Kevin M. Rank

Fecal Microbiota Transplant for Treatment of Clostridium difficile Infection in Immunocompromised Patients

OBJECTIVES:Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.METHODS:A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.RESULTS:Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3–46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.CONCLUSIONS:This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

Treatment of recurrent Clostridium difficile infection using fecal microbiota transplantation in patients with inflammatory bowel disease

ABSTRACT We recently compared results of fecal microbiota transplantation (FMT) in patients with refractory, recurrent Clostridium difficile infection (rCDI), with and without underlying inflammatory bowel disease (IBD). Here we extend this cohort and analyze outcomes in greater detail by subtype of IBD. We find that FMT is generally effective in breaking the cycle of CDI recurrence, but its effects on overall IBD progression are much less predictable. We discuss several challenges intrinsic to this complex clinical situation and outline the next steps that can address these challenges going forward.

Intravenous lipid rescue and ropivacaine systemic toxicity.

To the Editor: Serious cardiac toxicity following ropivacaine infusion is rare. Side effects that responded to lipid infusions have been described [1]. A 57-year-old man with impaired liver function and end-stage renal disease (ESRD) was admitted for an belowknee amputation. Postoperatively, ropivacaine catheters were placed. Later, the patient became lethargic, and bradycardic, with tinnitus, dysgeusia, and hallucinations. EKG showed widened QRS and prolonged QT without ST changes (Supplementary Figure 1a, b). Echocardiography revealed an ejection fraction (EF) of 20 % without wall motion abnormality. Peak troponin-I-ES = 4.3. We estimated the infusion to be 1,540 mg ropivacaine. A total of 2,480 ml intralipids 20 %, and one round of plasmapheresis, were given with transient response. The patient ultimately died of cardiac arrest (Supplementary Table 1.) Cardiac toxicity has been reversed using infusion of lipids in animal models. Reports have suggested its clinical efficacy in humans [1]. The mechanism of lipid rescue is thought to be a combination of reduced tissue binding by reestablished equilibrium in a plasma lipid phase and a beneficial energetic-metabolic effect. Ropivacaine may be less responsive to lipid rescue therapy because of its decreased lipophilicity. Slow accumulation into tissues may be more difficult to reverse than a sudden bolus [2]. We have evidence of ropivacaine toxicity considering the Naranjo algorithm score of 6, which correlates to the category of a probable adverse drug reaction. The pharmacokinetics are not affected by renal failure, and the liver accounts for the majority of clearance [3]. In this patient, the impaired liver was further hypoperfused, considering myocardial depression. This report suggests the failure of lipid rescue.

CON: Anticoagulation for Portal Vein Thrombosis in Advanced Cirrhosis: Anticoagulation for PVT in Advanced Cirrhosis

• There is not sufficient quality of evidence to suggest that anticoagulation results in higher rates of complete portal vein thrombosis (PVT) resolution. • There is evidence to suggest that the presence of PVT does not impact decompensation, rates of transplantation, or mortality. • There is no reliable manner to assess whether anticoagulation is therapeutic for patients with advanced cirrhosis, and the additional risks of anticoagulation are not clear. • The presence of PVT in advanced cirrhosis is a surrogate marker for disease severity and decompensation and is not the driver of hepatic decompensation. By the time advanced cirrhosis and PVT develop, the benefits of anticoagulation are likely gone.

Fecal Microbiota Transplantation: Current Status in Treatment of GI and Liver Disease

&NA; Fecal microbiota transplantation was originally introduced as a method to repair intestinal microbiota following failure of multiple treatments of recurrent Clostridium difficile infection with antibiotics. However, it is hypothesized that intestinal dysbiosis may contribute to the pathogenesis of many diseases, especially those involving the gastrointestinal tract. Therefore, fecal microbiota transplantation is increasingly being explored as a potential treatment that aims to optimize microbiota composition and functionality. Here, we review the current state of fecal microbiota transplantation development and applications in conditions of greatest interest to a gastroenterologist.

Stool Based Testing for Colorectal Cancer: an Overview of Available Evidence

Purpose of ReviewThe goal of this review is to summarize stool-based testing for colorectal cancer (CRC). The key questions answered in this review were the advantages and limitations of each available stool-based test for CRC and to examine their comparative efficacy.Recent FindingsGuaiac-based fecal occult blood testing (gFOBT) is no longer a relevant test for CRC screening. fecal immunochemical testing (FIT) tests, especially quantitative assays, are clearly a reliable stool-based test. Multitarget DNA (mtsDNA) stool testing may represent a viable option as well, although cost and test characteristics are yet fully defined.SummaryFIT and mtsDNA represent the options for stool-based CRC screening. In larger screening centers, quantitative FIT assays represent an attractive option for stool-based testing. Qualitative FIT has applicability in smaller centers. Although a large validation trial showed promising results for mtsDNA, further head-to-head trials with FIT will help define the ultimate role of mtsDNA. Ultimately, however, the best test for CRC screening is the one performed stool-based CRC screening as an initial or alternative option can increase participation in CRC screening.