International Journal of Urology (2018)
Urological Note
Prospective, randomized controlled study of the preventive effect of fosfomycin
tromethamine on post-transurethral resection of bladder tumor urinary tract infection
Jing Yang M.D.,1,† Peng Zhang Ph.D.,2,† Hong Zhou M.D.,2 Sujuan Feng Ph.D.2 and Xiaodong Zhang Ph.D.2
Abbreviations & Acronyms
FOT = fosfomycin
tromethamine
TURBT = transurethral
resection of bladder tumor
UTI = urinary tract infection
1
Department of Urology, Beijing
Huairou Hospital, University of
Chinese Academy of Sciences,
and 2Institute of Uro-
Nephrology, Beijing Chaoyang
Hospital, Capital Medical
University, Beijing, China
353791712@qq.com
†These authors contributed
equally to this work.
DOI: 10.1111/iju.13719
© 2018 The Japanese Urological Association
TURBT is the main treatment for non-muscle-invasive urothelial carcinoma of the bladder.
There is some controversy surrounding preoperative antibiotic prophylaxis. In times of
increasing antimicrobial resistance rates, we want to find new ways to reduce antimicrobial
use without increasing the rates of postoperative infections. FOT is a phosphate derivative.
This antibiotic is specifically used for UTI treatment, which is conducive to preventing
antimicrobial resistance induced by multisystem drug administration.1 The present study
aimed to compare the outcomes (UTI rate) between prophylactic administration of FOT and
administration of cefoxitin sodium (one of the second-generation cephamycin antibiotics for
TURBT recommended by almost all urological association guidelines) in patients with or
without infection risks (Table 1), and to evaluate the feasibility and effectiveness of a single
oral administration of FOT preventing post-TURBT UTI in patients with non-muscle-invasive
bladder cancer.
The study was carried out in accordance with the Declaration of Helsinki and approved by
the ethics committee of Beijing Chaoyang Hospital of Capital Medical University. Between
August 2015 and August 2016, a total of 100 patients who received TURBT were included
in the study. All patients were randomly divided into two groups using the method of simple
randomization. One group received intravenous administration of 2 g of cefoxitin sodium pro-
duced by Huabei Pharmaceutical (Hebei, China) 30 min before the TURBT procedure and
another 2 g of cefoxitin sodium within 24 h after the procedure (cefoxitin group). The other
group was given a single oral dose of 3 g of FOT produced by Shanxi Qianyuan Pharmaceu-
tical (Shanxi, China) at 22.00 hours the night before the TURBT procedure (FOT group).
UTI was diagnosed based on the patients’ symptoms and urine culture (UTI is defined by
counts of ≥105 c.f.u./mL and ≥104 c.f.u./mL, in the midstream urine of women and men,
respectively. If a straight catheter urine sample is taken, ≥104 c.f.u./mL can be considered rel-
evant).2 The experimental results were statistically analyzed using SPSS 22.0 statistical software
(IBM, Armonk, NY, USA). P-values <0.05 were considered statistically significant. No statis-
tically significant differences were detected between the two randomly divided groups of
patients’ characteristics (Table S1).
As shown in Table 1, although the postoperative infection rate of the FOT group is lower
than the cefoxitin group (1 case [2%] against 3 cases [6%]), this did not reach a statistically
significant level (P = 0.617). In the patients with infection risks, it was one case (FOT group,
5.6%) against 0 case (cefoxitin group, 0%), this also did not reach a statistically significant
level (P = 0.999). The group of patients who were treated with FOT powder had a postopera-
tive infection rate of 2.0%, which was significantly lower than the previously reported infec-
tion rates in the absence of preoperative antibiotic treatment (10–40%).3,4 Therefore, a single
oral administration of FOT is not inferior to intravenous administration of cefoxitin sodium in
the prevention of post-TURBT UTI.
According to the present study, altered antibacterial–albumin binding in the presence of
hypoalbuminemia is likely to produce significant variations in the pharmacokinetics of
many highly protein-bound antibacterials.5 Dose optimization of these antibacterials in crit-
ically ill patients with hypoalbuminemia should be considered well. As shown in
Table S2, the preoperative and postoperative laboratory test results of patients who experi-
enced no UTI were analyzed by t-test. We can see the postoperative mean albumin level
was lower in the cefoxitin group in comparison with that in the FOT group, and the dif-
ference was statistically significant (P = 0.023). The reason was unknown, but some possi-
ble reasons are as follows: (i) the albumin combining with the cefoxitin, which was one
of the protein-bound antibacterials, caused some of the albumin to be unable to be tested,
but the FOT did not;6 and (ii) during the operation, the bladder irrigation fluid was
absorbed into the blood, which caused the increase of blood volume, and the hemodilution
led to the decrease of albumin. The water absorbed into the blood is difficult to measure.
Here, we take operation time to replace it. The mean operation time of the cefoxitin
sodium group was longer than the FOT group (Table S1), which coincided with this
1
UROLOGICAL NOTE

Table 1 Postoperative infections of the patients undergoing TURBT Conflict of interest

between April 2015 and April 2016
None declared.
Cefoxitin
group FOT group P-value
All patients n = 50 n = 50
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an advantage over intravenous administration of cefoxitin Supporting information
sodium in that FOT has a smaller impact on the postopera-
tive decrease in albumin levels. Additional supporting information may be found online in
the Supporting Information section at the end of the article:

Acknowledgments Table S1. Clinical characteristics of the 100 patients under-

going TURBT between April 2015 and April 2016.
This work was supported by China Postdoctoral Science Table S2. Laboratory examinations of the two groups before
Foundation (2015M581131). and after operation.

2 © 2018 The Japanese Urological Association