Clinical Manifestations and Stool Load of Atypical Enteropathogenic Escherichia coli Infections in United States Children and Adults.

BACKGROUND & AIMS: There is debate whether atypical enteropathogenic Escherichia coli (aEPEC) causes disease in adults. aEPEC is commonly detected in symptomatic and asymptomatic individuals. aEPEC, in contrast to typical EPEC, lacks bundle-forming pili, altering its pathogenicity. Here, we define for the first time the clinical manifestations of sporadic aEPEC infection in United States children and adults and determine whether EPEC load correlates with disease. METHODS: This is a retrospective case-control study of 380 inpatients/outpatients of all ages. EPEC load in stools was determined by quantitative polymerase chain reaction. RESULTS: Diarrhea, vomiting, abdominal pain, and fever were more prevalent in EPEC-positive cases than in EPEC-negative controls. aEPEC infection caused mostly acute, mild diarrhea lasting for 6 to 13 days. However, some had severe diarrhea with 10 to 40 bowel movements per day or had persistent/chronic diarrhea. Fever, vomiting, and abnormal serum sodium levels were more common in children. Adults more often reported abdominal pain and longer duration of diarrhea. Symptomatic aEPEC infection was associated with leukocytosis in 24% of patients. EPEC load >0.1% was associated with symptomatic infection; however, loads varied greatly. Co-infecting pathogens did not alter diarrhea severity or EPEC load. Longitudinal data reveal that some are colonized for months to years or are repeatedly infected. CONCLUSIONS: aEPEC is associated with a wide array of symptoms in adults, ranging from asymptomatic carriage to severe diarrhea. Higher EPEC loads are associated with presence of symptoms, but bacterial load does not predict disease or severity. Future studies are needed to understand bacterial and host factors that contribute to aEPEC pathogenicity to improve diagnostic tools and clinical care.

Shiga Toxin-Producing Escherichia coli Transmission via Fecal Microbiota Transplant.

Fecal microbiota transplantation (FMT) is recommended therapy for multiply recurrent Clostridioides difficile infection. We report adverse events in 7 patients who received FMT from a stool donor who was colonized with Shiga toxin-producing Escherichia coli (STEC). No patients died of FMT-transmitted STEC. Improved screening can likely avoid future transmission.

Successful treatment of fulminant Clostridioides difficile infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia.

We present a patient with acute myeloid leukemia and prolonged, severe neutropenia who developed fulminant Clostridioides difficile infection refractory to medical therapy and was high-risk for surgical intervention. He was treated with fecal microbiota transplantation (FMT) for life-saving cure. The patient had subsequent clinical improvement, however, developed multidrug-resistant Pseudomonas aeruginosa bacteremia 2 days post-procedure. We describe subsequent investigation of this event that found this bacteremia was not related to the donor stool administered during FMT. This case adds to the literature that FMT could be considered in heavily immunocompromised patients with fulminant Clostridioides difficile infection where maximal medical therapy has been ineffective and surgery may carry an excessively high mortality risk.

Stool Banking for Fecal Microbiota Transplantation: Methods and Operations at a Large Stool Bank.

Objectives: Fecal microbiota transplantation (FMT) is a recommended therapy for recurrent Clostridioides difficile infection and is being investigated as a potential therapy for dozens of microbiota-mediated indications. Stool banks centralize FMT donor screening and FMT material preparation with the goal of expanding access to FMT material while simultaneously improving its safety, quality, and convenience. Although there are published consensuses on donor screening guidelines, there are few reports about the implementation of those guidelines in functioning stool banks. Methods: To help inform consensus standards with data gathered from real-world settings and, in turn, to improve patient care, here we describe the general methodology used in 2018 by OpenBiome, a large stool bank, and its outputs in that year. Results: In 2018, the stool bank received 7,536 stool donations from 210 donors, a daily average of 20.6 donations, and processed 4,271 of those donations into FMT preparations. The median time a screened and enrolled stool donor actively donated stool was 5.8 months. The median time between the manufacture of an FMT preparation and its shipment to a hospital or physician was 8.9 months. Half of the stool bank's partner hospitals and physicians ordered an average of 0.75 or fewer FMT preparations per month. Conclusions: Further knowledge sharing should help inform refinements of stool banking guidelines and best practices.

Modeling Donor Screening Strategies to Reduce the Risk of Severe Acute Respiratory Syndrome Coronavirus 2 Transmission via Fecal Microbiota Transplantation.

The potential for transmission of severe acute respiratory syndrome coronavirus 2 shed in stool via fecal microbiota transplantation is not yet known, and the effectiveness of various testing strategies to prevent fecal microbiota transplantation-based transmission has also not yet been quantified. In this study, we use a mathematical model to simulate the utility of different testing strategies.

Lactate as a predictor of mortality in Malawian children with WHO-defined pneumonia.

OBJECTIVES: To determine whether blood lactate measured at the time of presentation to hospital predicted outcome in children with pneumonia in Malawi, and to understand the factors associated with high blood lactate concentrations in pneumonia. DESIGN: Analysis of data from a prospective study of children presenting to Queen Elizabeth Central Hospital, Blantyre, with WHO-defined severe or very severe pneumonia. RESULTS: Among 233 children with pneumonia, the median serum lactate concentration was 2.7 mmol/l (IQR 1.8-4.4 mmol/l). 77 children (33%) had a lactate concentration of 2.1-4.0 mmol/l, and 72 children (31%) had a lactate concentration >4.0 mmol/l. 92% of children who died (23/25) had lactate >2.0 mmol/l at the time of admission to hospital. There were 10 deaths (13%) among 77 children who had a serum lactate concentration of 2.1-4.0 mmol/l; and 13 deaths (18%) in the 72 children who had lactate >4.0 mmol/l. The relative risk of death if the lactate level was above 2 mmol/l was 7.48 (1.72-32.6); sensitivity 0.92, specificity 0.39, positive predictive value 0.15, negative predictive value 0.98. Multivariable analysis showed that hypoxaemia, hyperlactataemia and age ≤12 months were independent risk factors for death from pneumonia. CONCLUSIONS: Used in conjunction with clinical risk factors and pulse oximetry for measuring oxygen saturation, lactate could play an important role in identifying the sickest patients with pneumonia in developing countries.