Infectious Disease

Intravesical phage remedy can deal with urinary tract infections in males who’re present process TURP

Intravesical bacteriophage therapy was not inferior to standard antibiotic treatment, but was placebo in terms of safety or effectiveness in treating urinary tract infections (UTIs) in patients undergoing transurethral resection of the prostate (TURP), according to published study results not superior to Lancet infectious diseases.

Researchers conducted a randomized, placebo-controlled, double-blind study (ClinicalTrials.gov ID: NCT03140085) in men over the age of 18 undergoing TURP at the Alexander Tsulukidze National Urology Center in Tbilisi, Georgia. Patients who underwent TURP had a complicated urinary tract infection or a recurrent uncomplicated urinary tract infection with no evidence of systemic infection. The patients were assigned to the study treatment groups in a ratio of 1: 1: 1. Bacteriophages were actively instilled into the bladder (pyophage; 20 ml) and compared with either the bladder instillation of sterile bacteriophage buffer (placebo) in a double-blind manner or systemically applied antibiotics as an open standard care comparison.

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 the response to microbiological treatment, as measured by urine culture collected via a urinary catheter, at the end of treatment on day 7 or upon discontinuation of the study. Secondary outcomes included clinical and safety parameters during the treatment period. The analyzes were performed 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 enrolled in the study, 97 (86%) received at least one dose of their assigned intervention. Treatment success rates, defined as normalization of urine culture, did not differ significantly between treatment groups. After 7 days of treatment, 18% (n = 5/28) of the patients in the pyophage group achieved normalization of the urine culture compared to 28% (n = 9/32) of the patients in the placebo group (odds ratio) [OR]1.60; 95% CI, 0.45-5.71; P = 0.47) and 35% (n = 13/37) of the patients in the antibiotic group (OR 2.66; 95% CI 0.79-8.82; P = 0.11).

Adverse events were similar in type and incidence between the three 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. = 0.089) and 30% (n = 11/37) of the patients in the antibiotic group (OR 0.66; 95% CI 0.21-2.07; P = 0.47).

The researchers observed a non-inferiority of bacteriophages in terms of effectiveness compared to antibiotics as well as a high tolerance and safety of the therapy. However, the results showed no superiority of the bacteriophages over the placebo, “most likely due to a therapeutically relevant effect of the placebo treatment, which was caused by an unexpected mechanical reduction in the bacterial load after repeated bladder irrigation over 7 days.”

Limitations of this study included short observation and follow-up times in close proximity to a surgical event, which may have affected the results, and limited treatment times and follow-up times due to the patient’s distance from the study site.

The researchers concluded that the study results “were encouraging and provided important incentives for physicians and authorities to support further large-scale clinical trials of bacteriophages for otherwise virtually untreatable infections to further demonstrate their effectiveness.”

reference

Leitner L., Ujmajuridze A., Chanishvili N. et al. Intravesical bacteriophage for the treatment of urinary tract infections in patients undergoing transurethral resection of the prostate: a randomized, placebo-controlled, double-blind clinical trial. Published online September 16, 2020. Lancet Infect Dis. doi10.1016 / S1473-3099 (20) 30330-3

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