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Letters to the Editor
of the National Health Authority (Consiglio Superiore Sanità) (http://www.regione.lazio.it/binary/rl_sanita/tbl_nor- mativa/SAN_DCA_U00111_14_03_2019.pdf). FMT emul- sion was prepared under aerobic conditions, from either frozen or fresh preparation, according to stool bank avail- ability and clinical need. FMT infusion was performed via esophagogastroduodenoscopy (EGDS) in the duode- num. A naso-gastric tube was placed after FMT in order to protect the patient from vomiting/inhalation. During the week before FMT, no systemic antibiotics were administered. All patients, except one, received a 3-day course of oral colistin before FMT to improve decoloniza- tion efficacy. Stool sample collection was performed at the FMT day (T0), day 1(T1), 3(T2), 7±1(T3), 10±2(T4), 20±3(T5), 25±2(T6), 28±2(T7), according to patients’ clinical condition and sample availability.
After a minimum of three days post-FMT, based on physician's evaluation, the conditioning regimen for HSCT was started. Anti-infectious prophylaxis/treatment strategy is reported in the Online Supplementary Appendix. Adverse events (AE) were graded according to Common Terminology Criteria for Adverse Events (CTCAE), ver- sion 4.03. MDR bacteria surveillance and gut microbiota profiling are reported in the Online Supplementary Appendix.
Multi-drug resistant decolonization was achieved within one week in 4 of 5 patients (80%), for whom RT- PCR for bla alleles resulted negative on stools. However, at 1-month follow-up, the only patient who was still col- onized after FMT, achieved decolonization, while the four previously decolonized patients switched to a new colonization status (from the same pathogen identified before FMT) (see Figure 1 for details). At last microbio-
logical follow-up (mean time 56 days, range 28-113 days), 4 of 5 patients were colonized by MDR pathogens. Details on gut microbiota ecology are reported in Figure 2 and in the Online Supplementary Appendix.
Patient 1, after achieving decolonization, experienced a sepsis due to the same MDR-colonizing pathogen (Figure 1) 5 days post-HSCT (17 days after FMT). Patient 5 expe- rienced a sepsis 24 hours after FMT from the same pathogen colonizing her stools; however, after careful clinical revision, this was attributed to contamination of the central venous line by the caregiver. Both episodes were promptly treated with targeted antibiotics, and patients fully recovered without sequelae. The remaining three patients did not present any major infective episodes. Other AE recorded were nausea (two patients with grade 1 and 2, respectively), abdominal pain (grade 1), and bloating (grade 1) in single patients.
Globally, FMT for MDR decolonization in pediatric patients has been reported only twice. The first case refers to a 14-year-old patient treated for hemophagocyt- ic lymphohistiocytosis, experiencing recurrent carbapen- em-resistant Klebsiella pneumoniae (CR-KP) infections, successfully decolonized by FMT, and with no recurrence of infection in the following 1.5 years.8 The second patient described in a recent retrospective study focusing on adult hematologic patients was a 16-year-old female with acute myelogenous leukemia.9 This patient under- went two FMT for VRE (Vancomycin-resistant Enterococci) and CP-producing bacteria colonization 98 days after HSCT, resulting in decolonization of VRE and persistence of carbapenemase (CP)-producing bacteria, with no reported AE.
In our study, FMT using samples from the same donor
Figure 1. Distribution of multidrug resistant (MDR) pathogens isolated before and after fecal microbiota transplantation (FMT) and characterized. CF Citrobacter freundii; EC: Escherichia coli; EntCl: Enterobacter cloacae; KP: Klebsiella pneumoniae; Kor: Klebsiella ornithinolytica; KO: Klebsiella oxytoca; NDM New Delhi metallo-beta-lactamase; OXA: oxacillinase; PA: Pseudomonas aeruginosa; Pt: patient; VIM: Verona imipenenase.
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