Controlled Human Urine Transfusion for UTI
Controlled Human Urine Transfusion for UTI
The primary objective of this pilot study is to investigate the safety and tolerability of
 controlled human urine transfusion in female patients with recurrent UTI's.

 Seconday and exploratory objectives are to evaluate the diversity of the urine microbiome
 after urine transfusion, to assess the longevity of changes in the urine microbiome in
 patients after urine transfusion over a period of 6 months and to assess the frequency of
 UTI's after the transfusion.
Recurrent urinary tract infections (UTIs) are the most common bacterial infections in nursing
 homes, in acute care and the general practice. Increasing antibiotic resistance of
 enterobacteriaciae poses a challenge to the treatment of UTIs. Unlike previously thought, the
 bladder is colonized with bacteria, which together form the urine microbiome. Recurrent
 urinary tract infections are associated with a decreased urinary microbiota diversity,
 potentially making recolonization by bacterial interference in the bladder an alternative
 therapy for UTI. Pioneering studies showed that local bacterial interference in the bladder
 can be performed safely and has potential as prophylactic intervention.

 We now propose to expand this bacterial interference to a polymicrobial inoculum to increase
 adherence of the donor microbiome and as such expand the prophylactic effect. This pilot
 trial will investigate the safety and tolerability of urine transfusion from healthy donors
 to the bladders of patients with recurrent UTIs.

 The primary objective of this pilot study is to investigate the safety and tolerability of
 controlled human urine transfusion in female patients with recurrent UTI's.

 Secondary and exploratory objectives are to evaluate the diversity of the urine microbiome
 after urine transfusion, to assess the longevity of changes in the urine microbiome in
 patients after urine transfusion over a period of 6 months and to assess the frequency of
 UTI's after the transfusion.
Inclusion Criteria:

 -  Subject is premenopausal, aged ≥ 18 and ≤45 years

 -  Subject had recurrent UTI's (≥3 documented UTI's in the last year with documented
 symptom-free interval of at least 2 weeks) following the definition of a urinary tract
 infection: the presence of significance bacteruria (10^3 CFU/ml or more), pyuria and
 fever plus one or more of the following signs and symptoms: suprapubic or flank
 discomfort, dysuria, bladder spasms or pollakiuria

 -  Subject has a documented urinary tract infection (see definition), for which oral
 antibiotic therapy has been initiated.

 -  Subject has adequate understanding of the procedures of the study and agrees to abide
 strictly thereby.

 -  Subject is able to communicate well with the investigators and is available to attend
 all study visits.

 -  Subject has signed informed consent.

 -  Subject will remain available during the first 3 weeks of the study period
 (recruiting, intervention and first follow-up).

 Exclusion Criteria:

 -  Any history, or evidence at screening, of clinically significant symptoms, physical
 signs or abnormal laboratory values suggestive of systemic conditions, such as
 cardiovascular, pulmonary, renal, hepatic, neurological, dermatological, endocrine,
 malignant, haematological, immune-deficient, psychiatric and other disorders, which
 could compromise the health of the recipient during the study. These include, but are
 not limited to, any of the following: positive HIV, HBV or HCV screening tests; the
 use of immune modifying drugs within three months prior to study onset (inhaled and
 topical corticosteroids and oral anti-histamines exempted) or expected use of such
 during the study period.

 -  Documented vesico-urethral reflux

 -  Documented urinary retention > 100 milliliters post-void residual urine

 -  Anatomic urogenital abnormalities

 -  Urolithiasis

 -  Nephrostomy catheters

 -  Extra-urogenital infections that require prolonged antibiotic therapy

 -  Pregnancy

 -  Use of probiotics and or cranberry juice

 -  Allergy or intolerance for multiple common prescribed antibiotics

 -  Carriage of multi drug resistant organisms in faeces and/or urine without regular
 antibiotic treatment options