Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients

Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.     

Mycobacterium gordonae urinary infection in a renal transplant recipient

Abstract: The authors present a case of urinary infection by a non-tuberculous mycobacteria (NTM) species, Mycobacterium gordonae , in a renal transplant recipient. A 29-year-old female patient had persistent sterile pyuria after her second kidney transplant. An NTM, M. gordonae , was isolated, and the patient was started on antituberculous treatment, with resolution of leukocyturia. Ureteral stenosis with hydronephrosis and deterioration of allograft function was diagnosed later on and, despite the introduction of intraureteral catheter and resolution of hydronephrosis, there was no recovery of baseline renal function. She ultimately resumed dialysis after a severe pyelonephritis. The authors discuss the problems of establishing diagnosis of infection (versus colonization) by NTM and highlight the difficulty of treating these infections, especially because of the possible interaction with immunosuppressant agents, facilitating anti-allograft immune response.     

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.     

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.     

Mycobacterium avium complex disseminated infection in a kidney transplant recipient

Mycobacterium avium‐intracellulare complex (MAC) infections are well known in immunocompromised patients, notably in human immunodeficiency virus infection, but remain scarcely described in kidney transplantation. Moreover, cutaneous involvement in this infection is very unusual. We describe here a disseminated infection caused by MAC in a kidney transplant recipient revealed by cutaneous lesions. This case highlights the need for an exhaustive, iterative microbiologic workup in the context of an atypical disease presentation in a renal transplant patient, regardless of the degree of immunosuppression.     

Prospective study of urinary tract infection surveillance after kidney transplantation

Background  

Urinary tract infection (UTI) remains one of the main complications after kidney transplantation and it has serious consequences.     

Fecal microbiota transplantation for management of Clostridium difficile infection

The widespread use of antibiotics has led Clostridium difficile infection (CDI) to become a common problem with pronounced medical and economic effects. The recurrence of CDI after treatment with standard antibiotics is becoming more common with the emergence of more resistant strains of C. difficile. As CDI is an antibiotic-associated disease, further treatment with antibiotic is best avoided. As the gut flora is severely disturbed in CDI, approaches that restore the gut microbiota may become good alternative modes of CDI therapies. Fecal microbiota transplantation (FMT) is the procedure of transplantation of fecal bacteria from a healthy donor individual into a patient for restoration of the normal colonic flora. Thus, FMT helps in the eradication of C. difficile and resolution of clinical symptoms such as diarrhea, cramping, and urgency. Though this approach to treatment is not new, presently, it has become an alternative and promising way of combating infections. The procedure is not in regular use because of the time required to identify a suitable donor, the risk of introducing opportunistic pathogens, and a general patient aversion to the transplant. However, FMT is gaining popularity because of its success rate as a panacea for recurrent attacks of CDI and is being increasingly used in clinical practice. This review describes the rationale, the indications, the results, the techniques, the potential donors, the benefits as well as the complications of fecal microbiota instillation to CDI patients in order to restore the normal gut flora.     

Treatment of recurrent urinary tract infections in a 60‐year‐old kidney transplant recipient. The use of phage therapy

We would like to demonstrate the difficulty of treatment in a patient after kidney transplantation (KTX) who developed chronic urinary tract infection (UTI) with a multi‐drug resistant ESBL‐producing Klebsiella pneumoniae. The patient underwent several treatment interventions including supportive therapy with bacteriophages. This article presents a case of a 60‐year‐old patient after KTX repeatedly admitted to the hospital with recurrent UTIs caused by ESBL‐producing Klebsiella pneumoniae showing variable susceptibility to carbapenems and full susceptibility to colistin only. KTX was performed due to renal insufficiency caused by polycystic kidney disease. The patient experienced 12 severe episodes of UTI due to K pneumoniae within 15 months since transplantation. In an attempt to curb the ongoing infections, phage therapy (PT) was applied on the experimental basis, coordinated by the Phage Therapy Unit of the Hirszfeld Institute in Wroclaw, Poland. Eventually, the patient fully recovered following nephrectomy of his own left kidney where cysts were the suspected reservoir of bacteria. The patient completed 29 days of PT. PT caused no reported side effects in the described case of the KTX recipient, although its role in controlling chronic UTI caused by K pneumoniae is unclear. More studies are needed in the population of kidney transplant recipients.     

Severe recurrent cytomegalovirus disease revealed by a colocutaneous fistula in a kidney transplant recipient

Abstract: Intestinal disorders are classical complications of cytomegalovirus (CMV) infection in kidney transplant recipients (H elderman JH , G oral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002: 13: 277–287). Severe ulcerative colitis that is sometimes lethal has been reported (F oucar E , M ukai K , F oucar K , S utherland DE , V an B uren CT. Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 1981: 76: 788–801 and F rankel AH , B arker F , W illiams G , B enjamin IS , L echler R , R ees AJ . Neutropenic enterocolitis in a renal transplant patient. Transplantation 1991: 52: 913–914). The immunosuppressive drugs currently used, and notably mycophenolate mofetil (Cellcept^®), cause significant changes in the incidence, duration, and viral load of CMV infections with severe atypical forms of CMV disease (D e M aar EF , V erschuuren EA , H oman vd H eide JJ, et al. Effects of changing immunosuppressive regimen on the incidence, duration and viral load of cytomegalovirus infection in renal transplantation: a single center report. Transpl Infect Dis 2002: 4: 17–24 and P erez V alentin MA , C ofan F , S ole M, et al. Atypical cytomegalovirus in renal transplantation: a new form of presentation. Nefrologia 2002: 22: 381–385). This report describes a patient who suffered from several episodes of colitis due to an unusual and late‐appearing CMV infection.     

Cutaneous Mycobacterium haemophilum infection in a kidney transplant recipient after acupuncture treatment

A.N. Castro‐Silva, A.O. Freire, R.S. Grinbaum, M.R. Elmor de Araújo, H. Abensur, M.R.T. Araújo, J.E. Romão Jr, J.L.M. Sampaio, I.L. Noronha. Cutaneous Mycobacterium haemophilum infection in a kidney transplant recipient after acupuncture treatment.
Transpl Infect Dis 2011: 13: 33–37. All rights reserved Abstract: Mycobacterium haemophilum is a slow‐growing nontuberculous mycobacterium that can cause disease in both immunocompetent and immunocompromised patients. The most common clinical presentations of infection are the appearance of suppurative and ulcerated skin nodules. For the diagnosis, samples collected from suspected cases must be processed under the appropriate conditions, because M. haemophilum requires lower incubation temperatures and iron supplementation in order to grow in culture. In this case report, we describe the occurrence of skin lesions in a kidney transplant recipient, caused by M. haemophilum, associated with acupuncture treatment. The diagnosis was established by direct smear and culture of material aspirated from cutaneous lesions. Species identification was achieved by characterization of the growth requirements and by partial sequencing of the hsp65 gene. The patient was successfully treated with clarithromycin and ciprofloxacin for 12 months. Considering that the number of patients receiving acupuncture treatment is widely increasing, the implications of this potential complication should be recognized, particularly in immunosuppressed patients.     

Laryngeal histoplasmosis in a kidney transplant recipient

Histoplasma capsulatum is an endemic fungus that most oftenly causes a self‐limiting illness but can result in severe infections in immunocompromised patients including pulmonary or extra‐pulmonary disease. Rarely it can also cause a chronic progressive infection of the larynx. Herein, we report a case of laryngeal histoplasmosis in a kidney transplant patient who presented with progressive symptoms of several weeks of hoarseness, dysphagia and odynophagia. Laryngoscopic examination revealed thick plaques in the oropharynx with surrounding hyper‐erythema and histopathology showed numerous intracellular yeasts forms consistent with H capsulatum. Patient was initiated on treatment with itraconazole. Infection of the larynx due to H capsulatum is highly uncommon and therefore can result in an inappropriate or delayed diagnosis. A review of literature showed four previously reported cases of laryngeal histoplasmosis in patients with solid organ transplant. This is the first case series of laryngeal histoplasmosis in transplant recipients.     

Purpureocillium lilacinum tattoo‐related skin infection in a kidney transplant recipient

Purpureocillium lilacinum is an emerging pathogenic mold among immunocompromised hosts that causes cutaneous infections related to skin breakdown. We present the first reported case of P. lilacinum tattoo‐related skin infection, to our knowledge. A kidney transplant recipient recently treated for acute cellular rejection presented with skin papules overlying a tattoo. Diagnosis was confirmed on culture, histology, and 18S ribosomal RNA polymerase chain reaction. The morphological features on culture characteristic of P. lilacinum included violet colonies on malt extract agar, long tapering brush‐like phialides, and elliptical conidia attached in chains. P. lilacinum has intrinsic resistance to many antifungal agents including amphotericin B, but voriconazole and posaconazole have good in vitro activity. The patient was treated with voriconazole with subsequent resolution of the papules after 3 months of therapy.     

Ecthyma gangrenosum in a kidney transplant recipient with Pseudomonas septicemia

This report describes a renal transplant recipient in whom Pseudomonas septicemia and ecthyma gangrenosum developed within days of renal transplantation. Microscopic skin sections showed perivascular bacillary invasion. Pseudomonas organisms were cultured and microscopically visualized in sections from the transplanted kidney. Although cultures from the donor kidney preservation perfusate fluid showed no growth, Pseudomonas aeruginosa was found in the recipient's urine, blood, and peritoneal fluid. The recipient's course was complicated by septic shock, cardiopulmonary arrest, coma, and extensive skin lesions; but his condition improved with appropriate antibiotic therapy, wound debridement, and an aggressive rehabilitative program. He is now a candidate for retransplantation. This is the first known case of ecthyma gangrenosum in a renal transplant recipient.     

粪菌移植与肝癌

<正>人体胃肠道栖息着大量的、种类繁多的微生物,其中最主要的是细菌,我们称之为肠道菌群。作为人体最复杂的微生态系统之一,肠道菌群对人类健康有着重要的影响。通过与肠粘膜相互作用,肠道菌群参与机体营养物质的新陈代谢和免疫调节等过程~([1])。不仅如此,肠道菌群和人体疾病的发生发展亦有重要的联系~([2])。肠道菌群失调不仅打破了所处肠道微环境的动态平衡,直接导致肠道疾病,而     

粪菌移植与慢性肝脏疾病

<正>成人胃肠道粘膜表面积达到300 m2,是人体与外界环境发生相互作用最大的区域。在成人胃肠道中定殖着超过1×10~(14)个微生物。各种不同的环境信号和不同的饮食习惯使肠道微生物群产生大量的代谢产物以及脂多糖/内毒素、胆汁酸、短链脂肪酸、三甲胺等物质。肝脏作为肠道营养物质、细菌产物、毒素以及其他各种代谢产物的接受者和过滤者,经受着这些物质的作用,可能造成许多肝脏疾     

Fecal microbiota transplantation and emerging applications

Fecal microbiota transplantation (FMT) has been utilized sporadically for over 50 years. In the past few years, Clostridium difficile infection (CDI) epidemics in the USA and Europe have resulted in the increased use of FMT, given its high efficacy in eradicating CDI and associated symptoms. As more patients request treatment and more clinics incorporate FMT into their treatment repertoire, reports of applications outside of CDI are emerging, paving the way for the use of FMT in several idiopathic conditions. Interest in this therapy has largely been driven by new research into the gut microbiota, which is now beginning to be appreciated as a microbial human organ with important roles in immunity and energy metabolism. This new paradigm raises the possibility that many diseases result, at least partially, from microbiota-related dysfunction. This understanding invites the investigation of FMT for several disorders, including IBD, IBS, the metabolic syndrome, neurodevelopmental disorders, autoimmune diseases and allergic diseases, among others. The field of microbiota-related disorders is currently in its infancy; it certainly is an exciting time in the burgeoning science of FMT and we expect to see new and previously unexpected applications in the near future. Well-designed and well-executed randomized trials are now needed to further define these microbiota-related conditions.