Page 198 - 2020_11-Haematologica-web

Letters to the Editor
Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes
Fecal microbiota transplantation (FMT) is playing a prominent role in the treatment of recurrent Clostridium difficile infection in adults, showing high efficacy and safety.1 It has also been proposed for treatment of other diseases associated with alterations of intestinal micro- biota, including intestinal inflammatory diseases (inflam- matory bowel disease)2 and graft-versus-host disease (GvHD).3 Moreover, FMT has been proposed for decolo- nization of multi-drug resistant (MDR) germs from the intestinal tract, with good results in adults.4,5 Indeed, antimicrobial resistance (AMR) is of great concern in the hemato-oncologic field, since a very high mortality rate has been demonstrated in patients infected by MDR bac- teria (up to 36-95% in patients undergoing allogeneic
hematopoietic stem cell transplantation [HSCT]).6 Moreover, up to 70% of cases of bacteremia originate from the gut in these patients.7
Between October 2018 and March 2019, five consecu- tive patients colonized by MDR bacteria underwent FMT before HSCT (see Table 1 for details), on a compassion- ate use basis after local ethical committee approval and informed consent of parents/legal guardians of patients. Notably, three patients had a prior history of systemic infections by a colonizing MDR pathogen, which had required intensive care unit admission. Isolated MDR pathogens were Pseudomonas aeruginosa and carbapenem- resistant Enterobacteriaceae (CRE) (Table 1); three patients had isolation of different species of CRE in stools (Figure 1). Real-time polymerase chain reaction (RT-PCR) targeting carbapenemases detected blaVIM in three cases, blaNDM in one case, and blaOXA48-181-232 in another case.
For each subject, the same unrelated healthy volunteer adult donor was used. Donor screening was performed according to European consensus guidelines on FMT,1 our institutional FMT protocol and Italian recommendations
Table 1. Characteristics of patients undergoing fecal microbiota transplantation (FMT) for multidrug resistant (MDR) decolonization. Patient 1 Patient 2 Patient 3 Patient 4 Patient 5
Age(years)atFMT
Gender
Hematologic disease
Phase of disease
MDR pathogen
AMR gene
Pre-FMT relevant infections
Donor
Stool
N.ofFMT
Volume administered
Preparation with oral antibiotic
MDR bacteria clearance at 1 week
MDR bacteria clearance at 1 month MDR bacteria clearance at last follow-up Last microbiological follow-up (days) Time elapsing between FMT and HSCT Type of donor and stem cell source
Conditioning regimen
Graft manipulation CD34+ infused/kg Engraftment Y/N, days Acute/chronic GvHD
Follow-up (days after FMT)
18 17 11 9 2
MMMMF
AML
CR1
PA
blaVIM
Sepsis by Carb-R-PA
AML AML CR1 CR1 CF, KOr, EntCl KP,EC blaVIM blaVIM Sepsis by Carb-R-EC None
ALL
CR2
EC
blaOXA 48-181-232 None
SCID
Disease present
EC, KO, KP
blaNDM
Multiple sepsis and meningoencephalitis
by Carb-R-EC UDUDUDUDUD
Fresh 1
170 mL N
Y
N
N
44
12 days HLA-haploidentical relative, PBSC TBI+TT+LPAM+ ATLG + rituximab
TCRaβ/CD19-depletion 9.6x106
Y,9
N
302
Frozen 1
200 mL Y
Y
N
N
28
14 days HLA-haploidentical relative, PBSC TBI+TT+LPAM+
ATLG + rituximab
TCRaβ/CD19-depletion 14.4x106
Y,12
Y, acute, grade I,
+40 after HSCT
264
Frozen 1
150 mL Y
N
Y
Y
53
13 days HLA-identical sibling, BM Bu+Cy+
LPAM
None 5.2x106 Y,17 N
204
Frozen 1
240 mL Y
Y
N
N
42
16 days HLA-haploidentical relative, PBSC TBI+TT+
162
Frozen 1
100 mL Y
Y
N
N
113
16 days HLA-haploidentical relative, PBSC Treo+Flu+
ATLG + rituximab
TCRaβ/CD19-depletion 18.0x106
Y,12
N
120
Flu + ATLG + rituximab
TCRaβ/CD19-depletion 18.2x106
Y,16
N
AMR: antimicrobial resistant; ALL: acute lymphoblastic leukemia; AML: acute myeloid leukemia; ATLG: anti-T lymphocyte globulins; blaNDM: New Delhi metallo-beta-lactamase; blaVIM: Verona imipenenase;blaOXA oxacillinase;BM:bonemarrow;Bu:busulfan;CF:Citrobacterfreundii;Carb-R:carbapenem-resistant;CR:completeremission;Cy:cyclophosphamide;EC:Escherichia coli; EntCl: Enterobacter cloacae; Flu: fludarabine; GvHD: graft-versus-host disease; HSCT: hematologic stem cell transplantation; KP: Klebsiella pneumoniae; KOr: Klebsiella ornithinolytica; KO: Klebsiella oxytoca; LPAM: melphalan; M: male; N: number; PA: Pseudomonas aeruginosa; PBSC: peripheral blood stem cells; SCID: severe combined immune deficiency; TBI: total body irradiation; TCR: T-cell receptor; Treo: treosulfan; TT: thiotepa; UD: universal donor.
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haematologica | 2020; 105(11)