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G. Battipaglia et al.
Figure 1. Results of fecal microbiota transplantation. FMT: fecal microbiota transplantation; allo-HSCT: allogeneic hematopoietic stem cell transplantation; CPE: car- bapenemase-producing Enterobacteriaceae; CP-Pseudomonas Aeruginosa: carbapenemase producing Pseudomonas Aeruginosa; VRE: vancomycin resistant ente- rococci. *A third patient achieved decolonization from vancomycin-resistant enterococci and then experienced recurrence of colonization 20 months after fecal microbiota transplantation, concomitantly to disease relapse.
enema was the preferred method of administration in all but one patient who presented a compromised neurologi- cal status due to a cerebral toxoplasmosis and was not considered eligible for enema. Median donor stool quan- tity was 84 g (range, 43-104 g). At the time of FMT, neu- trophil count was >1x109/L in all patients but one who had a neutrophil count of 0.17x109/L (with steroid-resis- tant GvHD). Platelet count was count >20x109/L in all patients.
Three patients required a second FMT. In one patient, after initial efficacy, VRE was again detectable two months after the first FMT. This patient developed multi- ple infectious episodes (particularly sinusitis and pneumo- nia), prompting the frequent use of large spectrum antibi- otics; this probably led to recurrence of VRE colonization. In the other two patients, a second attempt was made due to the failure of the first procedure. In one patient, failure was mainly attributable to incorrect preparation with PEG (insufficient intake). After a second attempt with a correct preparation, VRE eradication was achieved and main- tained until 20 months after FMT, at which point, VRE was detectable at the same time as recurrence of hemato- logic disease. In the last patient, administration of first and second FMT was mainly for compassionate use to treat active grade IV gut GvHD and multiple infectious episodes which made withdrawal of antibiotics impossi- ble, even during the 72 hours (h) following FMT (see below).
Globally, major decolonization (three consecutive nega- tive microbiological cultures) was achieved in seven of ten patients, including two patients after a second FMT (Figure 1). Persistent decolonization (negative microbio- logical cultures at last follow up) was achieved in six of ten patients after a median follow up of 13 months (range, 4-40 months) from FMT. Indeed, as already mentioned, one patient presented a positive rectal swab for ERV 20 months after FMT contemporary to disease relapse. She later died due to hematologic progression.
Failure occurred in the remaining three patients. The patient undergoing FMT for compassionate use had pre- sented multiple infectious episodes from CP-Pseudomonas aeruginosa, making it impossible to stop antibiotics during the 72 h after FMT. Moreover, grade IV gut GvHD was associated with intestinal occlusion,
requiring aspiration via a nasogastric tube, at time of FMT. Despite two attempts with FMT, the procedure was a fail- ure and the patient later died. In the second patient, due to the problems encountered in the positioning of a nasogas- tric tube, FMT was administered by enema and the patient was not able to retain the product for the advised 2-3 h; she refused a second attempt. The third patient underwent FMT by enema from an unrelated donor and the reason given for FMT failure was that she had not received sufficient stool quantity (43 g); however, this is not logical given that decolonization from concomitant ESBL-producing Enterobacteriaceae had been achieved. A second attempt in this patient was not possible due to the unavailability of additional material.
Among the six patients concomitantly colonized from ESBL-producing Enterobacteriaceae, three obtained con- comitant decolonization.
Details on FMT performed before or after allo-HSCT are reported in Table 1. As an example of successful FMT, Figure 2 shows the case of the patient undergoing FMT from nasogastric tube, after experiencing breakthrough infectious episodes related to colonization from CP-Pseudomonas aeruginosa requiring continuous hospital- ization for the first year after allo-HSCT. After FMT, this patient did not experience any other infectious episode and could finally be cared for as an outpatient.
With regards to the safety of FMT procedure, one patient presented constipation during the first five days after FMT which was favorably resolved after the use of laxatives, while two patients presented grade I diarrhea the day after FMT. No other major adverse events were observed.
Only one patient undergoing FMT before allo-HSCT developed a grade III acute gut GvHD at day +30 after allo-HSCT and at day +51 after FMT. A differential diag- nosis with CMV colitis was made and she responded favorably to both antiviral and steroid treatment.
When looking at severe infectious episodes during the 90 days following FMT, in two of those patients undergo- ing FMT before allo-HSCT, documented bacteriemia without sepsis occurred early after allo-HSCT; these responded favorably to the introduction of large-spectrum antibiotics. In particular, one patient experienced a docu- mented bacteriemia from multi-sensitive Pseudomonas
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