<i>Clostridium difficile</i>‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes

Dubberke, Erik R.; Reske, Kimberlay A.; Srivastava, Anand; Sadhu, Justin S.; Gatti, Robert; Young, Rebecca M.; Rakes, Lauren; Dieckgraefe, Brian K.; DiPersio, John F.; Fraser, Victoria J.

doi:10.1111/j.1399-0012.2009.01035.x

Cited by 74 publications

(88 citation statements)

References 19 publications

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“…Stevens et al 19 showed that cumulative increase in number of antibiotic doses and duration increased the risk of CDI exponentially. Third-and fourth-generation cephalosporins and ciprofloxacin are the most common antibiotics associated with increased risk of recurrent CDI, 6,20 and we found a similar trend with exception that penicillins were more commonly used. Hensgens et al 20 showed that risk of colonization with C. diff was high during and after 3 months of stopping antibiotic therapy.…”

Section: Discussionsupporting

confidence: 69%

Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients

Mani

Rybicki

Jagadeesh

et al. 2016

Bone Marrow Transplant

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Clostridium difficile infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of preparative regimen and GvHD-induced gut mucosal damage. Our study evaluated risk factors (RF) for recurrent CDI in HSCT recipients given the ubiquity of traditional RF for CDI in this population. Of the 499 allogeneic HSCT recipients transplanted between 2005 and 2012, 61 (12%) developed CDI within 6 months before transplant or 2 years after transplant and were included in the analysis. Recurrent CDI occurred in 20 (33%) patients. One year incidence of CDI recurrence was 31%. Multivariable analyses identified the number of antecedent antibiotics other than those used to treat CDI as the only significant RF for recurrence (hazard ratio 1.96, 95% confidence interval 1.09-3.52, P = 0.025). Most recurrences occurred within 6 months of the first CDI, and the recurrence of CDI was associated with a trend for increased risk of mortality. This prompts the need for further investigation into secondary prophylaxis to prevent recurrent CDI. INTRODUCTIONClostridium difficile (C. diff) infection (CDI) is one of the leading causes of hospital-acquired infections in recent times. Allogeneic hematopoietic stem cell transplantation (HSCT) confers increased risk for CDI because of prolonged hospital stay, immunosuppression, the need to use broad-spectrum antibiotics and a complex interplay of chemo-preparative regimen and GvHD-induced gut mucosal damage. The incidence of CDI following autologous and allogeneic HSCT ranges from 5 to 20% 1-8 and recurrence rate has been~20%; 1 consistent with the general population. There are numerous studies describing the epidemiology and risk factors (RFs) of recurrent CDI in the general population, namely receipt of antibiotics, age 460 years, length of hospital stay and concomitant receipt of antacid medications. 9-12 Allogeneic HSCT recipients are a unique patient population, given the ubiquity of traditional risk factors and gut involvement with GvHD, with three studies showing an increased risk of CDI in patients with GvHD, 1,3,7 and there is a need to understand the risk of recurrence in this highly vulnerable group of immunosuppressed patients. Identifying these RFs will enable us to establish preventive measures for CDI by modifying our infection prevention and antibiotic utilization policies.

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Section: Discussionsupporting

confidence: 69%

Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients

Mani

Rybicki

Jagadeesh

et al. 2016

Bone Marrow Transplant

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“…In most studies, there do not appear to be any unique risk factors among HSCT recipients that are not shared by other nontransplant at-risk patients (256,263). However, in a large study by Dubberke et al, patients who received a third-or fourth-generation cephalosporin were more at risk for development of C. difficile disease (264). This study also demonstrated that the receipt of growth factors was associated with decreased risk (264).…”

Section: Hematopoietic Stem Cell Transplant Patientssupporting

confidence: 48%

“…However, in a large study by Dubberke et al, patients who received a third-or fourth-generation cephalosporin were more at risk for development of C. difficile disease (264). This study also demonstrated that the receipt of growth factors was associated with decreased risk (264). These findings, especially the potentially protective effect of growth factors, need to be verified by prospective studies.…”

Section: Hematopoietic Stem Cell Transplant Patientsmentioning

confidence: 67%

“…Once patients develop symptomatic C. difficile disease, the incidence of graft-versus-host disease (GVHD) greater than grade 2 and mortality not related to relapse of the underlying malignancy are higher than in uninfected patients (264,265). In a study by Alonso et al, there was a strong relationship between early C. difficile disease and the development of GVHD in the year following infection.…”

Section: Hematopoietic Stem Cell Transplant Patientsmentioning

confidence: 97%

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Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

2013

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SUMMARY Clostridium difficile is a formidable nosocomial and community-acquired pathogen, causing clinical presentations ranging from asymptomatic colonization to self-limiting diarrhea to toxic megacolon and fulminant colitis. Since the early 2000s, the incidence of C. difficile disease has increased dramatically, and this is thought to be due to the emergence of new strain types. For many years, the mainstay of C. difficile disease diagnosis was enzyme immunoassays for detection of the C. difficile toxin(s), although it is now generally accepted that these assays lack sensitivity. A number of molecular assays are commercially available for the detection of C. difficile . This review covers the history and biology of C. difficile and provides an in-depth discussion of the laboratory methods used for the diagnosis of C. difficile infection (CDI). In addition, strain typing methods for C. difficile and the evolving epidemiology of colonization and infection with this organism are discussed. Finally, considerations for diagnosing C. difficile disease in special patient populations, such as children, oncology patients, transplant patients, and patients with inflammatory bowel disease, are described. As detection of C. difficile in clinical specimens does not always equate with disease, the diagnosis of C. difficile infection continues to be a challenge for both laboratories and clinicians.

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“…Although the exact relationship between GVHD and CDI remains unknown, they may be interrelated, as studies have shown an increased risk for gut and severe GVHD after CDI (Chakrabarti et al, 2000;Dubberke et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Risk factors, outcomes and epidemiology associated with Clostridium difficile infection in patients with haematological malignancies in a tertiary care hospital in China

Chen

et al. 2015

Journal of Medical Microbiology

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The purpose of this study was to evaluate the risk factors, outcomes and epidemiology associated with Clostridium difficile infection (CDI) in patients with haematological malignancies in a tertiary care hospital in China. C. difficile screening was performed on patients admitted for chemotherapy or haematopoietic stem cell transplantation between 2009 and 2013. C. difficile isolates were analysed by multilocus sequence typing, and a retrospective chart review was performed on all patients with a positive toxin assay. CDI was diagnosed in 21 haematologyoncology ward patients and 14 marrow transplantation service patients for a cumulative incidence of 1.89/1000 and 3.69/1000 patient-days, respectively. Univariate analyses showed that patients who received etoposide had an increased risk of CDI (odds ratio 4.25, 95 % confidence interval 1.32-13.64). There was only one patient death, for which CDI was not the primary cause. Ten sequence types (STs) were identified, of which ST-3 and ST-54 were the most common; the hypervirulent ST-1 (ribotype 027) and ST-11 (ribotype 078) C. difficile strains were not detected in the patients in this study. The incidence of CDI did not differ between patients receiving chemotherapy and those receiving haematopoietic stem cell transplantation. The only risk factor for chemotherapy patients was treatment with etoposide.

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Clostridium difficile‐associated disease in allogeneic hematopoietic stem‐cell transplant recipients: risk associations, protective associations, and outcomes

Cited by 74 publications

References 19 publications

Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients

Risk factors for recurrent Clostridium difficile infection in allogeneic hematopoietic cell transplant recipients

Diagnosis of Clostridium difficile Infection: an Ongoing Conundrum for Clinicians and for Clinical Laboratories

Risk factors, outcomes and epidemiology associated with Clostridium difficile infection in patients with haematological malignancies in a tertiary care hospital in China

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