Clinical trial NCT06017479
Conditions: Urological System Complication of Procedure Urinary Tract Infections
Keywords: urodynamic urinary tract infections fosfomycin levofloxacin
Sponsor: Indonesia University
Start date: 2022-12-30; Completion date: 2024-03-25
Enrollment: 126 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The goal of this clinical trial is to compare the use of single dose fosfomycin and single dose levofloxacin as pre-urodynamic antibiotic prophylaxis for urinary tract infection prevention post-urodynamic in patients with lower urinary tract symptoms. The main question\[s\] it aims to answer are:

* What is the difference between the effectiveness of administering a single dose of fosfomycin and levofloxacin prior to the procedure in terms of the incidence rate of urinary tract infection (UTI) post-urodynamic examination?
* What is the incidence rate of UTI in the administration of single-dose fosfomycin and levofloxacin prior to the procedure on the incidence rate of UTI post-urodynamic examination? Participants fulfilling the inclusion criteria will be taken their history and vital signs and consume either fosfomycin or levofloxacin based on the randomisation prior to urodynamic procedure. Afterwards, participants will undergo urine analysis 4 days post urodynamic to evaluate if there's any urinary tract infection. If there is any bacteria present, the sample will be cultured to identify bacteria found in the urine.

Detailed description:
This study employs a single-blinded randomized clinical trial design to compare the proportion of UTI post-urodynamic examination between the group receiving single-dose levofloxacin pre-urodynamic examination and the group receiving levofloxacin post-urodynamic examination for three days. The target population consists of patients undergoing urodynamic examination at Dr. Cipto Mangunkusumo National Referral Hospital, Persahabatan National Hospital, and Siloam Asri Hospital. The total sample size required for this study is 126 patients. On the fourth day post-urodynamic examination, urinalysis and urine culture are performed to determine the diagnosis of UTI. To analyze the association between UTI and therapy groups, a chi-square test is used. Results are considered statistically significant if p \< 0.05.

Arms: arm 1: Fosfomycin 3 g single dosage 1 hour before the urodynamic examination arm 2: Levofloxacin 500 miligrams single dosage 1 hour before the urodynamic examination
Interventions: intervention 1: Fosfomycin 3000 MG intervention 2: Levofloxacin 500mg
Intervention descriptions: intervention 1: Fosfomycin 3 g single dosage 1 hour before the urodynamic examination intervention 2: Levofloxacin 500 mg single dosage 1 hour before the urodynamic examination

Protocol documents:
Prot_SAP_000.pdf: 
Effectiveness of Single Dose Fosfomycin and Single Dose Levofloxacin as Pre-
Urodynamic Antibiotic Prophylaxis for Urinary Tract Infection Prevention in 
Post-Urodynamic Examination 
 
 
 
 
Harrina Erlianti Rahardjo 
Fina Widia 
Andika Afriansyah 
Cindy Wijaya 
Muhammad Hanif Arfiananda 
 
NCT Number: 
NCT06017479 
 
 
 
 
 
 
 
 
 
October 27th, 2022 
Department of Urology 
RSUPN dr. Cipto Mangunkusumo 
 


Research Title 
Effectiveness of Single Dose Fosfomycin and Single Dose Levofloxacin as Pre-Urodynamic 
Antibiotic Prophylaxis for Urinary Tract Infection Prevention in Post-Urodynamic Examination 
 
Abstract 
a) Study aims 
This study aims to compare the effectiveness of administering single doses of fosfomycin and 
levofloxacin pre-procedure on the incidence of urinary tract infections (UTIs) following 
urodynamic examination. 
b) Research Method 
This study utilized a single-blinded randomized clinical trial design to compare the proportion of 
post-urodynamic UTIs in the group receiving single-dose levofloxacin pre-urodynamic versus the 
group receiving levofloxacin post-urodynamic for three days. The target population consisted of 
patients undergoing urodynamic examination at RSUPN dr. Cipto Mangunkusumo from 
November 2022 to August 2023. The total sample size in this study was 100 patients. On the fourth 
day post-urodynamic, urinalysis and urine culture were performed to determine the diagnosis of 
UTI. Chi-square test was used to analyze the association between UTI and treatment group. Results 
were considered statistically significant if p < 0.05. 
c) Expected Results 
The expected results are data regarding the comparison of UTI incidence post-urodynamic 
examination in the group given single-dose levofloxacin and single-dose fosfomycin prior to 
urodynamic examination. 
d) Outcome 
The incidence of UTI in the group receiving single-dose levofloxacin pre-urodynamic compared 
to the group receiving single-dose fosfomycin pre-urodynamic. 
e) Benefits 
By obtaining data comparing the effectiveness of single-dose pre-urodynamic levofloxacin and 
fosfomycin on the incidence of UTIs following urodynamic examination, it can serve as a basis 
for selecting therapy regimens to prevent post-urodynamic UTIs. This can directly contribute to 
quality improvement, such as reducing antibiotic resistance rates and cost-saving in service 
delivery at dr. Cipto Mangunkusumo Hospital 
 
 


Background 
In the field of Urology, urodynamic examination is a functional assessment of the lower 
urinary tract that is useful for diagnosing the causes of incontinence. The number of these 
examinations increases by 15-20% annually. Aspects of bladder and urethral function assessed 
include the filling phase, storage phase, and voiding phase. This examination is invasive and 
carries a high risk of urinary tract infection (UTI) in patients, hence the need for prophylactic 
antibiotic use to prevent infection. Previous research by Rahardjo et al. in 2016 stated that the 
administration of prophylactic antibiotics for 3 days post-urodynamic examination could reduce 
the incidence of secondary urinary tract infections by 55% compared to placebo. The occurrence 
of infections and the cost aspect of post-urodynamic prophylactic antibiotic administration are 
concerns in healthcare provision at Dr. Cipto Mangunkusumo General Hospital (RSCM). 
Data from the Clinical Pathology Department of RSUPD Dr. Cipto Mangunkusumo from 
July to December 2021 showed that 33% of 415 E. coli urine isolates were sensitive to 
levofloxacin. During the same period, 84% of 219 E. coli urine isolates were sensitive to 
fosfomycin. The majority of this data was obtained from inpatients. Considering the good 
sensitivity of fosfomycin to UTIs, researchers intend to compare the use of fosfomycin with 
levofloxacin as effective prophylactic antibiotics in patients undergoing urodynamic examination. 
 
 


Study of Literature 
 
Urodynamic Examination 
Urodynamic examination is a functional assessment of the lower urinary tract that objectively 
demonstrates functional capacity and pathological conditions, thus determining the appropriate 
treatment according to the type of incontinence.3 Bladder and urethral function is assessed during 
the filling phase, storage phase, and voiding phase, with several provocative maneuvers such as 
coughing, sneezing, and laughing used to assess correlation with the patient's clinical symptoms.4 
Urodynamic examination includes uroflowmetry and measurement of post-void residual urine 
volume, cystometry, ambulatory urodynamics, videocystometry, and urethral pressure 
measurement. Uroflowmetry is used as an initial examination to assess urinary dysfunction. 
Parameters assessed in uroflowmetry include flow rate, maximum flow rate, voided volume, time 
to maximum flow, flow time, and average flow rate.5 
 
Urodynamic Indication 
Indications for performing urodynamic examination include patients with obstructive complaints 
in the lower urinary tract (LUTS) and neurological abnormalities, young men with LUTS 
complaints, patients with neurological disorders who have neurogenic bladder dysfunction 
conditions, children with urgency and urgency incontinence occurring outside of sleep, children 
with persistent diurnal enuresis, children with spinal nerve disorders, patients with neurological 
disorders with incongruity between symptoms and clinical findings, patients with persistent LUTS 
under appropriate/correct therapy, patients at high risk of complications from a planned therapy, 
situations where therapy decisions are unclear and require more specific diagnosis confirmation, 
patients with recurrent incontinence and planned surgery, patients with mixed incontinence of 
stress and urgency types and those with urinary disorders.6 
Generally, urodynamic examinations use water/saline solution as a medium to fill the bladder. 
Multichannel urodynamic examinations are more complex and can be used to measure data that 
can complement information beyond routine urodynamic assessments of the bladder and abdomen, 
such as abdominal leak-point pressure (ALPP) and electromyography (EMG). The most advanced 
form of urodynamic examination is videourodynamics, which is equipped with static cystography 
and voiding cystourethrography using radiological contrast.4,7 
 
UTI Classifications 
Urinary tract infection (UTI) is an infection that occurs in the urinary tract, including the kidneys, 
ureters, bladder, and urethra. According to the EAU guidelines, UTIs are classified into 
uncomplicated UTIs, complicated UTIs, recurrent UTIs, catheter-associated UTIs, and urosepsis 
(Table 1)8. Based on location, urinary tract infections can be divided into two categories: upper 


UTIs, which involve the kidneys and ureters, and lower UTIs, which involve the bladder and 
urethra.9 
 
Table 1. UTI Classifications8 
UTI Classifications 
Non-complicated UTI 
Acute, sporadic, or recurrent infections in the upper 
and/or lower urinary tract affecting non-pregnant 
women, postmenopausal women without anatomical 
abnormalities and comorbidities in the urinary tract. 
Complicated UTI 
All UTIs that cannot be classified as uncomplicated. In 
other words, UTIs in patients with a higher risk of 
complications, such as: men, pregnant women, patients 
with anatomical or functional abnormalities in the 
urinary tract, and/or with other underlying immune 
disorders such as diabetes or HIV. 
Recurrent UTI 
Uncomplicated and/or complicated recurrent UTIs with 
a frequency of at least 3 times per year or 2 times in the 
last 6 months. 
Catheter-related UI 
Catheter-associated UTIs refer to UTIs that occur in 
patients who use catheters regularly and have used a 
catheter for at least the past 48 hours. 
Urosepsis 
Urosepsis is defined as life-threatening organ 
dysfunction resulting from dysregulation of the host 
response to infection originating from the urinary tract 
and/or male reproductive organs. 
 
And these followings are the common terminology used to describe UTI clinically.10 
 
Terminology 
Definition 
Pyuria 
Presence of more than 10 white blood cells/mm3 per large visual field 
Bacteriuria 
More than 105 colony-forming of urinary pathogens units per mL 
Confirmed UTI 
Pyuria accompanied by bacteriuria 
Asymptomatic 
bacteriuria 
Presence of bacteriuria in the absence of genitourinary symptomps or 
sings 
 
 
 


Diagnostic Evaluation 
 
Diagnosing UTIs can be established through a focused assessment of lower urinary tract symptoms 
such as dysuria, frequency, and urgency. Diagnostic tests for UTIs consist of three main 
examinations: dipstick urinalysis, microscopic urinalysis, and urine culture. Urine culture is 
utilized for patients suspected of acute pyelonephritis, patients whose symptoms do not improve 
or have recurrent symptoms within 2-4 weeks after completion of treatment, women with atypical 
symptoms, pregnant women, and male patients suspected of UTI.10 
 
Urinary Tract Infections after Urodynamic Testing 
 
Previous studies have reported that the incidence of UTIs following urodynamic examination 
ranges from 1% to 30%. Another study mentioned that urodynamic testing without prophylactic 
antibiotic use has a bacteriuria incidence of 4-9%.11 In previous research, prophylactic antibiotics 
were administered 1 hour before urodynamic examination. 
 
Levofloxacin for Pre-Urodynamic UTI Prevention 
 
Levofloxacin is a fluoroquinolone antibiotic with broad-spectrum activity against both Gram-
positive and Gram-negative bacteria, as well as atypical pathogens. Levofloxacin exhibits 
antimicrobial effects against Streptococcus pneumoniae, both penicillin-susceptible and penicillin-
resistant strains.12 Previous studies have noted an increasing resistance of Gram-negative bacilli to 
quinolones.11 
 
Fosfomycin for Pre-Urodynamic UTI Prevention 
 
Fosfomycin is a bactericidal antibiotic with activity against several Gram-positive and Gram-
negative 
bacteria, 
including 
vancomycin-resistant 
enterococci, 
methicillin-resistant 
Staphylococcus aureus, and carbapenem-resistant Enterobacteriaceae.13 Research indicates that 
Escherichia coli and Enterococcus faecalis have high susceptibility to fosfomycin.14 Single-dose 
oral fosfomycin 3 grams shows peak urine concentration within 4 hours and remains high (>128 
mg/L) for 24 to 48 hours, sufficient to prevent pathogens in the urinary tract.11 
 
Research Methodology 
 
This study is an experimental research with a single-blinded randomized clinical trial design to 
compare the proportion of UTIs in patients receiving a single dose of 500 mg levofloxacin and 
patients receiving a single dose of 3 grams fosfomycin one hour before urodynamic examination. 
Treatment group allocation was determined using block randomization technique. 
 
This study utilizes a single-blinded design because the outcome assessed in this study is objective 
urinalysis. The urinalysis evaluator is unaware of the drug regimen received by the research 
subjects. 
 
UTIs will be assessed based on bacteriuria conditions evaluated within 4 days post-urodynamic 
using urinalysis examination. 


Conceptual Framework 
 
 
Picture 1. Conceptual Framework 
 
Definition of Work 
 
1. Single Dose of Levofloxacin  
A single dose of levofloxacin is defined as the administration of 500 mg of levofloxacin one 
hour before urodynamic examination. 
2. Single Dose of Fosfomycin 
A single dose of fosfomycin is defined as the administration of 3 g of fosfomycin one hour 
before urodynamic examination. 
3. Urinary Tract Infection (UTI) 
Urinary tract infection is defined based on urinalysis results showing any of the following 
conditions: leukocyturia (presence of >5 leukocytes/HPF), positive bacteria, positive nitrites, 
and/or positive leukocyte esterase. 
4. Urodynamic 
Urodynamic examination in this study consists of non-invasive uroflowmetry, post-void 
residual volume (PVR) measurement, and cystometrography (CMG) measurement. 
 
Research Hypothesis 
 
The administration of single-dose fosfomycin pre-urodynamic examination is more effective than 
single-dose levofloxacin pre-urodynamic examination in preventing UTIs. 
 
Source 
 
The data source for this research is primary data collected from patients with indications for 
urodynamic examination at the urology clinics of RSUPN Dr. Cipto Mangunkusumo, RS 
Persahabatan, and RS Siloam Asri from November 2022 to August 2023. 
 
 
 
Single dose of 500mg 
levofloxacin 1 hour before 
urodynamic examination 
Single dose of 3g 
fosfomycin 1 hour before 
urodynamic examination 
Patients with 
indications for 
urodynamic testing 
UTI (-) Posturodynamic 
UTI (+) Posturodynamic 
UTI (+) Posturodynamic 
UTI (-) Posturodynamic 


Number of Samples 
 
The sample size calculation is based on the 'Fundamentals of Clinical Research Methodology' 
regarding proportion calculation for 2 independent groups. Based on literature, the effectiveness 
of levofloxacin antibiotic against post-urodynamic bacteriuria incidence is believed to have a 20% 
difference from P2 (P1=0.7) because the effectiveness of fosfomycin against post-urodynamic 
bacteriuria incidence is 0.9 (P2).11 
 
𝑛1 = 𝑛2 = [𝑍𝛼√2𝑃𝑄+ 𝑍𝛽√𝑃1𝑄1 + 𝑃2𝑄2]
2
(𝑃1 − 𝑃2)2
 
where P = 
1
2 (𝑃1 + 𝑃2) and Q = 1-P 
𝑛1 = 𝑛2 = [1,96√2𝑥0,8𝑥0,20 + 0,842√0,7𝑥0,3 + 0,9𝑥0,1]
2
(0,7 − 0,9)2
=  
𝑛1=𝑛2 = 61,5 ~ 62 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑓𝑜𝑟 𝑒𝑎𝑐ℎ 𝑔𝑟𝑜𝑢𝑝 
 
Considering the possibility of drop-out, it was decided to take a total sample of 126 patients, with 
63 patients in each group, who will then undergo screening for eligibility and will be randomized 
equally. 
 
Data Collection Technique 
 
The data collection technique employs consecutive sampling method until the required number of 
subjects is reached. 
 
Inclusion and Exclusion Criteria 
 
The inclusion criteria for this study are: 
• Male/female patients aged >18 years who have indications for urodynamic testing 
• Willing to participate in the study 
 
The exclusion criteria for this study are: 
• Allergy to levofloxacin 
• Allergy to Fosfomycin 
• Pregnancy 
• Uncontrolled diabetes mellitus 
• Urinary catheterization 
• History of UTI prior to urodynamic testing, based on clinical symptoms and urine 
examination results 
• Refusal to participate in the study 
 
 
 


Statistical Analysis Technique 
 
Descriptive presentation is used to assess subject characteristics, such as age, gender, and 
indications for urodynamic testing. The relationship between UTI occurrence and treatment groups 
is assessed using chi-square analysis. Data will be processed using SPSS version 24 and considered 
significant if p<0.05. 
 
Type of Research Activity 
 
This research activity is experimental with the following research flowchart: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Group A 
Single dose of Levofloxacin 500 
mg 1 hour prior to urodynamic 
Group B 
Single dose of Fosfomycin 1 g 1 
hour prior to urodynamic 
Patients with indication for 
urodynamic examination 
Urinalysis pre-urodynamic 
Urinalysis on the fourth day after 
urodynamic 
In accordance with the inclusion and 
exclusion criteria? 
Randomization 
Not included in 
the research 
UTI (+) 
UTI (-) 
UTI (+) 
UTI (-) 
Urine Culture 
Urine Culture 
Data analysis 
Making research 
report 
No 
Yes 
Picture 2. Research Flowchart 


Research Places 
 
The study will be conducted at the urology outpatient clinic of the Department of Urology, RSUPN 
dr. Cipto Mangunkusumo, Uronephrology Cluster of RSCM Kencana, RSUP Persahabatan, and 
RS Siloam Asri. 
 
References 
 
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a Three Day Course Antibiotic Post-urodynamic Study in Preventing Lower Urinary Tract 
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10th Edition. Philadelphia: Elsevier; 2012. p. 1847–70.  
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Netherlands: EAU Guidelines Office; 2022.  
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