Effect of standard antibiotic prophylaxis versus enhanced prophylactic measures on rate of urinary tract infection after exible ureteroscopy: A randomized clinical study

El-Sayed I. El-Agamy Al-Azhar University Faculty of Medicine Mohamed A. Elhelaly. Al-Azhar University Faculty of Medicine Tamer A. Abouelgreed (  dr_tamer_ali@yahoo.com ) Al-Azhar University, Faculty of Medicine, Department of urology https://orcid.org/0000-0003-26403425 Abdrabuh M. Abdrabuh Al-Azhar University Faculty of Medicine Mohamed F. Elebiary Al-Azhar University Faculty of Medicine Mohamed A. Abdelaal Al-Azhar University Faculty of Medicine


Abstract
Background Prevention of urinary tract infections (UTIs) after exible ureteroscopy (fURS) remains controversial. The present study aimed to compare the rate of post-procedural UTI in patients subjected to the standard antibiotic prophylaxis alone versus enhanced prophylactic measures.
Methods from August 2018 to September 2020, a total of 100 patients subjected to fURS for management of ureteral and/or renal stones were included in this study. Patients were equally and randomly divided to two treatment groups using randomly computer-generated allocation tables and concealed envelope technique. Treatment groups included standard antibiotic prophylaxis group and enhanced prophylaxis group. Patients in the standard antibiotic prophylaxis group IV, uoroquinolone 1 hour preoperatively and oral antibiotics were used for 24h postoperatively. In the enhanced prophylaxis group, patients had urine culture 10 days before the procedure. In addition to the antibiotic prophylaxis, hydrophilic-coated ureteral access sheaths were systematically used.

Results
Comparison between the baseline and operative characteristics of the studied groups revealed no

Conclusions
Urinary tract infection after fURS can be signi cantly reduced by using the suggested enhanced prophylactic approach.

Background
Thanks to the continuous technological developments, exible ureteroscopy (fURS) has become one of the most reliable tools in upper urinary tract endourology. Weaponed by creative ancillary instruments such as graspers and baskets, effective energy sources and digital and robotic enhancements, fURS could expand its diagnostic and therapeutic applications to many upper urinary tract pathologies beyond their common use in management of renal stones [1]. (fURS can be used as a conservative treatment for urothelial tumors of the upper urinary tract (UTUC) and can serve as follow up aid after radical treatment of UTUC [2]. However, use of fURS isn't without drawbacks. Signi cant complications including urinary tract infection (UTI) and ureteric trauma are frequently reported [3]. In one study, febrile UTI was reported in 14.1 % of patients submitted to exible ureteroscopic lithotripsy [4]. Unfortunately, prevention of postoperative UTI after fURS remains a debatable issue with Current practice lacks well-established clinical evidence based on randomized clinical studies and is mostly based on retrospective studies [5]. In an effort to standardize the periprocedural systemic antimicrobial administration, the American Urological Association best practice policy statement was developed [6]. However, real-world practice is widely variable and observational studies show relatively low compliance with these recommendations [5]. To guard against postprocedural infection, the most common practice is single dose antibiotic prophylaxis [7]. On the other hand, some centers use more enhanced precautions including centralized collection and examination of preoperative urine cultures, standardized antibiotic prophylaxis and use of ureteral access sheath. Even with these precautions, postoperative UTI was encountered in 6.7 % of patients [8]. The present randomized study aimed to compare the rate of post-procedural UTI in patients subjected to the standard antibiotic prophylaxis alone versus enhanced prophylactic measures.
Methods the present randomized study was conducted at department of Urology, Armed forced Hospital, Alhada, KSA in the period from August 2018 to September 2020. The study protocol was approved by the local ethical committee of the author's institute and informed written consent was obtained from all patients before enrollment. The study is registered at clinical trials.gov (NCT04731090). The study included all patients subjected to fURS for management of ureteral and/or renal stones. Exclusion criteria were symptomatic UTI, use of rigid ureteroscope and antegrade ureteroscopy. Preoperatively, all patients were subjected to careful history taking, thorough clinical examination and non-contrast computed tomography scan to evaluate the stone characteristics. Patients were equally and randomly allocated into one of the two treatment groups using randomly computer-generated allocation tables and concealed envelope technique. Randomization and patients allocation were supervised by an independent researcher. Treatment groups included standard antibiotic prophylaxis group and enhanced prophylaxis group. Patients in the standard antibiotic prophylaxis group IV uoroquinolone 1 hour preoperatively and oral antibiotics were used for 24h postoperatively. In the enhanced prophylaxis group, patients had urine culture 10 days before the procedure. Patients with sterile culture received standard antibiotic prophylaxis while patients with polymicrobial preoperative urine culture (de ned by a urine culture isolating at least three microorganisms, of which none is predominant) were treated by ceftriaxone 48 h before the intervention which was continued until 1 day after surgery. Those having positive urine culture were contacted by the urologist to assess if they had symptoms of UTI. In asymptomatic cases, according to the speci c pathogens identi ed, a full course of antibiotics was started 5 days prior to surgery until 48 h after the intervention. For those having clinically signi cant infection, intervention was deferred. In addition to the antibiotic prophylaxis, hydrophilic-coated ureteral access sheaths were systematically used. The primary outcome in the present study is occurrence of postoperative UTI withing 30 days postoperative. Postoperative UTI was de ned as the occurrence of a temperature higher than 38°C associated with pyuria and/or bacteriuria without any other focal infectious sites.
Data obtained from the present study were presented as number and percent or mean and standard deviation (SD). Numerical data were compared using t test while categorical data were compared using chi-square test. Logistic regression was used to identify predictors of outcome. All statistical operations were computed using SPSS 25 (IBM, USA) and p value less than 0.05 was considered statistically signi cant.

Results
The present study comprised 100 patients submitted to FURS. They were simply and equally randomized into two groups according to the used prophylaxis protocol against postoperative UTI. The standard prophylaxis group (n = 50) received standard antibiotic prophylaxis while the enhanced prophylaxis group (n = 50) had preoperative culture and coated ureteral access sheaths in addition to the antibiotic prophylaxis. Comparison between the baseline and operative characteristics of the studied groups revealed no statistically signi cant differences (Table-1 Table-2).

Discussion
Urinary tract infections after fURS are commonly seen in clinical practice. Even in the absence of microbial invasion, the surgical procedure itself elicits signi cant systemic in ammatory response which is related to the duration of the procedure and can predispose to infectious complications [9]. The present randomized study assessed the value of standard antibiotic prophylaxis versus enhanced prophylaxis in prevention of UTI after fURS. Postoperative UTI was diagnosed in 8 patients (16.0 %) in the standard prophylaxis group versus 2 patients (4.0 %) in the enhanced prophylaxis group (p = 0.046). Clearly, the bene cial effects of enhanced prophylaxis are attributed to additional measures included in the protocol namely the preoperative culture and treatment of identi ed infections and coated ureteral access sheaths. The relation between positive preoperative culture and postoperative UTI in patients submitted to fURS was discussed by the study of Senocak et al., [10] In their work, positive preoperative urine culture with multidrug resistance isolates was recognized as an independent risk factor of postoperative UTI. Of note, none of our patients had such isolates. Also, in the study of Alezra et al., [11] positive day-1 culture was a signi cant predictor of severe UTI. In addition, the study of Auge BK et al., [12] highlighted the value of ureteral access sheath (UAS) in reduction of postoperative UTI after fURS. Similar conclusions were reported by the randomized study of Özkaya et al., [13] who noted that use of UAS in impacted mid-upper ureteral stones is related to fewer infectious complications. The UAS serve to reduce the irrigation pressures transmitted to the renal pelvis and parenchyma [12]. Moreover, appropriate UAS selection is important to optimize the renal blood ow during fURS. Adequate renal blood ow is essential to maintain local immune defensive mechanisms [14]. In our study, logistic regression analysis identi ed female sex as an independent risk factor of postoperative UTI. This nding is in conformity with the study of Baboudjian et al., [8]. In their study, they also added preoperative polymicrobial urine culture and increased operative time as predictors of postoperative UTI. Our conclusions are also supported by the recent meta-analysis of Ma et al. [15]. In contrast, the study of Baseskioglu et al., [16] recognized preoperative infection history, comorbidity score and residual fragments as signi cant predictors of UTI after fURS while the relevant risk factors in the study of Ozgor et al., [17] were longer operation time, presence of renal abnormality and age ≤ 40 years.

Conclusion
The present study concluded that UTI after fURS can be signi cantly reduced by using the suggested enhanced prophylactic approach. 3. Informed consent for participation and publish: Informed written consent was obtained from all patients before the study for participation and publish.

Ethical approval
All procedures performed in this study were in accordance with the ethical standards of the Institution and/or National Research Committee and the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The protocol and written informed consent were approved by the local ethical committee of Armed forced Hospital, Alhada, KSA. Rec No: 536).