-Sud, Faculté de Médecine, Le Kremlin-Bicêtre, CNRS UMR 8621, Génétique Quantitative et Evolution, Le Moulon, France 5: Service de Parasitologie-Mycologie-Médecine tropicale Centre Hospitalier Régional Universitaire, Tours, France 6: Hôpital Henri Mondor, DHU VIC, APHP; EA 7380, DYNAMYC, Université Paris Est Créteil, Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire, Rennes; Université Rennes 1 Inserm U1085 -IRSET, 35000 Rennes, France 8: Centre Hospitalo-Universitaire, Amiens, France. 9: Laboratoire de Parasitologie-Mycologie, Centre Hospitalo-Universitaire Grenoble; Université Grenoble Alpes, Grenoble, France 10: Laboratoire de Parasitologie Mycologie, Centre Hospitalo-Universitaire, Dijon, France. Université Bourgogne -Franche Comté, UMR PAM, Dijon, France 11: AP-HP, Groupe Hospitalier La Pitié-Salpêtrière, Service de Parasitologie Mycologie, Paris, Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France 13 : Sorbonne Universités, UPMC Univ Paris 06, INSERM U1135, CNRS ERL 8255, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France; AP-HP, Hôpital St Antoine, Service de Parasitologie-Mycologie, Paris, France 14: Laboratoire de Parasitologie-Mycologie, Institut de Biologie en Santé-PBH, Centre Hospitalier Universitaire, Angers, France 15: Laboratoire de Parasitologie-Mycologie, Institut de Biologie, Centre Hospitalier Universitaire de Nantes, Nantes, France 16: Parasitologie & Mycologie, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France; IP-TPT UMR MD3, Aix-Marseille Université, Marseille, France 17: Centre Hospitalier Universitaire de Lille; Université de Lille; Inserm U995-Team 2, Lille; Inflammation Research International Center (LIRIC), Lille, France

  Nevertheless, because these reference methods are labor intensive and time-consuming, most clinical microbiology laboratories use commercial methods, such as the Etest®, for routine determination of minimum inhibitory concentrations (MICs). It is therefore essential to evaluate these commercial tests and to determine their ability to give MIC values that agree with those from the reference methods. With this aim, a prospective, multicenter French study was performed to compare the EUCAST and Etest® methods for micafungin susceptibility testing of a large panel of clinical isolates of different Candida species. Sixteen centers (six in Paris area and 10 across France) participated in the study. Over a 2-month period, each center was asked to test 64 Candida isolates, from any clinical sample, of the following species: 10 isolates of each of the six most common pathogenic species (C. albicans, C. glabrata, C. tropicalis, C. parapsilosis, C. kefyr

  lusitaniae (23), C. guilliermondii (9), C. norvegensis (5), C. inconspicua (5), C. famata (3), C. pelliculosa (2), C. lambica (2), C. sphaerica (1), C. ciferrii (1), C. catenulata (1), C. utilis (1), C. colliculosa (1), C. nivariensis (1).# ± 2 log2 dilutions.

Figure 1

 1 Figure 1 Correlation between EUCAST and Etest® methods for in vitro susceptibility testing of 933 Candida isolates to micafungin

Table 1 : Distribution of micafungin MICs (µg/ml) for different Candida species (n=933) determined by the EUCAST broth microdilution method Species (number of isolates) Number of isolates with an MIC (µg/ml) of

 1

	% R/non
	WT*

* Resistance (R) or non-wild-type (WT) was defined based on EUCAST clinical breakpoints or ECOFFs when clinical breakpoints were not available. # C. guilliermondii (9), C. norvegensis (5), C. inconspicua (5), C. famata (3), C. pelliculosa (2), C. lambica (2), C. sphaerica (1), C. ciferrii (1), C. catenulata (1), C. utilis (1), C. colliculosa (1), C. nivariensis (1).

Table 2 In vitro susceptibilities of the 933 Candida isolates to micafungin as determined by the Etest® method and EUCAST broth microdilution method Species (number of isolates)

 2

		Etest® MIC (µg/ml)		EUCAST MIC (µg/ml)
		Range	MIC50 MIC90 GM Range	MIC50 MIC90 GM	Essential agreement #
	C. albicans (159)	≤0.015 -0.06 0.015 0.015 0.016 ≤0.015 -0.06 0.015 0.015 0.016	100
	C. glabrata (152)	≤0.015 -0.125 0.015 0.015 0.016 ≤0.015 -1	0.015 0.015 0.018	98.7
	C. parapsilosis (152)	0.06 -4	0.5	2	0.63 ≤0.125 -4	1	2	1.15	96.7
	C. tropicalis (152)	≤0.015 -0.5	0.015 0.03 0.019 ≤0.015 -1	0.015 0.03 0.021	99.3
	C. kefyr (136)	≤0.015 -0.25	0.03 0.125 0.036 ≤ 0.015 -0.125 0.03	0.06 0.044	97.8
	C. krusei (127)	≤0.015 -0.25	0.125 0.125 0.084 ≤0.015 -0.25	0.125 0.125 0.089	98.4
	Other Candida spp.* (55)	≤0.015 -1	0.03	0.25 0.057 ≤0.015 -1	0.06	0.5	0.068	98.2
	Total number (933)	≤0.015 -4	0.03	0.5	0.046 ≤0.015 -4	0.03	1	0.054	98.5

*C.

18: Université François Rabelais, INSERM U1100, Centre d'Étude des Pathologies Respiratoires (CEPR), 37000, Tours, France

Acknowledgments

We thank Mélanie Girard (Paris) and Nadine François (Lille) for their technical help.

This study was supported by a grant from AstellasPharma.

Conflicts of interest

: MEB received grants from Astellas, Gilead and Merck and speaker's fees from Astellas and Merck. ED has received grants from Gilead, Ferrer, and Biorad, payment for lectures from Gilead, MSD, and Schering, and has been consultant for Astellas and Innothera. IA received speaker's fees from Merck. AA received funds for speaking from Merck and for travel from Astellas, Merck and Pfizer. EB received grants from Merck. FB received grants from Astellas and speaker's fees from Merck. TC received speaker's fees from Merck and Gilead. MC received travel grants from Gilead, Pfizer and Merck and received remuneration for talks on behalf of Pfizer. FD received grants from Astellas, Pfizer and Merck. AF received funds for speaking from Merck; for consultancy from Pfizer; and for travel from Astellas, Gilead, Merck and Pfizer. JPG received speaker's fees from Astellas, MSD, Gilead and Pfizer. CH received travel grants from MSD, Astellas, Pfizer and Gilead and fees for oral speaker by MSD and Astellas. YLG received grant support from Merck. PLP is a consultant to Basilea and received grants from Astellas and Pfizer and speaker's fees from Merck and Gilead. DM received travel grants from Pfizer. BS received grant support from Astellas, Merck, and bio-Mérieux. JC received grants from Astellas, Pfizer and Merck and speaker's fees from Astellas and Pfizer. SC, TC, ADa, ADu, JG, SR, and MS declare no conflict of interest.