Intravesical bacteriophage therapy was noninferior to standard-of-care antibiotic treatment, but was not superior to placebo, regarding safety or efficacy in treating urinary tract infections (UTIs) in patients undergoing transurethral resection of the prostate (TURP), according to study results published in The Lancet Infectious Diseases.
Researchers conducted a randomized, placebo-controlled, double-blind trial (ClinicalTrials.gov identifier: NCT03140085) in men over 18 years of age undergoing TURP at the Alexander Tsulukidze National Centre of Urology in Tbilisi, Georgia. Patients undergoing TURP presented with complicated UTI or recurrent uncomplicated UTI without signs of systemic infection. In a 1:1:1 ratio, patients were assigned to study treatment groups. Bacteriophages were actively instilled into the bladder (Pyophage; 20 mL) and compared with either bladder instillation of sterile bacteriophage buffer (placebo) in a double-blind manner or systemically applied antibiotics as an open-label standard-of-care comparator.
All patient urine cultures had to be positive for pathogens covered by the Pyophage cocktail (Enterococcus spp.; Escherichia coli; Proteus mirabilis; Pseudomonas aeruginosa; Staphylococcus spp; Streptococcus spp.). The primary outcome was microbiological treatment response, measured by urine culture taken via urinary catheter, at the end of treatment on day 7 or at withdrawal from the trial. Secondary outcomes included clinical and safety parameters during the treatment period. Analyses were done in a modified intention-to-treat population of patients who received at least one dose of bacteriophage, placebo, or antibiotic treatment.
Of the 113 patients included in the study, 97 (86%) received at least one dose of their allocated intervention. Rates of treatment success, defined as urine culture normalization, were not significantly different between treatment groups. After 7 days of treatment, 18% (n=5/28) of patients in the Pyophage group achieved normalization of urine culture compared with 28% (n=9/32) of those in the placebo group (odds ratio [OR], 1.60; 95% CI, 0.45-5.71; P =.47), and 35% (n=13/37) of patients in the antibiotic group (OR, 2.66; 95% CI, 0.79-8.82; P =.11).
Adverse events were similar in type and incidence between the 3 groups. They were reported in 21% (n=6/28) of patients in the Pyophage group compared with 41% (n=13/32) of patients in the placebo group (OR, 0.36; 95% CI, 0.11-1.17; P =.089), and 30% (n=11/37) of patients in the antibiotic group (OR, 0.66; 95% CI, 0.21-2.07; P =.47).
Researchers observed noninferiority of bacteriophages regarding efficacy compared with antibiotics, along with high tolerability and safety of therapy. However, findings did not show superiority of bacteriophages over placebo, “most likely because of a therapeutically relevant effect of the placebo treatment caused by unanticipated mechanical reduction of the bacterial load following repeated bladder irrigation over 7 days.”
Limitations of this study included a short observation and follow-up period in close proximity to a surgical event which may have influenced results, and limited treatment times and follow-up due to distance of patients from the trial site.
Investigators concluded that study findings were “encouraging and provide important stimuli for physicians and authorities to support further large-scale clinical studies using bacteriophages for otherwise virtually untreatable infections, in order to further establish their efficacy.”
Leitner L, Ujmajuridze A, Chanishvili N, et al. Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: a randomised, placebo-controlled, double-blind clinical trial. Published online September 16, 2020. Lancet Infect Dis. doi10.1016/S1473-3099(20)30330-3