Clostridium difficile colitis in cystic fibrosis patients with and without lung transplantation

Background. Despite a large carriage rate of Clostridium difficile among cystic fibrosis (CF) patients, C. difficile- associated disease (CDAD) is rather rare. In case of lung transplantation, the incidence and clinical aspects of CDAD in this patient population are not well known.
Methods. We reviewed the medical files of all CF patients who presented with symptomatic C. difficile infection from January 1998 to December 2004 and compared the incidence, clinical aspects, severity of disease, and clinical outcome between non-transplanted and transplanted CF patients.
Results. Between 1998 and 2004, 106 adult CF patients were followed at our clinic. Forty-nine patients underwent lung transplantation; 15 before 1998 and 34 after 1998. The incidence density of CDAD was higher in transplanted CF patients as compared with non-transplanted CF patients (24.2 vs. 9.5 episodes/100,000 patient-days; risk ratio: 2.93 [1.41–6.08]; P =0.0044). Diarrhea was a very frequent feature, but was notably absent in 20% of the cases. Rates of moderate and severe colitis were similar in both groups. However, only transplanted patients developed complicated colitis. CT scan and endoscopy were performed more frequently in the transplant group. Two transplant recipients died because of CDAD.
Conclusion. CF patients who undergo lung transplantation are at a higher risk of developing CDAD and seem to present more often atypical and/or complicated disease. CDAD should be part of the differential diagnosis in case of digestive symptoms, even in the absence of diarrhea, and requires early treatment.     

Clostridium difficile colitis in patients after kidney and pancreas–kidney transplantation

Limited data exist about Clostridium difficile colitis (CDC) in solid organ transplant patients. Between 1/1/99 and 12/31/02, 600 kidney and 102 pancreas-kidney allograft recipients were transplanted. Thirty-nine (5.5%) of these patients had CDC on the basis of clinical and laboratory findings. Of these 39 patients, 35 have information available for review. CDC developed at a median of 30 days after transplantation, and the patients undergoing pancreas-kidney transplantation had a slightly higher incidence of CDC than recipients of kidney alone (7.8% vs. 4.5%, P>0.05). All but one patient presented with diarrhea. Twenty-four patients (64.9%) were diagnosed in the hospital, and CDC occurred during first hospitalization in 14 patients (40%). Treatment was with oral metronidazole (M) in 33 patients (94%) and M+oral vancomycin (M+V) in 2 patients. Eight patients had recurrent CDC, which occurred at a median of 30 days (range 15-314) after the first episode. Two patients (5.7%) developed fulminant CDC, presented with toxic megacolon, and underwent colectomy. One of them died; the other patient survived after colectomy. CDC should be considered as a diagnosis in transplant patients with history of diarrhea after antibiotic use, and should be treated aggressively before the infection becomes complicated.     

High prevalence of gastroesophageal reflux in children after lung transplantation

Bronchiolitis obliterans and its clinical correlate bronchiolitis obliterans syndrome (BOS) are a major cause of morbidity and mortality following lung transplantation. Gastroesophageal reflux disease (GERD) may be a contributing factor for the development of BOS. Since 2002, all recipients of lung and heart-lung transplantation at our institution have been routinely investigated for GERD. In this observational study, we report on the prevalence of GERD in this population, including all pediatric patients undergoing single (SLTx) or double (DLTx) lung transplantation or heart-lung (HLTx) transplantation from January 2003-May 2004. GERD was assessed 3-6 months after transplantation by 24-hr pH testing. The fraction time (Ft) with a pH < 4 within a 24-hr period was recorded. Spirometry data, episodes of confirmed acute rejection, and demographic data were also collected. Ten transplant operations were performed: 4 DLTx, 1 SLTx, and 5 HLTx. Nine patients had cystic fibrosis. One patient had end-stage pulmonary disease secondary to chronic aspiration pneumonia and postadenovirus lung damage. Of 10 patients tested, 2 had severe GERD (Ft > 20%), 5 had moderate GERD (Ft 10-20%), 2 had mild GERD (Ft 5-10%), and 1 had no GERD. The only patient in this group with no GERD had a Nissen fundoplication pretransplant. All study patients were asymptomatic for GERD. All patients with episodes of rejection had moderate to severe GERD posttransplant. There was no association between severity of GERD and peak spirometry results posttransplant. Moderate to severe GERD is common following lung transplantation in children.     

Clostridium difficile associated infection, diarrhea and colitis

A new, hypervirulent strain of Clostridium difficile, called NAP1/BI/027, has been implicated in C. difficile outbreaks associated with increased morbidity and mortality since the early 2000s. The epidemic strain is resistant to fluoroquinolones in vitro, which was infrequent prior to 2001. The name of this strain reflects its characteristics, demonstrated by different typing methods： pulsed-field gel electrophoresis （NAP1）, restriction endonuclease analysis （BI） and polymerase chain reaction （027）. In 2004 and 2005, the US Centers for Disease Control and Prevention （CDC） emphasized that the risk of C. difficile-associated diarrhea （CDAD） is increased, not only by the usual factors, including antibiotic exposure, but also gastrointestinal surgery/manipulation, prolonged length of stay in a healthcare setting, serious underlying illness, immune-compromising conditions, and aging. Patients on proton pump inhibitors （PPIs） have an elevated risk, as do peripartum women and heart transplant recipients. Before 2002, toxic megacolon in C. dif/icile-associated colitis （CDAC）, was rare, but its incidence has increased dramatically. Up to two- thirds of hospitalized patients may be infected with C. difficile. Asymptomatic carriers admitted to healthcare facilities can transmit the organism to other susceptible patients, thereby becoming vectors. Fulminant colitis is reported more frequently during outbreaks of C. difficile infection in patients with inflammatory bowel disease （IBD）. C. diff/cile infection with IBD carries a higher mortality than without underlying IBD. This article reviews the latest information on C. difficile infection, including presentation, vulnerable hosts and choice of antibiotics, alternative therapies, and probiotics and immunotherapy. We review contact precautions for patients with known or suspected C. difficile- associated disease. Healthcare institutions require accurate and rapid diagnosis for early detection of possible outbreaks, to initiate specific therapy and implement effective control measures. A comprehensive C. difficile infection control management rapid response team （RRT） is recommended for each health care facility. A communication network between RRTs is recommended, in coordination with each country＇s department of health. Our aim is to convey a comprehensive source of information and to guide healthcare professionals in the difficult decisions that they face when caring for these oftentimes very ill patients.     

老年难辨梭菌性结肠炎患者八例临床分析

目的　探讨老年患者使用广谱抗生素诱发难辨梭菌性结肠炎的临床特点、内镜下改变及防治措施。　方法　分析８例老年难辨梭菌性结肠炎患者的临床资料,对难辨梭菌分离、鉴定,并行细胞毒素测定。　结果　所用抗生素的种类繁多,在使用抗生素后３ 天至２周内发生腹泻,重者伴腹膜炎,４ 例行纤维结肠镜检查均见有小片至大斑片伪膜附着;治疗措施为停用原抗菌药物,应用万古霉素和（或）甲硝唑及加强支持疗法。８ 例中７例治愈,１例死亡。　结论　老年人特别是术后使用广谱抗生素者易诱发难辨梭菌性结肠炎     

Clostridium difficile and cytomegalovirus colitis co‐infection: search for the hidden ‘bug’

D.F. Florescu, C. Mindru, H.E. Chambers, A.C. Kalil. Clostridium difficile and cytomegalovirus colitis co‐infection: search for the hidden ‘bug’.
Transpl Infect Dis 2011: 13: 411–415. All rights reserved Abstract: Few cases of co‐infection with cytomegalovirus (CMV) and Clostridium difficile colitis have been reported previously. We describe 2 cases of CMV and C. difficile colitis, and review 7 previously published reports. We aim to raise awareness of possible CMV–C. difficile co‐infection, especially in refractory cases of C. difficile colitis.     

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.     

Management of chronic rejection after lung transplantation

Outcomes after lung transplantation are limited by chronic lung allograft dysfunction (CLAD). The incidence of CLAD is high, and its clinical course tends to be progressive over time, culminating in graft failure and death. Indeed, CLAD is the leading cause of death beyond the first year after lung transplantation. Therapy for CLAD has been limited by a lack of high-quality studies to guide management. In this review, we will discuss the diagnosis of CLAD in light of the recent changes to definitions and will discuss the current clinical evidence available for treatment. Recently, the diagnosis of CLAD has been subdivided into bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The current evidence for treatment of CLAD mainly revolves around treatment of BOS with more limited data existing for RAS. The best supported treatment to date for CLAD is the macrolide antibiotic azithromycin which has been associated with a small improvement in lung function in a minority of patients. Other therapies that have more limited data include switching immunosuppression from cyclosporine to tacrolimus, fundoplication for gastroesophageal reflux, montelukast, extracorporeal photopheresis (ECP), aerosolized cyclosporine, cytolytic anti-lymphocyte therapies, total lymphoid irradiation (TLI) and the antifibrotic agent pirfenidone. Most of these treatments are supported by case series and observational studies. Finally, we will discuss the role of retransplantation for CLAD.     

Relevance of maintenance triple‐drug immunosuppression to bridle the amplification of rat cytomegalovirus infection after experimental lung transplantation

Immunosuppressive therapy required to treat rejection after lung transplantation (LTx) contributes significantly to the pathogenesis of cytomegalovirus (CMV) infection and disease. In a weak allogeneic left LTx model in the rat (Fisher 344 [F344] to Wistar Kyoto [WKY] rats) we analyzed the influence of acute CMV infection on postoperative day (POD) 3, with application of standard triple‐drug immunosuppression (TD‐IS) (cyclosporin A, azathioprine, prednisolone) on late outcome after LTx. Native right lungs and syngeneic grafts (WKY to WKY) served as controls. Rats were sacrificed on POD 15, 30, 60, and 100. TD‐IS completely prevented acute and chronic rejection in non‐infected rats. Allografts of CMV‐infected rats treated with TD‐IS showed only mild perivascular infiltrations in 6/10 rats (POD 15 and 30), which persisted up to POD 100 in 4/10 rats. In the long‐term course, mild isolated interstitial and alveolar changes were found in 40% of these animals. In conclusion, rat CMV infection partially neutralized the immunosuppressive effect of TD‐IS. However, an amplification of CMV infection under TD‐IS can be controlled and does not result in fatal outcome.     

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.     

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.     

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.     

Treatment of Clostridium difficile infection in pediatric patients

Clostridium difficile causes infections that can either remain asymptomatic or manifest as clinical disease. In this report, problems, possible solutions, and future perspectives on the treatment of C. difficile infections (CDIs) in pediatric patients are discussed. CDI, despite increasing as a consequence of the overuse and misuse of antibiotics, remains relatively uncommon in pediatrics mainly because younger children are poorly susceptible to the action of C. difficile toxins. In most such cases, C. difficile disease is mild to moderate and discontinuation of the administered antibiotics in patients receiving these drugs when CDI develops, or administration of metronidazole, is sufficient to solve this problem. In severe or frequently relapsing cases, vancomycin is the drug of choice. Probiotics do not seem to add significant advantages. Other treatment options must be reserved for severe cases and be considered as a salvage treatment, although potential advantages in pediatric patients remain unclear.     

单肺移植治疗艾森曼格综合征(附1例报告)

目的总结单肺移植治疗艾森曼格综合征围手术期处理的经验教训。方法对1例52岁的房间隔缺损合并艾森曼格综合征女性患者在全麻体外循环下行同种异体右全肺移植术,同时行房间隔缺损修补术。供体为32岁男性,术前未作HLA配型,供肺保护采用4C改良低钾右旋糖酐液（LPD）灌洗,4CUW液保存。术后给予三联免疫抑制剂。结果术后心肺功能恢复良好。但术后12h发生超急性排斥反应,术后第5天导致急性肝肾功能衰竭,用人工透析维持。第9天出现口腔感染和泌尿系感染,给予口腔护理及氯霉素膀胱冲洗,第12天因全身感染死亡。结论术前供肺保护和手术技巧是单肺移植治疗艾森曼格综合征手术成功的关键;抗排斥和抗感染是手术后处理的重要环节。     

Clinical spectrum of gram-positive infections in lung transplantation

Purpose. Gram-positive (GP) organisms are among the most common cause of infections in early postsurgical and immunocompromised populations. Patients recovering from lung transplantation (LT) are particularly susceptible owing to the physiologic stress imposed by surgery and induction with intense immunosuppression. Sites, types, and timing of GP infections following LT  are not well documented. This report describes the clinical spectrum of GP infections and their effects on surgical airway complications (SAC) and bronchiolitis obliterans syndrome (BOS) following LT.
Methods and materials. Data were collected from 202 patients undergoing 208 LT procedures at a single institution between November 1990 and November 2005. Data were retrospectively analyzed according to timing, location, and causative pathogen.
Results. In the median follow-up period of 2.7 years (range, 0–13.6 years), 137 GP infections were confirmed in 72 patients. Sites of infection included respiratory tract (42%), blood (27%), skin, wound and catheter (21%), and other (10%). GP pathogens identified were Staphylococcus species (77%), Enterococcus species (12%), Streptococcus species (6%), Pneumococcus (4%), and Eubacterium lentum (1%). The likelihood of SAC and BOS was increased in lung allograft recipients with GP pneumonia as compared with those without (hazard ratio 2.1; 95% confidence interval=1.5–3.1).
Conclusions. GP organisms were responsible for infections in 40% of lung allograft recipients and most commonly isolated from the respiratory tract and blood stream. Staphylococcal species were most frequently identified, 42% of which were methicillin-resistant Staphylococcus aureus (MRSA). Given the strong association of respiratory tract infections with the development of SAC and BOS, empiric antimicrobial strategies after LT should include agents directed against GP organisms, especially MRSA.     

Clostridium difficile infection in patients with inflammatory bowel disease: a case control study

Objective: Characterization of predisposing factors for Clostridium difficile infection recurrence (rCDI) and outcome in inflammatory bowel disease (IBD) patients.

Methods: Clinical characteristics of 167 inflammatory bowel disease patients with Clostridium difficile infection (IBD-CDI cohort) treated in Helsinki University Central Hospital were gathered. Medical history of the last three months preceding a toxin positive CDI test was recorded. Parameters, including ribotype of C. difficile, mortality and recurrence were compared with age and gender-matched C. difficile patients (CDI cohort).

Results: No difference was found in rCDI between IBD-CDI and CDI cohorts. As compared with IBD subtypes, rCDI was least common among patients with Crohn’s disease. The use of immunosuppressant therapy was higher in IBD patients with two or more CDI episodes. C. difficile ribotype 027 increased the rates for rCDI in IBD patients but not in non-IBD-CDI patients. The prevalence of 027 ribotype and mortality rates did not differ significantly among the cohorts. None of the IBD patients underwent colectomy upon CDI.

Conclusion: IBD patients are not more susceptible for rCDI than non-IBD patients. Predisposing factors for rCDI among IBD patients are associated with immunosuppressant treatments, colon affecting IBD and CDI caused by ribotype 027. CDI does not worsen the prognosis of IBD patients.     

Factors Related to Outcomes of Fecal Microbiota Transplantation in Patients with Clostridioides difficile Infection

Background/AimsThe aim of this study was to evaluate factors related to outcomes of fecal microbiota transplantation (FMT) in patients with Clostridioides difficile infection (CDI) and viability of frozen stock for FMT.MethodsClinical data of patients who had received FMT for CDI were prospectively collected. Next-generation 16S rRNA gene sequencing of bacteria was performed from donors’ and recipients’ stool. Colony-forming units (CFUs) of cultures from frozen stock solutions for FMT were measured at 0, 4, 8, 12, 24, 48 weeks after preparation of the solutions.ResultsIn total, 25 FMT procedures were performed in 20 cases (14 fresh and 11 frozen FMT). Forty-five percent of cases involved fulminant CDI. The overall success rate was 55% after the 1st FMT and 75% after the 2nd FMT. The success rate was significantly higher in partially treated CDI than in refractory CDI (100% vs 71.4%; p=0.001). In successful cases only, the decrease in alpha-diversity in the recipient stool microbiomes was recovered after FMT to a level similar to that in donor stools. There was a significant difference in the microbiome composition in pre-FMT recipients’ stool between successful and failed cases (p=0.001). The CFUs of frozen solution for FMT did not decrease for 48 weeks in both aerobic and anaerobic cultures.ConclusionsFMT is highly effective in partially treated CDI but not in refractory CDI. The microbiome differs between failed and successful cases. Frozen stock for FMT is viable up to 48 weeks.     

Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen

The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease. C. difficile is an opportunist pathogen that employs many factors to infect and damage the host, often with devastating consequences. This review will focus on the role of the 2 major virulence factors, toxin A (TcdA) and toxin B (TcdB), as well as the role of other putative virulence factors, such as binary toxin, in C. difficile-mediated infection. Consideration is given to the importance of spores in both the initiation of disease and disease recurrence and also to the role that surface proteins play in host interactions.