Feasibility analysis of nasoduodenal feces administration to eradicate resistant enterobacteriaeceae.

Among renal transplant recipients urinary tract infections (UTIs) and
especially UTIs with tissue invasion such as transplant pyelonephritis and
urosepsis are a major cause of graft deterioration, prolonged hospitalization
and patient morbidity. They also lead to antimicrobial resistance resulting
from repeated antibiotic use. Most concerning are the Extended-Spectrum
Beta-Lactamase (ESBL) producing Enterobacteriaceae, which have gained the
ability to hydrolyse extended-spectrum beta-lactam antibiotics such as
ceftriaxone. The latter is commonly used in the treatment of UTIs among renal
transplant recipients. Frequent exposure to beta-lactam antibiotics leads to
colonization of the gastrointestinal tract by ESBL producing
enterobacteriaeceae, which may persist for many years and is associated with
(recurrent) ESBL related infections of the urogenital tract. The majority of
these infections are caused by the same ESBL producing enterobacteriaeceae as
those found in the feces of the patient.
The incidence of UTIs caused by ESBL producing Enterobacteriaceae has
dramatically increased over the last few years. ESBL related UTIs tend to
re-occur and require treatment with long term intravenous meropenem, risking
the development of carbapenem resistance. Therefore the development of an ESBL
decolonization scheme will be a cornerstone in the prevention of ESBL related
UTIs in renal transplant recipients.

Donor feces infusion has been demonstrated to be effective against recurrent
Clostridium difficile infections. In this current study we want to investigate
whether donor feces infusion is also effective in clearing ESBL producing
Enterobacteriaceae residing in the large intestine of renal transplant
recipients.

Primary objective is to investigate if donor feces infusion is effective in
eradication of ESBL producing Enterobacteriaceae in the large intestine.

Secondary objective is to determine whether ESBL decolonisation of the large
intestine actually leads to decreased incidence of ESBL related urinary tract
infection within 24 weeks follow-up after donor feces infusion.
Secondary objective is also the evaluation of the infuence of donor feces
infusion on the microbiome.

The aim of this study is to perform a single center, single cohort,
non-randomised, proof of principle study about donor feces infusion in 10 renal
transplant recipients colonised by ESBL producing Enterobacteriaeceae in the
large intesine.
Renal transplant recipients who were known to be carriers of ESBL producing
Entereobacteriaeceae in 2012 will be recruited. ESBL culture of the rectum,
urine and throat will be performed. If the recipient is at least ESBL positive
in the rectum, inclusion will take place. It might be possible that besides the
rectum, ESBL producing Enterobacteriaceae are also present in the urine and/or
throat. These two site will be decolonized with chlorhexidine mouth rinse and
nitrofurantoin respectively. When eventually the rectum remains ESBL positive,
donor feces infusion will take place. Diet inventory will also be made of each
subject via a questionnaire.
Prior to donor feces infusion, a feces sample of the subject will be taken and
stored for microbiome analysis.
The intervention is donor feces infusion. At 4 time points after donor feces
infusion (1, 2, 4 and 12 weeks) cultures will be taken of the rectum, urine and
the throat. Feces samples will also be collected anda stored at these 4 time
points for microbiome analysis. Each subject will be followed for 24 weeks
after donor feces infusion for development of ESBL related urinary tract
infection.

Donor feces infusion.

Prior to inclusion, diet pattern will be investigated via questionnaire.
Recipients may experience colon lavage and insertion of nasoduodenal tube as
inconvenient. There is a theoretical risk of malpositioning of the tube (for
example in the lungs): this risk is considered to be extremely rare.
Main side effects of donor feces infusion are abdominal cramps, diarrhoea and
nausea which resolve within few days after donor feces infusion. Infusion of
feces might cause vomiting, however this risk is reduced by positioning the
tube in the duodenum instead of the stomach. Furthermore, patients with
diminished bowel passage will be excluded. Risk of contagious diseases through
feces will be kept low as possible by throughout screening of healthy feces
donors by questionnaires and laboratory examination.
Other adverse influences of donor feces infusion in immunecompromised patients
is unknown, however 2 renal transplant recipients have undergone succesfully
donor feces infusion against recurrent Clostridium difficile infections without
serious adverse events.

Subjects who underwent donor feces infusion have to be cultured five times
(prior to donor feces infusion and at week 1, 2, 4 and 12 after donor feces
infusion). Furthermore, they also have to collect samples of their feces at
these time points.