Leukemia & Lymphoma, January 2015; 56(1): 2 6 0 -2 6 2
informa
© 2014 In fo rm a UK, Ltd. ISSN: 1042-8194 p r i n t / 1029-2403 o n lin e
healthcare
DOI: 10.3109/10428194.2014.917637
LETTER TO THE EDITOR
Transplant related outcomes in patients with hematopoietic stem cell transplant with Clostridium difficile associated diarrhea Kari Neemann, Veenu Minhas, Fausto R. Loberiza & Alison Freifield Internal Medicine - Infectious Diseases, University o f Nebraska Medical Center, Omaha, NE, USA
Clostridium difficile is the leading cause of infectious diar rhea in hospitalized patients, and has been associated with significant morbidity and mortality [1,2]. Hematopoietic stem cell transplant (HSCT) recipients are particularly at risk for C. difficile associated diarrhea (CDAD) as a conse quence of cytotoxic chemotherapy that disrupts the enteric mucosal barrier, the wide use of prophylactic and empiric antibiotics and prolonged hospitalizations [3]. The incidence of CDAD in both allogeneic and autologous HSCT popula tions has been reported to be 4-18%, compared to 2.8% in general inpatient cohorts [4-12]. The impact of CDAD on underlying progression-free survival, non-relapse mortality and overall cancer mortality in patients with HSCT has not been clearly defined. Prior studies have shown conflicting results regarding oncologic outcomes, ranging from no effect on mortality to an increase in non-relapse mortality in those with either severe CDAD or CDAD and concomitant acute graft-versus-host disease (GHVD) [6,9,10]. The aim of the present study was to compare cancer-related transplant out comes between patients with and without CDAD in the first 100 days post-transplant. Additionally, we evaluated initial CDAD treatments as well as recurrence of CDAD in the first 100 post-transplant days. We retrospectively assessed 765 consecutive patients with autologous (n = 570) and allogeneic (n = 186) HSCT admit ted to our hospital from 1 January 2005 through 30 June 2011, after approval from our local Institutional Review Board. Underlying diseases requiring transplant included leuke mia (16.5%), Hodgkin (8.9%) and non-Hodgkin lymphoma (51.9%), myelodysplastic syndrome (3.0%) and multiple myeloma (19.7%). CDAD was defined as the constellation of compatible clinical history, diarrheal stool and positive stool testing for C. difficile toxin. C. difficile laboratory testing methodology varied over the study period. From January 2005 through June 2009 testing was performed via toxin A/B antigen by enzyme immunoassay (EIA) (C. difficile Tox A/B II; TechLab, Blacksburg, VA); from July 2009 through June 2011 detection of both the C. difficile toxin antigen A/B
and the common antigen (glutamate dehydrogenase) were required to signify disease (C. Diff Quik Chek Complete; TechLab). From September 2010 onward, any discordance between toxin and common antigen results by the EIA was resolved via polymerase chain reaction (PCR) for the toxin A/B gene (Illumigene C. difficile-, Meridian Bioscience, Cin cinnati, OH). The C. difficile isolates were not typed. Clinical cure of CDAD was defined if there was no documentation of recurrent symptoms or positive C. difficile assay in the medi cal record within 8 weeks of the initial episode. Recurrence was defined if diarrhea and assay positivity recurred within 8 weeks of the initial episode, provided that symptoms of C. difficile infection (CDI) from the earlier episode were com pletely resolved. Since all patients are followed carefully in the first 100 days post-transplant, recurrence of symptoms would be readily detected during review of the medical record. Since the isolates were not typed, it was not feasible to distinguish recurrence due to relapse (renewed symptoms from already present CDI) from recurrence due to reinfec tion [13]. Severity of CDAD could not be assessed as there was not consistent documentation of stool output volume in the medical record. Parameters analyzed included age, sex, Karnofsky performance status, hematopoietic cell transplant (HCT) comorbidity score, type of underlying malignancy, disease stage at transplant, transplant conditioning regimen, presence and duration of neutropenia defined as absolute neutrophil count (ANC) below 500 cells/mm3, antibiotic uti lization, specific antibiotic therapy for CDAD, recurrence of CDAD and transplant outcomes. Characteristics of the two cohorts were compared using Wilcoxon test or %2 test. Uni variate outcomes were estimated using cumulative incidence or Kaplan-Meier estimator. Multivariate Cox proportional hazards regression analysis was used to compare outcomes between the two cohorts utilizing CDAD as a time-dependent covariate while adjusting for other significant variables. CDAD was observed in 125 of 765 evaluated patients (16.5%). The overall incidence of CDAD was 16.7% (95 of 570 patients) and 16.1% (30 of 186 patients) in autologous and
Correspondence: Kari Neemann, University of Nebraska Medical Center, Internal Medicine - Infectious Diseases, 982162 Nebraska Medical Center, Omaha, NE 68198-2162, USA. E-mail: [email protected] Received 18 N ovem ber 2013; revised 14 April 2014; accepted 19 April 2014 260
Letter to the Editor
261
Figure 1. Initial and recurrent CDAD treatment. CDAD, Clostridium difficile associated disease; Auto, autologous; Alio, allogeneic; HSCT, hematopoietic stem cell transplant; M, metronidazole; V, vancomycin (oral); R, rifaximin; MaV, vancomycin (oral) added to therapy after initial single therapy with metronidazole.
allogeneic HSCT recipients, respectively. Of the 125 patients with CDAD in the first 100 days post-transplant, 114 (91.2%) had only a single episode of CDAD. Among those with one episode of CDAD (114 patients), 110 were initially treated with metronidazole, the currently recommended first-line therapy for mild to moderate CDAD [14]. Among the 110 recipients treated with metronidazole alone, 97 (88.2%) were successfully treated and had no recurrence of disease. Fail ure to improve with metronidazole prompted a switch to oral vancomycin in 13 patients (11.8%), all of whom responded. There were eight patients (6.4%) who experienced recur rence of their CDAD within 8 weeks of the initial episode. Of these, four were autologous HSCT recipients compared to four allogeneic recipients (4.2% vs. 13.3%; p = 0.08). Recur rences of CDAD disease were treated with metronidazole (orally) or vancomycin (orally) alone, or a combination of the two were used. Three autologous HSCT recipients (3.2%) had a second episode of CDAD which occurred more than 8 weeks from the initial episode (Figure 1). Outcomes from transplant were evaluated in relation to the occurrence of CDAD. On univariate analysis, the 100day and 1-year cumulative incidence of tumor relapse and non-relapse mortality in patients without and with CDAD showed no differences. At 100 days tumor relapse was 9.8% (95% confidence interval [Cl] 7.6-12.3) vs. 11.7% (95% Cl 6.7-18.2), p = 0.20, and at 1 year was 25% (95% Cl 20-30) vs. 26% (95% Cl 16-37), p = 0.89; while non-relapse mortal ity at 100 days was 3% (95% Cl 2-5) vs. 6% (95% Cl 2-11), p = 0.53, and at 1 year was 9% (95% Cl 7-12) vs. 14% (95% Cl 8-21), p = 0.21. Additionally, the probability of relapse-free survival and overall survival between patients without and with CDAD showed no differences; relapse-free survival at 100 days was 87.3% (95% Cl 84.5-89.7) vs. 83.2% (95% Cl 75.4-88.7), p = 0.16, and at 1 year was 72% (95% Cl 66-76) vs. 70% (95% Cl 57-80), p = 0.78; while overall survival at 100 days was 94.2% (95% Cl 92.1-95.8) vs. 92.0% (95% Cl 85.6-95.6), p = 0.36, and at 1 year was 85% (95% Cl 81-89) vs. 82% (95% Cl 71-90), p = 0.6. This lack of difference persisted when the two groups were stratified by type of transplant:
autologous vs. allogeneic. Given the multiple factors that can affect outcomes in these highly complex patients, a multi variate analysis was performed to evaluate for relapse-free survival, non-relapse mortality, relapse and overall mortality while adjusting for prognostic factors such as age, underly ing disease, disease stage at transplant and type of transplant (Table I). These analyses suggested that CDAD has no effect on HSCT outcomes (both autologous and allogeneic) in the first 100 days post-HSCT or at 1 year. There are several limitations to this study, including its retrospective design, single-center site and different test ing modalities used throughout the study period to detect CDAD. The C. difficile Tox A/B II assay utilized throughout the majority of the study period has a reported sensitivity of only 84.6%, the C. Diff Quik Chek sensitivity has been reported as 98.7% for the antigen and 87.8% for the toxin, and the highest sensitivity is reported with the Illumigene PCR at 95.2% [15-17]. The incidence of CDAD may have been underestimated. Lastly, the strains were not typed, and therefore the prevalence of the more virulent NAP1/BI/027 strain in the study population is unknown. However, this is one of the largest contemporary cohorts reported to evaluate the impact of CDAD on transplant outcomes. In conclusion, we have shown that CDAD continues to complicate the course of patients with HSCT, with increased incidence rates compared to that previously described in general inpatient cohorts. However, our data indicate that Table I. Multivariate analysis of cancer clinical outcomes adjusted for prognostic factors. Clostridium difficile infection, HR* (95% Cl) No Yes p-Value Relapse-free 1 1.16(0.86-1.56) 0.38 survival Non-relapse 1 1.19 (0.71-2.01) 0.51 mortality Relapse 1 1.16(0.90-1.50) 0.26 Overall mortality 1 1.21 (0.59-2.46) 0.6 Cl, confidence interval; HSCT, hematopoietic stem ceil transplant. ’ Hazard ratio (HR) within first 100 days post-HSCT.
262
K. Neemann e ta l.
most HSCT recipients with CDAD tolerate the disease fairly well, predominantly responding to treatment with metron idazole as first-line therapy. Recurrences occurred more often among allogeneic (13.3%) than autologous (4.2%) transplant recipients, perhaps because the latter are gener ally less profoundly immunosuppressed and for a briefer duration. Most importantly, in our population, transplantrelated outcomes in the first 100 days appear to be similar between HSCT recipients with or without CDAD. Therefore, most HSCT recipients with concomitant CDAD should be treated in accordance with published guidelines, beginning with metronidazole in most cases.
Potential conflict o f interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal. References [1] Hensgens MP, Goorhuis A, Dekkers OM, et al. All-cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a multicenter cohort study. Clin Infect Dis 2013;56:1108-1116. [2] Wenisch JM, Schmid D, Tucek G, et al. A prospective cohort study on hospital mortality due to Clostridium difficile infection. Infection 2012;40:479-484. [3] Anand A, Glatt AE. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 1993;17:109-113. [4] van Kraaij MG, Dekker AW, Verdonck LF, et al. Infectious gastro enteritis: an uncomm on cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients. Bone Marrow Transplant 2000;26:299-303. [5] Arango JI, Restrepo A, Schneider DL, et al. Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma. Bone Marrow Transplant 2006;37:517-521. [6] Dubberke ER, Reske KA, Srivastava A, et al. Clostridium difficileassociated disease in allogeneic hematopoietic stem-cell transplant
recipients: risk associations, protective associations, and outcomes. Clin Transplant 2010;24:192-198. [7] Chopra T, Chandrasekar P, Salimnia H, et al. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation. Clin Transplant 2011;25:E82-E87. [8] Willems L, Porcher R, Lafaurie M, et al. Clostridium difficile infection after allogeneic hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Biol Blood Marrow Transplant. 2012;18:1295-1301. [9] Alonso CD, Marr KA. Clostridium difficile infection among hematopoietic stem cell transplant recipients: beyond colitis. Curr Opin Infect Dis 2013;26:326-331. [10] Trifilio SM, Pi J, Mehta I. Changing epidemiology of Clostridium difficile-associated disease during stem cell transplantation. Biol Blood Marrow Transplant 2013; 19:405-409. [11] Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011;365:1693-1703. [12] Alonso CD, Treadway SB, Hanna DB, et al. Epidemiology and outcom es of Clostridium difficile infections in hem atopoietic stem cell transplant recipients. Clin Infect Dis 2012;54:1053-1063. [13] Debast SB, Bauer MP, Kuijper EJ et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): update of the treatment guidance docum ent for Clostridium difficile infection (CDI). Clin Microbiol Infect 2014;20(Suppl. 2):l-26. [14] Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55. [15] Snell H, Ramos M, Longo S, et al Perform ance of the TechLab C. DIFF CHEK-60 enzyme im m unoassay (ELA) in com bination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol 2004;42:4863-4865. [16] Quinn CD, Sefers SE, Babiker W, et al. C. Diff Quik Chek complete enzyme immunoassay provides a reliable first-line method for detection of Clostridium difficile in stool specimens. J Clin Microbiol 2010;48:603-605. [17] Wince JL, Elagin S, Kozak K, et al. Illumigene C. difficile: a novel new molecular approach for the detection of Clostridium difficile. Presented at the 110th General Meeting of the American Society for Microbiology, 23-27 May 2010, San Diego, CA: Poster Board Number 204.
Copyright of Leukemia & Lymphoma is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
informa
© 2014 In fo rm a UK, Ltd. ISSN: 1042-8194 p r i n t / 1029-2403 o n lin e
healthcare
DOI: 10.3109/10428194.2014.917637
LETTER TO THE EDITOR
Transplant related outcomes in patients with hematopoietic stem cell transplant with Clostridium difficile associated diarrhea Kari Neemann, Veenu Minhas, Fausto R. Loberiza & Alison Freifield Internal Medicine - Infectious Diseases, University o f Nebraska Medical Center, Omaha, NE, USA
Clostridium difficile is the leading cause of infectious diar rhea in hospitalized patients, and has been associated with significant morbidity and mortality [1,2]. Hematopoietic stem cell transplant (HSCT) recipients are particularly at risk for C. difficile associated diarrhea (CDAD) as a conse quence of cytotoxic chemotherapy that disrupts the enteric mucosal barrier, the wide use of prophylactic and empiric antibiotics and prolonged hospitalizations [3]. The incidence of CDAD in both allogeneic and autologous HSCT popula tions has been reported to be 4-18%, compared to 2.8% in general inpatient cohorts [4-12]. The impact of CDAD on underlying progression-free survival, non-relapse mortality and overall cancer mortality in patients with HSCT has not been clearly defined. Prior studies have shown conflicting results regarding oncologic outcomes, ranging from no effect on mortality to an increase in non-relapse mortality in those with either severe CDAD or CDAD and concomitant acute graft-versus-host disease (GHVD) [6,9,10]. The aim of the present study was to compare cancer-related transplant out comes between patients with and without CDAD in the first 100 days post-transplant. Additionally, we evaluated initial CDAD treatments as well as recurrence of CDAD in the first 100 post-transplant days. We retrospectively assessed 765 consecutive patients with autologous (n = 570) and allogeneic (n = 186) HSCT admit ted to our hospital from 1 January 2005 through 30 June 2011, after approval from our local Institutional Review Board. Underlying diseases requiring transplant included leuke mia (16.5%), Hodgkin (8.9%) and non-Hodgkin lymphoma (51.9%), myelodysplastic syndrome (3.0%) and multiple myeloma (19.7%). CDAD was defined as the constellation of compatible clinical history, diarrheal stool and positive stool testing for C. difficile toxin. C. difficile laboratory testing methodology varied over the study period. From January 2005 through June 2009 testing was performed via toxin A/B antigen by enzyme immunoassay (EIA) (C. difficile Tox A/B II; TechLab, Blacksburg, VA); from July 2009 through June 2011 detection of both the C. difficile toxin antigen A/B
and the common antigen (glutamate dehydrogenase) were required to signify disease (C. Diff Quik Chek Complete; TechLab). From September 2010 onward, any discordance between toxin and common antigen results by the EIA was resolved via polymerase chain reaction (PCR) for the toxin A/B gene (Illumigene C. difficile-, Meridian Bioscience, Cin cinnati, OH). The C. difficile isolates were not typed. Clinical cure of CDAD was defined if there was no documentation of recurrent symptoms or positive C. difficile assay in the medi cal record within 8 weeks of the initial episode. Recurrence was defined if diarrhea and assay positivity recurred within 8 weeks of the initial episode, provided that symptoms of C. difficile infection (CDI) from the earlier episode were com pletely resolved. Since all patients are followed carefully in the first 100 days post-transplant, recurrence of symptoms would be readily detected during review of the medical record. Since the isolates were not typed, it was not feasible to distinguish recurrence due to relapse (renewed symptoms from already present CDI) from recurrence due to reinfec tion [13]. Severity of CDAD could not be assessed as there was not consistent documentation of stool output volume in the medical record. Parameters analyzed included age, sex, Karnofsky performance status, hematopoietic cell transplant (HCT) comorbidity score, type of underlying malignancy, disease stage at transplant, transplant conditioning regimen, presence and duration of neutropenia defined as absolute neutrophil count (ANC) below 500 cells/mm3, antibiotic uti lization, specific antibiotic therapy for CDAD, recurrence of CDAD and transplant outcomes. Characteristics of the two cohorts were compared using Wilcoxon test or %2 test. Uni variate outcomes were estimated using cumulative incidence or Kaplan-Meier estimator. Multivariate Cox proportional hazards regression analysis was used to compare outcomes between the two cohorts utilizing CDAD as a time-dependent covariate while adjusting for other significant variables. CDAD was observed in 125 of 765 evaluated patients (16.5%). The overall incidence of CDAD was 16.7% (95 of 570 patients) and 16.1% (30 of 186 patients) in autologous and
Correspondence: Kari Neemann, University of Nebraska Medical Center, Internal Medicine - Infectious Diseases, 982162 Nebraska Medical Center, Omaha, NE 68198-2162, USA. E-mail: [email protected] Received 18 N ovem ber 2013; revised 14 April 2014; accepted 19 April 2014 260
Letter to the Editor
261
Figure 1. Initial and recurrent CDAD treatment. CDAD, Clostridium difficile associated disease; Auto, autologous; Alio, allogeneic; HSCT, hematopoietic stem cell transplant; M, metronidazole; V, vancomycin (oral); R, rifaximin; MaV, vancomycin (oral) added to therapy after initial single therapy with metronidazole.
allogeneic HSCT recipients, respectively. Of the 125 patients with CDAD in the first 100 days post-transplant, 114 (91.2%) had only a single episode of CDAD. Among those with one episode of CDAD (114 patients), 110 were initially treated with metronidazole, the currently recommended first-line therapy for mild to moderate CDAD [14]. Among the 110 recipients treated with metronidazole alone, 97 (88.2%) were successfully treated and had no recurrence of disease. Fail ure to improve with metronidazole prompted a switch to oral vancomycin in 13 patients (11.8%), all of whom responded. There were eight patients (6.4%) who experienced recur rence of their CDAD within 8 weeks of the initial episode. Of these, four were autologous HSCT recipients compared to four allogeneic recipients (4.2% vs. 13.3%; p = 0.08). Recur rences of CDAD disease were treated with metronidazole (orally) or vancomycin (orally) alone, or a combination of the two were used. Three autologous HSCT recipients (3.2%) had a second episode of CDAD which occurred more than 8 weeks from the initial episode (Figure 1). Outcomes from transplant were evaluated in relation to the occurrence of CDAD. On univariate analysis, the 100day and 1-year cumulative incidence of tumor relapse and non-relapse mortality in patients without and with CDAD showed no differences. At 100 days tumor relapse was 9.8% (95% confidence interval [Cl] 7.6-12.3) vs. 11.7% (95% Cl 6.7-18.2), p = 0.20, and at 1 year was 25% (95% Cl 20-30) vs. 26% (95% Cl 16-37), p = 0.89; while non-relapse mortal ity at 100 days was 3% (95% Cl 2-5) vs. 6% (95% Cl 2-11), p = 0.53, and at 1 year was 9% (95% Cl 7-12) vs. 14% (95% Cl 8-21), p = 0.21. Additionally, the probability of relapse-free survival and overall survival between patients without and with CDAD showed no differences; relapse-free survival at 100 days was 87.3% (95% Cl 84.5-89.7) vs. 83.2% (95% Cl 75.4-88.7), p = 0.16, and at 1 year was 72% (95% Cl 66-76) vs. 70% (95% Cl 57-80), p = 0.78; while overall survival at 100 days was 94.2% (95% Cl 92.1-95.8) vs. 92.0% (95% Cl 85.6-95.6), p = 0.36, and at 1 year was 85% (95% Cl 81-89) vs. 82% (95% Cl 71-90), p = 0.6. This lack of difference persisted when the two groups were stratified by type of transplant:
autologous vs. allogeneic. Given the multiple factors that can affect outcomes in these highly complex patients, a multi variate analysis was performed to evaluate for relapse-free survival, non-relapse mortality, relapse and overall mortality while adjusting for prognostic factors such as age, underly ing disease, disease stage at transplant and type of transplant (Table I). These analyses suggested that CDAD has no effect on HSCT outcomes (both autologous and allogeneic) in the first 100 days post-HSCT or at 1 year. There are several limitations to this study, including its retrospective design, single-center site and different test ing modalities used throughout the study period to detect CDAD. The C. difficile Tox A/B II assay utilized throughout the majority of the study period has a reported sensitivity of only 84.6%, the C. Diff Quik Chek sensitivity has been reported as 98.7% for the antigen and 87.8% for the toxin, and the highest sensitivity is reported with the Illumigene PCR at 95.2% [15-17]. The incidence of CDAD may have been underestimated. Lastly, the strains were not typed, and therefore the prevalence of the more virulent NAP1/BI/027 strain in the study population is unknown. However, this is one of the largest contemporary cohorts reported to evaluate the impact of CDAD on transplant outcomes. In conclusion, we have shown that CDAD continues to complicate the course of patients with HSCT, with increased incidence rates compared to that previously described in general inpatient cohorts. However, our data indicate that Table I. Multivariate analysis of cancer clinical outcomes adjusted for prognostic factors. Clostridium difficile infection, HR* (95% Cl) No Yes p-Value Relapse-free 1 1.16(0.86-1.56) 0.38 survival Non-relapse 1 1.19 (0.71-2.01) 0.51 mortality Relapse 1 1.16(0.90-1.50) 0.26 Overall mortality 1 1.21 (0.59-2.46) 0.6 Cl, confidence interval; HSCT, hematopoietic stem ceil transplant. ’ Hazard ratio (HR) within first 100 days post-HSCT.
262
K. Neemann e ta l.
most HSCT recipients with CDAD tolerate the disease fairly well, predominantly responding to treatment with metron idazole as first-line therapy. Recurrences occurred more often among allogeneic (13.3%) than autologous (4.2%) transplant recipients, perhaps because the latter are gener ally less profoundly immunosuppressed and for a briefer duration. Most importantly, in our population, transplantrelated outcomes in the first 100 days appear to be similar between HSCT recipients with or without CDAD. Therefore, most HSCT recipients with concomitant CDAD should be treated in accordance with published guidelines, beginning with metronidazole in most cases.
Potential conflict o f interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal. References [1] Hensgens MP, Goorhuis A, Dekkers OM, et al. All-cause and disease-specific mortality in hospitalized patients with Clostridium difficile infection: a multicenter cohort study. Clin Infect Dis 2013;56:1108-1116. [2] Wenisch JM, Schmid D, Tucek G, et al. A prospective cohort study on hospital mortality due to Clostridium difficile infection. Infection 2012;40:479-484. [3] Anand A, Glatt AE. Clostridium difficile infection associated with antineoplastic chemotherapy: a review. Clin Infect Dis 1993;17:109-113. [4] van Kraaij MG, Dekker AW, Verdonck LF, et al. Infectious gastro enteritis: an uncomm on cause of diarrhoea in adult allogeneic and autologous stem cell transplant recipients. Bone Marrow Transplant 2000;26:299-303. [5] Arango JI, Restrepo A, Schneider DL, et al. Incidence of Clostridium difficile-associated diarrhea before and after autologous peripheral blood stem cell transplantation for lymphoma and multiple myeloma. Bone Marrow Transplant 2006;37:517-521. [6] Dubberke ER, Reske KA, Srivastava A, et al. Clostridium difficileassociated disease in allogeneic hematopoietic stem-cell transplant
recipients: risk associations, protective associations, and outcomes. Clin Transplant 2010;24:192-198. [7] Chopra T, Chandrasekar P, Salimnia H, et al. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation. Clin Transplant 2011;25:E82-E87. [8] Willems L, Porcher R, Lafaurie M, et al. Clostridium difficile infection after allogeneic hematopoietic stem cell transplantation: incidence, risk factors, and outcome. Biol Blood Marrow Transplant. 2012;18:1295-1301. [9] Alonso CD, Marr KA. Clostridium difficile infection among hematopoietic stem cell transplant recipients: beyond colitis. Curr Opin Infect Dis 2013;26:326-331. [10] Trifilio SM, Pi J, Mehta I. Changing epidemiology of Clostridium difficile-associated disease during stem cell transplantation. Biol Blood Marrow Transplant 2013; 19:405-409. [11] Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med 2011;365:1693-1703. [12] Alonso CD, Treadway SB, Hanna DB, et al. Epidemiology and outcom es of Clostridium difficile infections in hem atopoietic stem cell transplant recipients. Clin Infect Dis 2012;54:1053-1063. [13] Debast SB, Bauer MP, Kuijper EJ et al. European Society of Clinical Microbiology and Infectious Diseases (ESCMID): update of the treatment guidance docum ent for Clostridium difficile infection (CDI). Clin Microbiol Infect 2014;20(Suppl. 2):l-26. [14] Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010;31:431-55. [15] Snell H, Ramos M, Longo S, et al Perform ance of the TechLab C. DIFF CHEK-60 enzyme im m unoassay (ELA) in com bination with the C. difficile Tox A/B II EIA kit, the Triage C. difficile panel immunoassay, and a cytotoxin assay for diagnosis of Clostridium difficile-associated diarrhea. J Clin Microbiol 2004;42:4863-4865. [16] Quinn CD, Sefers SE, Babiker W, et al. C. Diff Quik Chek complete enzyme immunoassay provides a reliable first-line method for detection of Clostridium difficile in stool specimens. J Clin Microbiol 2010;48:603-605. [17] Wince JL, Elagin S, Kozak K, et al. Illumigene C. difficile: a novel new molecular approach for the detection of Clostridium difficile. Presented at the 110th General Meeting of the American Society for Microbiology, 23-27 May 2010, San Diego, CA: Poster Board Number 204.
Copyright of Leukemia & Lymphoma is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
