Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial

Abstract

Background: Urinary tract infections (UTI) are among the most prevalent microbial diseases and their financial burden on society is substantial. The continuing increase of antibiotic resistance worldwide is alarming. Thus, well-tolerated, highly effective therapeutic alternatives are urgently needed. Although there is evidence indicating that bacteriophage therapy may be effective and safe for treating UTIs, the number of investigated patients is low and there is a lack of randomized controlled trials.

Methods and design: This study is the first randomized, placebo-controlled, double-blind trial investigating bacteriophages in UTI treatment. Patients planned for transurethral resection of the prostate are screened for UTIs and enrolled if in urine culture eligible microorganisms ≥104 colony forming units/mL are found. Patients are randomized in a double-blind fashion to the 3 study treatment arms in a 1:1:1 ratio to receive either: a) bacteriophage (i.e. commercially available Pyo bacteriophage) solution, b) placebo solution, or c) antibiotic treatment according to the antibiotic sensitivity pattern. All treatments are intended for 7 days. No antibiotic prophylaxes will be given to the double-blinded treatment arms a) and b). As common practice, the Pyo bacteriophage cocktail is subjected to periodic adaptation cycles during the study. Urinalysis, urine culture, bladder and pain diary, and IPSS questionnaire will be completed prior to and at the end of treatment (i.e. after 7 days) or at withdrawal/drop out from the study. Patients with persistent UTIs will undergo antibiotic treatment according to antibiotic sensitivity pattern.

Discussion: Based on the high lytic activity and the potential of resistance optimization by direct adaptation of bacteriophages, and considering the continuing increase of antibiotic resistance worldwide, bacteriophage therapy is a very promising treatment option for UTIs. Thus, our randomized controlled trial investigating bacteriophages for treating UTIs will provide essential insights into this potentially revolutionizing treatment option.

Trial registration: This study has been registered at clinicaltrials.gov ( www.clinicaltrials.gov/ct2/show/NCT03140085 ). April 27, 2017.

Keywords: Antibiotics; Bacteriophages; Randomized placebo-controlled double-blind trial; Resistance; Urinary tract infection.

Conflict of interest statement

Ethics approval and consent to participate

This trial will be performed in accordance with the World Medical Association Declaration of Helsinki [20], the guidelines for Good Clinical Practice [21]. The study protocol has been approved by the The Local Ethic Committee of the National Center of Urology, Tbilisi, Georgia, (TNCU-02/283). The trial has been registered at www.clinicaltrials.gov/ct2/show/NCT03140085). The findings of the study will be published in peer-reviewed journals and presented at national and international scientific meetings. Written informed consent will be obtained from all participants.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Flow chart of the procedures

Fig. 2

Bacteriophage sensitivity testing to Escherichia coli: The Escherichia coli culture reacts positively to 12 phages out of 16. Confluent (complete) lysis can be seen for phages #9, 14 and 16, overgrown (partial) lysis for phages #4, 6, 7, 8, 10, 11, 12, 13, 15 and 16, respectively