FMT for Recurrent C. Difficile Infection
FMT for Recurrent C. Difficile Infection
Background Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The finding of suitable donor, donor screening and preparation of faecal transplants are challenging in clinical work.
Aim To develop a practical protocol for preparing frozen transplants and to compare the efficacy of previously frozen and fresh faeces in treating rCDI.
Methods Two healthy volunteers acted as universal donors for the frozen faecal preparations, which were prepared by suspending faeces into physiological saline, adding glycerol to a final concentration of 10% and storing at −80 °C. We compared the outcomes of patients with rCDI who had undergone FMT at colonoscopy and received infusion of previously prepared, freeze-stored faeces (n = 23) or fresh faeces from individual (n = 15) or universal donors (n = 11) (total n = 49). Clinical failure was defined as persistent or recurrent symptoms with a positive C. difficile toxin stool test, and a need for new therapy.
Results At 12 weeks post-FMT, symptoms were resolved in 22 of 23 patients receiving previously frozen faeces, and in all 11 or 14 of 15 patients receiving fresh faeces from the universal or individual donors respectively (totally 25 of 26; P = ns, success rate 96%). Mild transient fever appeared for two patients receiving frozen faeces, but no other significant side effects were observed. 42 patients were followed up for a year post-FMT and the success rate was 88% in both fresh and frozen faeces groups.
Conclusions Preparation of frozen transplants simplifies the practical aspects of faecal microbiota transplantation without loss of efficacy or safety.
Clostridium difficile is a major cause of antibiotics-associated diarrhoea with increasing frequency, severity and relapse rates after conventional treatment with antibiotics, generally metronizadole or vancomycin. A subset of patients experience multiple recurrences of C. difficile infection (CDI) and new approaches, including novel antibiotics such as fidaxomicin and rifaximin, immune-therapy and faecal microbiota transplantation (FMT), have been used to treat multiple CDI recurrences. Paradoxically, antibiotics that are used to treat CDI, also disrupt the normal intestinal microbiota and thereby, may favour the blooming of C. difficile from antibiotic-resistant spores after the discontinuation of the antibiotic.
Thus far, faecal microbiota transplantation has been shown to be the most successful treatment option for recurrent CDI (rCDI) with a recovery rates of over 80% or 90% when faeces is administered once by duodenal or caecal infusion respectively. In FMT, the intestinal microbiota is re-established by transferring faecal material from a healthy, pre-screened donor to the patient via nasogastric tube, through colonoscopy or using an enema. The re-established normal, healthy microbiota offers protection against CDI. FMT therapy and restoration of normal intestinal microbiota usually normalises bowel functioning within days and results in a sustainable clinical outcome. In addition to the efficacy, FMT also seems to be very safe treatment.
Despite the high success rate of FMT in treating recurrent CDI, it's wider practice is hampered by a number of factors including the availability and screening of donors and aesthetic concerns. The use of universal donors for FMT can straighten up the laborious, costly and time-consuming donor screening. Further, the availability of stored, frozen faecal material would allow FMT to be used in clinical practice whenever needed. Recently, the use of standardised frozen preparation for FMT for recurrent CDI was introduced by Hamilton and co-workers. The protocol for processing the faecal material for frozen preparations involved suspension the faecal material into normal saline under N2 gas, followed by several filtration steps, centrifugation and final suspension and addition of glycerol before freezing at −80 °C. While the efficacy of the previously frozen faecal material was comparable to that of fresh faeces in treating rCDI and the protocol resulted in a nearly odourless preparation with reduced viscosity and colour, the preparation procedure is rather demanding to be widely used in a clinical setting. A more recent study presented a protocol for the preparation of frozen faeces, which does not involve working under N2 gas, but still involved several filtrations and a centrifugation step.
Previously, in the Helsinki University Central Hospital, we have treated rCDI patients with FMT via colonoscopy and by using both individual and universal donors and fresh faeces as a transplant. Later, we have changed to use increasingly universal donors and in this study we compared the outcomes of the rCDI patients treated with fresh faeces from individual and universal donors. The main objectives of this study were to develop a simple and practical, one-step protocol for preparing frozen faecal material for FMT and to assess the efficacy of frozen preparations in treating rCDI by using the same administration technique that we have used previously. The clinical outcomes of patients receiving previously frozen or fresh faeces either from individual or universal donors were compared.
Abstract and Introduction
Abstract
Background Faecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The finding of suitable donor, donor screening and preparation of faecal transplants are challenging in clinical work.
Aim To develop a practical protocol for preparing frozen transplants and to compare the efficacy of previously frozen and fresh faeces in treating rCDI.
Methods Two healthy volunteers acted as universal donors for the frozen faecal preparations, which were prepared by suspending faeces into physiological saline, adding glycerol to a final concentration of 10% and storing at −80 °C. We compared the outcomes of patients with rCDI who had undergone FMT at colonoscopy and received infusion of previously prepared, freeze-stored faeces (n = 23) or fresh faeces from individual (n = 15) or universal donors (n = 11) (total n = 49). Clinical failure was defined as persistent or recurrent symptoms with a positive C. difficile toxin stool test, and a need for new therapy.
Results At 12 weeks post-FMT, symptoms were resolved in 22 of 23 patients receiving previously frozen faeces, and in all 11 or 14 of 15 patients receiving fresh faeces from the universal or individual donors respectively (totally 25 of 26; P = ns, success rate 96%). Mild transient fever appeared for two patients receiving frozen faeces, but no other significant side effects were observed. 42 patients were followed up for a year post-FMT and the success rate was 88% in both fresh and frozen faeces groups.
Conclusions Preparation of frozen transplants simplifies the practical aspects of faecal microbiota transplantation without loss of efficacy or safety.
Introduction
Clostridium difficile is a major cause of antibiotics-associated diarrhoea with increasing frequency, severity and relapse rates after conventional treatment with antibiotics, generally metronizadole or vancomycin. A subset of patients experience multiple recurrences of C. difficile infection (CDI) and new approaches, including novel antibiotics such as fidaxomicin and rifaximin, immune-therapy and faecal microbiota transplantation (FMT), have been used to treat multiple CDI recurrences. Paradoxically, antibiotics that are used to treat CDI, also disrupt the normal intestinal microbiota and thereby, may favour the blooming of C. difficile from antibiotic-resistant spores after the discontinuation of the antibiotic.
Thus far, faecal microbiota transplantation has been shown to be the most successful treatment option for recurrent CDI (rCDI) with a recovery rates of over 80% or 90% when faeces is administered once by duodenal or caecal infusion respectively. In FMT, the intestinal microbiota is re-established by transferring faecal material from a healthy, pre-screened donor to the patient via nasogastric tube, through colonoscopy or using an enema. The re-established normal, healthy microbiota offers protection against CDI. FMT therapy and restoration of normal intestinal microbiota usually normalises bowel functioning within days and results in a sustainable clinical outcome. In addition to the efficacy, FMT also seems to be very safe treatment.
Despite the high success rate of FMT in treating recurrent CDI, it's wider practice is hampered by a number of factors including the availability and screening of donors and aesthetic concerns. The use of universal donors for FMT can straighten up the laborious, costly and time-consuming donor screening. Further, the availability of stored, frozen faecal material would allow FMT to be used in clinical practice whenever needed. Recently, the use of standardised frozen preparation for FMT for recurrent CDI was introduced by Hamilton and co-workers. The protocol for processing the faecal material for frozen preparations involved suspension the faecal material into normal saline under N2 gas, followed by several filtration steps, centrifugation and final suspension and addition of glycerol before freezing at −80 °C. While the efficacy of the previously frozen faecal material was comparable to that of fresh faeces in treating rCDI and the protocol resulted in a nearly odourless preparation with reduced viscosity and colour, the preparation procedure is rather demanding to be widely used in a clinical setting. A more recent study presented a protocol for the preparation of frozen faeces, which does not involve working under N2 gas, but still involved several filtrations and a centrifugation step.
Previously, in the Helsinki University Central Hospital, we have treated rCDI patients with FMT via colonoscopy and by using both individual and universal donors and fresh faeces as a transplant. Later, we have changed to use increasingly universal donors and in this study we compared the outcomes of the rCDI patients treated with fresh faeces from individual and universal donors. The main objectives of this study were to develop a simple and practical, one-step protocol for preparing frozen faecal material for FMT and to assess the efficacy of frozen preparations in treating rCDI by using the same administration technique that we have used previously. The clinical outcomes of patients receiving previously frozen or fresh faeces either from individual or universal donors were compared.