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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 31  |  Issue : 5  |  Page : 216-220

Comparison of prophylactic antibiotics in patients without pyuria undergoing ureterorenoscopic surgery


Department of Urology, National Taiwan University Hospital, Taipei, Taiwan

Date of Submission02-Dec-2019
Date of Decision16-Apr-2020
Date of Acceptance13-May-2020
Date of Web Publication27-Oct-2020

Correspondence Address:
Yuan-Ju Lee
Department of Urology, National Taiwan University Hospital, Taipei
Taiwan
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/UROS.UROS_40_20

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  Abstract 


Purpose: The objective of this study was to evaluate the efficacy of antibiotic prophylaxis in patients with a tentative diagnosis of ureteral stones undergoing ureterorenoscopic surgery. Materials and Methods: This is a single-surgeon, open-label randomized controlled trial, which enrolled 109 patients from May 2014 to September 2018. The patients were equally randomized into three groups: a group with a single dose of intravenous cefazolin (1g), a group with oral cefuroxime (500 mg), and a control group with no prophylactic antibiotics. The primary end points were the rate of febrile urinary tract infections (UTIs) and postoperative pyuria. Results: The rate of postoperative fever was 9.4% in the cefazolin group (3 in 32), 0% in the cefuroxime group (0 in 29), and 6.9% in the control group (2 in 36). There was no statistically significant difference between the cefazolin and control groups (P = 0.1). The rate of postoperative pyuria was 64.3% in the cefazolin group, 58.3% in the cefuroxime group, and 33.3% in the control group, without statistically significant differences between the groups. Conclusion: Antibiotic prophylaxis could not reduce the incidence of postoperative febrile UTI and pyuria in ureterorenoscopic lithotripsy.

Keywords: Antibiotic prophylaxis, ureteroscopy, urinary tract infections, urolithiasis


How to cite this article:
Li MW, Lee YJ. Comparison of prophylactic antibiotics in patients without pyuria undergoing ureterorenoscopic surgery. Urol Sci 2020;31:216-20

How to cite this URL:
Li MW, Lee YJ. Comparison of prophylactic antibiotics in patients without pyuria undergoing ureterorenoscopic surgery. Urol Sci [serial online] 2020 [cited 2020 Nov 28];31:216-20. Available from: https://www.e-urol-sci.com/text.asp?2020/31/5/216/299260




  Introduction Top


Antibiotic prophylaxis is widely used in various surgeries to lower perioperative infection, but it is often overused.[1],[2],[3],[4] However, previous studies showed conflicting evidence, and the use of antibiotic prophylaxis accompanying urinary tract endoscopy remains controversial.[5],[6],[7]

Ureteral stone is a common disease resulting in pain, hematuria, and urinary tract infection (UTI). Ureterorenoscopic lithotripsy (URSL) is widely used to treat ureteral stones. The reported incidence of febrile UTIs was ≤2.2%.[8] A meta-analysis enrolling four randomized controlled trials showed that antibiotic prophylaxis can reduce the incidence of pyuria and bacteriuria after URSL but not that of febrile UTI.[4] The guidelines of the European Association of Urology (EAU) do not strongly recommend using antibiotic prophylaxis to reduce the rate of symptomatic UTI following ureteroscopy (URS) and transurethral resection of the bladder.[9] On the other hand, the use of antibiotic prophylaxis is strongly recommended for percutaneous nephrolithotomy (PCNL) and transurethral resection of the prostate.[9]

Currently, in the Urology Department of the National Taiwan University Hospital (NTUH), we routinely gave prophylactic intravenous cefazolin to patients before their endoscopic surgery according to the recommendation of the Taiwan Urological Association. The regimen was adjusted if the patients had a documented urine culture with sensitivity test. Nowadays, antibiotics are widely used against infections in every division, but they are sometimes overused in general clinics. There is a concern that cefazolin is not enough because of the growing antibiotic resistance in Taiwan. There is no national high-level research in Taiwan investigating antibiotic prophylaxis in the urinary tract. Therefore, we designed this study to evaluate the efficacy of antibiotic prophylaxis in patients undergoing URSL.

The objective of this study is to evaluate the efficacy of intravenous cefazolin and oral cefuroxime. The primary end points were the rate of febrile UTI and postoperative pyuria. Logistic regression was conducted with factors influencing the rate of fever.


  Materials and Methods Top


We conducted a single-surgeon, prospective, open-label randomized controlled trial at NTUH. The study protocol was approved by the internal Ethics Committee at NTUH (IRB approval number:201301067MINB).

One hundred and nine patients were enrolled from May 2014 to September 2018. The patients were randomly assigned to one of the three groups, receiving one of the following three treatments: a single dose of intravenous cefazolin (1g), oral cefuroxime (500 mg), and no prophylactic antibiotics. We used block randomization with a random number generator. The inclusion criteria were an age range of 20–75 years, negative urine culture result–no pyuria (white blood cell [WBC] high power field <10/HPF), and being diagnosed with hydronephrosis, ureteral stone, or ureteral stricture as indicated by an ureterorenoscopic surgery. The exclusion criteria were the absence of UTI preoperatively, receipt of antibiotics within the past two weeks, presence of a congenital or neurological anomaly, presence of implants of any organ, pregnancy, allergy to antibiotics, usage of a urinary catheter (urethral catheter, cystostomy), and immunocompromised conditions, including diabetes mellitus, neoplasm, HIV, and tuberculosis.

The patients were admitted the day before operation. Routine examinations were performed, including complete blood count, WBC classification, liver function examination, urine analysis, and blood urea nitrogen, creatinine, sodium, potassium, total bilirubin, and urine culture examinations. Preoperative cefazolin was diluted to 10 ml and given by intravenous push in 3–5 minutes. The URSL was performed with standard sterile methods and instruments by a single surgeon. A 6-Fr semi-rigid URS and a holmium: yttrium-aluminum-garnet laser were used for lithotripsy. If a ureteral stricture was encountered, internal dilatation with URS or laser ureterotomy was performed. Postoperative ureteral stenting was performed per a surgeon's decision with a 6- or 7-Fr Double-J catheter (DBJ). The catheter was removed after a month if no ureteral stricture was found intraoperatively. Postoperative kidney, ureter, and bladder X-ray was conducted routinely for the DBJ position. The urethral catheter was removed after 24 hours. No postoperative antibiotics were given to patients unless febrile UTI was diagnosed. Urine culture and urine analysis were rechecked on the 7th day postoperative. Antibiotics were given if symptomatic UTI was diagnosed.

The data were statistically analyzed with a Chi-square test, Fisher's exact test, a Mann–Whitney U-test, or a Kruskal–Wallis test according to the type of variables.


  Results Top


A total of 109 patients were enrolled and randomly assigned. Ten patients were excluded due to various reasons, such as pyuria found before surgery, violation of the standard protocol, or cancellation of the operation because of spontaneous stone passage. Furthermore, two patients had their treatment plan changed during operation: one patient to PCNL and the other to percutaneous nephrostomy insertion. Both of them were excluded from the analysis. Ninety-seven patients were eligible for analysis. The recruitment flowchart is shown in [Figure 1]. No patient dropped out after operation.
Figure 1: Randomization and exclusions. Three patients in the i.v. group were excluded according to exclusion criteria; one was changed to PCNL because of intraoperative decision-making. One patient in the PO cefuroxime group was changed to PCN because of intraoperative decision-making. Seven patients in the no-prophylaxis group were excluded according to exclusion criteria. Abbreviations: i.v: Intravenous. PO: Per os, PCNL: Percutaneous nephrolithotomy. PCN: Percutaneous nephrostomy

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[Table 1] shows the baseline characteristics of the patients. The recruited patients were equally distributed over the three groups with respect to gender, age, physiological condition, and severity of the disease. The mean age was 51.5 years, the mean body mass index 26.0 kg/m2, the mean creatinine level 0.98 mg/dL, the mean stone size 0.94 cm, the mean operational time 28.4 minutes, and the meantime to DBJ removal 16.2 days. Among the preoperative factors, age and size of the stone were unbalanced between the groups (P > 0.05). The average size of the stone was slightly larger, and the patients were older in the intravenous group than in the oral group. Logistic regression was performed to assess the impact of the size of the stone and age in the study, and both were found to be unpredictive of the rate of fever (P > 0.05).
Table 1: Characteristics of patients

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Besides URSL, the patients received additional procedures according to the operative findings: 16 patients received only ureterorenoscopy without lithotripsy, 3 received laser ureterotomy, 2 received cystolithotripsy, and 3 with ureteral tumors received URS biopsy.

[Table 2] shows the surgical outcomes. Postoperative pyuria was defined as WBC >10/HPF. The rate of pyuria was not significantly different between the groups, even when comparing each experimental group with the control group. The rate of fever was 9.4% in the cefazolin group (3 in 32), 0% in the cefuroxime group (0 in 29), and 6.9% in the control group (2 in 36).
Table 2: Surgical outcomes

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In the subgroup analysis, the location of the stone was compared in stratification: upper stones and middle/lower stones. There were no significant differences in postoperative pyuria and the rate of fever. However, a higher stone-free rate was noted for the middle/lower stones (relative risk: 4.9; 95% confidence interval: 1.7–14.2).

[Table 3] shows the perioperative characteristics of five febrile patients. The timing of fever ranged from postoperative day (POD) 1–9. Three of them received URSL, one received URS biopsy, and one received URS. Two other postoperative adverse events were noted. One patient who received internal dilatation with URS came to the Emergency Department (ER) due to flank pain at POD 1. Another who received retrograde intrarenal surgery came to the ER at POD 5 and was diagnosed with UTI with acute renal injury.
Table 3: Characteristics of patients with febrile urinary tract infection

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  Discussion Top


Antibiotic prophylaxis was recommended for endoscopy of the urinary tract in old reviews.[5] Antibiotics should be given to patients with preoperative UTI or bacteriuria, but it is still controversial whether antibiotic prophylaxis should be given to patients with sterile urine before surgery. Only a few randomized controlled trials focused on this topic in the past decade.[4] Other risk factors of perioperative infection are age, malnutrition, smoking, anatomic anomalies, immunodeficiency, diabetes, stone size and location, surgical time, tissue trauma, and ureteral stenting.[10] However, a limited number of studies focused on assessing each factor separately, thus yielding sparse evidence about the relative importance of each of these factors. We sought to address some of the factors.

There is no definitive evidence regarding the duration of antibiotic prophylaxis. The guidelines of the EAU, the American Urological Association (AUA), and the Japanese Urological Association (JUA) suggest single-dose prophylaxis. Besides, no definite regimen was established. There are slight differences between the guidelines. The EAU guidelines suggest trimethoprim-sulfamethoxazole, second- or third-generation cephalosporin, or penicillins with beta-lactamase inhibitors.[9] The AUA guidelines suggest fluoroquinolone or trimethoprim-sulfamethoxazole.[11] The JUA guidelines suggest penicillins with beta-lactamase inhibitors, first- or second-generation cephalosporin, or aminoglycosides.[10] Due to the different drug resistances in different countries, only national multicenter studies could unveil the optimal agents.

The advantage of our study was that the study design was based on real-world practice. In daily practice, the diagnosis of ureteral stones is often made by plain-film or intravenous pyelography, which cannot definitely differentiate ureteral stones from ureteral strictures or tumors before operation. Computed tomography has a better diagnostic value but is not a routine first-line examination. Therefore, we did not strictly limit the preoperative diagnosis to ureteral stones. In our case series, 16 patients were finally diagnosed with ureteral stricture and three with ureteral tumors.

In our study, the rate of febrile UTI was lower in the cefuroxime group (0%) than in the cefazolin group (9.4%, n = 3), but this difference was not statistically significant (P = 0.1). It is known that Gram-negative bacilli are prevalent in the urinary tract. This can explain why second-generation cephalosporin (cefuroxime) has better coverage in Gram-negative bacilli than first-generation cephalosporin (cefazolin).[12] In another randomized controlled trial in Taiwan, the treatment of single-dose cefazolin, ceftriaxone, and levofloxacin prophylaxis gave a similar rate of postoperative febrile UTI.[13]

The rate of postoperative pyuria was 64.3% in the cefazolin group, 58.3% in the cefuroxime group, and 33.3% in the no-prophylaxis group. No statistical significance was found between the prophylaxis groups and the no-prophylaxis group [Table 2]. Our results conflict with previous findings by Hsieh et al.[13] that prophylaxis reduced the incidence of pyuria. The median time to postoperative urine analysis was 7 days in our study. The difference in pyuria between the groups may diminish as patients recover from the operation.

In a review article in 2004, the expected rate of febrile UTI after URS without prophylaxis was 4%–25%.[14] The incidence of febrile UTI dropped to ≤2.2% in 2015.[8] The decline might be induced by the heterogeneity of patients' characteristics among studies. Another possible reason is the evolution of surgical instruments and techniques.[15]

A panel discussion about the EAU guidelines concluded that despite low-quality evidence suggesting no benefit in reducing the risk of clinical UTI, clinicians and patients would prefer to use prophylaxis to prevent kidney infection or sepsis. Ideally, this should be examined in a robustly designed clinical study.[9]

There were limitations to this study. First, patients with diabetes, which is common in the elderly, were not enrolled. Second, the preoperative factors age and the size of the stone were unbalanced between the groups, possibly owing to the small sample size. However, these two factors were found to be unable to predict the outcome by logistic regression.


  Conclusion Top


Antibiotic prophylaxis could not reduce the incidence of postoperative febrile UTI and pyuria in patients with sterile urine undergoing URSL. Middle and lower stones had a higher clearance rate than upper stones, but the location of the stones was not related to the rate of fever after surgery. Therefore, in cases with simple sterile ureteral stones, not giving antibiotic prophylaxis might be an alternative to avoid antibiotic resistance and adverse events.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Childs SJ. Appropriate surgical prophylaxis in transurethral genitourinary surgery and potential reduction in nosocomial infections. Urology 1986;27:415-20.  Back to cited text no. 1
    
2.
De Lalla F. Perioperative antibiotic prophylaxis: A critical review. Surg Infect (Larchmt) 2006;7 Suppl 2:S37-9.  Back to cited text no. 2
    
3.
Kanamaru S, Terai A, Ishitoya S, Kunishima Y, Nishiyama H, Segawa T, et al. Assessment of a protocol for prophylactic antibiotics to prevent perioperative infection in urological surgery: A preliminary study. Int J Urol 2004;11:355-63.  Back to cited text no. 3
    
4.
Lo CW, Yang SS, Hsieh CH, Chang SJ. Effectiveness of Prophylactic Antibiotics against Post-Ureteroscopic Lithotripsy Infections: Systematic Review and Meta-Analysis. Surg Infect (Larchmt) 2015;16:415-20.  Back to cited text no. 4
    
5.
Amin M. Antibacterial prophylaxis in urology: A review. Am J Med 1992;92:114S-117S.  Back to cited text no. 5
    
6.
Bootsma AM, Laguna Pes MP, Geerlings SE, Goossens A. Antibiotic prophylaxis in urologic procedures: A systematic review. Eur Urol 2008;54:1270-86.  Back to cited text no. 6
    
7.
Yamamoto S, Shima H, Matsumoto T. Controversies in perioperative management and antimicrobial prophylaxis in urologic surgery. Int J Urol 2008;15:467-71.  Back to cited text no. 7
    
8.
Martov A, Gravas S, Etemadian M, Unsal A, Barusso G, D'Addessi A, et al. Postoperative infection rates in patients with a negative baseline urine culture undergoing ureteroscopic stone removal: A matched case-control analysis on antibiotic prophylaxis from the CROES URS global study. J Endourol 2015;29:171-80.  Back to cited text no. 8
    
9.
Guidelines E. EAU Guidelines. Edn. Presented at the EAU Annual Congress Barcelona 2019; 2019.  Back to cited text no. 9
    
10.
Yamamoto S, Shigemura K, Kiyota H, Wada K, Hayami H, Yasuda M, et al. Essential Japanese guidelines for the prevention of perioperative infections in the urological field: 2015 edition. Int J Urol 2016;23:814-24.  Back to cited text no. 10
    
11.
Wolf JS Jr., Bennett CJ, Dmochowski RR, Hollenbeck BK, Pearle MS, et al. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol 2008;179:1379-90.  Back to cited text no. 11
    
12.
Marshall WF, Blair JE. The cephalosporins. Mayo Clin Proc 1999;74:187-95.  Back to cited text no. 12
    
13.
Hsieh CH, Yang SS, Lin CD, Chang SJ. Are prophylactic antibiotics necessary in patients with preoperative sterile urine undergoing ureterorenoscopic lithotripsy? BJU Int 2014;113:275-80.  Back to cited text no. 13
    
14.
Grabe M. Controversies in antibiotic prophylaxis in urology. Int J Antimicrob Agents 2004;23 Suppl 1:S17-23.  Back to cited text no. 14
    
15.
Whitehurst LA, Somani BK. Semi-rigid ureteroscopy: Indications, tips, and tricks. Urolithiasis 2018;46:39-45.  Back to cited text no. 15
    


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    Tables

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