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By Stan Deresinski, MD, FACP, FIDSA
Clinical Professor of Medicine, Stanford University
Dr. Deresinski reports no financial relationships relevant to this field of study.
SYNOPSIS: Two patients developed bacteremia due to an extended-spectrum beta-lactamase producing Escherichia coli that had been transmitted to them via stool transplantation.
SOURCE: DeFilipp Z, Bloom PP, Torres Soto M, et al. Drug-resistant E. coli bacteremia transmitted by fecal microbiota transplant. N Engl J Med 2019 Oct 30. doi: 10.1056/NEJMoa1910437. [Epub ahead of print].
A 69-year-old man with cirrhosis due to chronic hepatitis C virus infection received fecal microbiota transplantation (FMT) oral capsules upon enrolling in an open-label trial to assess its role in prevention of hepatic encephalopathy, for which he also received rifaximin. He developed fever and a pulmonary infiltrate 17 days after his last FMT dose and was given levofloxacin, which was changed to piperacillin-tazobactam when blood cultures yielded aerobic Gram-negative bacilli. A further therapeutic change was made to carbapenem therapy when the organism was found to be an extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, and the infection resolved.
A 73-year-old man with myelodysplastic syndrome was admitted for receipt of an allogeneic hematopoietic stem cell transplant (allo-HCT) from an unrelated HLA-mismatched donor after reduced intensity conditioning. He was given two doses of cyclophosphamide, followed by ongoing sirolimus and mycophenolate mofetil as prophylaxis against graft-versus-host disease and also received antibacterial prophylaxis with cefpodoxime. He received multiple doses of FMT oral capsules as part of a study of its effects in allo-HCT. Five days after receipt of his transplant and eight days after receipt of his last FMT capsule, at which time his absolute neutrophil count was 0/mm3, he became febrile. Blood drawn for culture yielded an ESBL-producing E. coli. He worsened and died despite treatment with meropenem.
Both patients had received FMT capsules from the same lot, and ESBL-positive E. coli was detected in each of these lots. Although screening of donor stool for the presence of ESBL-producing E. coli was initiated prior to these cases in January 2019, these lots had been prepared before that time and did not undergo such screening. Isolates from the implicated lot and those from the patients were found to be essentially identical by whole genome sequencing.
Gram-negative bacteremia has been reported rarely as a complication of FMT. In fact, recent evidence indicates that, when used in the management of patients with recurrent Clostridioides difficile infection (CDI), FMT appears to protect from bloodstream infection.1
The two patients described here received FMT for reasons other than recurrent CDI, and both had disease states that predispose to bacteremia. One of the patients, who was treated in the setting of allogeneic stem cell transplantation and profound neutropenia, died as a consequence of bloodstream infection, despite having received appropriate antibiotic therapy.
If nothing else, this report illustrates the critical importance of extensive screening of donor stool before its clinical use.
Financial Disclosure: Peer Reviewer Patrick Joseph, MD, is a consultant for Genomic Health Reference Laboratory, Siemens Clinical Laboratory, and CareDx Clinical Laboratory. Infectious Disease Alert’s Editor Stan Deresinski, MD, FACP, FIDSA, Updates Author Carol A. Kemper, MD, FACP, Peer Reviewer Kiran Gajurel, MD, Executive Editor Shelly Morrow Mark, Editor Jason Schneider, and Editorial Group Manager Leslie Coplin report no financial relationships to this field of study.