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• W2132667420 abstract "Clostridium difficile (C. difficile) infection was observed in 13% of recipients after hematopoietic stem cell transplantation (HSCT), mainly in the first month posttransplantation. Risk factors were cord blood as the source of stem cells, acute graft-versus-host disease (GVHD), and total body irradiation (TBI). No association was found with an increased risk of mortality. The purpose of this study was to evaluate the incidence, risk factors, and outcome of C. difficile infection (CDI) after HSCT. We conducted a single-center, retrospective, cohort study on all patients who received an allogeneic HSCT from January 2004 to December 2007. All patients with diarrhea in the first year after HSCT were tested for the presence of C. difficile in stools. Among the 407 assessable patients, 53 presented at least 1 CDI in the first year post-HSCT. The total incidence rate was 5.6 cases of CDI per 10,000 patient-days. Fifty percent of cases were diagnosed in the first month after HSCT, and 95% occurred during the first 6 months. Fewer than 5% of patients with CDI had severe diarrhea and severe complications were never observed. TBI in the conditioning regimen, cord blood as the source of stem cells, and acute graft-versus-host disease (aGVHD) were independently associated with CDI. Six patients (11%) had a recurrence of CDI. Four patients required second-line treatment with vancomycin. With a median follow-up of 22 months, the 2-year overall survival rates were similar between patients who presented a CDI and those who did not. CDI was observed in approximately 13% of recipients after HSCT, mainly in the first month posttransplantation and was associated with CB, aGVHD, and TBI. CDI was not associated either with severe complications or with an increased risk of mortality in this large cohort of patients. Clostridium difficile (C. difficile) infection was observed in 13% of recipients after hematopoietic stem cell transplantation (HSCT), mainly in the first month posttransplantation. Risk factors were cord blood as the source of stem cells, acute graft-versus-host disease (GVHD), and total body irradiation (TBI). No association was found with an increased risk of mortality. The purpose of this study was to evaluate the incidence, risk factors, and outcome of C. difficile infection (CDI) after HSCT. We conducted a single-center, retrospective, cohort study on all patients who received an allogeneic HSCT from January 2004 to December 2007. All patients with diarrhea in the first year after HSCT were tested for the presence of C. difficile in stools. Among the 407 assessable patients, 53 presented at least 1 CDI in the first year post-HSCT. The total incidence rate was 5.6 cases of CDI per 10,000 patient-days. Fifty percent of cases were diagnosed in the first month after HSCT, and 95% occurred during the first 6 months. Fewer than 5% of patients with CDI had severe diarrhea and severe complications were never observed. TBI in the conditioning regimen, cord blood as the source of stem cells, and acute graft-versus-host disease (aGVHD) were independently associated with CDI. Six patients (11%) had a recurrence of CDI. Four patients required second-line treatment with vancomycin. With a median follow-up of 22 months, the 2-year overall survival rates were similar between patients who presented a CDI and those who did not. CDI was observed in approximately 13% of recipients after HSCT, mainly in the first month posttransplantation and was associated with CB, aGVHD, and TBI. CDI was not associated either with severe complications or with an increased risk of mortality in this large cohort of patients. Clostridium difficile (C. difficile) is an anaerobic, gram-positive bacillus, responsible for 20% of antibiotic-associated diarrheas in industrialized countries with various clinical presentations from mild diarrhea to life-threatening toxic megacolon, colon perforation, and death [1McFarland L.V. Bauwens J.E. Melcher S.A. Surawicz C.M. Greenberg R.N. Elmer G.W. Ciprofloxacin-associated Clostridium difficile disease.Lancet. 1995; 346: 977-978Abstract PubMed Google Scholar]. The rates of colonization are usually only 2% to 3% for healthy adults and increase to 20% to 30% among hospitalized patients [2Bartlett J.G. Historical perspectives on studies of Clostridium difficile and C. difficile infection.Clin Infect Dis. 2008; 46: S4-11Crossref PubMed Scopus (157) Google Scholar]. Diagnosis of C. difficile infection (CDI) requires identification of a toxin-producing C. difficile strain in patients' stools. A 2-step protocol, first using an enzyme-linked immunoassay (EIA) for glutamate dehydrogenase (GDH) antigen and for toxins A and B followed by toxigenic stool culture if GDH is positive, has a high sensitivity [3Barbut F. Lalande V. Daprey G. et al.Usefulness of simultaneous detection of toxin A and glutamate dehydrogenase for the diagnosis of Clostridium difficile-associated diseases.Eur J Clin Microbiol Infect Dis. 2000; 19: 481-484Crossref PubMed Scopus (32) Google Scholar, 4Bartlett J.G. Gerding D.N. Clinical recognition and diagnosis of Clostridium difficile infection.Clin Infect Dis. 2008; 46: S12-S18Crossref PubMed Scopus (425) Google Scholar]. The major risk factors for CDI are hospitalization, old age (ie, ≥65 years), and exposure to antibiotics [5Owens Jr., R.C. Donskey C.J. Gaynes R.P. Loo V.G. Muto C.A. Antimicrobial-associated risk factors for Clostridium difficile infection.Clin Infect Dis. 2008; 46: S19-S31Crossref PubMed Scopus (491) Google Scholar]. In the general population, the cumulative attributable mortality to CDI at 30 days ranges from 0.9% to 16.7%, with greater morbidity and mortality in recent years [6Gravel D. Miller M. Simor A. et al.Health care-associated Clostridium difficile infection in adults admitted to acute care hospitals in Canada: a Canadian Nosocomial Infection Surveillance Program Study.Clin Infect Dis. 2009; 48: 568-576Crossref PubMed Scopus (210) Google Scholar, 7Pépin J. Valiquette L. Cossette B. Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec.CMAJ. 2005; 173: 1037-1042Crossref PubMed Scopus (506) Google Scholar, 8Sánchez-Somolinos M. Alcalá L. Peláez T. et al.High levels of resistance to fluoroquinolones among Clostridium difficile isolates in a Spanish hospital.Clin Infect Dis. 2008; 47: 818-822Crossref PubMed Scopus (13) Google Scholar, 9Karas J.A. Enoch D.A. Aliyu S.H. A review of mortality due to Clostridium difficile infection.J Infect. 2010; 61: 1-8Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 10Redelings M.D. Sorvillo F. Mascola L. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004.Emerg Infect Dis. 2007; 13: 1417-1419Crossref PubMed Scopus (365) Google Scholar]. Increasing incidence associated with the emergence of more virulent strains since 2002 raises new concerns regarding the impact on mortality, especially in immunocompromised patients [10Redelings M.D. Sorvillo F. Mascola L. Increase in Clostridium difficile-related mortality rates, United States, 1999-2004.Emerg Infect Dis. 2007; 13: 1417-1419Crossref PubMed Scopus (365) Google Scholar]. After hematopoietic stem cell transplantation (HSCT), patients are exposed to several well-recognized risk factors for the development of CDI, including broad-spectrum antibiotic exposure, length of hospitalization, altered integrity of the intestinal mucosa [11Issa M. Ananthakrishnan A.N. Binion D.G. Clostridium difficile and inflammatory bowel disease.Inflamm Bowel Dis. 2008; 14: 1432-1442Crossref PubMed Scopus (185) Google Scholar], and immunodeficiency [12Anand A. Glatt A.E. Clostridium difficile infection associated with antineoplastic chemotherapy: a review.Clin Infect Dis. 1993; 17: 109-113Crossref PubMed Scopus (252) Google Scholar, 13Gorschlüter M. Glasmacher A. Hahn C. et al.Clostridium difficile infection in patients with neutropenia.Clin Infect Dis. 2001; 33: 786-791Crossref PubMed Scopus (125) Google Scholar]. Furthermore, the use of allogeneic HSCT has expanded progressively to older patients due to the development of reduced-intensity conditioning regimens [14Deeg H.J. Sandmaier B.M. Who is fit for allogeneic transplantation?.Blood. 2010; 116: 4762-4770Crossref PubMed Scopus (67) Google Scholar]. However, until now, CDI after HSCT has been reported in a small number of studies. CDI accounts for 4% to 20.4% of the episodes of diarrhea in HSCT recipients [15Bobak D. Arfons L.M. Creger R.J. Lazarus H.M. Clostridium difficile-associated disease in human stem cell transplant recipients: coming epidemic or false alarm?.Bone Marrow Transplant. 2008; 42: 705-713Crossref PubMed Scopus (54) Google Scholar]. The rate of CDI relapse after correctly administered treatment, the frequency of complications, as well as the rate of mortality remains unknown in this setting. Only 1 study found an association between CDI and acute graft-versus-host disease (aGVHD) as well as an increase in mortality of the patients who developed CDI after allogeneic HSCT [16Chakrabarti S. Lees A. Jones S.G. Milligan D.W. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality.Bone Marrow Transplant. 2000; 26: 871-876Crossref PubMed Scopus (107) Google Scholar]. The purpose of this retrospective, single-center study was to determine the incidence, risk factors, and prognostic significance of CDI after HSCT. A retrospective review of all patients who underwent allogeneic HSCT at Saint-Louis Hospital (Paris, France) between January 1, 2004, and December 31, 2007, was undertaken using database and medical records. All patients with diarrhea after the beginning of the conditioning regimen and during the first posttransplantation year were tested for the presence of C. difficile in stools. Patients' stools were also systematically tested for other bacterial, fungal, and viral pathogens. C. difficile was first detected in stools by EIA for C. difficile glutamate dehydrogenase (Wampole C Diff quick check, TechLab, Blacksburg,VA). If the results were positive, EIA for toxins A and B in stools (Wampole ToxA/B check, TechLab, Blacksburg, VA) and toxin EIA on C. difficile colonies after culture were performed to determine the presence of a toxin-producing C. difficile strain. Positive results were reported if GDH and EIA toxins or toxigenic culture were positive. Only primary episodes of CDI were included. All patients were hospitalized in private rooms. Antimicrobial prophylaxis consisted of amoxicillin from the beginning of the conditioning regimen (until fever called for intravenous antibiotics) plus ofloxacin in cases of neutropenia-inducing conditioning regimen. Oral acyclovir and fluconazole were started at the onset of the conditioning regimen. Fluconazole was discontinued if the patient required treatment with any other systemic antifungal agent. Prophylactic trimethoprim/sulfamethoxazole was given after engraftment. First-line intravenous empiric therapy usually included a broad-spectrum beta-lactam. CDI was defined according to the European Society of Clinical Microbiology and Infectious Diseases [17Bauer M.P. Kuijper E.J. van Dissel J.T. European Society of Clinical Microbiology and Infectious DiseasesEuropean Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI).Clin Microbiol Infect. 2009; 15: 1067-1079Crossref PubMed Scopus (328) Google Scholar]. Briefly, CDI diagnosis required diarrhea (semi-liquid or liquid stool twice or more in 24 hours) without evidence of another cause and a stool test result for the presence of toxigenic C. difficile. The severity of gastrointestinal symptoms was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events [18National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. Available at: http://www.ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcaev3.pdf. Accessed August 9, 2006.Google Scholar]. Severe CDI was defined by admission to an intensive care unit for complications, colectomy, and/or death related to CDI. Recurrence was a new episode of diarrhea and a positive toxin assay within 8 weeks after a first correctly treated episode. CDI treatment failure was defined by an increase in stool frequency as reported by the patient, lack of improvement in stool consistency after 3 days, or new signs of severe colitis [17Bauer M.P. Kuijper E.J. van Dissel J.T. European Society of Clinical Microbiology and Infectious DiseasesEuropean Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI).Clin Microbiol Infect. 2009; 15: 1067-1079Crossref PubMed Scopus (328) Google Scholar]. GVHD was defined and graded according to standard criteria [19Thomas E.D. Storb R. Clift R.A. et al.Bone-marrow transplantation (second of two parts).N Engl J Med. 1975; 292: 895-902Crossref PubMed Scopus (960) Google Scholar]. We first analyzed the incidence and risk factors of CDI in the first year after HSCT. Incidence rates (ie, average hazards) over post-HSCT time periods were estimated using standard methodology and graphically illustrated by a cumulative hazard curve. Risk factors were analyzed using univariable and multivariable Cox proportional hazard cause-specific models, in which transplantation characteristics were time-fixed covariates and clinical parameters in the posttransplantation period time-dependent covariates. The proportional hazards assumption was checked by examination of Schoenfeld's residuals and Grambsch and Therneau's lack-of-fit test. Because hazards were not found to be proportional, time-varying effects were used in the models by separating early and late effects with a cutoff arbitrarily defined according to the shape of the cumulative hazard of CDI. The association between CDI (either at the time of HSCT or thereafter) and the outcome was also analyzed. Survival probabilities were then estimated by the Kaplan-Meier estimator and analyses performed using proportional hazard or proportional cause-specific hazard models. All tests were 2-sided and P values ≤.05 were considered as indicating significant association. All analyses were performed using the R statistical software version 2.10.1 (R Development Core Team, Vienna, Austria). During the study period (2004-2007), 414 patients received an allogeneic HSCT. Grading for aGVHD was not available for 6 of them, and 1 other patient was excluded from the analysis because of a late C. difficile infection occurring more than 500 days after transplantation. Clinical characteristics of the 407 remaining patients (249 men, 61.2%) are detailed in Table 1. Clinical data were similar between patients who presented a CDI and patients who did not, except for the use of total body irradiation (TBI; 32.1% and 19%, respectively) and cord blood as the source of stem cells (22.6% and 13.8%, respectively) as illustrated in Table 2.Table 1Characteristics of Patients with or without CDI after HSCTVariablesNo CDI (n = 354)CDI (n = 53)Male gender, no. (%)214 (60.5)35 (66)Median age years (range)32 (4-68)26 (4-59)Underlying disease, no. (%) Acute leukemia165 (46.6)28 (52.8) Myelodysplastic/myeloproliferative42 (11.9)6 (11.3) Chronic leukemia25 (7.1)4 (7.5) Lymphoma37 (10.5)6 (11.3) Plasma cell disorder20 (5.6)1 (1.9) Aplastic anemia40 (11.3)5 (9.4) Hemoglobinopathy23 (6.5)3 (5.7) Inherited disorder2 (0.6)0 (0)Malignant disease, no. (%)289 (81.6)45 (84.9)RIC regimen, no. (%)∗Reduced intensity conditioning regimen excluded all conditioning regimens with either irradiation >10 Gy or busulfan ≥16 mg/kg or cyclophosphamide ≥150 mg/kg/day.147/352 (41.8)17/51 (33.3)TBI ≥12 Gy, no. (%)65/343 (19)17 (32.1)Source of stem cells, no. (%) Bone marrow146 (41.2)20 (37.7) Peripheral blood stem cell159 (44.9)21 (39.6) Cord blood49 (13.8)12 (22.6)Matched related donor, no. (%)182/351 (51.9)22 (41.5)Male donor, no. (%)165/318 (51.9)30/45 (66.7)Positive CMV serology, patient, no. (%)205/333 (61.6)27/50 (54)Positive CMV serology, donor, no. (%)172/333 (51.7)17/51 (33.3)GVHD prophylaxis Cyclosporine, no. (%)332 (93.8)52 (98.1) Methotrexate, no. (%)175 (49.4)31 (58.5) Cellcept, no. (%)101 (28.5)10 (18.9)CDI indicates Clostridium difficile infection; HSCT, hematopoietic stem cell transplantation; RIC, reduced intensity conditioning; TBI, total body irradiation; Gy, Gray; CMV, cytomegalovirus; GVHD, graft-versus-host disease.∗ Reduced intensity conditioning regimen excluded all conditioning regimens with either irradiation >10 Gy or busulfan ≥16 mg/kg or cyclophosphamide ≥150 mg/kg/day. Open table in a new tab Table 2Risk Factors for CDI including Gut GVHD Taking into Account the Variation of Influence of TBI and aGVHD with TimeVariablesHR (95% CI)P valueTBI ≥12 Gy CDI 0-2 months post-HSCT2.3 (1.2-4.5).01 CDI >2 months post-HSCT0.6 (0.1-2.5).50aGVHD grade ≥2 CDI 0-2 months post-HSCT1.4 (0.6-3.4).50 CDI >2 months post-HSCT7.5 (1.7-34.3).01Acute gut GVHD ≥2 CDI 0-2 months post-HSCT1.8 (0.7-4.6).20 CDI >2 months post-HSCT27.2 (3.5-210.4).002Cord blood2 (1-3.8).04CDI indicates Clostridium difficile infection; GVHD, graft-versus-host disease; TBI, total body irradiation; aGVHD, acute graft-versus-host disease; HR, hazard ratio; CI, confidence interval; Gy, Gray; HSCT, hematopoietic stem cell transplantation. Open table in a new tab CDI indicates Clostridium difficile infection; HSCT, hematopoietic stem cell transplantation; RIC, reduced intensity conditioning; TBI, total body irradiation; Gy, Gray; CMV, cytomegalovirus; GVHD, graft-versus-host disease. CDI indicates Clostridium difficile infection; GVHD, graft-versus-host disease; TBI, total body irradiation; aGVHD, acute graft-versus-host disease; HR, hazard ratio; CI, confidence interval; Gy, Gray; HSCT, hematopoietic stem cell transplantation. Of the 407 patients, 53 (13%) developed a CDI. The mean incidence during the first year after HSCT was 5 per 10,000 patient-days. This incidence varied according to the delay after the HSCT procedure with a peak incidence of 61 per 10,000 patient-days during the first week immediately after HSCT. At this point, the incidence decreased progressively until 1.6 per 10,000 patient-days 2 months after HSCT (Figure 1). The 1-year cumulative incidence was 13%. Nevertheless, 50% of CDI occurred during the first month and 95% during the first 6 months after HSCT. The median time to develop CDI was 25 days after HSCT (range from 3 days before transplantation to 276 days after transplantation). We also observed an increase of CDI incidence during the study period with more cases in 2006 to 2007 compared with 2004 to 2005, although these results were not significantly different (hazard ratio [HR] = 1.26 and 1.79, respectively, overall P = .068). The new emergent epidemic strain ribotype 27 was not isolated in our cohort, and all cases resulted from the classic strain of C. difficile. No C. difficile outbreak in the bone marrow transplantation unit was reported during the study period. Clinical and biological characteristics of patients who developed CDI are described in Table 3. A systematic concomitant test for other pathogens allowed other causes of infectious diarrhea to be excluded, although concomitant infections were frequently identified on blood samples (25 patients), including mostly viral infections (7 cytomegalovirus [CMV], 2 herpes simplex virus, 1 adenovirus, and 12 others) or bacterial infections (5 cocci gram-positive and 3 bacille gram-negative bacteremia, and 2 others). Four patients were diagnosed with concomitant invasive aspergillosis.Table 3Characteristics of Patients with CDI after HSCTCDI (n = 53)Not AvailableMedian number of antibiotics used in the previous 4 weeks (range)4 (1-7)-Neutropenia (WBC count <500), no. (%)24 (45)-Albumin level ≤2.5 mg/dL, no. (%)3 (7)7Proton pump inhibitor53 (100)-Clinical symptoms Fever, no. (%)20 (39)2 DiarrheaWHO 3-4, no. (%)47 (96)4WHO 1-2, no. (%)2 (4)4 Abdominal cramps, no. (%)12 (25)5Concomitant infections, no. (%)25 (48)1CDI indicates Clostridium difficile infection; HSCT, hematopoietic stem cell transplantation; WBC, white blood cell; WHO, World Health Organization.None of the patients had a creatinine level >2.5 mg/dL, and bloody stools were never present.WHO 1-2: increase of 2 to 6 stools per day or nocturnal stools or moderate cramping.WHO 3-4: increase of ≥7 stools per day or incontinence or severe cramping or grossly bloody diarrhea or need for parenteral support.For 4 patients who had diarrhea, WHO grading was not available. Open table in a new tab CDI indicates Clostridium difficile infection; HSCT, hematopoietic stem cell transplantation; WBC, white blood cell; WHO, World Health Organization. None of the patients had a creatinine level >2.5 mg/dL, and bloody stools were never present. WHO 1-2: increase of 2 to 6 stools per day or nocturnal stools or moderate cramping. WHO 3-4: increase of ≥7 stools per day or incontinence or severe cramping or grossly bloody diarrhea or need for parenteral support. For 4 patients who had diarrhea, WHO grading was not available. For the risk factor analysis, variables are mentioned in Table 1. Any case of aGVHD was analyzed as a time-dependant covariable, and only aGVHD that had occurred before CDI was considered for the CDI group. Multivariate analysis identified the following risk factors for CDI: cord blood as the source of stem cells, TBI ≥12 Gy, and aGVHD grade 2 or more. The effect of TBI and aGVHD on the hazard of CDI were not found to be constant with time (P = .01). A model with separate effects on early CDI (ie, CDI occurring in the first 2 months after HSCT) and late CDI (CDI occurring more than 2 months after HCST) is shown in Table 2. A separate model including gut aGVHD instead of grade 2 or more aGVHD (Table 2) shows that gut aGVHD is strongly associated with the occurrence of late CDI. Notably, CDI was not found to be significantly associated with the risk of occurrence of a subsequent grade 2 or more aGVHD (HR, 1.24; 95% confidence interval [CI], 0.72-2.15; P = .43) or gut GVHD (HR, 1.23; 95% CI, 0.67-2.28; P = .51). All patients except 5 received oral metronidazole as the first-line treatment with a median treatment length of 15 days (range, 4-55 days) for each episode. Other patients (n = 5) received intravenous metronidazole when the oral route was not feasible. Five patients (2.6%) experienced a recurrence of CDI, 2 of them having more than 1 recurrence. Five patients required treatment with oral vancomycin as the second-line treatment, replacing metronidazole. Reasons for vancomycin use were heterogeneous including multiple recurrences (1 patient), persistent diarrhea combined with Crohn disease (1 patient), persistent toxin excretion after metronidazole treatment (1 patient), and also incomplete data (2 patients). Nevertheless, medical or surgical complications were never observed and every patient responded to medical treatment. No severe CDI was observed in our cohort. Thirty-day mortality arising from CDI was zero. With a median follow-up of 29 months, we did not observe any difference in the mortality rates between both groups of patients, with or without CDI (Figure 2). Little has been published about the incidence of CDI posttransplantation and most of the available data concern autologous HSCT [15Bobak D. Arfons L.M. Creger R.J. Lazarus H.M. Clostridium difficile-associated disease in human stem cell transplant recipients: coming epidemic or false alarm?.Bone Marrow Transplant. 2008; 42: 705-713Crossref PubMed Scopus (54) Google Scholar] and solid-organ transplantation [20Fishman J.A. Infection in solid-organ transplant recipients.N Engl J Med. 2007; 357: 2601-2614Crossref PubMed Scopus (1387) Google Scholar]. In this setting, the rate of incidence ranges from 3% to 15% [21Arango J.I. Restrepo A. Schneider D.L. 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: 517-521Crossref PubMed Scopus (55) Google Scholar, 22Tomblyn M. Gordon L. Singhal S. et al.Rarity of toxigenic Clostridium difficile infections after hematopoietic stem cell transplantation: implications for symptomatic management of diarrhea.Bone Marrow Transplant. 2002; 30: 517-519Crossref PubMed Scopus (37) Google Scholar, 23Bilgrami S. Feingold J.M. Dorsky D. et al.Incidence and outcome of Clostridium difficile infection following autologous peripheral blood stem cell transplantation.Bone Marrow Transplant. 1999; 23: 1039-1042Crossref PubMed Scopus (79) Google Scholar, 24Mitu-Pretorian O.M. Forgacs B. Qumruddin A. Tavakoli A. Augustine T. Pararajasingam R. Outcomes of patients who develop symptomatic Clostridium difficile infection after solid organ transplantation.Transplant Proc. 2010; 42: 2631-2633Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 25Riddle D.J. Dubberke E.R. Clostridium difficile infection in solid organ transplant recipients.Curr Opin Organ Transplant. 2008; 13: 592-600Crossref PubMed Scopus (73) Google Scholar]. However, in most studies, the incidence was only estimated among patients who had developed diarrhea and may not reflect the real incidence in patients who underwent transplantation. Our retrospective study represents the largest study to date conducted in patients after HSCT. Our findings indicate a cumulative incidence of 13% at 1 year, with 50% of infections occurring during the first month after HSCT. Similar or higher rates (13% and 18%) have previously been reported in studies of 75 and 216 allo-HSCT recipients, respectively [16Chakrabarti S. Lees A. Jones S.G. Milligan D.W. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality.Bone Marrow Transplant. 2000; 26: 871-876Crossref PubMed Scopus (107) Google Scholar, 26Chopra T. Chandrasekar P. Salimnia H. Heilbrun L.K. Smith D. Alangaden G.J. Recent epidemiology of Clostridium difficile infection during hematopoietic stem cell transplantation.Clin Transplant. 2011; 25: E82-E87Crossref PubMed Scopus (86) Google Scholar]. Another study found an incidence of almost 30% among 26 allo-HSCT recipients [27Leung S. Metzger B.S. Currie B.P. Incidence of Clostridium difficile infection in patients with acute leukemia and lymphoma after allogeneic hematopoietic stem cell transplantation.Infect Control Hosp Epidemiol. 2010; 31: 313-315Crossref PubMed Scopus (28) Google Scholar]. The peak incidence observed during the first week posttransplantation may be partly explained by colonic mucosal damage resulting from the conditioning regimen. This is illustrated in our study by the association between TBI and a higher risk of CDI in the early posttransplantation period. Furthermore, CDI does not only result from the acquisition of toxigenic strains of C. difficile but also requires alteration of the digestive tract, arising from the conditioning regimen (including TBI) and from gut GVHD in allo-HSCT recipients. Clinical expression of CDI is highly variable, and the immunocompromised status of our patients limits the value and the specificity of clinical symptoms. Co-infections were frequent, as already reported in this setting [16Chakrabarti S. Lees A. Jones S.G. Milligan D.W. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality.Bone Marrow Transplant. 2000; 26: 871-876Crossref PubMed Scopus (107) Google Scholar], and in some cases may have caused fever, abdominal pain, or diarrhea. Diarrhea from gut GVHD with concomitant C. difficile toxin detection may have led to an overestimation of the rate of CDI. Only a prospective study would remove this bias. Although the 2-step detection on C. difficile used in our study has a high sensitivity, a recent study has shown that the performance of antigen-based methods varies with the genotype of C. difficile, contrary to molecular methods [28Tenover F.C. Novak-Weekley S. Woods C.W. et al.Impact of strain type on detection of toxigenic Clostridium difficile: comparison of molecular diagnostic and enzyme immunoassay approaches.J Clin Microbiol. 2010; 48: 3719-3724Crossref PubMed Scopus (175) Google Scholar]. Nucleic acid amplification tests are generally more sensitive than toxin EIA and could therefore limit false-negative results [29Kufelnicka A.M. Kirn T.J. Effective utilization of evolving methods for the laboratory diagnosis of Clostridium difficile infection.Clin Infect Dis. 2011; 52: 1451-1457Crossref PubMed Scopus (61) Google Scholar]. In multivariate analysis, not only TBI but also aGVHD and the use of cord blood as the source of stem cells were identified as risk factors for CDI. Chakrabarti et al. [16Chakrabarti S. Lees A. Jones S.G. Milligan D.W. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality.Bone Marrow Transplant. 2000; 26: 871-876Crossref PubMed Scopus (107) Google Scholar] also found aGVHD grade 3 to 4 to be a risk factor for CDI, but our study is the first to report the use of cord blood as a risk factor. This probably stems from higher immunodeficiency and longer engraftment periods leading to longer hospitalization and exposure to antibiotics [30Brown J.A. Boussiotis V.A. Umbilical cord blood transplantation: basic biology and clinical challenges to immune reconstitution.Clin Immunol. 2008; 127: 286-297Crossref PubMed Scopus (133) Google Scholar]. GVHD and cord blood transplantations delay the immune reconstitution and are a precursor to other infections like CMV [31Miller W. Flynn P. McCullough J. et al.Cytomegalovirus infection after bone marrow transplantation: an association with acute graft-v-host disease.Blood. 1986; 67: 1162-1167PubMed Google Scholar] or invasive aspergillosis [32van Burik J.A. Carter S.L. Freifeld A.G. et al.Higher risk of cytomegalovirus and aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease.Biol Blood Marrow Transplant. 2007; 13: 1487-1498Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar], leading again to prolonged hospitalization and exposure to antibiotics. Inability to produce toxin-neutralizing antibodies is associated with a higher risk of developing an active infection in colonized patients [33Kyne L. Warny M. Qamar A. Kelly C.P. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A.N Engl J Med. 2000; 342: 390-397Crossref PubMed Scopus (776) Google Scholar] and may theoretically result from GVHD and its treatment. Furthermore, gut GVHD may increase the direct effects of C. difficile toxins on enterocytes by altering the integrity of the intestinal mucosa, as illustrated by an approximately 30-fold increased risk of CDI in patients with gut GVHD in our study. Conversely, in a case-control study of 37 allogeneic HSCT recipients with CDI, Dubberke et al. [34Dubberke E.R. Reske K.A. Srivastava A. et al.Clostridium difficile-associated disease in allogeneic hematopoietic stem-cell transplant recipients: risk associations, protective associations, and outcomes.Clin Transplant. 2010; 24: 192-198Crossref PubMed Scopus (72) Google Scholar] found an increased risk of GVHD, severe GVHD, and gut GVHD after CDI, contrary to our findings. The high rate of severe CDI (57%) in their cohort may provide at least a partial explanation of this disparity. The difficulties in identifying other known risk factors, such as exposure to antibiotics or the use of proton pump inhibitors [35Ananthakrishnan A.N. Clostridium difficile infection: epidemiology, risk factors and management.Nat Rev Gastroenterol Hepatol. 2011; 8: 17-26Crossref PubMed Scopus (271) Google Scholar, 36Howell M.D. Novack V. Grgurich P. et al.Iatrogenic gastric acid suppression and the risk of nosocomial Clostridium difficile infection.Arch Intern Med. 2010; 170: 784-790Crossref PubMed Scopus (368) Google Scholar], are probably due to the ubiquity of these traditional risk factors among HSCT recipients. All our patients with CDI had received at least 1 of the 3 most commonly administered antibiotic families, including third-generation cephalosporin, broad-spectrum penicillin, and quinolone [2Bartlett J.G. Historical perspectives on studies of Clostridium difficile and C. difficile infection.Clin Infect Dis. 2008; 46: S4-11Crossref PubMed Scopus (157) Google Scholar, 5Owens Jr., R.C. Donskey C.J. Gaynes R.P. Loo V.G. Muto C.A. Antimicrobial-associated risk factors for Clostridium difficile infection.Clin Infect Dis. 2008; 46: S19-S31Crossref PubMed Scopus (491) Google Scholar], during the month preceding CDI. Another study has shown that diabetes mellitus, administration of a third or fourth-generation cephalosporin, and being in the pre-engraftment phase are risk factors for CDI after allogeneic HSCT [34Dubberke E.R. Reske K.A. Srivastava A. et al.Clostridium difficile-associated disease in allogeneic hematopoietic stem-cell transplant recipients: risk associations, protective associations, and outcomes.Clin Transplant. 2010; 24: 192-198Crossref PubMed Scopus (72) Google Scholar]. Several studies have compared metronidazole favorably over vancomycin as an effective treatment for CDI [37Wenisch C. Parschalk B. Hasenhündl M. Hirschl A.M. Graninger W. Comparison of vancomycin, teicoplanin, metronidazole, and fusidic acid for the treatment of Clostridium difficile-associated diarrhea.Clin Infect Dis. 1996; 22: 813-818Crossref PubMed Scopus (420) Google Scholar, 38Teasley D.G. Gerding D.N. Olson M.M. et al.Prospective randomised trial of metronidazole versus vancomycin for Clostridium-difficile-associated diarrhoea and colitis.Lancet. 1983; 2: 1043-1046Abstract PubMed Scopus (564) Google Scholar], and metronidazole may reasonably be proposed to patients with nonsevere CDI on the basis of cost and concerns to limit vancomycin-resistant enterococcus selection provided by oral vancomycin [17Bauer M.P. Kuijper E.J. van Dissel J.T. European Society of Clinical Microbiology and Infectious DiseasesEuropean Society of Clinical Microbiology and Infectious Diseases (ESCMID): treatment guidance document for Clostridium difficile infection (CDI).Clin Microbiol Infect. 2009; 15: 1067-1079Crossref PubMed Scopus (328) Google Scholar, 39Gerding D.N. Is there a relationship between vancomycin-resistant enterococcal infection and Clostridium difficile infection?.Clin Infect Dis. 1997; 25: S206-S210Crossref PubMed Scopus (111) Google Scholar]. In our study, all patients received oral metronidazole as a first-line treatment, which was efficacious in all cases. The reported recurrence rate ranges from 5% to 66%, with a mean of 20% after therapy with either vancomycin or metronidazole [40Fekety R. McFarland L.V. Surawicz C.M. Greenberg R.N. Elmer G.W. Mulligan M.E. Recurrent Clostridium difficile diarrhea: characteristics of and risk factors for patients enrolled in a prospective, randomized, double-blinded trial.Clin Infect Dis. 1997; 24: 324-333Crossref PubMed Scopus (318) Google Scholar]. Our findings indicate a recurrence rate of only 9.4%, despite persisting exposure to additional antibiotics for treatment or prophylaxis of other infections, with no associated complications. Notably, we did not observe either severe CDI or death attributable to CDI, contrary to both previous studies of allo-HSCT recipients [16Chakrabarti S. Lees A. Jones S.G. Milligan D.W. Clostridium difficile infection in allogeneic stem cell transplant recipients is associated with severe graft-versus-host disease and non-relapse mortality.Bone Marrow Transplant. 2000; 26: 871-876Crossref PubMed Scopus (107) Google Scholar, 34Dubberke E.R. Reske K.A. Srivastava A. et al.Clostridium difficile-associated disease in allogeneic hematopoietic stem-cell transplant recipients: risk associations, protective associations, and outcomes.Clin Transplant. 2010; 24: 192-198Crossref PubMed Scopus (72) Google Scholar]. In the first study of 37 patients, the increased risk of death was evaluated at 180 days and restricted to patients with severe CDI (57% of patients) [34Dubberke E.R. Reske K.A. Srivastava A. et al.Clostridium difficile-associated disease in allogeneic hematopoietic stem-cell transplant recipients: risk associations, protective associations, and outcomes.Clin Transplant. 2010; 24: 192-198Crossref PubMed Scopus (72) Google Scholar]. The other study dealt with 75 patients who underwent HSCT between 1994 and 1999. Seven of 10 patients who developed CDI died from GVHD or infections, compared with 19 of 65 patients in the noninfected group. Better outcome and reduced mortality resulting from advances in the daily care of patients undergoing HSCT over the last decade make it difficult to make comparisons between these results [41Gooley T.A. Chien J.W. Pergam S.A. et al.Reduced mortality after allogeneic hematopoietic-cell transplantation.N Engl J Med. 2010; 363: 2091-2101Crossref PubMed Scopus (1126) Google Scholar]. CDI-related mortality may also depend on the virulence of the predominant strain and, as such, further prospective studies should be able to confirm our findings. Nevertheless, several prophylactic infectious procedures must be respected to avoid the spread of CDI, including patient isolation, enhanced environment cleaning with chlorine-based agents, appropriate protective clothing, and strict hand hygiene [42Gerding D.N. Muto C.A. Owens Jr., R.C. Measures to control and prevent Clostridium difficile infection.Clin Infect Dis. 2008; 46: S43-S49Crossref PubMed Scopus (251) Google Scholar]. In conclusion, CDI is observed in approximately 13% of recipients after HSCT, mainly in the first month post-HSCT. Risk factors for CDI are TBI, cord blood as the source of stem cells, and prior aGVHD. Contrary to previously published data, the outcome was favorable upon administration of appropriate treatment in this particular population. Authorship Statement: Lise Willems designed the study, collected and analyzed the data, and wrote the paper; Raphaël Porcher designed the study and did the statistical analysis; Matthieu Lafaurie designed the study, collected the data, and edited the manuscript; Isabelle Casin, Marie Robin, Aliénor Xhaard, Anna Lisa Andreoli, Paula Rodriguez-Otero, Nathalie Dhedin, Raphaël Porcher, and Gérard Socié designed the study, collected the data, and edited the manuscript; Raphaël Porcher and Régis Peffault de Latour designed the study, collected the data, and wrote the manuscript. Financial disclosure: The authors declare no financial interests. Conflict of Interest: The authors declare no conflict of interest." @default.
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• W2132667420 cites W1510406735 @default.
• W2132667420 cites W193514409 @default.
• W2132667420 cites W1974590693 @default.
• W2132667420 cites W1975101868 @default.
• W2132667420 cites W1983443607 @default.
• W2132667420 cites W1991320124 @default.
• W2132667420 cites W1995090169 @default.
• W2132667420 cites W2001337739 @default.
• W2132667420 cites W2004444336 @default.
• W2132667420 cites W2015831032 @default.
• W2132667420 cites W2019639929 @default.
• W2132667420 cites W2020347902 @default.
• W2132667420 cites W2028632020 @default.
• W2132667420 cites W2033486769 @default.
• W2132667420 cites W2047690009 @default.
• W2132667420 cites W2072071265 @default.
• W2132667420 cites W2089818775 @default.
• W2132667420 cites W2092815053 @default.
• W2132667420 cites W2093057490 @default.
• W2132667420 cites W2093885593 @default.
• W2132667420 cites W2100344755 @default.
• W2132667420 cites W2106391200 @default.
• W2132667420 cites W2111990189 @default.
• W2132667420 cites W2116671076 @default.
• W2132667420 cites W2120005441 @default.
• W2132667420 cites W2123831499 @default.
• W2132667420 cites W2124167692 @default.
• W2132667420 cites W2125304534 @default.
• W2132667420 cites W2125756825 @default.
• W2132667420 cites W2127283488 @default.
• W2132667420 cites W2130043670 @default.
• W2132667420 cites W2131696316 @default.
• W2132667420 cites W2142261360 @default.
• W2132667420 cites W2145988176 @default.
• W2132667420 cites W2147298941 @default.
• W2132667420 cites W2152015464 @default.
• W2132667420 cites W2164524378 @default.
• W2132667420 cites W2171405304 @default.
• W2132667420 cites W2317879110 @default.
• W2132667420 cites W2341427843 @default.
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