MD Gunnar Jacobsson
email: gunnar.jacobsson@vgregion.se

Patricia Colque-Navarro

Erik Gustafsson

Rune Andersson

Roland Möllby

Antibody Responses in Patients with Invasive Staphylococcus aureus infections

Should read: S. aureus pathogenicity is multifactorial and related to the array of virulence factors among different S. aureus isolates and the inability of Has been changed accordingly humans to develop protective immunity against this pathogen.

[Not sure what you mean by diagnostic tools. The tools are there; therapeutics are not.] Page 2. Line 50-60 reads: The use of S. aureus serology is of limited clinical value. For diagnostic purposes serology is dependent upon accurate quantitative test methods and a proper combination of antigens, however, there is no evidence that any serological assay or combination of assays can distinguish between complicated and uncomplicated S. aureus bacteraemia ?11?. Instead, there is a mounting interest in the human humoral response to S. aureus in perspective of future passive and active vaccine development ?10, 12?. This evolvement is hampered by a lack of knowledge about the production of possible specific, protective antibodies in humans during infection, especially in large clinical surveys.

Should read:

Because the use of S. aureus serology is of limited clinical value for diagnostic purposes (there is no evidence that any serological assay or combination of assays can distinguish between complicated and uncomplicated S. aureus bacteraemia ?11?) there is a mounting interest in the human humoral response to S. aureus in the context of developing future passive and active vaccination strategies ?10, 12?. However, the development of these formulations has been hampered by a lack of knowledge regarding the nature of the specific, protective antibodies in humans during infection, especially in large clinical surveys.

Has been changed to: The use of S. aureus serology is of limited clinical value for diagnostic purposes (there is no evidence that any serological assay or combination of assays can distinguish between complicated and uncomplicated S. aureus bacteraemia 11). However, there is a mounting interest in the human humoral response to S. aureus in the context of developing future passive and active vaccine strategies 10, 12. The development of these formulations ha s been hampered by a lack of knowledge regarding the nature of the specific, protective antibodies in humans during infection, especially in large clinical surveys Materials section:

Study population Should read:

A prospective study was performed in consecutive patients with ISA over a two year period between 2003-2005, in western Sweden using healthy individuals as controls ?13,14?. The antibody response in patients was determined by taking three serum samples; one at the time of diagnosis (n=96), one following completion of antibiotic treatment (n=71) and the last sample collected during convalescence i.e, one month after the end of treatment (n=51). From the 115 healthy control individuals one serum sample was obtained. Consent was obtained from the patients or their relatives after written and oral information.

Has been changed accordingly

Definitions Should read:

Severe sepsis and complicated bacteraemia are described in [14]. For this study, all patients presenting with either hypotension, hypoperfusion or organ dysfunction were diagnosed with severe sepsis. Complicated bacteraemia was defined as bacteraemia presenting with a secondary focus, such as endocarditis, spondylitis, osteomyelitis, arthritis, as a deep-seated abscess or pneumonia. Lineassociated infections, urinary tract infections nor soft-tissue infections with no metastatic seeding or bacteraemia without focus were not defined as complicated bacteraemia.

Has been changed accordingly ELISA Should read: two-fold not twofold. Also the authors stated that Clf had been changed to CflA. It Still reads Clf in this section.

Has been changed accordingly Statistics Should read: 'geometric means' not 'geometric mean'. Also should read 'using the Chi-square test' not 'with Chi-square test'.

Has been changed accordingly Page 8. Line 7 reads: PFGE group 1 was also correlated with tst carriage (p?0.001) among the strains and strains. I suggest it be changed to 'correlated with the presence of tst among.' since the word 'carriage' in the context of S. aureus is used specifically to define the colonization status of humans.

Has been changed accordingly Page 8. Line 8 reads: 'belonging to PFGE group 1 significantly correlate' Should read: 'belonging to PFGE group 1 significantly correlated' Has been changed accordingly Page 9. Lines 24-25 read: Patient with osteomyelitis (n=13) showed a significantly high proportion of increasing levels of Clf A, and.

Should read:

Patients with osteomyelitis (n=13) showed a significantly high proportion of increasing levels of ClfA, and.

Has been changed accordingly Page 9. Line 39-41 reads: (83% had a first high response compared to 31%). Not sure what you mean by 'first high response'.

Has been changed to: (83% had high antibody level at presentation as compared to 31% in patients with no previous history of ISA). Page 10. Lines 36-39 reads: Clf A in sample 1 and 3, and the antibody levels for alpha-toxin in sample 1 and 3.

Should read:

ClfA in sample 1 and 3 and the antibody levels to alpha-toxin in samples 1 and 3.

Has been changed accordingly Page 10. Line 41 reads: to Efb in sample 1 and 3, and to the antibody levels to Clf A in sample 1, 2 and 3.

Should read:

to Efb in samples 1 and 3 and to the antibody levels against ClfA in samples 1, 2 and 3.

Has been changed accordingly Page 10. Line 54 reads: 'Dryla ?7??reported of a pronounced heterogeneity of antibody .' Should read: Dryla ?7??reported a pronounced heterogeneity in antibody.' Has been changed accordingly Page 11. Lines 5-10. Our cohort was more homogenous, with only invasive infections, and still great variations in antibody levels were seen. The timing of the samples was not the reason for this, as there was no major correlation between time from start of symptoms to sampling and antibody levels.

Should read: 'Our cohort was more homogenous consisting of only invasive infections and great variations in antibody levels were still observed. The timing of when serum samples were examined for anti-S. aureus antibodies was not the reason for this, as there was no major.'

Has been changed accordingly

Don't know what you mean by 'correlation between time from start of symptoms to sampling and antibody levels.'

Answer: There was no correlation between antibody levels and symptom time, i.e. the time from start of symptoms and to serum sampling Page 11. Lines 11-17 reads: '.develop a dysregulation of the humoral immunity affecting quality and quantity of the antibody response. They display lower levels against several antigens and notably towards the superantigens included in this study' Should read: '.develop a dysregulation of humoral immune responses that can affect the quality and quantity of the antibody response. They displayed lower antibody levels against several antigens; notably towards the superantigens examined in this study.' Has been changed accordingly Page 11. Lines 34-42 reads: 'In fact, it is seen in Figure 2B that about 70 % of the patients had a high (H) level against lipase in one of the samples and 95 % of all patients showed a "positive serology (PS)" against this antigen alone. This finding indicates that patients in general do react to S. aureus antigens, although to varying extent.' Should read: 'In fact, as seen in Figure 2B, about 70% of patients had high (H) antibody levels against lipase in one of the samples and 95% of all patients showed "positive serology (PS)" against this antigen alone. This finding indicated that patients in general do react to S. aureus antigens, although to varying extents.' Has been changed accordingly Page 11. Line 51 reads: '.rise in antibody level in.' Should read: '.rise in antibody levels in.'

Has been changed accordingly Page 11 line 59 and page 12 line 1 reads: '.immune response, as opposed to other risk groups as patients with diabetes mellitus.' Should read: '.immune response, compared to other risk groups, for example, patients with diabetes mellitus.' Has been changed accordingly Page 12. Lines 1-2 read: 'In order to implement successful strategies as immunoglobulin therapy or vaccination it is important to know the patients' immune status.' Should read: 'In order to implement successful strategies such as immunoglobulin therapies or vaccinations, it will be important to know the patient's immune status.' Has been changed accordingly Page 11. Line 24-25 reads: 'Still, we do not believe this is the cause why we did not register more diagnose-specific differences.' Should read: 'Still, we do not believe this is the reason why we did not observe more diagnosis-specific differences.' '.which invasive infection, a polyclonal B-cells response is generated.' Should read: '.which type of invasive infection, a polyclonal B-cells response is generated.' Has been changed accordingly Page 11. Line 37. Should read 'in antibody levels' not 'of antibody levels.' Has been changed accordingly Page 11 and 12. Last line of Page 11 and lines 1-5 page 12 read: 'The significance of this observation could be argued. We can not conclude if the observed correlation between low initial antibody levels and a fatal outcome (Table 3) is of causative art or due to a general weak immune response.' Should read: 'The significance of this observation could be argued since we cannot conclude if the observed correlation between low initial antibody levels and a fatal outcome (Table 3) was the cause of the infection or if it resulted from generally weak immune responses.'

Has been changed to: The significance of this observation could be argued since we cannot conclude whether the observed correlation between low initial antibody levels and a fatal outcome (Table 3) was caused by a lack of specific immune responses or if it resulted from general weak immune responses Page 12. Lines 17-22 read: 'The innate immunity in old patients with concurrent diseases could be a major denominator of clinical outcome. A lack of specific immune response to other antigens than tested in our study is possible.' Should read: 'The innate immune response in older patients presenting with concurrent infections could be a major denominator of clinical outcome. A lack of specific immune response to other antigens than those tested in this study is also likely.'

Has been changed to: The innate immune response in older patients presenting with concurrent diseases could be a major denominator of clinical outcome. A lack of specific immune response to other antigens than those tested in this study is also possible. Page 12. Line 32. Is ASTA defined?

Has been defined: ASTA (Anti-staphylolysin assay)

Yours sincerely

Gunnar Jacobsson

Introduction

Staphylococcus aureus continues to cause medical problems in the community and healthcare settings. The emergence of multidrug-resistant strains 1-3 has heightened the need for nonantimicrobial approaches.

A microbiological enigma is the immunologic response in humans towards this bacterium since most individuals are exposed to S. aureus and can be classified as carriers, intermittent carriers or non-carriers of the bacteria. High levels of exposure to this organism (among humans) is supported by the observation of human populations describing serum antibodies to most antigens tested for, while rises in serum antibody levels during invasive infections vary greatly 4. Data from experimental animal studies 5, 6 indicated that this mainly polyclonal B-cell response with antibodies of low affinity is not protective. The vast majority, 60 to 85%, of antibodies in healthy individuals are induced by lipoteichoic acid, which fails to promote opsonisation 7, 8. An individual who has suffered from a S. aureus infection is usually not protected from a subsequent infection and to date in clinical trials the development of protective active immunization schedules has failed 9, 10.

S. aureus pathogenicity is multifactorial and related to the array of virulence factors among different S. aureus isolates and the inability of humans to develop protective immunity against this pathogen.

The use of S. aureus serology is of limited clinical value for diagnostic purposes (there is no evidence that any serological assay or combination of assays can distinguish between complicated and uncomplicated S. aureus bacteraemia 11). However, there is a mounting interest in the human humoral response to S. aureus in the context of developing future passive and active vaccine strategies 10, 12. The development of these formulations has been hampered by a lack of knowledge regarding the nature of the specific, protective antibodies in humans during infection, especially in large clinical surveys.

The objective of this study was to describe the humoral immune response to S. aureus in a well-characterized patient cohort with Invasive S. aureus infections (ISA).

Materials and methods

Study population

A prospective study was performed in consecutive patients with ISA over a two year period between 2003-2005, in western Sweden using healthy individuals as controls 13,14. The antibody response in patients was determined by taking three samples: one at the time of diagnosis (n=96), one following completion of antibiotic treatment (n=71), and the last sample collected during convalescence i.e. one month after the end of treatment (n=51). From 115 healthy individuals one serum sample was obtained.

Consent was obtained from the patients or their relatives after written and oral information.

Definitions

Severe sepsis and complicated bacteraemia are described in [14].

For this study, all patients presenting with either hypotension, hypoperfusion or organ dysfunction, were diagnosed with severe sepsis. Complicated bacteraemia was defined as bacteraemia presented with a secondary focus, such as endocarditis, spondylitis, osteomyelitis, arthritis, as a deep-seated abscess or pneumonia. Line-associated infections, urinary tract infection nor soft-tissue infection with no metastatic seeding or bacteraemia without focus were not defined as complicated bacteraemia.

Antigens

Ribitol teichoic acid (TA) and Alpha-toxin (AT) were purchased from PhPlate AB (Stockholm, Sweden). Enterotoxin A (SEA), Toxic Shock Syndrome Toxin 1 (TST), and Scalded Skin Syndrome toxin (SSS) were purchased from Toxin Technology (Florida, USA).

Lipase was kindly supplied by S. Tyski (Medical University of Warzaw, Poland), Clumping factor A (ClfA) and Extracellular fibrinogen binding protein (Efb) by J.I. Flock (Karolinska Institute, Stockholm).

ELISA

The enzyme-linked immunosorbent assay (ELISA) to determine serum IgG antibodies has been described earlier [15]. The antigen coating concentration was 1 g/ml for TA, 3.5 g/ml for AT, 2 µg/ml for ClfA, 0.6 µg/ml for Efb, and 1 g/ml for TST, SEA and SSS. Serum samples were diluted two-fold in PBS-T (1/250 to 1/2000) in AT, ClfA, Efb, TST and SSS assays and (1/2500 to 1/20000) in TA and lipase assays. The reference serum consisted of pooled sera from six patients with confirmed sepsis 15. The four dilutions, controls and reference serum were applied and incubated for 1 h at 37°C. Thereafter alkaline phosphatase conjugated to goat anti-human antibodies (γ-chain) (Sigma Chemical Co., St. Louis, Mo.) diluted 1/3000 in PBS-T was added, and incubation was continued for 2 h at 37°C. Finally, the enzymatic reaction was measured at 405 nm in a Titertek Multiscan microplate reader (Flow Laboratories, Irvine, Scotland) after approximately 20 min incubation.

Interpretations of ELISA results.

The absorbance values were transformed into arbitrary units by using the reference line units calculation method 16. The dilution curve of each sample was drawn up in parallel to that of the reference serum, after which the two curves were compared. The reference serum was given the value of 1,000 (arbitrary) units for all antigens and the patient serum antibody levels were expressed in these units. Thus the unit levels obtained for each antigen cannot be directly compared others, since the absolute values are contingent on those of the reference serum.

The upper limits for "normal antibody levels" were established as the upper 95th percentiles of the levels in the healthy individuals. Levels above this cut-off point were designated as high levels (H). A significant increase in antibodies was defined as a 50% increase between two samples (I) and a significant decrease of antibodies was defined as a 50% decrease (D).

Positive serology (PS) was considered to exist when a high level was noted in at least one serum sample from a patient with at least two samples and/or a significant increase/decrease of antibody levels. Some sera were designated as low levels (L). The limits for these levels varied from 50 to 150 for the different antigens as determined in terms of the reproducibility of each respective test. The actual limit values for high and low levels are plotted in Figure 1.

Typing of isolated S.aureus strains

Agr group typing was performed as previously described 14.

Genome typing by pulse field gel electrophoresis was performed in principle as described by Tenover 17. Visual interpretation of the banding pattern according to cited criteria were made, resulting in a cut-off level of 75% in the dendrograms generated, above which strains were considered to be closely related.

Production of alpha-haemolysin

Screening for alpha-haemolysin production was carried out on nutrient agar plates (8 mm high) containing rabbit erythrocytes. The diameter of the bacterial colonies on the agar plates after incubation at 37C overnight was < 3 mm and the diameter of the zone of haemolysis (mm), was determined.

Statistics

Data were analyzed with SPSS (version 15.0) and Excel 97. Antibody levels were presented as arithmetic/geometric means, and comparisons between groups regarding quantitative variables were analyzed using the Mann-Whitney U nonparametric test regarding. Category variables were analyzed using the Chi-square test.

Results

The median age was 68 y (mean 64 y) in the patient group as compared with 70 y (mean 61 y) among the controls. Fifty-six percent of the infected patients were men, while the corresponding figure for the healthy individuals was 59%.

Antibody levels in all patients

The antibody levels of all patients were distributed as depicted in Figure 1 for the various antigens. It is evident that antibody levels against teichoic acid, α-toxin and lipase were higher than those of healthy individuals of corresponding ages. Great interindividual variation in antibody levels was seen, ranging from 50 to 5000 units against the same antigen in the same sample category. As expected, the levels achieved in the second sample (T2), at the end of treatment, were generally the highest, while the median levels varied relatively little between the three sample occasions. Exceptions to this were lipase and α-toxin.

High levels (H) were, concordantly, most common for teichoic acid, α-toxin and lipase, where 25 to 42% of the samples were positive in the second sample (Figure 2A). In the third sample, drawn at least on month after finished treatment, the levels against alpha-toxin and lipase remained high.

The kinetics of the antibody levels are shown in Figure 2B, which shows the frequencies at which the patients appeared to react to the different antigens. With the exception of SSS, 40 to 95% of the patients reacted to a staphylococcal antigen, where lipase stimulated the highest number of patients, regardless of kinetic parameter measured. Sixty per cent of the patients showed an increase in antibody levels against this antigen, and almost 40% showed a decrease. This latter value was probably related to the high levels of antibodies in the first two samples (Figures 1 and2).

Bacterial properties

Bacterial strains belonging to agr groups I and II produce significantly larger zones of hemolysis as compared with strains belonging to agr group III (Table 1), indicating a correlation between agr group and production of alpha-toxin. The zones of hemolysis were significantly correlated with levels of antibodies against alpha-toxin at presentation (Table 1).

We also found a significant correlation between agr group III and a low initial anti-alphatoxin antibody level (p0.001) as determined Chi-square analysis (Table 2).

Screening for tst among the strains revealed that 17% of the strains were positive for the tst gene with 90% of the tst-positive isolates belonging to agr group III (p0.001). A correlation between tst among the strains and absolute anti TST antibody levels (sample 1 p=0.002 and 2 p0.001) was found among the patients. As seen in Table 2, agr-group III correlates to higher TST antibody levels.

A significant correlation between agr groups and PFGE groups was found in agreement with earlier studies. Interestingly, we also found that PFGE group 1, which was correlated with small zones of hemolysis (Table 1), was correlated with low levels of anti alpha-toxin (Table 2). PFGE group 1 was also correlated with the presence of tst (p0.001) among the strains and strains belonging to PFGE group 1 correlated significantly with high levels of anti TST antibody among the patients (Table 2).

Surprisingly, levels of antibodies to teichoic acid, a cell wall constituent expressed in all strains, was significantly correlated to agr-group. Strains belonging to agr-group 1 showed a positive serology response in 45% of the patients, ascompared with 78% of strains belonging to agr-group 3 (Table 2). This pattern was even more pronounced in the PFGE groups, as seen in Table 2.

We did not screen for the gene for Scalded Skin Syndrome toxin, SSS. However, in accordance with the antibody response against the other superantigen TST, differences were found between the various agr-groups and PFGE-groups. PGFE-group 2 and agr-group 1 were correlated with initial low levels of antibodies, as compared with agr-group 2 which correlated with higher initial antibody levels (Table 2).

Clinical outcome

Patients with a fatal outcome only displayed significantly lower initial antibody levels to 4 antigens (Table 3). The same trend was noted for 5 antigens in patients with complicated bacteraemia, but not for TST, SEA and SSS. The mean age was significantly higher in the patients with a fatal outcome (79y vs. 63y, p=0.014). Patients with severe sepsis were also significantly older (75 y vs. 60 y, p<0.001), but no difference in mean age was registered in patients with complicated bactaeremia (65 y vs. 64 y). We did not detect any significant differences in the time from start of symptoms to inclusion in the study, or to the first blood sample, in any group, although patients with a fatal outcome tended to have shorter duration of symptoms.

The antibody levels in sample 2 and 3 did not differ significantly between patients with different clinical outcome, such as in patients with bacteraemia (n=84), complicated bacteraemia (n=32), severe sepsis (n=28), or in patients suffering from a sequelae (n=37).

No major differences in the antibody production related to the tissue involved were noted.

However, patients with endovascular infections (n=7) tended to have initial lower antibody levels towards all antigens. Patients with bacteraemia without focus (n=19) tended to have higher antibody levels towards several antigens. Patients with osteomyelitis (n=13) showed a significantly high proportion of increasing levels of ClfA, and a significantly higher frequency of positive serology, than patients without osteomyelitis.

Patients with a previous history of ISA (n=14) had a trend toward lower risk of both a fatal outcome and complicated bacteraemia. They were also significantly less prone to developing severe sepsis, and their initial antibody response to alpha-toxin tended to be higher (83% had high antibody level at presentation as compared to 31% in patients with no previous history of ISA). No endovascular infections were registered in patients with a previous history of ISA.

Figure 4 shows the antibody levels in patients with collagenosis (n=14), a group at risk of developing ISA [6]. Low antibody levels as compared with patients without collagenosis were noted. Patients with collagenosis were not significantly older (69 y vs. 66 y), had the same duration of symptoms (4 days), but received longer antibiotic treatment (94 days vs. 46 days), and tended to have longer periods of hospitalization (31 days vs. 18 days). Other patients at risk of developing ISA, such as patients with diabetes mellitus (n=27), and patients with kidney disease (n=13) showed no major differences in antibody levels. Patients with liver disease (n=13) showed (as opposed to collagenosis patients) significantly higher antibody levels against several antigens. Older people (>65 y) displayed significantly lower proportion of positive serology against the superantigens TST, SEA and SSS (Table 4). The mean antibody levels in older patients were also lower than in younger patients against all the antigens except Efb in the first sample, while they were significantly lower (Mann-Whitney) only against SSS at the end of antibiotic therapy and one month later (data not shown).

We did not discern any major differences in the antibody response of men and women.

The duration of symptoms correlated positively only to the antibody level to lipase in sample 2, but correlated negatively to lipase in sample 1. We noted a positive correlation between duration of hospitalization and the antibody levels to ClfA in samples 1 and 3, as well as the antibody levels for alpha-toxin in samples 1 and 3. The length of antibiotic treatment was positively correlated with the antibody levels against Efb in sample 1 and 3, and to the antibody levels against ClfA in samples 1, 2 and 3.

Discussion

This is one of few studies comparing the humoral immune response in a cohort of wellcharacterized patients with ISA with healthy individuals. Dryla 7 reported a pronounced heterogeneity in antibody levels against 19 S. aureus antigens among both healthy individuals and patients with an S. aureus infection. However, the patient group was not uniform, consisting of 17 patients with wound infection, 15 subjects with bacteraemia and sepsis, and 10 patients with miscellaneous infections.

Our cohort was more homogenous consisting of only invasive infections and great variations in antibody levels were still observed. The timing of when serum samples were examined for anti-S.aureus antibodies was not the reason for this, as there was no major correlation between time from start of symptoms to sampling and antibody levels. One obvious explanation is that older people (65 y) develop a dysregulation of humoral immunity responses that can affect the quality and quantity of the antibody response. They displayed lower antibody levels against several antigens: notably towards the superantigens examined in this study (Table 4). Aging is associated with a shift in antibody isotype from IgG to IgM, and a decline in the activity of lymphocytes 18, 19. Staphylococcal serology is further complicated by the findings of immunomodulating activities in S. aureus, which may be exerted by antigens such as EAP, lipoteichoic acid and peptidoglycan 20-22.

In spite of weak antibody response in general, Figures 1 and2 show elevated levels of antibodies, as compared with the healthy control group, especially against alpha-toxin and lipase. In fact, as seen in Figure 2B, about 70 % of patients had high (H) antibody levels against lipase in one of the samples and 95 % of all patients showed a "positive serology (PS)" against this antigen alone. This finding indicated that patients in general do react to S. aureus antigens, although to varying extent. Analysis of serum IgG with reactivity against teichoic acid and alpha-toxin identified 80 % of patients with "positive serology". These contradictory findings may be explained by the fact that, in spite of relatively low absolute levels, the immune system is activated during disease and increases and/or decreases in antibody levels can therefore be detected. There was a rise in antibody levels in more than 40 % of the patients even against the TST antigen (Figure 2B). Different groups, displaying variable antibody levels, are at higher risk of ISA 13. Patients with rheumatic disorders develop weak immune responses, compared to other risk groups, for example, patients with diabetes mellitus. In order to implement successful strategies such as immunoglobulin therapies or vaccinations, it will be important to know the patient"s immune status. We did not demonstrate significantly lower antibody levels among haemodialysis patients. Trials with an anti-capsular vaccine in these patients 9,10 have been unsuccessful in eliciting a protective immune response. One proposed explanation is their weak immune response.

Invasive infections include infections with variable tissue-tropism, for example, endovascular infections, bone infections, and deep soft tissue infections. Surprisingly, we detected only minor differences in antibody levels related to clinical diagnosis. In some cases it is questionable whether the clinical diagnosis was correct. Only 40 % of the patients were examined with ultrasound examination as part of the diagnosis of endocarditis 14, so we may have underestimated the rate of endocarditis. Still, we do not believe this is the reason why we did not observe more diagnosis-specific differences. Regardless of which type of invasive infection, a polyclonal B-cells response is generated 5, 6,23 and may mask a specific, tissue-orientated reaction. However, patients with very high antibody levels were tested for antibody levels against non-related bacterial antigens such as E. coli endotoxin and S. pneumoniae pneumolysin (data not shown), and there was no sign of a polyclonal increase in antibody levels.

There was a tendency, in some instances significantly, towards a lower antibody response against several antigens in patients with complicated bacteraemia as compared to patients with uncomplicated bacteraemia (Table 3). We have shown this previously for alpha-toxin, teichoic acid and lipase 4. Others, however, have not made the same observation 24, 25.

To our knowledge, this is the first time an association has been found between a fatal outcome and initial low antibody response in ISA, with the exception of TST 26-28. The significance of this observation could be argued since we cannot conclude whether the observed correlation between low initial antibody levels and a fatal outcome (Table 3) was caused by a lack of specific immune responses or if it resulted from general weak immune responses.

The potential of improved treatment including immunoglobulin therapy has not yet been properly evaluated. A clinical trial with a pooled human immunoglobulin preparation with high antibody titers against ClfA failed, as compared with placebo, to reduce sepsis and mortality 29. The patient group consisted of infants; interpretation for other age groups is unclear.

The innate immune response in older patients presenting with concurrent diseases could be a major denominator of clinical outcome. A lack of specific immune response to other antigens than those tested in this study is also possible. However, we cannot rule out the possibility that among the examined antibodies, there may be a protective response embedded in the polyclonal reaction. Teichoic acid has been shown to be an essential factor for colonization 30. In our study, patients with endovascular infections tended to have lower initial antibody levels to all antigens. Ruotsalainen 31 found an elevated initial ASTA (Anti-staphylolysin assay) titer significantly more often among injection drug users without endocarditis than among individuals with endocarditis (44% vs. 6%). There were no endovascular infections among our patients with recurrent ISA infections, and they displayed higher initial levels of antibodies against alpha-toxin. Vaccination with alpha-toxin in an animal model has been found to protect against S. aureus pneumonia 32.

Dryla 7 showed that high-titer antistaphylococcal antibodies remain stable for years in healthy individuals, providing evidence of these antibodies being functional on the basis of opsonophagocytic and neutralizing activity. In a study of paediatric patients infected with community-acquired S. aureus isolates 33, it has been demonstrated that patients infected with Panton-Valentin leucocidin (PVL)-positive strains developed a dominant IgG anti-PVL antibody response. This response was attributable to a specific humoral response against the antigens Lukf and LukS at the expense of antibody response against other virulence factors.

Holtfreter 34 reported that carriers neutralize superantigens with antibodies specific for their colonizing strain which may explain the observation 35 that carriers who develop sepsis have a better prognosis than to non-carriers. Animal studies have also demonstrated that it is possible to elicit a protective response to various bacterial components including MSCRAMMs (e.g. ClfA, FnBp and collagen binding protein) 36-39, surface polysaccharides (type 5 and 8) 40 as well as secreted toxins 41-43.

We found an association between both the PFGE group and the agr group and the antibody level to different virulence factors, such as cell wall constituent (teichoic acid), exotoxins (alpha-toxin), and superantigens (TST and SSS) (Table 2). The immune response against alpha-toxin was related both to bacterial factors based on typing groups (agr and PFGE), and to TST based on gene-occurrence (tst). A correlation between antibody response to teichoic acid and SSS based on typing groups was also seen in Table 2.

In conclusion, the antibody response varied among both patients and antigens. Patients with collagenosis showed a lower response and patients with a fatal outcome had lower initial levels of antibodies. A relationship between antibody levels and the nature of the infecting [START_REF] Colque-Navarro | Antibody response in Staphylococcus aureus septicaemiaa prospective study[END_REF] Number of patients that did not present a high/low level at presentation and that belong to the respective clinical outcome group [START_REF] Bremell | Histopathological and Serological Progression of experimental Staphylococcus aureus Arthritis[END_REF] Relative risk for a patient with high/low level of antibodies at presentation to develop the respective clinical outcome, i.e. the quotient between the percent positive [START_REF] Chang | Infection with vancomycinresistant Staphylococcus aureus containing the vanA resistance gene[END_REF] and the percent negative [START_REF] Colque-Navarro | Antibody response in Staphylococcus aureus septicaemiaa prospective study[END_REF] , plus the 95 % confidential interval

Fig1Figure 1 .

 1 Fig1

Figure 2A .

 2A Figure

Figure 2B .

 2B Figure 2B. Percent patients that shows an antibody response to various antigens. Bars represent the percentage of patients showing decrease of levels (D), rise of levels between any pair of samples (R), high level at any sample occasion (H), positive serology i.e. high and/or rise and /or decrease in antibody levels achieved at any of the previous reactions.(PS).

Figure 3 .

 3 Figure 3. Antibody levels against four different antigens in patients with and without collagenosis. A: patients with collagenosis B: patients without collagenosis Symbols as in Figure 1.

  p<0.001, Chi-square L = Low = low first level, sample drawn 0-14 days within start of infection, see M&M for definition H = High = any high level, value over 95 th percentile among controls PS = Positive serology = either high, increase or decrease (increase = 50%, decrease = 50%)

Table 2 . Antibody level to S. aureus in relation to agr-group and PFGE typing group

 2 . 4 antigens, 3 agr-groups, 2 PFGE groups shown.

	Antigen	Antibody level	All	agr 1	agr 2	agr 3	PFGE 1	PFGE 2
			patients
			L,H n=96	L,H n=36	L,H n=23	L,H n=32	L,H n=21	L,H n=23PS
			PS n=71	PS n=29	PS n=14	PS n=23	PS n=16	n=18
			(%)	(%)	(%)	(%)	(%)	(%)
	Teichoic acid	Low	10	6	9	16	10	13
		High	24	22	22	28	33	9
		Pos. serology	61	45*	71	78*	88*	28**
	Alphatoxin	Low	21	11	4*	44**	43*	22
		High	50	61	61	31*	24*	48
		Pos. serology	70	72	86	61	50	67
	TST	Low	25	19	30	25	14	26
		High	13	6	9	25*	33*	4*
		Pos.serology	51	34*	71	61	75*	28*
	SSS	Low	40	53*	22*	41
		High	12	11	13	9
		Pos. serology	29	34	29	22

Table 3 . The initial antibody levels presented as Relative Risk for different clinical outcomes.

 3 Five antigens are shown. Number of patients with high/low levels of antibodies at presentation 2 Number of patients that did not present high/low levels at presentation 3 Number of patients with a high/low level at presentation that belong to the respective clinical outcome group

			All			28 days mortality		Severe sepsis		Compl. bacteremia
			patients
			n = 96			n = 10		n = 28				n = 32
	Antigen	Ab	Yes 1 No 2 Pos 3 Neg 4 RR 5 (95% CI) Pos Neg RR (95%) CI Pos Neg	RR (95% CI)
		level
	TA	High	15	81	0	10	-	4	24	0.9		27	1.0
		Low	9	87	3	7	4.1 (1.3-13.3)*	4	24	1.6		26	2.2 (1.3-3.9)
	AT	High	33	63	2	8	0.5	12	16	1.4	11	21	1.0
		Low	21	75	3	7	1.5	4	24	0.6	10	22	1.6
	Lipase	High	24	72	1	9	0.3	6	22	0.8		26	0.7
		Low	13	83	4	6	4.3 (1.3-13.1)*	4	24	1.1		24	2.1 (1.2-3.7)*
	SEA	High	7	89	1	9	1.4	2	26	1.0		29	1.3
		Low	28	68	6	4	3.6 (1.1-11.9)*	9	19	1.2		24	0.8
	SSS	High	7	89	0	10	-	2	26	1.0		29	1.3
		Low	39	57	9	1	13.2 (1.7-	15	13	1.7	12	20	0.9
							99.7)*
	Any of	High	61	35	3	7	0.2 (0.1-0.9)*	17	11	0.9	20	12	1.0
	8 antigens	Low	71	24	9	1	3.0	28	8	0.8	25	7	1.2
	*) p < 0.05
	1

Table 4 .

 4 Antibody levels in relation to age. Four antigens are shown. Chi-square, p<0.05 L= Low= low first level, sample drawn 0-14 days within start of infection, see M&M for definition H= High= any high level, value over 95 th percentile among controls I= Increase= any increase 50% D= Decrease= any decrease 50% PS= Positive serology= either high, increase or decrease

	Antigen	Antibody levels	All patients	Age < 65y	Age > 65 y
			L, H n=96	L, H n=45	L, H n=51
			I, D, PS n=71	I, D, PS n=34	I, D, PS n=37
			(%)	(%)	(%)
	Lipase	Low	14	13	14
		High	53	58	49
		Increase	59	59	60
		Diminish	37	50*	24*
		Pos serology	94	97	92
	TST	Low	26	24	28
		High	12	22*	4*
		Increase	44	62*	27*
		Diminish	6	9	3
		Pos serology	51	71*	32*
	SEA	Low	29	24	33
		High	16	24*	8*
		Increase	31	50*	14*
		Diminish	14	12	16
		Pos serology	48	62*	35*
	SSS	Low	41	29*	51*
		High	12	18	6
		Increase	14	21	8
		Diminish	4	9	0
		Pos serology	28	44*	14*

*


Gregory Wegmann
email: gregory.wegmann@u-bourgogne.fr

Activity-based Management in France: A focus on the information systems department of a bank

Keywords: Activity based costing, activity-based management, case study, bank I

The aim of the paper is to describe the Activity-based Costing and Management methods applied in France. For that purpose, we use a literature review and a case study. In a first time, we analyse the origins of the methods and their diffusion. Then we present the French situation. Finally, we propose a case study that takes place in a French bank. Our paper shows that the ABC and ABM methods are as developed in France as in the Anglo-Saxon countries and that the methods are strategically oriented.

INTRODUCTION

Traditional management accounting practices have been under attack for their failure to provide detailed and timely information [START_REF] Cooper | The Design of Cost Management Systems: Text, Cases and Readings[END_REF][START_REF] Gosselin | The effect of strategy and organizational structure on the adoption and implementation of activity-based costing[END_REF][START_REF] Kaplan | The evolution of management accounting[END_REF][START_REF] Maiga | Balanced scorecard, activity-based costing and company performance: An empirical analysis[END_REF]. Since the work of [START_REF] Johnson | Relevance Lost: The Rise and Fall of Management Accounting Systems[END_REF] on the "Relevance Lost" of management accounting practices, the Anglo-Saxon scholars have been very dynamic about the study of the diffusion of cost and management accounting innovations [START_REF] Anderson | The Impact of Contextual and Process Factors on the Evaluation of Activity-Based Costing Systems[END_REF][START_REF] Chenhall | The relationship between strategic priorities, management techniques and management accounting: An empirical investigation using a systems approach[END_REF][START_REF] Cooper | The Design of Cost Management Systems: Text, Cases and Readings[END_REF][START_REF] Gosselin | The effect of strategy and organizational structure on the adoption and implementation of activity-based costing[END_REF][START_REF] Johnson | Relevance Regained: From Top-Down Control to Bottom-up Empowerment[END_REF]. Organizations like the Cam-i (Consortium of Advanced Management, International: http://www.cam-i.org), the IMA (Institute of Management Accountants: http://www.imanet.org) and the Harvard Business School support the investigations about management accounting innovations. The ABC method appeared in this context.

The ABC method was designed in the United-States during the 80's [START_REF] Cooper | Measure Costs Right: Make the Right Decisions[END_REF]. It is a refined cost system which enables classifying more costs as direct, to expend the number of indirect-cost pools and to identify cost drivers. ABC favors better cost allocation using smaller cost pools called activities. Using cost drivers, the costs of these activities are the basis for assigning costs to other cost objects such as products or services. The Activity-based Management (ABM) represents a way of managing a firm with activities using the results of the ABC technic. Practically, there is a continuum between these two methods in a firm using them.

II. THE ABC/ABM METHODS IN FRANCE

A. The diffusion of ABC in the western countries

ABC was initially popularized in the USA in the mid-1980s [START_REF] Jones | The ABC bandwagon and the juggernaut of modernity[END_REF]. It was then diffused gradually in many other western countries throughout the 1990s (Bjornenak, 1997; [START_REF] Malmi | Activity-based costing diffusion across organizations: an exploratory empirical analysis of Finnish firms[END_REF]. We can say nowadays that it is a widely developed method in the western countries. But differences in its diffusion remain strong.

U.K. Australian and Scandinavian firms followed the ABC adoption in the U.S. in its early days without too much gap in the implementation time frame. Based on a questionnaire survey of food companies in the U.S. and the Netherlands, [START_REF] Groot | Activity-Based Costing in U.S. and Dutch Food Companies[END_REF] finds no significant difference in the adoption rates among the firms in the two countries. In the U.S., [START_REF] Green | Accounting Innovations: A Cross-Sectional Survey of Manufacturing Firms[END_REF] find that 45% of the firms surveyed use, to some extent at least, an ABC system. In the UK, the percentage of firms reported to have considered ABC varies between 32% [START_REF] Bright | The Deployment of Costing Techniques and Practices: A UK Study[END_REF], 37.6% [START_REF] Drury | A Survey of Management Accounting Practices in UK Manufacturing Companies[END_REF], and 48% [START_REF] Innes | ABC: A Survey of CIMA Members[END_REF]. However, when it comes to implementation, lower levels are reported. Different reasons were provided by researchers as to why companies may consider ABC system but end up with a decision not to implement it. [START_REF] Bright | The Deployment of Costing Techniques and Practices: A UK Study[END_REF] suggest that the most important barriers to the introduction of the ABC system were the cost of change, the lack of relevant skills, and the quality of existing supporting data/systems. The major problems associated with the introduction of ABC system have been enumerated as follow [START_REF] Green | Accounting Innovations: A Cross-Sectional Survey of Manufacturing Firms[END_REF]: the increased amount of detailed information needed by the new system, the increased paperwork, the difficulty in cost driver identification, and the insufficient support by top management.

In Japan [START_REF] Lee | Activity-based costing and Japanese cost management techniques: A comparison[END_REF], firms are quite pessimistic about ABC, discounting the role and utility substantially and using standard costing systems for costing purposes and relying on non-financial measures for strategic cost management (while ABC is more positive on the role and utility in strategic decision-making activities).

In European countries (except Great Britain), the gap in the implementation time frame was more important with a lower degree of diffusion.

As described by [START_REF] Bright | The Deployment of Costing Techniques and Practices: A UK Study[END_REF], firms use cost management mainly to:  Cost control.  Fix prices  Choose the investments.  Manage performance.

Several inquiries find the same results [START_REF] Mills | Pricing decisions in UK manufacturing and service companies[END_REF] in Great-Britain, [START_REF] Govindarajan | How Firms Use Cost Data in Price Decisions[END_REF] in the U.S., Ask and Ax (1992) in Sweden, and [START_REF] Yoshikawa | Japanese Management Accounting: Comparative Survey[END_REF] in Japan.

But some differences between countries can be put in evidence. In France, cost techniques are traditionally used to fix the selling prices, then to reduce the costs. [START_REF] Bescos | La comptabilité par activités et la gestion des activités : comparaison entre le Canada et la France[END_REF] explain that French techniques to fix selling prices are less market oriented than Anglo-Saxon ones where the customer profitability analysis is essential.

B. The impact of cultural differences

We have to take into account the cultural dimension concerning the management accounting tools diffusion. An important fact is that the Management Control is built on a North-American reference grounded on strong hypotheses about the representation of the firm and motivations of employees and managers' role. It fits more with a contractual type of management. It suggests a disciplinary approach (Agency and Transaction Costs theories) where the objectives of the management control activities are [START_REF] Jensen | Specific and General Knowledge, and Organizational Structure[END_REF][START_REF] Brickley | Managerial Economics and Organizational Architecture[END_REF]):

 To reduce conflicts and provide control.  To tie the strategy to the resources allocation.  And to facilitate the firm's internal coherence.

The situation is clearly different in countries like France, Germany or Northern countries of Europe where the cultural features are different [START_REF] Hofstede | The interaction between national and organizational value system[END_REF]. For instance, French and German managers see the checking behind control, while the Anglo-Saxons see steering there. In the French tradition, management accounting is mainly used to identify the cost of a product, an activity or a process whereas in the North American approach, Management accounting is used in a cybernetic process, by which the standards are compared with the real data and the deviations are identified and decomposed (variances analyses). French tended to calculate the prices starting from the costs, whereas the Americans start more readily from the principle according to which the prices result from the market. Firms from Northern countries of Europe (Sweeden, Danemark …) are more sensitive to knowledge-based approach of management (cf. Argyris and Schön, 1978: Organizational Learning Theory) where the participative approaches are favored. In this context, the value creation is the result of an increase of resources (Resource-based View approach, Penrose, 1959) and human competencies (Core-Competencies theory, [START_REF] Hamel | The Core Competence of the Corporation[END_REF].

How to allocate the indirect costs was the major problem for French management accounting pioneers (and German ones). This problem led them to build an accounting technique very similar to Activity-based Costing (method of the homogeneous sections).

C. The diffusion of ABC/ABM in France

The rate of innovation has been slowed in France by the existence of a legislation concerning management accounting until 1999. Today, the situation is quite similar as in the other European countries.

The first works on ABC date back to the late 1980s [START_REF] Lorino | L'économiste et le manager (The economist and the manager)[END_REF]. Mevellec (1991) and [START_REF] Lebas | Comptabilité analytique basée sur les activités, analyse et gestion des activités (Management accounting based on activities, analysis et management of activities)[END_REF] had a first contact with ABC during their trip to the USA in the mid-1980s. Lorino became president of the Cost Management System group for CAM-I Europe and promoted the ABC method (1989,1991).

In France, like in the U.S., ABC was therefore problematized as a remedy for the crisis of management accounting. At the beginning, French scholars dedicated their works to the technical aspects of the method (architecture of the system, calculations and cost driver concept). [START_REF] Bescos | Le Management de la Performance (The Performance Management)[END_REF] were the first scholars who reported implementations in French companies.

ABC faced rapidly a controversy in France. It concerned the fact that some specialists contest its innovative character in comparison with an older French method called the "Sections Homogenes" (the homogenous sections). As explains Bouquin (1996), when implemented correctly, there is no difference between ABC and the Sections Homogenes. The problem is that the French method is frequently oversimplified.

Several studies are dedicated to ABC/ABM diffusion in France: De La Villarmois and Tondeur (1996), Nikitin (2000), [START_REF] Bescos | La comptabilité par activités et la gestion des activités : comparaison entre le Canada et la France[END_REF], [START_REF] Alcouffe | La diffusion et l'adoption des innovations managériales en comptabilité et contrôle de gestion : le cas de l'ABC en France[END_REF], [START_REF] Godowski | La dynamique d'assimilation des approches par activités dans le domaine bancaire (The assimilation process of the ABC approaches in the Banking system)[END_REF] and [START_REF] Rahmouni | La mise en oeuvre de la comptabilité par activités dans les entreprises françaises : caractéristiques et facteurs d'adoption et de succès (the settling of the ABC method in the French firms: features and adoption and success variables)[END_REF]. [START_REF] Bescos | La comptabilité par activités et la gestion des activités : comparaison entre le Canada et la France[END_REF] find a rate of adoption of 23%, Alcouffe a rate of 16% whereas [START_REF] Bescos | La comptabilité par activités et la gestion des activités : comparaison entre le Canada et la France[END_REF] find an equivalent level of adoption between Canada (22.6%) and France (23%) (Japan: 7%). French managers express a good opinion on ABC/ABM methods, thanks to professional journals. But they frequently hesitate to entirely adopt the method. They prefer limited experiments. Alcouffe (2004) used the « innovations diffusion theory » (Roger, 1983(Roger, , 1995) ) to the subject of ABC/ABM diffusion. [START_REF] Godowski | La dynamique d'assimilation des approches par activités dans le domaine bancaire (The assimilation process of the ABC approaches in the Banking system)[END_REF] studied the ABC diffusion in the French banking system.

A more recent inquiry (see table 1, Rahmouni, 2008), find higher rate of adoption: 33.8% implemented and 18.2% in progress. Now, the level of diffusion in France seems as important as in the Anglo-Saxon countries. It could be even more important than for instance in Ireland and New Zealand (p. 226).

More precisely, the inquiry of Rahmouni (p. 227) reports that 30.2% of the firms of services use ABC, whereas this is the case for 39.1% of the industrial firms. Concerning the firms of services, 62.5% of the banks and insurances companies use ABC/ABM. About the firms that have the project to implement ABC/ABM, 23.2% of them are delivering services whereas only 8.7% are industrial ones; which means that the future of the ABC method in France concerns more specifically the activities of services. Maybe it could be explained by the high level of competition in those sectors in such a country like France. In most of the cases (82%), the ABC method covers all the processes of the firms. The first objective of the method is to calculate commercial costs and the customers' profitabilities, than the administrative (73%), research and development (64%) and information systems costs (59%).

These results show that it is quite interesting to describe a French experience that takes place in the information systems department of a bank.

III. A STRATEGIC APPROACH OF THE ABC/ABM METHODS

Looking for management accounting methods which could clarify the decision making process, Johnson and Kaplan suggest: First, to analyze more deeply the organization activities and processes and second, to link together the strategic and the operational management. The ABC method was conceived at first to correct misleading overhead allocations. It was a response to the inaccurate standard costing American methods. But several scholars, like [START_REF] Lebas | Why ABC? Accounting Based on Causality Rather than Activity-Based Costing[END_REF] in France explain that rapidly, the ABC method has gained managerial (ABM, Activity based Management) and strategic dimensions [START_REF] Jones | The ABC bandwagon and the juggernaut of modernity[END_REF]. Today, the ABC/ABM systems follow three objectives:

 To improve the cost allocation process.  To improve the measure of performances.  To better manage processes and strategies.

To explain the strategic dimension of the ABC/ABM methods, it is important to understand the importance of the cost drivers' concept. Porter (1985, p. 63) was one of the first to use this concept. He explained that the cost drivers are the structural determinants of the costs of the organizational activities. [START_REF] Riley | Competitive cost based investment strategies for industrial companies[END_REF] and [START_REF] Shank | Strategic Cost Analysis: The Evolution from Managerial to Strategic Accounting[END_REF] developed a typology distinguishing two categories of cost drivers:

 "Structural" drivers (the strategic choices concerning the economic structure of the firm).  "Executional" drivers (concerning operational activities). Shank and Govindarajan explained that the cost drivers are keys success factors that management accounting sets along the firm's value chain. They have developed an operational model with the definition of Key Success Factors, determined in using a competitive analysis of the environment and an analysis of the internal processes of the company, with the help of the ABC method. They explained that the ABC method is able to put in evidence these cost drivers. In that way, the cost drivers are able to explain the costs consumption and to describe the value chain, integrating the customers and suppliers dimensions in the cost allocation system. This approach materializes the link between strategic and operational management. Now, in the western countries, the ABC/ABM models are based on a process approach of management accounting. In this context, the company is described as a network of horizontal, flat and transverse structures where the activities are organized according to market imperatives. Then, the ABC/ABM methods represent a competencies-based tool because there is a significant relationship between the processes and the competencies of an organization.

In France, ABC has also been perceived by most of the scholars as a management tool, referring to the Activitybased Management. This approach contains two dimensions: an organizational one, to model another way of the functioning of organizations, and a strategic one, to link strategy to operation management. One of the first French books about ABC [START_REF] Lorino | Le pilotage stratégique des coûts (Strategic Cost Management)[END_REF] suggests using ABC as a way to link strategy to operational management. [START_REF] Chauvey | Les apports de l'ABC à l'analyse stratégique : les enseignements d'une recherche-intervention (Contributions of the ABC method to the strategic analysis: Learnings from a research-action study)[END_REF]

IV. ILLUSTRATION IN A FRENCH BANK

A. Case description

The ABC/ABM project of the Bank X began in 2004-2005. The purpose was to strengthen the cost allocation process so that we could assign relevant costs for customers and services. For the chief executive officer of the group, the ABC/ABM project is a priority. The department "Management Accounting and Information Systems Projects" is in charge of the project. Moreover, the topmanagement is strongly involved in the project and wants fast results. About six employees work for it with the help of a consultant. Let us precise that the bank X delivers banking services to big customers like "Carrefour" so that it needs a refined management accounting system that enables to calculate the cost of the services delivered to this company. The computing costs are a main part of the value of these services. This is the reason why the project group has to adapt the ABC method to the specificities of computing activities in a banking context.

At the end of 2008, a main task of the project group is to differentiate the types of credits. Because of a diversified credits offer, the analytical system to build needs to be quite refined. The types of the resources consumed are more diversified and a "time driver" is not enough to explain the costs causality. Moreover, several activities are subcontracted so that we need an interorganizational approach to construct the ABC model.

The figure 1 describes the ABC process applied to the computing services of the bank X. The figure 2 presents a map of the computing activities of this bank. Costs of the resources are allocated to the computing activities (operational, support, projects, …) thanks to the resources drivers (time consumed, m², quantities, types of orders, …) Costs of activities are then allocated to the types of computing services thanks to activities drivers (mainframe power, specificities of the proposal, …), these services consuming the activities. They are finally allocated to the customers, service per service. Recurrent activities consume about 55% of the total of resources.

The process described leads to full costing by type of services, customers, geographic areas and countries. We can calculate for instance a cost for a service in progress, for a service ended, for saving files or covering costs. The main banking processes are modeled such as the credit process, the risk management process, etc.

The project group did some statistical tests to evaluate the degree homogeneity of the activities costs and to correlate the cost drivers so that the models would be more accurate.

The last step of the project occurred from June 2009 until the end of the year 2010. At this time, the group project leader was able to present an income statement by service/customer/country built from the ABC architecture. Since July 2009, the main customers have been concerned so that a costs interorganizational investigation could be developed. We observe in our case study that the customers and processes dimensions are very important. We put in evidence a strategic orientation of the ABC method. Concretely, the managers of the bank studied have used the results of the method to adjust the prices. Controllers could calculate costs per credit and per customer so that selling managers decide the relevant price for the delivered services. To conclude, we can say the ABC/ABM system of the bank X represents a strategic management accounting tool. The management accounting system of the bank X is also quite refined because it appears in an environment where processes are immaterial and costs less homogeneous than in an industrial one.

For a future research, we would like to observe ABC experiences in Asia.

  described in the same way the strategic potential of ABC. More recently, Alcouffe et al. (2010) have developed a typology of environmental cost drivers.

Figure 1 .

 1 Figure 1. ABC process applied to the computing services of Bank X.

Figure 2 .

 2 Figure 2. Map of the computing activities of bank X

TABLE I .

 I LEVELS OF DIFFUSION OF ABC IN FRANCE

	ABC system	Rahmouni (2008)	Bescos et al. (2002)
	In progress	33.3 %	23 %
	In project	18.2 %	23 %
	Not retained	48.5 %	54 %
	Total	100 % (66 French firms)	100 % (122 French
			firms)