Conditions: Urinary Tract Infections
Keywords: Urodynamics Antibiotics Prophylaxis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 134
Healthy volunteers: yes

Brief summary:
This study aims to compare the effectiveness of preoperative single dose of levofloxacin with postoperative levofloxacin for three days on the incidence of urinary tract infections (UTI) after urodynamic examination.

Detailed description:
This study aims to compare the effectiveness of preoperative single dose of levofloxacin with postoperative levofloxacin for three days on the incidence of urinary tract infections (UTI) after urodynamic examination. This study uses a randomized single-blind trial design to compare the proportion of posturodynamic UTI in the group receiving preurodynamic single-dose levofloxacin with the group receiving three days - once daily of Levofloxacin posturodynamic. The target population is patients who undergo urodynamic examination at the RSUPN dr. Cipto Mangunkusumo, Siloam ASRI Hospital, and Persahabatan Hospital during the given time.

of the study. The total sample size in this study was determined based on a two-proportion analytical sample calculation formula with type 1 error of 5% and type 2 error of 80%. On the fourth posturodynamic day, urinalysis and urine culture were performed to determine the diagnosis of UTI. To analyze the association between UTI and the treatment group, the chi-square test was used. Results were considered statistically significant if p \< 0.05.

The expected results are data on the comparison of the incidence of UTI after urodynamic examination in the group given a single dose of levofloxacin and levofloxacin for three days post-examination.

The incidence of UTI in the group receiving a single preurodynamic dose of levofloxacin compared to the group receiving levofloxacin for three days posturodynamics.

Arms:
arm 1: Levofloxacin 500 mg single dosage 1 hour before the urodynamic examination arm 2: Levofloxacin 500 mg will be given for 3 days, once daily, post-urodynamic examination

Interventions: intervention 1: Pre-urodynamic Levofloxacin intervention 2: Post-urodynamic Levofloxacin
Intervention descriptions: intervention 1: Levofloxacin 500 mg single dosage 1 hour before the urodynamic examination intervention 2: Administering once daily Levofloxacin 500 mg for 3 days after urodynamic study

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
 
Comparison of the Effectiveness of Preurodynamic Single Dose 
Levofloxacin with Posturodynamic Levofloxacin for Three Days 
on the Incidence of Urinary Tract Infections 
 
 
 
 
 
 
 
 
 
 
Harrina Erlianti Rahardjo 
Fina Widia 
Mega Anara Manurung 
Indra Wicaksono 
 
NCT Number: 
NCT05219877 
 
 
 
 
 
 
 
 
 
 
 
 
 
January 10th, 2022 
Department of Urology 
RSUPN dr. Cipto Mangunkusumo 
 
 


Research Title 
Comparison of the Effectiveness of Preurodynamic Single Dose Levofloxacin with 
Posturodynamic Levofloxacin for Three Days on the Incidence of Urinary Tract Infections 
 
Abstract 
a) 
Study aims 
This study aims to compare the effectiveness of preoperative single dose of levofloxacin with 
postoperative levofloxacin for three days on the incidence of urinary tract infections (UTI) after 
urodynamic examination. 
b) 
Research Method 
This study uses a randomized single-blind trial design to compare the proportion of 
posturodynamic UTI in the group receiving preurodynamic single-dose levofloxacin with the 
group receiving three days posturodynamic levofloxacin. The target population is patients who 
undergo urodynamic examination at the RSUPN dr. Cipto Mangunkusumo during any given time. 
The total sample size in this study is determined based on a two-proportion analytical sample 
calculation formula with type 1 error of 5% and type 2 error of 80%. On the fourth posturodynamic 
day, urinalysis and urine culture are performed to determine the diagnosis of UTI. To analyze the 
association between UTI and the treatment group, the chi-square test is used. Results are 
considered statistically significant if p < 0.05. 
c) 
Expected Results 
The expected result is data on the comparison of the incidence of UTI after urodynamic 
examination in the group given a single dose of levofloxacin and levofloxacin for three days after 
the examination. 
d) 
Outcome 
The incidence of UTI in the group receiving a single preurodynamic dose of levofloxacin compared 
to the group receiving levofloxacin for three days posturodynamics. 
e) 
Benefit 
By obtaining data on the comparison of the effectiveness of a single preurodynamic dose of 
levofloxacin and levofloxacin for three days posturodynamics on the incidence of UTI after a 
urodynamic examination, it can be used as a basis for selecting a therapeutic regimen to prevent 
the occurrence of posturodynamic UTI. This can directly contribute to quality improvement, 
namely the reduction of antibiotic resistance rates and savings in service costs at dr. Cipto 
Mangunkusumo Hospital 
 
 
 
 
 
 
 
 
 
 
 
 


Background 
Urodynamic examination is an important examination in the field of urology. Through urodynamic 
examination, the function of the lower urinary tract can be determined and a diagnosis of the cause of 
incontinence can be established. However, given the invasive nature of the examination, the patient's 
risk of urinary tract infection is high. For this reason, prophylactic antibiotics are given so that post-
urodynamic infections can be avoided. This statement is also supported by the results of research by 
Rahardjo, et al. in 2016 where prophylactic antibiotics for 3 days post-urodynamics can reduce the rate 
of UTI by 55% compared to placebo. And considering the number of urodynamic examinations which 
is increasing by 15-20% annually, the incidence of infection and the cost aspect in giving prophylactic 
antibiotics after urodynamics is a burden on health services that need special attention in RSCM. 
Data from the Department of Clinical Pathology RSUPD dr. Cipto Mangunkusumo from January 
– December 2017 showed that 41.3% of 978 isolates of urinary E. coli were sensitive to ciprofloxacin 
and 33% of 973 isolates were sensitive to cotrimoxazole. In the same period, 49.6% of 1097 isolates of 
E. coli urine were sensitive to levofloxacin. The majority of these data were obtained from hospitalized 
patients. Given the good sensitivity of levofloxacin to UTI, the investigators saw the potential for using 
levofloxacin as an effective prophylactic antibiotic in patients undergoing urodynamic examination. 
Through previous research (Rahardjo, et al. 2016), researchers have identified that giving 
levofloxacin 3 days has good efficacy in preventing post-urodynamic UTI. However, several other 
studies have shown that single-dose prophylactic antibiotics also have satisfactory efficacy in 
preventing post-urodynamic UTI. The results of this study are considered appropriate and in accordance 
with the theme because they directly support the quality of RSCM services, improve the quality of 
services in the field of Urology and reduce the use of unnecessary antibiotics so as to reduce antibiotic 
resistance and reduce service costs. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Study of Literature 
 
Urodynamic Examination 
Urodynamics is an examination tool that measures the relationship between abdominal-bladder pressure 
and urine flow through the urethra so that it can be used to assess the functional status of the lower 
urinary tract. The main function of urodynamics is to help establish the diagnosis of a lower urinary 
tract based on the appropriate pathophysiology. Urodynamic examination can examine the function of 
the bladder and urethra both in the filling phase, storage phase (storage), and voiding phase. In addition, 
several provocative maneuvers such as coughing, sneezing, laughing can also be used during the 
examination to see if the symptoms match the clinical complaints of the patient.2 
 
Some of the examinations included in routine urodynamics include: non-invasive uroflowmetry 
examination, post voiding residual (PVR) measurement, and cystometrography (CMG) measurement. 
CMG is used to assess the sensation of filling, a sense of fullness, and urgency. Bladder compliance 
and detrusor contractions (phasic contractions) can also be measured using CMG during the filling 
phase. Normally, water medium/physiological NaCl solution is used to fill the bladder during 
urodynamic examination. Multichannel urodynamics is a more complex examination and can be used 
to measure data that can complement information outside of routine urodynamics such as: abdominal 
leak-point pressure (ALPP) and electromyography (EMG) of the bladder and abdomen. The most recent 
form of urodynamics is videourodynamics which is complemented by static cystography and voiding 
cystourethrography on top of multichannel urodynamic examination. However, the medium used in 
videourodynamics is radiological contrast.2-3 
 
The usefulness of urodynamic examination lies in its ability to assess the pathophysiology of a particular 
clinical course so that it can lead to the appropriate diagnosis and therapy. Because without proper 
assessment, treatment such as surgery for incontinence cases can lead to unwanted morbidity and 
complications. Unfortunately, urodynamic examination is one of the most expensive examinations and 
requires tools and expertise to operate, thus limiting its widespread use. Therefore, it is very important 
to use urodynamics in case-specific and clinical cases that have been reviewed using an appropriate 
history.4 
 
Urodynamics is basically a non-physiological examination. Studies show that the normal range of 
uroflowmetry and cystometry results can vary. Although it can be a valuable examination tool, to be 
clinically meaningful the results of the urodynamic examination need to be adjusted to the patient's 
complaints. Especially if the condition of the complaint can be reproduced again during the urodynamic 
examination. Urodynamic examination that does not cause clinical symptoms according to the patient's 
complaints can be considered as an inconclusive examination. Likewise, if the urodynamic examination 
produces abnormal results without accompanying symptoms/complaints. However, by far, 
urodynamics is the best available examination tool for assessing lower urinary tract function.3-5 
 
Urodynamic Indication 
The history and physical examination often do not provide sufficient accurate information to determine 
therapy, but these data can be a good basis for determining whether a patient is eligible for more 
complex and/or invasive examinations.6 
 
The following clinical factors are indicative of the need for further urodynamic examination:6 


o 
Patients with obstructive complaints of lower urinary tract (LUTS) and neurological disorders 
o 
Young male with LUTS 
o 
All patients with neurological disorders who have neurogenic bladder dysfunction. 
o 
Children with urgency and urgency-type incontinence that occur outside of sleep 
o 
Children with persistent diurnal enuresis 
o 
Children with spinal nervous system disorders 
o 
Neurologically impaired patients with discrepancies between symptoms and clinical findings 
o 
Patients with persistent LUTS under appropriate therapy 
o 
Patients who are at high risk of complications from a therapy that will be carried out 
o 
Conditions where therapeutic decisions are unclear and a more specific diagnosis is needed 
o 
Patients with recurrent incontinence and planned surgery 
o 
Patients with mixed stress and urgency incontinence and those with urinary disorders 
 
Good Urodynamic Practice 
According to the standards of the International Continence Society, good urodynamic performance 
should follow the following criteria:7-8 
o causing clinical symptoms according to patient complaints 
o checking the recording results to guarantee the quality of inspection 
o interpreting of the results in the context of the appropriate clinical problem 
o taking into account the existence of physiological variability in the same subject. 
 
UTI Classifications  
The most widely used classification of urinary tract infections (UTIs) is the classification developed by 
the CDC, IDSA, ESCMID, and the US FDA. As adjusted for EAU guidelines, UTI can be classified 
according to clinical features, anatomic location, severity of infection, categorization of comorbid risk 
factors and presence of therapy.9 
 
The following is a UTI classification adapted from the EAU guidelines:9 
 
UTI Classifications 
Non-complicated UTI 
Acute, sporadic or recurrent infections of the lower and/or 
upper urinary tract, affecting nonpregnant women, 
postmenopausal women without anatomic abnormalities and 
comorbidities of the urinary tract 
Complitated UTI 
All UTIs that cannot be classified as non-complicated. In 
other words, UTI is in patients with a higher risk of 
complications, such as: men, pregnant women, patients with 
anatomic or functional abnormalities of the urinary tract, 
and/or with other coexisting immune disorders such as 
diabetes or HIV. 
Recurrent UTI 
Recurrent non-complicated and/or complicated UTI with a 
frequency of at least 3 times a year or 2 times in the last 6 
months. 


Catheter-related UTI 
Catheter-related UTI refers to UTI that occurs in patients 
who use repeated/routine catheters and have used a catheter 
for at least the last 48 hours. 
Urosepsis 
Urosepsis is defined as life-threatening organ dysfunction 
resulting from dysregulation of the supervisor's response to 
infections originating in the urinary tract and/or male 
reproductive organs. 
 
And these followings are the common terminology used to describe UTI clinically.10 
 
Asymptomatic bacteriuria 
Asymptomatic bacteriuria is the presence of bacteriuria without accompanying genitourinary 
symptoms/signs. This condition is common and can be caused by an imbalance of the normal flora of 
the urinary tract. Clinical studies suggest that this condition may be protective against other 
symptomatic bacterial infections. Therefore, the treatment of bacteriuria is aimed especially if it is 
believed that the administration of antibiotics will provide greater benefits than the risks. By giving 
antibiotics, at least there are commensal bacteria that are eradicated and reduce the protective effect of 
these normal flora against other pathogens that can cause symptomatic infection.9-10 
 
Epidemiology 
Asymptomatic bacteriuria occurs in about 1-5% of normal premenopausal women and will increase to 
4-19% in elderly women and men. Approximately 0.7-27% occur in diabetic patients and 2-10% in 
pregnant women and 15-20% in the elderly population living in nursing homes, and 23-89% in patients 
with spinal disorders. Asymptomatic bacteriuria in younger men is rare but may increase the risk of 
complications such as chronic bacterial prostatitis. The bacterial spectrum of asymptomatic bacteriuria 
is often similar to the normal flora found in non-complicated UTI although other risk factors should 
also be considered. 
 
Diagnostic Evaluation 
The diagnosis of asymptomatic bacteriuria can be made using a midstream urine collection technique. 
If the culture of this sample yields 105 colony forming/mL in 2 consecutive samples in women and a 
single sample in men, a diagnosis of asymptomatic bacteriuria can be made. If the sample is taken 
through a catheter, the diagnosis of bacteriuria can be made if the number of bacteria exceeds 102 
cfu/mL, including men and women. If urease-producing bacteria such as Proteus mirabilis are found, 
the diagnosis of urinary tract stones should be ruled out. In these patients a distal rectal examination 
(DRE) should be performed to rule out prostate disease.10 
 
Terminologi 
Definisi 
Pyuria 
Presence of >10 white blood cells/mm3 per large visual field 
Bacteriuria 
>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 
symptoms/signs 


Epidemiology of UTI on urodynamic examination 
Various studies show that a single episode of catheterization can increase the percentage risk of UTI by 
2%. Meanwhile, the magnitude of post-procedure UTI infection according to several studies can range 
from 3-20% despite using good asepsis techniques. Several studies also show that gender is the most 
influential risk factor for the incidence of urinary tract infections after invasive procedures. With regard 
to the high rate of urinary tract infections associated with invasive procedures in the urinary tract, 
several guidelines suggest the use of antibiotics as prophylactic agents to prevent postoperative UTIs. 
 
Levofloxacin as an antibiotic 
Levofloxacin is a fluoroquinolone antibiotic with a broad spectrum of activity against Gram-positive 
and Gram-negative bacteria and atypical pathogens. Levofloxacin has antimicrobial effect against both 
penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. In America, the prevalence of 
S. pneumoniae resistance to levofloxacin is <1% overall. A number of studies have shown that 
levofloxacin is effective in treating infections of the respiratory tract, genitourinary tract, skin and 
integumental system. In one study comparing the administration of antibiotics in patients with 
nosocomial pneumonia, oral administration of levofloxacin 750 mg orally once daily for 7-14 days was 
equivalent to that of an intravenous imipenem/cilastatin regimen of 500-1000 mg every 6-8 hours 
followed by oral ciprofloxacin 750 mg. twice a day. In patients with community pneumonia (CAP), 
levofloxacin 500 mg intravenously and/or orally once daily for 7-14 days has a similar effect to 
regimens such as amoxicillin/clavulanic acid, clarithromycin, azithromycin, ceftriaxone and/or 
cefuroxime axetil and gatifloxacin. Oral levofloxacin is as effective as ofloxacin in uncomplicated 
urinary tract infections or equivalent to ciprofloxacin in the treatment of complicated urinary tract 
infections. In men with chronic bacterial prostatitis, levofloxacin 500mg orally once daily achieves 
levels equivalent to 500 mg orally ciprofloxacin twice daily. Compared with other quinolone antibiotics, 
levofloxacin is generally well tolerated. Some of the most commonly reported side effects include 
nausea and diarrhea; while some of the side effects that are often encountered with quinolones such as 
photosensitivity are also less common with the use of levofloxacin.11 
 
Use of Levofloxacin in the prevention of post-urodynamic UTI 
Although the evidence regarding the use of antibiotics after urodynamic examination varies, the 
experience of researchers in previous studies has shown that giving 3 doses of the antibiotic 
levofloxacin 500 mg can reduce the magnitude of the risk of post-urodynamic UTI by 55% compared 
to patients who do not receive prophylactic therapy at all.12 
 
Pre-Urodynamic use of Levofloxacin for the prevention of UTI 
Although prophylactic administration to prevent UTI after urodynamic examination using levofloxacin 
has not been studied before, there have been many studies that have tried to use various antibiotics such 
as augmentin, ciprofloxacin, cotimoxazole, nitrofurantoin, norfloxacin, trimethopim, and cinoxacin as 
prophylactic therapy that can be given. And through a meta-analysis of these studies showed that the 
use of post-urodynamic prophylaxis can reduce the risk of infection by 40%.1 Therefore, prophylaxis 
using antibiotics is also applied in several guidelines, especially if the conditions under which 
urodynamics are performed cannot be regulated in such a way as to achieve ideal conditions.13 
 
 


Research methodology 
This study is an experimental study with a single-blinded randomized clinical trial design to compare 
the proportion of UTIs in a group of patients receiving levofloxacin 500 mg single dose one hour before 
urodynamic examination and patients receiving levofloxacin 500 mg once daily for three days 
postoperatively-urodynamic examination. To determine the sample treatment group, blocked 
randomization technique is used in this study. 
 
This study uses a single-blinded design because the outcome assessed in this study is urinalysis which 
is the objective outcome. The urinalysis evaluator is blinded to the drug regimen obtained by the 
research 
subjects. 
 
An additional consideration for the use of a single-blinded design is the limited facility for making 
placebos. 
 
Conceptual Framework 
 
 
 
 
 
 
 
 
 
 
 
 
Definition of work 
1. 
Single dose of Levofloxacin 
Single-dose levofloxacin is defined as the administration of 500 mg of levofloxacin one hour prior 
to urodynamic procedures. 
2. 
Levofloxacin for 3 days 
Levofloxacin for 3 days is defined as the administration of levofloxacin 500 mg/day for 3 days 
post-urodynamic examination. 
3. 
UTI 
Urinary tract infection is defined based on the results of urinalysis in which one of the following 
conditions is present: leukocyturia (found > 5 leukocytes/per field view), positive bacteria, positive 
nitrite, and/or leukocyte esterase positive. 
4. 
Urodynamic 
Urodynamic examination used in this study consist of non-invasive uroflowmetry examination, 
measurement of post voiding residual (PVR), and measurement of cystometrography (CMG). 
 
 
 
 
 
Single dose of 
levofloxacin 500mg 1 
hour before 
urodynamic 
Levofloxacin 500 mg 
once daily for 3 days 
after urodynamic 
examination 
Patients with 
indications for 
urodynamic 
examination 
UTI (+) Posturodynamic 
UTI (-) Posturodynamic 
UTI (-) Posturodynamic 
UTI (+) Posturodynamic 


Research hypothesis 
Preurodynamic single-dose levofloxacin administration is more effective than posturodynamic 
levofloxacin for three days against UTI events. 
 
Source 
The data source of this research is primary data taken from patients who have indications for 
urodynamic examination at dr. Cipto Mangunkusumo Hospital, Siloam Asri Hospital, and 
Persahabatan Hospital during any given time. 
 
Number of Samples 
Calculation of the sample is made based on “Dasar-dasar Metodologi Penelitian Klinis” (Sastroasmoro 
et al.) regarding the calculation of proportions for 2 independent groups.14 From the literature, the 
effectiveness of posturodynamic prophylactic antibiotics in preventing UTI is 0.40 (P1). The 
effectiveness of levofloxacin 500mg preurodynamic single dose is believed to be 30% different from 
P1 (P2=0.70). 
 
 
 
Considering the possibility of drop-out, it is decided that the number of samples taken is 100 patients, 
which will then be screened for eligibility and will be equally randomized. 
 
Data Collection Technique 
The data collection technique uses consecutive sampling method until the required number of subjects 
is reached. 
 
The inclusion criteria in this study are: 
o 
Male/female patients > 18 years who have indications for urodynamics 
o 
Willing to participate in research 
 
The exclusion criteria of this study are: 
o 
Allergy to levofloxacin 
o 
History of taking antibiotics in 1 month 
o 
pregnant 
o 
Uncontrolled DM 
o 
Using a urinary catheter 
o 
Having a UTI before urodynamics, based on clinical symptoms and urine examination results 


o 
Refuse to participate in research 
 
Statistical analysis technique 
Descriptive exposure is used to assess the characteristics of the subject, such as age, sex, and indications 
for urodynamics. To assess the relationship between the incidence of UTI with the treatment group, chi-
square analysis is used. The data will be processed using SPSS version 24 and is considered significant 
if p<0.05. 
 
Types of Research Activities 
This research activity is experimental with the following research flow chart: 
(next page) 


 


Research Places 
The research places are the urology outpatient clinic of the Urology Department, dr. Cipto 
Mangunkusumo Hospital and the Uronephrology Cluster of RSCM Kencana, Siloam Hospitals ASRI, 
and RSUP Persahabatan. At Siloam Hospitals ASRI, Prof. dr. Harrina Erlianti Rahardjo, Sp.U(K), PhD 
will be in charge, while at the RSUP Persahabatan, the person in charge is dr.Andika Afriansyah, Sp.U. 
 
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