Acta Clinica Belgica International Journal of Clinical and Laboratory Medicine
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
Joint Symposium - 24th April 2014 To cite this article: (2015) Joint Symposium - 24th April 2014, Acta Clinica Belgica, 70:sup2, S1S4, DOI: 10.1179/0001551215Z.000000000175 To link to this article: http://dx.doi.org/10.1179/0001551215Z.000000000175
Published online: 13 May 2015.
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Date: 25 March 2016, At: 16:51
Downloaded by [Gazi University] at 16:51 25 March 2016
Joint Symposium – 24th April 2014 Bridges Between Nephrology and Infectious Diseases
ß Acta Clinica Belgica 2015
DOI 10.1179/0001551215Z.000000000175
Acta Clinica Belgica
2015
VOL .
70
SUPPL
S2
S1
Abstract 1
Eculizumab for the treatment of atypical haemolytic uraemic syndrome: results from the largest prospective clinical trial to date in adults L.E. Weekers1, E.E. Minetti2, F. Fakhouri3, M. Hourmant4, J.M. Campistol5, S.R. Cataland6, M. Espinosa7, A.O. Gaber8, J. Menne9, F. Provot10, E. Rondeau11, P. Ruggenenti12, M. Ogawa13, C.L. Bedrosian13, C.M. Legendre14 1
University of Lie`ge Hospital, Belgium, 2Careggi University Hospital, Florence, Italy, 3CHU de Nantes, France, Institut d’ImmunoTransplantation Urologie et Nephrologie, Nantes, France, 5Servicio de Nefrologı´a, Barcelona, Spain, 6Ohio State University College of Medicine, Columbus, OH, USA, 7Hospital Universitario Reina Sofı´a, Co´rdoba, Spain, 8Methodist Hospital, Houston, TX, USA, 9Hannover Medical School, Germany, 10CHU Lille, France, 11Hoˆpital Tenon, Paris, France, 12IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy, 13 Alexion Pharmaceuticals Inc, Cheshire, CT, USA, 14L’Universite´ Paris Descartes and Hoˆpital Necker, Paris, France
Downloaded by [Gazi University] at 16:51 25 March 2016
4
Objective: Eculizumab is a terminal complement inhibitor approved for atypical haemolytic uraemic syndrome (aHUS), a life-threatening condition that causes systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Patients (pts) should be vaccinated against Neisseria meningitidis before treatment. In prior prospective studies of 37 pts with aHUS no meningococcal infections had been detected. Here, we report the results of the largest prospective trial conducted to date in adults with aHUS. Methods: Open-label, prospective, single-arm study in adults (i18 years) with aHUS. Eculizumab was administered at 900 mg/week for 4 weeks, 1200 mg in week 5 and 1200 mg every 2 weeks thereafter. The primary endpoint was proportion of pts with complete TMA response at 26 weeks (platelet and LDH normalisation and v25% increase in serum creatinine from baseline). Results: Forty-one pts were treated with eculizumab (mean age 40.3 years, 68% female) and 38 (93%) completed 26 weeks treatment. By 26 weeks, 30 pts (73%) achieved the primary endpoint, complete TMA response, 36/41 (88%) achieved haematologic normalisation (platelet and LDH normalisation), and eGFR improved by mean (SD) 29.3 mL/min/1.73 m2. Of 24 pts on dialysis at baseline, 20 (83%) were able to stop dialysis during the study (five within 3 weeks prior to first dose of eculizumab). Most adverse events were mild or moderate. Two pts (both female, aged 24 and 29 years) had meningococcal infections; both recovered with antibiotic treatment (Table 1). Conclusion: Eculizumab improved outcomes in pts with aHUS. There were no new safety concerns. Meningococcal infections remain the main risk of a treatment with eculizumab. The two meningococcal infections observed in this trial were the only ones among a total of 100 pts treated in the prospective trials conducted to date.
Table 1 Meningococcal infection in a HUS patients (pts) treated with eculizumab.
Vaccine Prophylactic antibiotics? Adverse event Eculizumab discontinued? Time to recovery (days) a
S2
Patient 1
Patient 2
Polysaccharide quadrivalent vaccine No Meningococcal sepsis, N. menigitidis serogroup B No 8
MenveoH No Meningococcal meningitis, N. menigitidis serogroup unknown Yesa 21
Dialysis started after eculizumab discontinuation.
Acta Clinica Belgica
2015
VOL .
70
SUPPL .
S2
Abstract 2
Invasive aspergillosis after kidney transplantation: a monocentric retrospective experience L. Heylen1, J. Maertens2, B. Bammens1, K. Claes1, P. Evenepoel1, B. Meijers1, M. Naesens1, D. Kuypers1, B. Sprangers1 1
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium, Department of Haematology, University Hospitals Leuven, Leuven, Belgium
Downloaded by [Gazi University] at 16:51 25 March 2016
2
Objective: Transplant recipients are among the most significant subgroups of immunosuppressed hosts at risk for invasive aspergillosis (IA), explaining 9.3–16.9% of all deaths in the first year after transplantation. Despite the relatively lower overall incidence in kidney transplantation compared to other organ transplant recipients, mortality remains unacceptably high. Studies regarding IA after transplantation mainly focussed on solid organ transplantation in general. Methods: We reviewed retrospectively the epidemiology, clinical manifestations and outcome of IA in kidney transplant recipients between 1995 and 2012 at the University Hospital Leuven. Results: Forty cases of IA after kidney transplantation were identified between 1995 and 2012. Mean recipient age at transplantation was 58 years. Twenty-three recipients were male (58%). Seven (18%) had a chronic lung disease, and 17 (43%) had diabetes mellitus at the time of infection. Median time between transplantation and diagnosis of IA was 137 days, with the highest incidence in the first 3 months after transplantation. In 27 recipients (68%) a predisposing condition could be identified: the administration of high dosed immunosuppressive drugs (for acute rejection, relapse of the underlying renal disease or other) in 13 patients (33%), long lasting neutropaenia in 3 (8%), the combination of both neutropaenia and administration of additional immunosuppressive drugs in 2 (5%), post-transplant lymphoproliferative disorder in 2 (5%) and hospitalisation at the intensive care unit in 6 (15%). The diagnosis of IA was probable in 23 (58%) recipients and proven in 17 (43%). In 5 recipients (13%) the infection was disseminated. From the recipients with a localised infection (35), 30 had invasive pulmonary aspergillosis, 4 had invasive bronchial aspergillosis and 1 had a cerebral abscess. From the 39 recipients with a respiratory infection, 11 out of 23 had a positive sputum culture, 16 out of 24 positive bronchial aspirate culture, 20 out of 31 positive bronchoalveolar lavage (BAL) culture and 0 out of 6 had a positive pleural fluid culture. 11 out of 31 recipients showed positivity of galactomannan antigen in the serum and 14 out of 15 in the BAL fluid. Microscopic evaluation of sputum or bronchial aspirate revealed Aspergillus in 2 out of 14 recipients. Regarding all cases, galactomannan antigen in the serum showed positivity in 11 out of 32 recipients (34%). Invasive aspergillosis had an unfavourable course, requiring admission at the intensive care unit in 28 patients (70%). Twenty recipients died (50%) and in 2 recipients the infection and therapy evoked transplant failure (5%). Discussion: Similar to other cohort studies, invasive aspergillosis after kidney transplantation was associated with a high case-fatality rate in our series. Although risk factors for IA after kidney transplantation are abundant, the incidence of IA after kidney transplantation is low, making it at this moment impossible to determine the risk of IA for an individual patient and direct antifungal prophylaxis towards a subset of recipients. Tools are needed to identify the transplant recipients with susceptibility to IA.
Acta Clinica Belgica
2015
VOL .
70
SUPPL .
S2
S3
Abstract 3
Active S. aureus surveillance in haemodialysis patients: results of a single hospital pilot point prevalence study L. Coucke1, C. Verfaillie1, J. Van Acker1, M. De Clippele2, J. Donck2, A-M. Van den Abeele1 1
Department of Clinical Microbiology, Laboratory Medicine, AZ Sint-Lucas Ghent, Belgium, 2Nephrology Department, AZ Sint-Lucas Ghent, Belgium
Downloaded by [Gazi University] at 16:51 25 March 2016
Objective: S. aureus (SA) is the primary pathogen involved in infectious complications of HD patients. Nasal colonisation usually precedes staphylococcal infections. S. aureus related blood stream infections (BSI) account for up to 20% mortality in HD patients. Regular surveillance for SA nasal carriage followed by decolonisation is a validated strategy to reduce infection rate and mortality. Despite its demonstrated efficacy, this practice is not widespread in Belgian HD units. In order to evaluate the feasibility of regular surveillance and to assess SA prevalence, a pilot point-prevalence survey (PPS) to determine the colonisation rate of HD patients with MSSA and methicillin resistant S. aureus (MRSA) was set up. Methods: One-hundred and fifty-four patients (mean age 70, range 27–95) from three separate dialysis units were screened: one in-hospital dialysis unit (n5107) and two outpatient dialysis centres (n547). Patients on home HD (n51) and peritoneal dialysis (n55) were excluded. Screening was performed during 1 week of the routine dialysis schedule. Separate swabs (ESwab, Copan, Brescia, Italy) were taken from the anterior nares, wounds and the insertion site of the dialysis catheter if present. For MSSA detection, the swabs were inoculated directly on a chromogenic SA plate (SaSelectTM medium, Bio-Rad Laboratories, Eke, Belgium). For MRSA isolation, 100 mL of ESwab Amies medium was diluted in tryptic soy broth (TSB) for overnight enrichment which was cultured subsequently on a selective chromogenic MRSA plate (BDTM BBL CHROMagar MRSA II, Becton-Dickinson, Erembodegem, Belgium). Suspected colonies were identified by gramme stain and matrix assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS). Definite confirmation of MRSA strains was obtained by mecA gene and nuc gene polymerase chain reaction. Results: Thirty-two patients were SA positive (21%), 2 were MRSA positive (1.3%). MSSA prevalence was higher in the outpatient dialysis centres (33 and 28%) than in the in-hospital dialysis unit (17%). Amongst 60 patients with a central line (39% of patients), 22% were SA nasal carriers. Of 15 patients sampled in one or multiple wounds, 3 were SA positive. None of the catheter insertion site swabs demonstrated SA. One patient with negative culture results was receiving MRSA decolonisation therapy. Conclusion and Discussion: Regular SA surveillance in the HD unit is feasible, provided that a sufficient number of trained staff is available to sample all patients. Timing of wound care can be adapted to the moment of sampling. A screening interval of 1–5 months is common in surveillance studies and enables identification of persistent carriers. For routine surveillance an interval of 4–5 months is achievable. Nasal MSSA prevalence in the study population equals the one in the general population (20%). In the US, a recent surveillance study in HD patients in 2011 showed a comparable SA nasal prevalence of 17%. This is in contrast to previous older studies, where SA prevalence rates of 32–57% were observed in HD patients. Current pilot PPS shows a low MRSA colonisation rate compared to MRSA prevalence in the total at risk population (4%) in our hospital. Over the last 30 years, MRSA has been a major focus of attention in infection prevention. Today, BSI in HD patients are mainly caused by MSSA. If a surveillance programme is introduced, MSSA as well as MRSA should be screened in all HD patients. Decolonisation trials in HD patients studied mainly intranasal mupirocin ointment, alone or combined with other topical or systemic agents. Few randomised controlled trials (RCT) have shown a clear long-term benefit in HD patients. Recolonisation is frequent, requiring maintenance therapy. With repeated mupirocin treatment, emergence of resistance is feared as well as selective pressure. Fucidin and chlorhexidine ointments are alternative topical decolonisation regimens that have not been compared yet with mupirocin in RCT for SA eradication.
S4
Acta Clinica Belgica
2015
VOL .
70
SUPPL .
S2
ISSN: 1784-3286 (Print) 2295-3337 (Online) Journal homepage: http://www.tandfonline.com/loi/yacb20
Joint Symposium - 24th April 2014 To cite this article: (2015) Joint Symposium - 24th April 2014, Acta Clinica Belgica, 70:sup2, S1S4, DOI: 10.1179/0001551215Z.000000000175 To link to this article: http://dx.doi.org/10.1179/0001551215Z.000000000175
Published online: 13 May 2015.
Submit your article to this journal
Article views: 25
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=yacb20 Download by: [Gazi University]
Date: 25 March 2016, At: 16:51
Downloaded by [Gazi University] at 16:51 25 March 2016
Joint Symposium – 24th April 2014 Bridges Between Nephrology and Infectious Diseases
ß Acta Clinica Belgica 2015
DOI 10.1179/0001551215Z.000000000175
Acta Clinica Belgica
2015
VOL .
70
SUPPL
S2
S1
Abstract 1
Eculizumab for the treatment of atypical haemolytic uraemic syndrome: results from the largest prospective clinical trial to date in adults L.E. Weekers1, E.E. Minetti2, F. Fakhouri3, M. Hourmant4, J.M. Campistol5, S.R. Cataland6, M. Espinosa7, A.O. Gaber8, J. Menne9, F. Provot10, E. Rondeau11, P. Ruggenenti12, M. Ogawa13, C.L. Bedrosian13, C.M. Legendre14 1
University of Lie`ge Hospital, Belgium, 2Careggi University Hospital, Florence, Italy, 3CHU de Nantes, France, Institut d’ImmunoTransplantation Urologie et Nephrologie, Nantes, France, 5Servicio de Nefrologı´a, Barcelona, Spain, 6Ohio State University College of Medicine, Columbus, OH, USA, 7Hospital Universitario Reina Sofı´a, Co´rdoba, Spain, 8Methodist Hospital, Houston, TX, USA, 9Hannover Medical School, Germany, 10CHU Lille, France, 11Hoˆpital Tenon, Paris, France, 12IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy, 13 Alexion Pharmaceuticals Inc, Cheshire, CT, USA, 14L’Universite´ Paris Descartes and Hoˆpital Necker, Paris, France
Downloaded by [Gazi University] at 16:51 25 March 2016
4
Objective: Eculizumab is a terminal complement inhibitor approved for atypical haemolytic uraemic syndrome (aHUS), a life-threatening condition that causes systemic thrombotic microangiopathy (TMA) and severe end-organ damage. Patients (pts) should be vaccinated against Neisseria meningitidis before treatment. In prior prospective studies of 37 pts with aHUS no meningococcal infections had been detected. Here, we report the results of the largest prospective trial conducted to date in adults with aHUS. Methods: Open-label, prospective, single-arm study in adults (i18 years) with aHUS. Eculizumab was administered at 900 mg/week for 4 weeks, 1200 mg in week 5 and 1200 mg every 2 weeks thereafter. The primary endpoint was proportion of pts with complete TMA response at 26 weeks (platelet and LDH normalisation and v25% increase in serum creatinine from baseline). Results: Forty-one pts were treated with eculizumab (mean age 40.3 years, 68% female) and 38 (93%) completed 26 weeks treatment. By 26 weeks, 30 pts (73%) achieved the primary endpoint, complete TMA response, 36/41 (88%) achieved haematologic normalisation (platelet and LDH normalisation), and eGFR improved by mean (SD) 29.3 mL/min/1.73 m2. Of 24 pts on dialysis at baseline, 20 (83%) were able to stop dialysis during the study (five within 3 weeks prior to first dose of eculizumab). Most adverse events were mild or moderate. Two pts (both female, aged 24 and 29 years) had meningococcal infections; both recovered with antibiotic treatment (Table 1). Conclusion: Eculizumab improved outcomes in pts with aHUS. There were no new safety concerns. Meningococcal infections remain the main risk of a treatment with eculizumab. The two meningococcal infections observed in this trial were the only ones among a total of 100 pts treated in the prospective trials conducted to date.
Table 1 Meningococcal infection in a HUS patients (pts) treated with eculizumab.
Vaccine Prophylactic antibiotics? Adverse event Eculizumab discontinued? Time to recovery (days) a
S2
Patient 1
Patient 2
Polysaccharide quadrivalent vaccine No Meningococcal sepsis, N. menigitidis serogroup B No 8
MenveoH No Meningococcal meningitis, N. menigitidis serogroup unknown Yesa 21
Dialysis started after eculizumab discontinuation.
Acta Clinica Belgica
2015
VOL .
70
SUPPL .
S2
Abstract 2
Invasive aspergillosis after kidney transplantation: a monocentric retrospective experience L. Heylen1, J. Maertens2, B. Bammens1, K. Claes1, P. Evenepoel1, B. Meijers1, M. Naesens1, D. Kuypers1, B. Sprangers1 1
Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Leuven, Belgium, Department of Haematology, University Hospitals Leuven, Leuven, Belgium
Downloaded by [Gazi University] at 16:51 25 March 2016
2
Objective: Transplant recipients are among the most significant subgroups of immunosuppressed hosts at risk for invasive aspergillosis (IA), explaining 9.3–16.9% of all deaths in the first year after transplantation. Despite the relatively lower overall incidence in kidney transplantation compared to other organ transplant recipients, mortality remains unacceptably high. Studies regarding IA after transplantation mainly focussed on solid organ transplantation in general. Methods: We reviewed retrospectively the epidemiology, clinical manifestations and outcome of IA in kidney transplant recipients between 1995 and 2012 at the University Hospital Leuven. Results: Forty cases of IA after kidney transplantation were identified between 1995 and 2012. Mean recipient age at transplantation was 58 years. Twenty-three recipients were male (58%). Seven (18%) had a chronic lung disease, and 17 (43%) had diabetes mellitus at the time of infection. Median time between transplantation and diagnosis of IA was 137 days, with the highest incidence in the first 3 months after transplantation. In 27 recipients (68%) a predisposing condition could be identified: the administration of high dosed immunosuppressive drugs (for acute rejection, relapse of the underlying renal disease or other) in 13 patients (33%), long lasting neutropaenia in 3 (8%), the combination of both neutropaenia and administration of additional immunosuppressive drugs in 2 (5%), post-transplant lymphoproliferative disorder in 2 (5%) and hospitalisation at the intensive care unit in 6 (15%). The diagnosis of IA was probable in 23 (58%) recipients and proven in 17 (43%). In 5 recipients (13%) the infection was disseminated. From the recipients with a localised infection (35), 30 had invasive pulmonary aspergillosis, 4 had invasive bronchial aspergillosis and 1 had a cerebral abscess. From the 39 recipients with a respiratory infection, 11 out of 23 had a positive sputum culture, 16 out of 24 positive bronchial aspirate culture, 20 out of 31 positive bronchoalveolar lavage (BAL) culture and 0 out of 6 had a positive pleural fluid culture. 11 out of 31 recipients showed positivity of galactomannan antigen in the serum and 14 out of 15 in the BAL fluid. Microscopic evaluation of sputum or bronchial aspirate revealed Aspergillus in 2 out of 14 recipients. Regarding all cases, galactomannan antigen in the serum showed positivity in 11 out of 32 recipients (34%). Invasive aspergillosis had an unfavourable course, requiring admission at the intensive care unit in 28 patients (70%). Twenty recipients died (50%) and in 2 recipients the infection and therapy evoked transplant failure (5%). Discussion: Similar to other cohort studies, invasive aspergillosis after kidney transplantation was associated with a high case-fatality rate in our series. Although risk factors for IA after kidney transplantation are abundant, the incidence of IA after kidney transplantation is low, making it at this moment impossible to determine the risk of IA for an individual patient and direct antifungal prophylaxis towards a subset of recipients. Tools are needed to identify the transplant recipients with susceptibility to IA.
Acta Clinica Belgica
2015
VOL .
70
SUPPL .
S2
S3
Abstract 3
Active S. aureus surveillance in haemodialysis patients: results of a single hospital pilot point prevalence study L. Coucke1, C. Verfaillie1, J. Van Acker1, M. De Clippele2, J. Donck2, A-M. Van den Abeele1 1
Department of Clinical Microbiology, Laboratory Medicine, AZ Sint-Lucas Ghent, Belgium, 2Nephrology Department, AZ Sint-Lucas Ghent, Belgium
Downloaded by [Gazi University] at 16:51 25 March 2016
Objective: S. aureus (SA) is the primary pathogen involved in infectious complications of HD patients. Nasal colonisation usually precedes staphylococcal infections. S. aureus related blood stream infections (BSI) account for up to 20% mortality in HD patients. Regular surveillance for SA nasal carriage followed by decolonisation is a validated strategy to reduce infection rate and mortality. Despite its demonstrated efficacy, this practice is not widespread in Belgian HD units. In order to evaluate the feasibility of regular surveillance and to assess SA prevalence, a pilot point-prevalence survey (PPS) to determine the colonisation rate of HD patients with MSSA and methicillin resistant S. aureus (MRSA) was set up. Methods: One-hundred and fifty-four patients (mean age 70, range 27–95) from three separate dialysis units were screened: one in-hospital dialysis unit (n5107) and two outpatient dialysis centres (n547). Patients on home HD (n51) and peritoneal dialysis (n55) were excluded. Screening was performed during 1 week of the routine dialysis schedule. Separate swabs (ESwab, Copan, Brescia, Italy) were taken from the anterior nares, wounds and the insertion site of the dialysis catheter if present. For MSSA detection, the swabs were inoculated directly on a chromogenic SA plate (SaSelectTM medium, Bio-Rad Laboratories, Eke, Belgium). For MRSA isolation, 100 mL of ESwab Amies medium was diluted in tryptic soy broth (TSB) for overnight enrichment which was cultured subsequently on a selective chromogenic MRSA plate (BDTM BBL CHROMagar MRSA II, Becton-Dickinson, Erembodegem, Belgium). Suspected colonies were identified by gramme stain and matrix assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI-TOF MS). Definite confirmation of MRSA strains was obtained by mecA gene and nuc gene polymerase chain reaction. Results: Thirty-two patients were SA positive (21%), 2 were MRSA positive (1.3%). MSSA prevalence was higher in the outpatient dialysis centres (33 and 28%) than in the in-hospital dialysis unit (17%). Amongst 60 patients with a central line (39% of patients), 22% were SA nasal carriers. Of 15 patients sampled in one or multiple wounds, 3 were SA positive. None of the catheter insertion site swabs demonstrated SA. One patient with negative culture results was receiving MRSA decolonisation therapy. Conclusion and Discussion: Regular SA surveillance in the HD unit is feasible, provided that a sufficient number of trained staff is available to sample all patients. Timing of wound care can be adapted to the moment of sampling. A screening interval of 1–5 months is common in surveillance studies and enables identification of persistent carriers. For routine surveillance an interval of 4–5 months is achievable. Nasal MSSA prevalence in the study population equals the one in the general population (20%). In the US, a recent surveillance study in HD patients in 2011 showed a comparable SA nasal prevalence of 17%. This is in contrast to previous older studies, where SA prevalence rates of 32–57% were observed in HD patients. Current pilot PPS shows a low MRSA colonisation rate compared to MRSA prevalence in the total at risk population (4%) in our hospital. Over the last 30 years, MRSA has been a major focus of attention in infection prevention. Today, BSI in HD patients are mainly caused by MSSA. If a surveillance programme is introduced, MSSA as well as MRSA should be screened in all HD patients. Decolonisation trials in HD patients studied mainly intranasal mupirocin ointment, alone or combined with other topical or systemic agents. Few randomised controlled trials (RCT) have shown a clear long-term benefit in HD patients. Recolonisation is frequent, requiring maintenance therapy. With repeated mupirocin treatment, emergence of resistance is feared as well as selective pressure. Fucidin and chlorhexidine ointments are alternative topical decolonisation regimens that have not been compared yet with mupirocin in RCT for SA eradication.
S4
Acta Clinica Belgica
2015
VOL .
70
SUPPL .
S2
