An Empirical Study of Competitive Advantage and Repeat

Keywords: competitive priorities, Repeat business customisation Manufacturing strategy, Empirical research, Engineer-to-order / Make-toorder, order winners / qualifiers, competitive priorities, cumulative capabilities, Repeat business customisation

Empirical evidence is presented from 24 UK based manufacturing companies, all offering a degree of product customisation, with most having a significant pure customisation Engineer-to-order (ETO) element. The evidence addresses the issue of competitive advantage, which has lacked empirical evidence in previous manufacturing strategy literature, and includes a detailed investigation of the strategic importance of repeat business. It contrasts its results with those previously found in the literature and concludes that there are significant differences in the competitive priorities theoretically associated with this sector. In particular, it is argued that cumulative capabilities are needed, with a low cost competence often included. Four different types of repeat business are identified, one relating to Repeat Business Customisers and three relating to Versatile Manufacturing Companies, and the strategic importance of repeat business is discussed. It is indicated that for some ETO companies, repeat business is perceived to be an important method to reduce costs and achieve business stability. However, a number of the other companies studied saw repeat business as infeasible and hence need to find other ways to reduce costs and improve company performance measures. Future research to extend this work into a longitudinal study or a broader survey is proposed.

Email: l.hendry@lancaster.ac.uk

Acknowledgements:

The author would like to acknowledge the contribution of Graca Amaro in collecting much of the case study evidence and Pairoj Lapanun, who began the process of collating the case study evidence as part of the requirement for his M.Sc. in Management dissertation.

Introduction

It has long been recognised that customisation is an important aspect of strategic decision making and that degrees of customisation can vary according to products, processes and transactions [START_REF] Lampel | Customizing Customization[END_REF]. One type of customisation has received much attention in recent years, that of mass customisation along with the associated Build-to-Order Supply Chain, (see for example, [START_REF] Brown | The manufacturing strategy-capabilities links in mass customisation and agile manufacturing: an exploratory study[END_REF][START_REF] Brown | The manufacturing strategy-capabilities links in mass customisation and agile manufacturing: an exploratory study[END_REF][START_REF] Gunasekaran | Build-to-order supply chain management: a literature review and framework for development[END_REF]Ngai, 2005 respectively). This increased level of customisation in supply chains that previously produced standard products has emerged due to the increasing desire for customers to receive a degree of individualism in either the products received or the manner in which they are delivered to them. However, mass customisation is by definition a middle ground in which there needs to be some standardisation of process for this strategic position to be feasible. Thus this strategy is on a different position on the customisation continuum to those companies that have a strong Make-to-Order (MTO) or Engineer-to-Order (ETO) element, and which offer pure or tailored customisation as described in [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF]. Such companies are usually organised as a jobbing process, thus allowing flexibility of process as well as product and transaction. The difference can be akin to the bespoke tailor, which makes any item in any material and any size, versus the mass customisation jeans manufacturer, which can make any size, but only jeans in a set range of colours and materials. This paper addresses the MTO/ETO sector, which has received relatively little attention in the manufacturing strategy literature. Yet it is an important sector consisting of many SME subcontractors within the supply chains of industries such as aerospace, as well as larger capital goods manufacturers of items such as industrial machinery. With the emergence and strengthening of the mass customisation sector, and the increase in globalisation, the competitive environment for the MTO/ETO sector is evolving and it is hence timely to study how issues of competitive advantage are developing in this sector.

The topic of competitive advantage has been addressed from a variety of angles by researchers, including the resource based view (sometimes also referred to as the routinebased view) and the market based view, whilst others have focussed on the need to develop dynamic capabilities. An excellent review of these approaches has been presented by De 3 [START_REF] Toni | Strategic planning and firms' competencies[END_REF]. Whichever viewpoint is adopted, it is clear that companies should aim to determine a means to achieve a sustainable competitive advantage by developing competences that are hard to imitate. Such competences must hence be unique and are developed through consideration of a number of factors including competitor characteristics, the desires of the customer and the internal resources available. Although there are a number of papers that address these issues, discussed in further detail in the literature review below, very few discuss the issue of competitive advantage in the specific context of the ETO/MTO sector. In addition, authors such as [START_REF] Ward | Manufacturing strategy in context: environment, competitive strategy and manufacturing strategy[END_REF] suggest that there is a need for further empirical evidence to support the development of the manufacturing strategy theory debated in the literature. This paper seeks to fill this gap by considering competitive advantage in the ETO/MTO sector using in-depth case study evidence from 24 companies in this sector. In particular, it considers how such companies win orders, which is an important and significant area of research in the current increasingly competitive climate of globalisation. Thus there is a further contribution towards the trade-off debate, as discussed by authors such as [START_REF] Boyer | Competitive priorities: Investigating the need for trade-offs in Operations Strategy[END_REF], along with evidence regarding order winners and order qualifiers as defined by [START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF].

In addition to the discussion of factors that affect competitive advantage, a second major theme of the paper is the topic of repeat business within the MTO/ETO sector.

Little has been written about this issue in the literature, indeed it is not an issue that is usually associated with ETO companies. However, it was suggested by [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF] that one way in which such ETO and MTO companies seek to gain a competitive advantage is by trying to attract repeat business from the same customers, thereby reducing costs. As most of the companies were SME's, with limited management resources, such companies are trying to supply standard products and customised products with the same infrastructure and management procedures. This is contrary to ideas that have been advocated by operations strategists such as [START_REF] Skinner | The Focused Factory[END_REF], as discussed in Hayes (2002)) and his 'manufacturing sins'. The empirical research presented by [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF] draws preliminary conclusions suggesting that a wider and deeper empirical study is needed to further investigate the strategic importance of repeat business in companies offering pure customisation. Thus the empirical evidence presented here also contributes to this debate. This paper is organised as follows. After the literature review of some of the key manufacturing strategy references in this area in section 2, section 3 then describes and justifies the research methodology employed in this empirical study. This is followed by a description of the case study company data in section 4 and a discussion of the case study evidence in section 5. Finally, in section 6, the conclusions fully describe how this paper contributes to various debates in the literature regarding the theory and practice of Operations Management, whilst also suggesting avenues of further research.

Literature Review

An excellent, extensive, review of the manufacturing strategy literature has been presented by [START_REF] Dangayach | Manufacturing Strategy: Literature review and some issues[END_REF]. They categorise the literature in this area into two basic types -process and content. The latter is then broken down further into research which addresses: manufacturing capabilities; strategic choices; best practices; transnational comparison; performance measurement and literature survey. The research presented in this paper falls into both the manufacturing capabilities and the strategic choices categories, as it seeks to determine the types of strategic choice that are successfully undertaken and the manufacturing capabilities developed in modern ETO/MTO manufacturing companies. Thus this review concentrates on research in these categories.

In terms of manufacturing capabilities, [START_REF] Gagnon | Resource-based competition and the new operations strategy[END_REF] presented a literature review on the 'resource based view' (RBV) of competition, stressing the importance of ensuring that operations capabilities are used to drive the strategic planning of companies, rather than allowing a market-based lead which assumes a completely adjustable manufacturing function. The latter assumption is clearly unrealistic, indicating that a purely 'market based view' (MBV) would be inappropriate. However, it must also be acknowledged that the opposite is equally true in that the market cannot be moulded to ensure acceptability of any products produced. The MBV has its origins in the work of [START_REF] Porter | Competitive strategy: techniques for analyzing industries and competitors[END_REF][START_REF] Porter | Competitive advantage: creating and sustaining competitive advantage[END_REF] and hence [START_REF] Porter | Towards a dynamic theory of strategy[END_REF], along with other authors such as [START_REF] Amit | Strategic intents and organizational rents[END_REF], has pointed out that the two views are not necessarily conflicting, but that an appropriate assessment of competitors, customers and resources should all play a role in the determination of strategy. An important issue that arises from this literature debate is the topic of competitive priorities, also referred to as "competitive capabilities" or "competences" (see for example:

Corbett & Van Wassenhove (1993), [START_REF] Boyer | Competitive priorities: Investigating the need for trade-offs in Operations Strategy[END_REF] and [START_REF] Frohlich | A taxonomy of manufacturing strategies revisited[END_REF]). [START_REF] Christiansen | A mapping of competitive priorities, manufacturing practices, and operational performance in groups of Danish manufacturing companies[END_REF] conclude that there is broad agreement on the important competitive priorities, listing cost, quality, delivery, flexibility and service, acknowledging that the latter has been added more recently by authors such as [START_REF] Miller | A taxonomy of manufacturing strategies[END_REF].

Although there is broad agreement on these five competitive priorities, authors such as [START_REF] Ward | Manufacturing strategy in context: environment, competitive strategy and manufacturing strategy[END_REF] argue that there has not been sufficient empirical testing of this set of factors. In addition, research continues in terms of the definition of the factors. In particular, a continuing research theme is to explore the definition of 'flexibility'.

Examples include the work by [START_REF] Narasimhan | Exploring flexibility and execution competences of manufacturing firms[END_REF] and [START_REF] Koste | Measuring dimensions of manufacturing flexibility[END_REF]. This is important research, which leads to a deeper understanding of the nature and meaning of the competitive priorities in practice. However, by concentrating on a specific priority, this research does not contribute to the debate on the relative importance of the different competitive priorities in the context of specific manufacturing sectors.

Research that links competitive priorities to manufacturing types is very limited, but a key exception is [START_REF] Hill | Manufacturing Strategy: The Strategic Management of the Manufacturing Function[END_REF][START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF] theory on Order Winners (OW) and Order Qualifiers (OQ), which considers the jobbing and project process choices often found in the ETO/MTO sector. [START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF] describes the OW for the project process choice to consist of delivery speed and unique design capability. Repeat business is added to this set for the jobbing process choice. The OQ for both the project and jobbing contexts are suggested to be price; on-time delivery and quality conformance. Yet no empirical evidence is presented to support this theory. Indeed, some authors such as [START_REF] Spring | One more time: how do we win orders?: a critical reappraisal of the Hill manufacturing strategy framework[END_REF] have been skeptical about the notion of OW/OQ, arguing that industrialists do not see a distinction between the two. They also suggest that the OW/OQ concept makes use of the trade-off model that was first introduced by Skinner ( 1969), but which is now a concept that is questioned by many other authors. For example, [START_REF] Kathuria | Competitive priorities and managerial performance: a taxonomy of small manufacturers[END_REF] presents empirical evidence that contradicts the traditional trade-off model. In contrast, [START_REF] Boyer | Competitive priorities: Investigating the need for trade-offs in Operations Strategy[END_REF] present empirical evidence that suggests that trade-offs remain.

Thus this is an issue that is still under discussion and more empirical evidence is needed to further the trade-off debate in general, along with the notion of OW/OQ's in particular. A particularly important contribution to the trade-off debate was given by [START_REF] Schmenner | On theory in operations management[END_REF], presenting a series of propositions that seek to resolve the conflict. They suggest that trade-offs exist when comparing plants at any given point in time, but that cumulative capabilities (as discussed by authors such as [START_REF] Flynn | An exploratory study of the nature of cumulative capabilities[END_REF]) occur within one firm over a period of time thereby leading to gradual improvement in all competitive priorities. This paper further explores the trade-off concept within the context of the OW/OQ concept; seeks to find evidence for some of the ideas presented by [START_REF] Schmenner | On theory in operations management[END_REF] and asks whether the latter leads to meaningful managerial implications in the ETO/MTO setting.

Given the argument for further empirical evidence made above, it is necessary to discuss here the key examples of the limited relevant empirical evidence available in the literature. An insightful empirical study that addresses the issue of customisation and strategic choice, by [START_REF] Spring | Product customisation and manufacturing strategy[END_REF], presents four case studies along with a thorough literature review including topics such as agility and flexibility. This develops an in-depth understanding of the nature of customisation, arguing that "specials" can be a drain on company resources rather than an important strategic weapon if management do not consider the business rationale for making customised products. The conclusions thereby have strong managerial implications, though specific competitive priorities in the ETO/MTO context are not discussed. [START_REF] Ward | Manufacturing strategy in context: environment, competitive strategy and manufacturing strategy[END_REF] use survey work to investigate the link between competitive strategy and manufacturing strategy. They conclude that the "differentiator" strategy is most closely linked to the competitive priority of quality; the second strongest link is with flexibility whilst low cost and delivery are also important. The "differentiator" is a broad competitive strategy covering all those companies who do not focus on the cost strategy. Thus it is broader than the MTO/ETO typology discussed here. However it is interesting to note that quality is higher on the list than that suggested by the OW/OQ theory of [START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF], whilst flexibility as linked to the unique design capability is seen to be of lower strategic importance. A key study that addresses the issue of OW/OQ in the context of the ETO/MTO sector is that reported by [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF] on mainly engineering companies in Denmark, the Netherlands and the UK. This study suggested that the theory developed by [START_REF] Hill | Manufacturing Strategy: The Strategic Management of the Manufacturing Function[END_REF][START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF] for the project/jobbing processes cannot be entirely supported by empirical evidence, indicating for example that for many jobbing companies the ability to customise (i.e. the unique design capability) is in fact an order qualifier, and that price is increasingly becoming an order winner. Furthermore the research also indicated that as price and hence costs are becoming more important to jobbing companies, they are searching for ways to reduce their operating expenses. This is particularly difficult in this sector as these firms are not always able to adopt the processing efficiencies of the mass production or even the mass customisation companies. Thus the issue of repeat business arose in many companies.

This study follows on quite closely from the research presented by [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF], as this is the only empirical paper identified that specifically looks at issues of competitive advantage and repeat business in the ETO/MTO sector. As pointed out by [START_REF] Dangayach | Manufacturing Strategy: Literature review and some issues[END_REF], most of the manufacturing strategy literature is cross sectional rather than addressing particular types of products or industrial markets.

Taxonomies of non Make-to-Stock companies

Before proceeding further, it is also necessary to clarify the definition of the ETO/MTO sector, as used in this paper. It is noted that this topic has been addressed by many authors including [START_REF] Hill | Manufacturing Strategy: The Strategic Management of the Manufacturing Function[END_REF][START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF]; [START_REF] Olhager | Strategic positioning of the order penetration point[END_REF] and [START_REF] Hallgreen | Differentiating Manufacturing Focus[END_REF]. Building on the previous taxonomies, [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF] presented a new empirically tested taxonomy for non Make-to-stock companies with 17 different categories. In this paper, an abridged version of that taxonomy is used to classify the types of companies that are studied, as this is sufficient to pick out the key characteristics of the companies that are relevant to competitive advantage and the nature of repeat business. Two key aspects of the original taxonomy used here are:

• The titles ETO, MTO and ATO (Assemble-to-order), where these titles indicate the amount of work carried out after the order has been placed. For ETO, the design, manufacture and assembly of the product takes place after the order is confirmed. For MTO, the basic design is already in place, and though there may be some modifications to the design, most of the work after the order is confirmed is in the manufacture and assembly of the product. Note that in this case, the design can be supplied by the customer or by the MTO company. In the ATO sector, it is just the assembly of the components that is carried out after receipt of a definite order; the components are produced to stock in advance.

• The nature of the customisation carried out by the company. The first three categories are as defined by [START_REF] Mintzberg | Generic Strategies: Toward a Comprehensive Framework[END_REF] and refined by [START_REF] Lampel | Customizing Customization[END_REF]. Firstly, there is pure (p) customisation, which entails producing a new design. Secondly there is tailored (ta) customisation, which entails the modification of an existing design. Thirdly, there is customised standardisation (cstan), where the customer can pick from a set of design options. In addition, a fourth category is used, which is described as 'none'. It is needed for those MTO and ATO companies that choose to await a customer order, even though they produce a standard product with no customisation options. This is in contrast to customisation companies that cannot complete ahead of the customer order as no two orders are alike.

Thus the following categories are used:

ETO (p), MTO (ta), MTO (cstan), MTO (none), ATO (cstan), ATO (none)

In addition, it has been postulated that a firm can be a 'Repeat Business Customiser' (RBC), negotiating business as a series of orders by contract, or a 'Versatile Manufacturing

Company' (VMC), negotiating each order separately. These definitions are discussed in detail in [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF], and explored further as part of the evidence on repeat business issues in this paper.

Methodology

The main research questions used in this study are as follows:

• What are the competitive priorities in the MTO/ETO sector and why do they lead to competitive advantage? In particular, when and why is pure customisation just a qualifier for companies offering purely customised products? Or, instead, when and why does it become an order-winner? • Do companies offering customised products select "repeat business" as a strategic choice, as a means to reduce their business cycles and therefore increase their efficiency and profitability? If so, why? If not, why not?

The data was collected from the 24 companies, all based in the North West of England, via semi-structured interviews. Thus the unit of analysis is the plant, which is argued to be an important unit of analysis by authors such as [START_REF] Brown | The manufacturing strategy-capabilities links in mass customisation and agile manufacturing: an exploratory study[END_REF].

The case study methodology was chosen as issues of competitive advantage are complex and it was felt that a postal survey would not be well answered. In addition, this methodology allowed a broad set of competitive priorities to be studied rather than limiting the findings to a predetermined set of factors. Thus the study allowed all of the issues currently identified in the literature to be explored, whilst also allowing interviewees to add other factors to the debate. In addition, the larger postal survey is generally better for discovering 'what' is happening rather than 'why'. In this study, the research questions begin with 'what are the competitive priorities', but the further exploration of 'why' these issues lead to competitive advantage is important so that the relevance to other companies can be determined clearly. Thus rich, qualitative, data was collected and analysed from which it would be possible to derive greater managerial implications. For further justification of the case study approach, the reader is referred to [START_REF] Yin | Case study research: design and methods[END_REF] and [START_REF] Voss | Case research in operations management[END_REF]. For other examples of empirical research using the case study approach, see [START_REF] Williams | Managing and developing suppliers: can SCM be adopted by SMES?[END_REF] and [START_REF] Stevenson | Theoretical development of a workload control methodology: evidence from two case studies[END_REF].

In choosing the 24 case studies, the literal replication logic, as advocated by [START_REF] Yin | Case study research: design and methods[END_REF], was employed. Thus the study sought to identify companies with a significant level of ETO/MTO business, for whom it was expected that similar competitive priorities and similar attitudes to repeat business might exist.

The data was collected using semi-structured interviews employing an interview protocol and allowing plenty of opportunity for interviewees to add other relevant information (the interview protocol is available from the author on request). The right hand column in Table 1 indicates the job role of the interviewee(s). In one company, two managers were interviewed. In all other cases bias introduced by the perspective given was carefully considered in analysing the data. Summaries of each interview were typed up and sent to the interviewee with any outstanding questions marked. This was followed up by a telephone query to clear up any such outstanding issues. Good feedback of this type, as recommended by [START_REF] Voss | Case research in operations management[END_REF], was received from most of the companies involved.

A pilot study was carried out in one company. As this did not lead to any issues that could not be resolved through a follow up telephone call, the data for this company is as complete as for the other companies. Therefore, it is included in the set of 24 companies discussed below. Thus the number of companies studied is sufficient to enable patterns to be considered in the data, such as allowing the level of customisation offered by competitors to act as an explanatory factor, though not sufficient to lead to any statistical tests. The patterns identified provide in-depth rich insights into the research questions posed.

In conducting case study research, it is important to carry out a rigorous approach to the analysis, to ensure that the chain of evidence is clearly documented and that high standards of validity and reliability are attained, see [START_REF] Eisenhardt | Building theories from case study research[END_REF], [START_REF] Yin | Case study research: design and methods[END_REF] and [START_REF] Voss | Case research in operations management[END_REF] for a detailed discussion of these issues. In this study, searching for cross-case patterns was of particular significance along with the enfolding of literature to discuss how the findings confirm or contradict previous studies.

The Case Study Data

The characteristics of the 24 companies studied are presented in Tables 1, 2 and 3 below.

Table 1 describes the companies in terms of the main business area and number of employees. It is noted that the majority of companies could be described as SME's, with 17 out of the 24 having a workforce of less than 150 employees. The main business area can be a manufacturing capability such as precision sheet metal components (e.g. companies B and C), or more commonly a type of product such as doors, windows or a type of industrial machinery. In all the latter cases, there is a degree of customisation involved in the manufacture; none of the companies studied produced entirely standard products. Although the study focuses on the ETO/MTO sectors, 4 companies with a main ATO focus were retained as they provided useful insights relevant to the discussion.

[Take in Table 2 categorises the companies using the abridged taxonomy described in the previous main section of this paper. In the second column, the main business type is given;

this refers to the type of business which is most common. In the third column, any other business type is also listed. This shows that 15 out of the 24 companies have some degree of ETO (p) activity and it is the main business line for 7 of those 15 companies. Note that many of these companies operate in several markets, either with the same product that can be customised or standard, or by supplying several types of product. The fourth column seeks to identify the % of ETO activity within the business. It is noted that this is not a static figure and many companies found it difficult to answer this question. However, the information provides an indication, which is sufficient for comparative purposes. Finally, the fifth column indicates whether the company operates as an RBC or a VMC firm.

[Take in Table 2]

Table 3 indicates which companies compete only against competitors which offer the same level of customisation; those companies which compete only against competitors offering less customisation and those which have a range of competitors, some offering less customisation and some offering the same. Note that none of the companies studied had competitors offering more customisation. The identification of this factor was an important aspect of the data analysis, which led to the discussion in the following section.

[Take in Table 3]

Discussion of the Case Study Evidence

The qualitative data is discussed in three sections:

• competitive advantage, with particular reference to OW/OQ and competitive priorities;

• repeat business and

• additional insights.

Competitive Advantage

Many of those interviewed began by declaring an overwhelming sense that everything is important, including price, design ability, delivery speed, delivery reliability, quality, flexibility and customisation. Hence, this would lead to the conclusion that no competitive priority can be neglected and modern manufacturing firms cannot afford to adopt the tradeoff stance. However, when questioned more deeply, patterns emerged, relating to the type of competition and the degree of customisation that the firm offered.

Firstly, it is noted that of the seven companies, A-G, for whom ETO (p) is the main line of business, 5 had competitors offering the same degree of customisation, whilst the other 2 had competitors with the same or lesser degrees of customisation. For these companies, customisation does not figure as a key order winner, in fact in some cases, such as company E, customisation is not even considered as an OQ. Hence, all of these companies support the theory that where competitors offer similar levels of customisation, other OW factors must be found. Companies A, D, F and G state that price is a key order winner. For example, the Operations Manager in company G stated that: "at the end of the day, price is the most important thing when contracts are fought for", thus the company "will invariably win orders on a price basis". Company A noted that though price is a key OW, this is only the case for the less sophisticated customer; for more sophisticated clients, price is less important and such clients may then try to squeeze the company on price through negotiation. Similarly, company F felt that price and customer relationships were key factors in winning business. If a long-lasting and trust based relationship exists, then "if the company happens to offer a higher price, it might be offered the option to adjust its price to the competition and so win the job". It was also noted that the buyer is not only interested in the cost of the initial purchase. If the company can offer a unique technical solution that can reduce the long term running cost of the equipment, then this may also be the OW. This suggests that design ability is then important, but in a manner that is linked to the long term cost of the solution for the customer.

Companies B and C both claimed that their key OW was the ability to offer the whole package to the client: to take "an original customer's requirement and to turn it into a final finished product". In fact company C claimed that the OW had already evolved beyond price and that as companies were now competitive on this factor, yet other newer competitive advantages had to be found.

Company E saw price as being an important OW, but only as part of an overall package, in which the company scored highly on price, quality and service. It was felt that 13 its advantage was "being good at all these things" consistently. However, it was also stated that technical ability was an important competitive advantage and the company was not clear about which factor was most important.

Overall, this evidence suggests that the world of the pure customiser is very competitive and that customisation alone is not sufficient to win business. Instead, other factors are now becoming important, and price is often one of the key issues. This conclusion is summarised in the first row of Table 4 andin Table 5, which also summarises the remainder of the discussion in this section below.

[Take in Table 4]

[Take in Table 5]

For most of the remaining companies for which the competitors offered the same level of customisation, the type of customisation on offer is either MTO (cstan) or ATO (cstan). These companies are O, Q, S, T, W, and X. For these companies, it is more difficult to identify a pattern in the OWs and OQs that were claimed by those interviewed.

However, again none of them suggested that customisation was an OW. Instead, companies O and X included price. The former also suggested that delivery speed and reliability are important for their MTO (cstan) business, but less so for the MTO (ta) and ETO (p) sector. Company X is smaller than its competitors and is therefore able to compete on price for low volume orders that the larger competitors do not want. However, the competitors could undercut them on price if they did want this business in the future.

The company also has two other key advantages: it currently offers larger concrete mixers than the other manufacturers and smaller customers prefer to work with smaller companies as they feel that they will receive a higher quality service. Other competitive priorities for companies Q and T are given in Table 5. For company W, the design was seen to be a key factor as it has the highest speed machinery and the greatest range of pattern attachments.

However, they acknowledged that smaller companies sometimes try to enter the market and undercut on price, but they rarely succeed as they do not have the efficiency of the larger organisation. This company appeared to have a degree of business confidence based on operating in a small market, with few clients and few competitors, in which it has a good reputation. For the MTO (ta) companies, two had a competitor offering the same degree of customisation, companies I and J. Of the remaining companies in this sector, K and L had competitors offering the same or lesser degrees of customisation, whilst companies H and M had competitors offering less customisation. Here a difference in the way they compete can be clearly attributed to the nature of their competitors. Company L claimed that there is a need to offer something which your competitors do not offer. So customisation is offered where their competitors do not offer this, or technical superiority is offered where they are competing against a similar level of customisation. For company M, customisation is the clear OW for the MTO (ta) part of their business. Company H also sees their expertise as the main way to win orders. They offer a consultancy service which advises the client on the best type of door, and so it is their design capability which is particularly pertinent. They aim to offer competitive though not necessarily the cheapest prices, thus suggesting that price remains an OQ. These conclusions contrast with Companies I and J, for which customisation is not an OW. For I price is more important as an OW than an OQ, but it never loses business on the basis of price, as it is always willing to adjust prices (though never at a loss).

For company K, competitive advantage still depends on the nature of the competitors, but it is now the size of the competitor as well as the degree of customisation that is important. If competing with a company of similar size, then it can be that price is a key OW. However, if the competitor is larger, then it is necessary to find an alternative competitive edge such as by offering more customisation or flexibility. Thus they perceive that they can charge a premium for true 'specials', as this is something that their competitors do not offer. As discussed above for company A, company K also felt that the sophistication of the client is important, with less sophisticated clients being more interested in price. The remaining companies with competitors offering the same or lesser degrees of customisation are companies P and U, offering mostly MTO (cstan) and ATO (cstan) respectively. Company P acknowledged that it is difficult to keep a steady flow of work;

hence there is a tendency to cut prices when they really want an order. In general, however, price is important for their MTO (cstan) market, but less so for their more customised business. Here it is the technological solutions that matter more, and it is here that the competitors offer lower levels of customisation. For company U, price is not seen to be an OW, instead quality and design capabilities are key. This is a small company, winning more small projects than large ones as it does not have the economy of scale necessary to win large orders. So again company size is important.

Of course, some companies also felt that the winning of orders was not necessarily based on good decision criteria. For example, companies G and I both pointed out that sometimes "national prejudice" is a factor that affects decision makers in the client organisation, with some buyers for company G biased towards German products, whilst others are biased towards British products.

Repeat Business

As discussed in the earlier literature review section, the term 'Repeat Business Customiser'

(RBC) was introduced by Amaro et al (1999) to refer to companies which negotiate business as a series of orders by contract. This was introduced alongside the term Versatile Manufacturing Company (VMC), which referred to those companies that negotiate each order separately. Thus in the RBC case the nature of the repeat business was to attain a series of orders for the same customer for the same product. However, during the analysis of the empirical data for this study, it became apparent that repeat business was also an important strategic objective in several of the companies categorised as VMC's. In this case, the nature of the repeat business could be one or more of the following three types:

• the repeat sale of a product initially designed for one customer, but then also sold to one or more other customers. If this type of repeat occurs on several occasions, then the company could be in the business of evolving its product lines from highly customised products to much more standard products. • repeat business for the same customer, but for a different product. Thus the company is benefiting from long term relationships with customers, which can lead to future orders, albeit with a fresh need to design and manufacture the product.

• repeat business for the same product for the same customer. This may seem similar to the RBC case, but here the number of similar orders is very small, and each product is generally ordered separately.

Figure 1 summarises these categories of repeat business, giving the labels R, V1, V2 and V3 Type, for ease of reference throughout this section. Table 5 then indicates the type of repeat business in which each company is involved. Note that not all VMC's are included in Table 6, as it was noted that some of these companies indicated that they do not experience any repeat business at all at present. In addition, the discussion focuses on repeat business of customised products, particularly ETO(p). Thus, if the repeat business only relates to products categorised as MTO or ATO, then these companies are excluded from the discussion below.

[Take in Figure 1]

[Take in Table 6]

Table 7 summarises the percentage of repeat business for the ETO(p) type of customisation, also indicating preference towards increasing this percentage and the impact that repeat business is perceived to have upon manufacturing profitability. As indicated earlier in Table 2, companies B, C, D and E are all RBC companies, the first three having 100% ETO(p) activity, whilst E has 90%. In each case, they are in the business of producing components for a larger manufacturer, with large contracts negotiated as a series of orders over a long period. Hence they all exhibit clear 'R' type repeat business. The case study evidence for companies B, C, D and E suggests that the repeat business nature of their work is of strategic importance. For company B, this is particularly pertinent as it is only for repeat orders that they typically make a profit. For new orders, it was stated that they only break even with a 0% profit margin as it was suggested that the aim at this stage is to win a longer-term contract. Despite the lack of profitability, the company stresses the need for new orders for new products, stating that ideally the company wants to attract at least one new customer per year, with at least one new product per month. The Managing Director referred to the "natural wastage of customers", claiming that "any company needs to get new businesses (new customers/ new products) each year otherwise it will die".

[Take in Table 7]

In contrast to company B, the Managing Director of company C stressed the need for repeat business rather than the need for new business. He stated that when the objective is to grow the operations, there must be a balance between new business and repeat business. In addition, he stressed that the bigger the company gets, the more it needs consistency, which only comes from repeat business. The strategic objective here is to increase the percentage of repeat business from 50% to 70%, retaining 30% of new orders as needed to develop new long term contracts, not to produce one-off batches unless this was seen as a special requirement for an existing customer. The reason for stressing the importance of repeat business in this case was due to the efficiency gains achieved. In this case, the customers provide a forecast of their requirements for the next 2/3 months.

Even though this is subject to change, these forecasts enable the company to make batches of products and to carry some stocks of raw materials or products (either at the final or part processed stage). Thus they are able to supply their customers on a Just-In-Time basis, assisting customers in minimising their inventories.

Similarly company D stated the advantage of repeat business from a company efficiency point of view. For example, long-term contracts with one client can lead to the purchase of specialised tooling. This can be problematic when making the initial investment for a small company, but has long-term benefits. As for company B, a significant proportion of new business is felt to be of strategic importance especially for expansion prospects. This explains the stated aim to decrease the percentage of repeat business to a slightly lower value than the stated 80%. Thus all three of companies B, C and D require a balance of new and repeat business, the former providing long term stability whilst the latter provides company efficiency gains and prospects for growth.

Although the preferred percentage of each type of business varies, all of them state a desire for a majority of repeat business, ranging from 70 -90%.

For company E, the costs of tooling are such that it cannot make anything as a oneoff, as it is too expensive to invest in the tooling. Therefore all of its ETO (p) business is for large volumes on an RBC basis for a twelve month period or more. Set-up times can be particularly costly here and hence the levels of repeat business are perceived to be essential to enable the company to make products in batches and stock items to meet orders. Thus this company provides an extreme example of an 'R' type RBC company, for which only repeat business is perceived to be viable.

From Table 7, it can be seen that there is not a clear pattern amongst companies B to E in terms of profitability differences between repeat orders and new orders. Thus there are a variety of reasons for the strategic importance of repeat business for these companies, which do not always include cost reduction.

For companies F, J, N, O, P and U, with relatively low levels of repeat ETO(p) business, a desire was expressed to see an increase in this aspect of their work, either by attracting more business from the same customer (V2 Type) or by converting some one-off special products into products that can be sold in a tailored customisation or standardised customisation manner to future clients (V1 Type). For example, company F, with the use of CAD design, is able to produce modified designs very quickly, thus reducing costs. The reduction in costs can either be converted into increased profits or into a lower price for the customer to improve the chance of winning the order. Usually a compromise is reached, leading to slightly more profitable repeat orders. Similarly, company J saw advantages in reduced costs through repeat business. However, for company J, when selling the same machine more than once there is often such a large time gap between the two orders that it is necessary to upgrade the machine design. Hence it may be regarded as a new product rather than a repeat from a design and cost point of view. For company O, the reasons for wanting more repeats were due to increased profits and lower levels of engineering works.

However, in this case the company Managing Director felt that it was unlikely to be feasible to increase the percentage of repeats above the 15% quoted. Thus for all three of these companies, producing capital goods, the strategic importance of repeat business is due to the increased ability to control lead times and the improved profitability.

In contrast, the Managing Director of company N claimed that it is difficult to estimate the difference in profit between new and repeat orders, but that profits are possibly slightly higher for the new orders. Despite this, a desire was expressed to develop a standard range of products from customer specific orders, increasing the level of repeats to a much higher percentage than the 10% quoted. The reasons given are however still cost related, as design and engineering employees are seen as overhead costs. The engineering design of a new product is clearly much higher than for a repeat order, and hence higher levels of repeats will lead to a bigger turnover to absorb the same overheads, hence reducing the cost burden in relative terms. However, the desire to increase the level of repeats is seen as problematic in practical terms due to the difficulty associated with combining the volume and the specials business. Thus consideration is being given to the development of a separate workshop for the repeat volume part of the business. At present, customised production gets priority because these contracts are perceived to be of higher importance to the company.

Similarly the sales manager of company P stated that repeat orders do not necessarily lead to a higher profit. Instead, the main advantage is that for a repeat order "the risk is taken out of the job". For new jobs, the estimation process has a high risk as the company is not as sure about the costs as the machine may prove to be more difficult to build than expected. Hence the company is more able to control costs with repeat orders, leading to greater control of other aspects of the management process including lead times.

For companies A and G, the nature of the capital goods they supply is such that repeat business is very unlikely as the equipment lasts for many years and hence a customer would only purchase another if they expand their operation. However, for company A, there are occasions when a client modifies its plant or wants to install some new machinery. Thus the company values repeat business from the same customer, but for different products (V3 Type). The Managing Director stressed: "you still have to sell to them, to keep in touch with them". It is no good just expecting them to come back for the next order, clients are visited regularly to ensure that company A is considered for future orders. However, this type of repeat business does not lead to any cost savings. Thus, for both company A and company G, other means to drive down costs must be found. Similar issues arise for company I, for the ETO(p) part of the business, giving further evidence of the possibility and perceived importance of 'V3' Type repeat business. However, much of the business for company I is for MTO production with standard components and hence costs are reduced in the usual way for manufacturing a standard product.

For the remaining VMC companies with an element of ETO(p), the issue of repeat business has a much lower strategic priority. For example, for company H, there are very Marketing & Sales Director is that the company "sells its expertise, which is the one unique thing the company has and that no other door manufacturer has". It was acknowledged that to grow might mean to generate volumes by moving into the standard door market. However, this was seen as a separate venture, which could lead to the setting up of a second company. There was a strong perception that mixing the production of standard and special doors was not a good idea and that it is better to commit resources to the production of special doors for major projects. Similarly, the Sales Manager of company K stressed that the company's aim is to take advantage of the niche market offered by making special machines. The number of competitors in this market is very small, and a recent contract was quoted in which there were no competitors for the order.

In this case, the price can be high to offset the level of risk involved in determining the method of manufacture etc. In this ETO (p) market, there is little scope for repeat business, but this is a situation, which the company is not trying to change. Although only two companies expressed this less favourable attitude to the strategic importance to repeat business, this evidence demonstrates that some companies still aim to sustain long-term viability depending heavily on one-off or small batch production, despite the risks involved when determining the prices to quote for products that have never been produced before.

Other Insights

The case study evidence also provides some very tentative evidence of the movement of companies along the line of the taxonomy presented in the earlier literature review section.

For example, company H has experienced growth by developing a separate standard doors business, which is perceived to have a very different strategic position to its specials business. Company R has a policy of making one-offs into standards, relying often on its customers to come up with the ideas for new product designs. Company U has moved in the opposite direction, having initially offered a standard product, they are now involved in customisation. In this case, it was suggested that the onset of mass customisation has killed the market for the more standard product.

In addition, for one of the companies studied, the importance of competitor analysis was seen to be key to their success. In particular, this company, K, indicated that Finally, the evidence suggested that several companies operate in more than more market. For example, company M offers both standards and specials and it was suggested that it is strategically important to keep a foot in both markets.

Conclusions

In order to draw conclusions, it is necessary to consider the case study evidence in the light of the literature discussed in section 2. Two research questions were posed in this paper, and these are now revisited, drawing conclusions for each one in turn in sections 6.1 and 6.2 below. Finally section 6.3 looks at the managerial implications that can be drawn from the findings in this paper, and identifies areas of future research.

Competitive priorities in the MTO/ETO sector

As posed in section 3, the first research question required the identification of the competitive priorities of the MTO/ETO sector, along with reasons as to why these priorities were believed to lead to competitive advantage. In particular, the question asked when and why pure customisation is an order winner rather than a qualifier. To some extent, this question assumed that the concept of OWs and OQs is a valid concept, although as discussed in the literature review, the paper has also sought to investigate whether the trade-off concept, an underlying principle of the OW/OQ concept, is itself valid.

The first important conclusion in response to this research question is that pure customisation is only a competitive priority and hence an order winner if this is not offered by a firm's competitors, as illustrated in Table 4. Thus this suggests that the theory put forward by [START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF] is overly simplistic in its statement that design capability is an OW for companies who adopt the jobbing or project process, as commonly found in the MTO/ETO sectors. Instead it is concluded that price is often an OW for these companies, a factor which is seen as only an OQ in Hill's (200) theory, with design ability then confined to be an OQ. This is the opposite of the generalisation in [START_REF] Hill | Manufacturing Strategy: Text and Cases[END_REF] theory. In 22 fact, it is argued here that no generalisation can be identified for this type of company as the nature of the competition can vary and it is this which affects the competitive priorities rather than the type of company itself.

This conclusion could be thought to provide evidence for the Market Based View (RBV) of the firm. However, a variety of alternative competitive priorities are given in the evidence, which include manufacturing competencies such as delivery speed and reliability and thus there is also evidence of the Resource Based View (RBV). The evidence therefore supports the view that there is no inherent conflict between the MBV and RBV, but that there is a need to consider external and internal factors when determining competitive priorities.

A further important conclusion relates to the trade-off debate. The evidence here supports the argument that there are cumulative capabilities, as discussed by authors such as [START_REF] Flynn | An exploratory study of the nature of cumulative capabilities[END_REF]. Over time, many firms are experiencing changes in the competitive priorities, claiming that as their competitors find ways to imitate one competence, it is then necessary to identify new unique areas of competence and so on.

For example, in many cases, the competitive advantage had historically been sought through customisation capabilities, but, as competitors have become increasingly able to offer this too, other factors such as price, reputation and customer relationships have also become important. Some interviewees further argued that the competitive priorities have become more stringent over time, with the need to continually review the most important area of competence to improve. This evidence provides support for the propositions of [START_REF] Schmenner | On theory in operations management[END_REF] that whilst cumulative capabilities must be built up over time, there is scope to concentrate on specific issues at certain points in time. They conclude that there is no conflict between cumulative capabilities and trade-offs, with the former relating to a longer period of time than the latter. This empirical evidence presented in this paper confirms this by suggesting that at any one point in time, competitive priorities depend on the nature of the competitor actions, and a trade-off then exists at that point as is realistic to resource allocation and budget constraints. Over time, as the market evolves, so do the competitive priorities leading to cumulative capabilities in the long run. Thus firms cannot afford to be complacent on issues such as price, even if they have strong design and customisation capabilities. In terms of how this relates to the concept of OWs and OQs, it is concluded that these too might exist in the short term, but in the longer term, it is not possible to be complacent on any issue. So for example, pure customisation might be an OW in the short term, with the firm needing to improve this competence, whilst being temporarily satisfied with other issues such as price. However, in the longer term, all issues need to be improved, and thus it is dynamic capabilities that become the key resource to cultivate, as discussed by authors such as De [START_REF] Toni | Strategic planning and firms' competencies[END_REF]. It is therefore strongly concluded that OW/OQs will change over time, may even vary at one point in time, given the variety of customers served by a firm, and thus that the identification of competitive priorities is far more complex than the concept of OW/OQs suggests. Thus, whilst this concept continues to be useful as a theoretical teaching tool to understand types of manufacturing company, it does not provide a useful concept for practicing managers to aid in the determination of competitive priorities.

Repeat Business as a Strategic Choice for ETO companies

The second research question, as posed in section 3, asked whether repeat business is a strategic choice for those companies offering pure customisation, aiming to gain an understanding of how and why this might be feasible in this sector. The conclusion to this question is that for many of the ETO SME's studied, some aspect of repeat business is believed to be essential to their survival and is therefore an important strategic choice.

Four main types of repeat business have been identified through the case study evidence, as illustrated in Figure 1, showing that this conclusion applies to Repeat Business Customisers (RBCs) and even some Versatile Manufacturing Companies (VMCs). The types of repeat business include sporadic repeat business for a different product to a previous client. This is seen by some VMCs as part of a strategic policy to pursue long term customer relationships in order to ensure as much repeat business as possible, even if this is for a unique product each time.

However, the key reasons for this strategic choice are varied, and do not necessarily include issues of profitability and efficiency as stated in the research question. Whilst one or both of these factors was seen to be a key driver for some of the case study companies, for others more important factors include reduced risk, ease of planning and lower operating costs. A clear distinction between cost and price was identified in the context of this evidence, with some interviewees suggesting that whilst costs might be lower for repeat orders, this did not necessarily translate into higher profits. As stated in the literature review, the study of [START_REF] Amaro | Competitive Advantage and a New Taxonomy for Non Make-to-Stock Companies[END_REF] is the only previous study that has considered this issue. This evidence adds more detail to the understanding of this issue, confirming that repeat business is important in this sector, but indicating that the reasons are more complex than those previously identified. It is also noted that there were some exceptions, with two of the ETO companies clearly stating that repeat business was not a strategic choice as it was not perceived to be viable in their particular business environment.

Managerial Implications and Future Research

From a managerial implications perspective, the research reinforces the need to understand competitors as well as customers. Competitive priorities are as much a result of the competitor actions as of the particular market segment that the company is aiming to attract. It is suggested that this is largely a result of a change in the manufacturing environment, whereby, as more companies gain the ability to customise goods efficiently, the customer is able to choose between a group of ETO/MTO companies when developing long term or short term supplier relationships. The results also confirm that there remain a number of manufacturing companies for which the level of repeat business remains low at 15% or less, and these companies need to seek other ways to reduce their operating costs than those that are available to the mass production and mass customisation industry.

Future research could include a larger survey to further confirm these results and the size of each of these sectors of industry with varying degrees of repeat business. An additional topic that could be covered in this survey would be the level of information system used and how this affects the level of customisation that can be offered. This may be important for the software market in establishing a need for software, which provides E, H, L, N, P, Q, R, U, V, W O, J X, K E, J, N, Q, R, T, U, V K, N, R, S, V

  S supported the claim of company B, that the OW and OQ are changing over time, or at least becoming more stringent. All its competitors are good on price and quality now, so it needs to find a new way to compete. Hence important factors include flexibility in terms of capacity adjustment or good personal relationships with clients.

  the company has no intention of changing this. The perception of the

  far as getting real quotes from its competitors and this lead to a better understanding of the competition than was apparent in most of the other companies studied.

Table 1 ]

 1

	F o r
	P
	e
	e r
	R
	e
	v i e
	w
	O n l
	y

Table 1 :

 1 Case study company characteristics *Calender bowls are used in industrial machines used by paper and textile manufacturers.

	alternative planning & control systems for the ETO/MTO sector, other than the ERP based
	systems currently widely available. For example, workload control is designed for

companies with a large VMC element and research is ongoing to develop this into a commercially viable alternative (see for example

[START_REF] Stevenson | A review of production planning and control: The applicability of key concepts to the make to order industry[END_REF]

. In addition, this study could be extended into a longitudinal study to investigate whether and how OW/OQs

Table 2 :

 2 Case study companies and the degree of ETO activity

	Degree of customisation
	Of competitors	Companies
	Same only	A, C, D, E, G, I, J, O, Q, S, T, W, X
	Less only	H, M, N, R, V
	Same or Less	B, F, K, L, P, U

Table 3 :

 3 Case study companies and their degree of customisation compared with their competitors

	Main	Level of customisation of Competitors
	Company
	Type	Same only	Less only	Same or Less
	ETO (p)	Price -A, D, E, G		Price -F
		Other -C, E		Other -B, F
	MTO (ta) Price -I F Other -J o MTO(cstan) Price -O r Other -O, Q, S, T	Customisation -H, M Other -H Customisation -N, R Other -N, R	Price -K Customisation -K, L Other -L Price -P Customisation -P
	ATO (cstan) Price -X P Other -W, X e r Customisation -V Other -U, V e	Price -X Customisation -X Other -W, X
			R
			e
			v i e
			w
			O n l
				y
			3

Table 4 :

 4 Competitive priorities by company type and the nature of the competitors

	Other Competitive Priorities Identified	Relevant companies
	Customer relationships / reputation	F, J, Q
	Whole package solution	B, C
	Technical/ design ability
	Delivery speed and reliability
	Company size
	Quality & Service
	Flexibility

Table 5 :

 5 Competitive priorities "other" than customisation and price

	Type of repeat Business Relevant Companies
	R Type	B, C, D, E
	V1 Type	F, J, O, N
	V2 Type	F, J, O, N, P, U
	V3 Type	A, G, I

Table 6 :

 6 Case study companies and the type of strategically important ETO(p) Repeat Business

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Table 7 :

 7 Repeat Business issues for companies with ETO(p) customisation

	Page 34 of 34

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uk International Journal of Production Research

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have evolved since the initial data collection and whether companies have evolved in terms of the degree of customisation they offer or the percentage of repeat business in their portfolio.


J M Marimon

M Ercibengoa

M Alonso

G García-Medina

E Pérez-Trallero

Prevalence and molecular characterization of Streptococcus pneumoniae serotype 6C causing invasive disease in Gipuzkoa, northern Spain, 1990-2009

The recently discovered pneumococcus serotype 6C was responsible for ten of the 1,530 invasive isolates studied between 1990 and 2009. These ten isolates belonged to seven sequence types (STs) and were isolated only from adult patients: six with bacteremia, three with meningitis, and one with peritonitis. All isolates but one were fully penicillin-susceptible.

Introduction

Streptococcus pneumoniae capsular serotype 6C was first described in 2007 [START_REF] Park | Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae[END_REF] and, to date, there have been no descriptions of invasive pneumococcal disease (IPD) caused by this new serotype in a European region [START_REF] Nunes | Temporal trends and molecular epidemiology of recently described serotype 6C of Streptococcus pneumoniae[END_REF][START_REF] Hermans | Low prevalence of recently discovered pneumococcal serotype 6C isolates among healthy Dutch children in the prevaccination era[END_REF]. Invasive disease caused by serotype 6C has previously been reported in North and South America [START_REF] Jacobs | Occurrence, distribution, and origins of Streptococcus pneumoniae Serotype 6C, a recently recognized serotype[END_REF][START_REF] Carvalho Mda | Active Bacterial Core Surveillance Team (2009) PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007[END_REF][START_REF] Campos | Prevalence of Streptococcus pneumoniae serotype 6C among invasive and carriage isolates in metropolitan Salvador, Brazil, from 1996 to 2007[END_REF], Australia [START_REF] Jin | Simple, accurate, serotype-specific PCR assay to differentiate Streptococcus pneumoniae serotypes 6A, 6B, and 6C[END_REF], and Africa [START_REF] Du Plessis | Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) (2008) Serotype 6C is associated with penicillin-susceptible meningeal infections in human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal isolates previously identified as serotype 6A in South Africa[END_REF]. The importance of this serotype lies in its non-inclusion in all of the current pneumococcal vaccines, its lack of immunological response to the homologous serotype 6B [START_REF] Park | Active Bacterial Core Surveillance Team (2008) Differential effects of pneumococcal vaccines against serotypes 6A and 6C[END_REF], and the penicillin and multidrug resistance found in some isolates [START_REF] Nunes | Temporal trends and molecular epidemiology of recently described serotype 6C of Streptococcus pneumoniae[END_REF][START_REF] Carvalho Mda | Active Bacterial Core Surveillance Team (2009) PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007[END_REF][START_REF] Campos | Prevalence of Streptococcus pneumoniae serotype 6C among invasive and carriage isolates in metropolitan Salvador, Brazil, from 1996 to 2007[END_REF]. More recently, isolation of the new serotype 6D from human carriers has also been described [START_REF] Jin | First report of putative Streptococcus pneumoniae serotype 6D among nasopharyngeal isolates from Fijian children[END_REF][START_REF] Bratcher | Identification of natural pneumococcal isolates expressing sero-type 6D by genetic, biochemical and serological characterization[END_REF]. The aim of this study was to identify the presence of these two new serotypes among IPD isolates in a European region (Gipuzkoa, northern Spain) in the last 22 years.

The study

Hospital Donostia is located in San Sebastián, the capital city of the province of Gipuzkoa, northern Spain. Between January 1990 and October 2009, 1,230 S. pneumoniae isolates causing IPD were recovered from sterile fluids (blood, cerebrospinal fluid, pleural fluid, etc.) in Hospital Donostia and another 300 invasive pneumococcal isolates sent from other hospitals in the province were serotyped with the Quellung reaction using rabbit polyclonal serogroup and serotype-specific antisera (Staten Serum Institute). Of them, 215 corresponded to isolates from children aged less than 15 years (93 between 1990 and 2001, and 122 between 2002 and 2009) and 1,315 to adults (599 between 1990 and 2001, and 716 between 2002 and 2009). Due to cross-reaction of serotypes 6C and 6D with serotypes 6A and 6B, respectively, all invasive isolates belonging to serogroup 6 were retyped using a recently described serotype-specific polymerase chain reaction (PCR) [START_REF] Jin | First report of putative Streptococcus pneumoniae serotype 6D among nasopharyngeal isolates from Fijian children[END_REF]. Serotype 6C isolates were further studied by multi-locus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility testing was performed by the broth microdilution method according to the Clinical and Laboratory Standards Institute (CLSI) M100-S19 guidelines. The presence of the ermB and mef genes of macrolide resistance and SXT resistance was studied as previously described [START_REF] Pérez-Trallero | Spectrum of antibiotic resistance of the Spain 14 -5 Streptococcus pneumoniae clone over a 22 year period[END_REF].

In children less than 15 years old, 17 cases of IPD caused by serotype 6B (11 between 1990 and 2001, and six since 2002) and five by serotype 6A (all of them after 2001) were diagnosed, while neither serotype 6C nor 6D were found among invasive isolates. Although in other studies serotype 6C has been frequently found in young children carriers [START_REF] Nunes | Temporal trends and molecular epidemiology of recently described serotype 6C of Streptococcus pneumoniae[END_REF], no serotype 6C invasive infections in this population age group was observed in our area; this low prevalence of serotype 6C IPD in children has also been observed in other studies [START_REF] Park | Active Bacterial Core Surveillance Team (2008) Differential effects of pneumococcal vaccines against serotypes 6A and 6C[END_REF].

In adults (>14 years old) between 1990 and 2001, serotypes 6A, 6B, and 6C caused 11, 29, and three cases of IPD, respectively; since 2002, these serotypes were responsible for 14, 12, and seven episodes, respectively. In adults, no serotype 6D was found throughout the entire study. The clinical picture of the ten patients with serotype 6C invasive infection consisted of three bacteremias, two of abdominal origin (cholangitis and cirrhosis), primary peritonitis in one, meningitis in three, and acute lower respiratory tract infections in three (pneumonia in two and acute exacerbation of chronic obstructive pulmonary disease [COPD] in one ) (Table 1). Most serotype 6C isolates were susceptible to all of the antimicrobials tested (Table 1). One isolate showed low-level penicillin resistance (minimum inhibitory concentration [MIC]=0.12 mg/L) and the only erythromycin-resistant isolate harbored the ermB gene. The two trimethoprimsulfamethoxazole-resistant isolates displayed the Ile-100 Leu change in the dihydrofolate reductase associated to trimethoprim resistance.

In our area, the first of the ten serotype 6C invasive isolates was detected in 1996, and five of the ten were isolated between 2007 and 2009 (Table 1). A similar slight increase in the last few years was found among adults in the USA, where 6C became the prevalent serogroup 6 serotype causing IPD in 2007 [START_REF] Carvalho Mda | Active Bacterial Core Surveillance Team (2009) PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007[END_REF]. Although the heptavalent pneumococcal conjugate vaccine (PCV7) has not been shown to confer protection against pneumococcal serotype 6C or 6D [START_REF] Park | Active Bacterial Core Surveillance Team (2008) Differential effects of pneumococcal vaccines against serotypes 6A and 6C[END_REF][START_REF] Bratcher | Identification of natural pneumococcal isolates expressing sero-type 6D by genetic, biochemical and serological characterization[END_REF], we found no case of IPD caused by these new serotypes in children, despite the 11 cases of serogroup 6 (five 6A and six 6B) invasive infection recorded since the introduction of the vaccine in our country (June 2001). To estimate the presence of these serotypes among non-invasive isolates in our area, we studied 208 pneumococci detected in a carriage study (nasopharyngeal samples) in children aged less than 2 years between 2004 and 2005. Among them, 19 belonged to serogroup 6: three serotype 6A, 15 serotype 6B, and one serotype 6C. No serotype 6D isolates were found.

One study found the over-representation of meningitis caused by serotype 6C in IPD [START_REF] Du Plessis | Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) (2008) Serotype 6C is associated with penicillin-susceptible meningeal infections in human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal isolates previously identified as serotype 6A in South Africa[END_REF]; in the present small series, three meningitis cases were recorded. In contrast, three of the bacteremic cases were related to intra- The ancestral origin of the new serotype 6C is still unknown. Serotypes 6A and 6B capsular loci only differ from those of serotypes 6C and 6D in that serotypes 6A and 6B have the wciN gene and serotypes 6C and 6D the wciN β gene [START_REF] Park | Discovery of a new capsular serotype (6C) within serogroup 6 of Streptococcus pneumoniae[END_REF][START_REF] Jin | First report of putative Streptococcus pneumoniae serotype 6D among nasopharyngeal isolates from Fijian children[END_REF]. In addition, serotypes 6A and 6B capsular loci only differ consistently in one nucleotide of the wciP gene. In our area, the first serotype 6C causing IPD was detected years after the isolation of serotypes 6A and 6B, and two of the three predicted primary founders of serotype 6C clonal complexes belonged to serotype 6B. Jacobs et al. [START_REF] Jacobs | Occurrence, distribution, and origins of Streptococcus pneumoniae Serotype 6C, a recently recognized serotype[END_REF] also found two clusters of serotype 6C isolates closely related to serotype 6B strains, suggesting a capsular switching from serotype 6B to serotype 6C. If serotype 6B was the ancestral origin of serotype 6C, apart from gaining the wciN β gene, another sequential or concomitant mutation in the wciP gene must have taken place, as, otherwise, serotype 6D would have been the serotype isolated. Like other authors [START_REF] Hermans | Low prevalence of recently discovered pneumococcal serotype 6C isolates among healthy Dutch children in the prevaccination era[END_REF][START_REF] Carvalho Mda | Active Bacterial Core Surveillance Team (2009) PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007[END_REF], we did not find the wciN β gene among the 58 invasive serotype 6B isolates studied.

Overall, seven different sequence types (STs) were found in the ten serotype 6C isolates, including the two new ST4534 and ST4535, described for the first time in this study. All STs except one singleton (ST2440) could be grouped into clonal complexes 1, 7, and 27, whose predicted founders are ST176, ST90, and ST395 of serotypes 6B, 6B, and 6A, respectively. Only two of the STs found in our study have been previously described among serotype 6C isolates: ST1150 and ST395 from nasal carriers from Portugal [START_REF] Nunes | Temporal trends and molecular epidemiology of recently described serotype 6C of Streptococcus pneumoniae[END_REF] and ST395 among invasive isolates from the USA [START_REF] Carvalho Mda | Active Bacterial Core Surveillance Team (2009) PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007[END_REF]. Indeed, most serotype 6C invasive isolates from North [START_REF] Jacobs | Occurrence, distribution, and origins of Streptococcus pneumoniae Serotype 6C, a recently recognized serotype[END_REF][START_REF] Carvalho Mda | Active Bacterial Core Surveillance Team (2009) PCR-based quantitation and clonal diversity of the current prevalent invasive serogroup 6 pneumococcal serotype, 6C, in the United States in 1999 and 2006 to 2007[END_REF] and South America [START_REF] Campos | Prevalence of Streptococcus pneumoniae serotype 6C among invasive and carriage isolates in metropolitan Salvador, Brazil, from 1996 to 2007[END_REF] showed no similarity among each other or to our isolates, which is in the line of thinking that this newly discovered serotype probably emerged by shuttling of the wciN β element within a preexisting diverse genetic background, whether followed or not by additional changes.

By PFGE, five different clusters were defined among serotype 6C invasive isolates (Table 1). Curiously, eBURST revealed that ST2667 and ST1624 isolates, which share no common allele, belonged to the same clonal complex and were grouped by PFGE in the same arbitrarily named clone B (PFGE pattern similarity 96%).

Conclusion

Our study describes, for the first time, the presence and characteristics of Streptococcus pneumoniae serotype 6C isolates causing invasive disease in a European region, with a trend toward a slight increase in its incidence in the adult population. No serotype 6D was found among invasive pneumococcal disease (IPD) isolates after 1990. Genotyping techniques showed two new sequence types (STs) within serotype 6C related to serotype 6B isolates included in the MLST database. Like other authors, we found that some of our isolates previously serotyped as 6A were, in fact, 6C [START_REF] Hermans | Low prevalence of recently discovered pneumococcal serotype 6C isolates among healthy Dutch children in the prevaccination era[END_REF][START_REF] Jacobs | Occurrence, distribution, and origins of Streptococcus pneumoniae Serotype 6C, a recently recognized serotype[END_REF][START_REF] Campos | Prevalence of Streptococcus pneumoniae serotype 6C among invasive and carriage isolates in metropolitan Salvador, Brazil, from 1996 to 2007[END_REF][START_REF] Du Plessis | Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA) (2008) Serotype 6C is associated with penicillin-susceptible meningeal infections in human immunodeficiency virus (HIV)-infected adults among invasive pneumococcal isolates previously identified as serotype 6A in South Africa[END_REF]. Whether serotype 6A strains included in the MLST database are the newly described serotype 6C or not should be determined in order to gain understanding on the ancestral origin of S. pneumoniae serogroup 6.

5 MLST

 5 multi-locus sequence typing; CSF cerebrospinal fluid; COPD chronic obstructive pulmonary disease; Pen penicillin; Amo amoxicillin; Ctx cefotaxime; Tet tetracycline; Eri erythromycin; Cli clindamycin; Cip ciprofloxacin; Lev levofloxacin; SXT trimethoprim-sulfamethoxazole a As determined by eBURST (http://spneumoniae.mlst.net/eburst/) b Isolates with a pulsed-field gel electrophoresis (PFGE) similarity pattern >80% but <100% were arbitrarily named with the same letter but different numbers c Minimum inhibitory concentration (MIC) in mg/L abdominal diseases, an unusual situation in bacteremic S. pneumoniae infections.

Table 1

 1 Microbiological characteristics and clinical pictures of the ten serotype 6C isolates from invasive diseases

	Sex Age
	Date
	Code

J. M. Marimon : M. Alonso : E. Pérez-Trallero (*) Servicio de Microbiología, Hospital Donostia, Paseo Dr. Beguiristain s/n, 20014 San Sebastián, Spain e-mail: mikrobiol@terra.es J. M. Marimon : M. Ercibengoa : M. Alonso : G. García-Medina : E. Pérez-Trallero Centro de Investigación Biomédica en Red Enfermedades Respiratorias CIBERES, San Sebastián, Spain E. Pérez-Trallero Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad del País Vasco, San Sebastián, Spain Eur J Clin Microbiol Infect Dis (2010) 29:1035-1038 DOI 10.1007/s10096-010-0947-6

Conflict of interest All authors: no conflict.

Financial support This study was partially supported by a grant from the Department of Health of the Basque Government, number 2009111012.