Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient

We present a case of severe Clostridium difficile infection (CDI) in a non‐neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso‐jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI.     

Fecal microbiota transplantation in treating Clostridium difficile infection

Clostridium difficile infection (CDI) is an increasingly common and severe international health problem. Customary treatment of this infection, usually with antibiotics, is often ineffective and its recurrence is common. In recent years the treatment of recurrent or refractory CDI by the transfer of stool from an uninfected person, so called fecal “microbiota transplantation” has become recognized as effective and generally safe. The effectiveness of this novel treatment is incompletely defined but is likely to be due to its correction of the intestinal dysbiosis that characterizes the disease. Practical methods for the administration of the transplantation have been described. This review summarizes the current reported experiences with fecal microbiota transplantation in the treatment for CDI.     

Clinical implications of antibiotic impact on gastrointestinal microbiota and Clostridium difficile infection

The human gastrointestinal (GI) microbiota plays an important role in human health. Anaerobic bacteria prevalent in the normal colon suppress the growth of non-commensal microorganisms, thus maintaining colonic homeostasis. The GI microbiota is influenced by both patient-specific and environmental factors, particularly antibiotics. Antibiotics can alter the native GI microbiota composition, leading to decreased colonization resistance and opportunistic proliferation of non-native organisms. A common and potentially serious antibiotic-induced sequela associated with GI microbiota imbalance is Clostridium difficile infection (CDI), which may become recurrent if dysbiosis persists. This review focuses on the association between antibiotics and CDI, and the antibiotic-induced disruption leading to recurrent CDI. Promoting antibiotic stewardship is pivotal in protecting native microbiota and reducing the incidence of CDI and other GI infections.     

Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection

Fecal microbiota transplantation (FMT ) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT ) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012‐December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT . The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was ?17.65 (95% CI ?1.25 to 0.58) (ng/mL)/(mg/kg/d), P ‐value .43 by Wilcoxon signed‐rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was ?0.33 (95% CI ?1.25 to 0.58) (ng/mL)/(mg/d), P ‐value .28 by Wilcoxon signed‐rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT , with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.     

Roseomonas bacteremia in a recipient of an allogeneic hematopoietic stem cell transplantation

Roseomonas are pink‐pigmented, oxidative, slowly growing, nonfermentative, gram‐negative coccobacilli whose identification may require extensive biochemical testing and molecular profiling. Roseomonas infections vary in severity and clinical presentation, and they predominantly occur in immunocompromised and chronically ill patients. The organism is generally susceptible to carbapenems and aminoglycosides, but resistant to most of the cephalosporins and broad‐spectrum penicillins. Reported here is a patient with lymphoblastic lymphoma who developed Roseomonas mucosa bacteremia after receiving her hematopoietic stem cell allograft. The bacteremic episode was successfully treated with imipenem and amikacin in addition to removal of the central venous catheter. To our knowledge, this is the first report of Roseomonas bacteremia in a stem cell transplantation recipient.     

Challenges in management of recurrent and refractory Clostridium difficile infection

Clostridium difficile infection (CDI) is the most common nosocomial infection in the United States and is associated with a high mortality. One quarter of patients treated for CDI have at least one recurrence. Spore persistence, impaired host immune response and alteration in the gastrointestinal microbiome due to antibiotic use are factors in recurrent disease. We review the etiology of recurrent CDI and best approaches to management including fecal microbiota transplantation.     

Serum macrophage migration inhibitory factor (MIF) levels after allogeneic hematopoietic stem cell transplantation

Macrophage migration inhibitory factor (MIF) may play an important role in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), as MIF plays an important role to regulate the production of tumor necrosis factor-alpha (TNF-alpha), one of the inflammatory cytokines which induces and exacerbates aGVHD. We examined the association between serum MIF levels and aGVHD vs. chronic GVHD (cGVHD) in allo-SCT patients in this study. We found a significant increase in the peak serum MIF (14.46 ng +/- 1.47 ng/ml) at onset in patients that developed aGVHD (n = 23, P = 0.009). We also found that mean serum MIF levels in patients who developed extensive type cGVHD within 6 months (12.58 +/- 2.18 ng/ml, n = 13) were significantly higher than MIF levels before allo-HSCT (7.86 +/- 1.17 ng/ml, n = 19, P = 0.04). Therefore, we speculated that serum MIF levels increase during the active phase of both aGVHD and cGVHD.     

Retrospective evaluation of fidaxomicin versus oral vancomycin for treatment of Clostridium difficile infections in allogeneic stem cell transplant

Objective/background

Clostridium difficile infection (CDI) is a potential complication during hematopoietic stem cell transplantation (HSCT), and no specific recommendations exist regarding treatment of CDI in allogeneic SCT patients. Use of metronidazole and oral vancomycin has been associated with clinical failure. Fidaxomicin has previously been found noninferior to the use of oral vancomycin for the treatment of CDI, and no studies have compared the use of oral vancomycin with fidaxomicin for the treatment of CDI in allogeneic SCT.

Effect of blood cyclosporine concentration on the outcome of hematopoietic stem cell transplantation from an HLA-matched sibling donor

We retrospectively evaluated the effect of the blood cyclosporine (CsA) concentration on the outcome of allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor in 171 patients who received a continuous infusion of CsA and short-course methotrexate to prevent graft-versus-host disease (GVHD). CsA was started at 3.0 mg/kg/day and the dose was adjusted to maintain the blood CsA concentration between 250 and 350 ng/ml. The actual dose of CsA averaged 1.9 mg/kg/day at the 3rd week after transplantation. The incidence of grade II-IV acute GVHD was 29.9%. Patient age and sex were identified as independent significant risk factors for acute GVHD. The CsA concentration during the 3rd week after transplantation most strongly affected the incidence of grade II-IV acute GVHD (RR 0.995 for an increase in CsA concentration by 1 ng/ml, P = 0.037) adjusted for other risk factors. The incidence of acute GVHD was significantly lower in patients with a 3rd-week CsA concentration higher than 300 ng/ml than in those with values between 200 and 300 ng/ml (20% vs. 35%, P = 0.036). We concluded that the blood CsA concentration at peri-engraftment period may be important in preventing acute GVHD.