Installation or exchange of double-J ureteral stent is a risk factor of febrile urinary tract infection in a compromised host

Background : To study the predictors of febrile urinary tract infections (febrile UTI) after the placement of Indwelling double-J ureteral stent (DJS), and effective prophylactic antimicrobial agent. Methods : Installation or exchange of 298 double-J stents (DJS) ( 66 men and 232 women, median age 67 years, range 4286) were examined. 258 patients had been given prophylactic antibiotic therapy after the placement of stents, 40 patients with no prophylactic antibiotic therapy. Results : 14 patients (4.2%) had febrile UTI after the placement of the stent. The pathogens was identified from the pelvic urine culture of 9 patients with febrile UTI. Enterococcus faecalis was the most common pathogen, it accounted for 25.0% of all pathogens. Compromised host was potential risk factors for the febrile UTI in patients with DJS. 1.1% of patients who received with fluoroquinolones or 4.7% of patients with cephalosporin developed a febrile UTI. Conclusions : Indwelling DJS is a risk factor of febrile UTI in a compromised host, fluoroquinolones may be effective for preventing febrile UTI after placement of DJS.

Conclusions : Indwelling DJS is a risk factor of febrile UTI in a compromised host, fluoroquinolones may be effective for preventing febrile UTI after placement of DJS.

Background
Placement of indwelling double-J ureteral stent (DJS) are common procedure in an urology department. This procedure is performed for disease to complicated hydronephrosis and relief of obstruction, prevention of stricture formation, treatment of urinary tract leaks. However, with accumulated experience, we know that patients with indwelling DJS experience some effects such as lower abdominal pain, urinariy frequency, hematuria, dysuria and febrile UTI.
The reported rates for bacterial colonization in adults within several weeks of double-J 3 stent insertion range from 28% to 90%, and rates for UTI range from 7% to 34% 1,2) .
Because pathogens responsible for febrile UTI caused by ureteral stenting and effective prophylactic antibiotics remain unknown, it is not clear that guidelines for infection control with transurethral ureteral stenting have been issued. We sought to identify predictors of the occurrence of febrile UTI following transurethral double-J ureteral stenting and responsible pathogens, with the ultimate aim of selecting the most appropriate prophylactic antibiotics.

Methods
The study was approved by the Ethics Committee of Hiroshima University (E-23, Hiroshima, Japan).

Infectious Complication
A febrile infectious complications including pyelonephritis, prostatitis and epididymitis were defined as an infection with fever (>38℃) occurring within 30 days of follow-up and bacteriuria as ≥ 10 3 coloney forming units (CFU)/ml 3) . Additionally we investigated risk factors such as age, sex, stent placement on one side or both side, installation at first time or exchange, causative disease (benign or malignancy), presence of pyuria, urinary dysfunction (neurogenic bladder, benign prostate hyperplasia, bladder output obstruction) renal failure (GFR< 60ml / min), malnutrition (serum Albmin< 3.7 g / dl), compromised host (steroid user, diabetes mellitus, still on using anticancer drug), administration of prophylactic antibiotics before and after the procedure, the choice of fluoroquinolone for prophylactic antibiotics.

statistical analysis
Chi-square test was used to analyze the association of bacterial stent colonization with events of UTI, patient backgrounds. Logistic-regression analysis was used to analyzed the risk factors of febrile UTI. In all statistical analysis, a pvalue of <0.05 was considered to indicate statistically significant differences. All statistical analyses were performed using JMP v10.0 software (SAS Institute, Cary, NC, USA).

Infectious Complication
Patient' characteristics are shown in Table 1.
There were 14 febrile UTI (4.2%) after the placement or exchange of DJS.
We compared the patient' characteristics between a group that developed UTIs and a group that didn't developed UTIs, there are many compromised hosts significantly in the group that developed UTIs, and numbers of patients administerd fluoroquinolone agents as prophylactic antibiotics is less significantly in the group that developed UTIs.
Pathogens cultured from urine Table 2 shows pathogens identified from urine cultures.
Of these 14 patients with febrile UTI, pathogens cultured from ureteropelvic urine were isolated in 9 patients. Because other 5 patients were admitted to other hospitals, culture test was not enforced. Half of the pathogens were gram-negative rods.
Of the 284 patients who had no onset of febrile UTI, 63 urine sampling for monitoring of 5 UTI were cultured. Pathogens cultured from urine were isolated in 38 patients (60.3%).
Gram-negative rods accounted for 47.9% (23 / 48 isolets) of all the pathogens. There were more bacteria that tend to resistant antibiotics such extended-spectrum β-lactamase producing E. coli and P. aeruginosa in surveillance group than in febrile UTI group.

Risk factors of infectious complication
Compromised host was potential risk factors for the febrile UTI in patients with DJS (p = 0.0098, odds = 4.35, Table3). The incidence of febrile UTI (1 / 92, 1.1%) in patients with fluoroquinolones is lower than the incidence with cephalosporin (10 / 131, 7.6%), but administration of fluoroquinolones was not independent predictor that prevented febrile UTI.

Discussion
To the best of our knowledge, this study is the first report to clarify that compromised host is a risk factor for febrile UTI onset.
The placement of DJS is associated with some complications while the use of indwelling DJS is one of the indispensable techniques in urological surgeons.
Early complications include low abdominal pain, hematuria, urinary urgency, frequency.
Stone formation, infection are late complications. [4][5][6][7][8][9] Bacteremia secondary to urological procedures has an incidence of around 30% in adults, 10) but the relationship between the placement of DJS and febrile UTI is not clear. In addition, there is no guidance on using antibiotic prophylaxis in the placement of DJS 11) . In our study, the incidence of febrile UTI in the patients with DJS was 4.7%, this was consistent with the results pf previous studies which reported that the rate of febrile UTI onset due to ureteral stent placement regardless of antibiotic treatment was 6-7% 12) . When we placed the ureteral stent, we sampled the ureteropelvic urine of the 63 patients to perform bacteriologic tests and 6 found that 38 patients had bacteriuria. Riedl et al. 13) and Farsi et al. 14) reported that bacteriuria associated with stent placement in 45% and 30% of patients, respectively. The positive rate at our hospital was 60.3%, which is higher than those reported by the other authors. However, the median duration of placement in this study was approximately 2 years, and patients who had been undergoing ureteral stent exchange continuously for 5 or more years have been included. In the surveillance cultures of ureteropelvic urine, Enterococcus faecalis was the most common bacterial species, and it was also the most common pathogen of febrile urinary tract infections occurring in our hospital. But in the surveillance cultures, there are drug resistance pseudomonas aeruginosa and drug resistance enterobacteriase. Careful attention must be paid to select antibiotics with the onset of febrile urinary tract infection.
In the present study, there were 21% of patients who did not receive antibiotics before and after treatments. However compromised host was only potential risk factor for febrile UTI in patients with DJS regardless of whethere antibiotics was administered. There were few reports that considered predictors of febrile UTI in patients with DJS, Moltzahn et al. 12) reported that urinary sediment threshold of leucocytes / HPF or nitrite reaction was't be usefulto predict febrile UTI. In many of previous studies, the duration of administration, and the choice of antibiotics for prophylaxis in the placement of DJS is not clear. In the study to compare the efficacy of single dose oral ciprofloxacin (500mg) with intravenous cefazolin (1g) as a antibiotic prophylaxis in patients undergoing endourologic procedures for outpatients including stent placement or exchange, retrograde pyelogram, diagnostic or therapeutic ureteroscopy, collagen injection, internal urethrotomy, cystoscopy, bladder biopsy, a single oral dose ciprofloxacin in the patients undergoing outpatient endourology surgery was equally effective as cefazolin 15) . In our study, the rate of onset of febrile urinary tract infection was significantly decreased in the fluoroquinolone using group compared to the cephalosporin group. While cephalosporin antibiotics were administered orally to 131 patients, cefazolin was administered intravenously to 16 patients This indicates the possibility that the oral cephalosporin antibiotics are not effective against febrile UTI. One of the reason why there are more febrile UTI in cephalosporin using group than in fluoroquinolone using group is that cephalosporin is not effectiveness against Enterococcus faecalis which is common pathogen of febrile UTI. Our data suggested that optimal choice for prophylactic antibiotics was required based on the procedures.

Conclusion
Our data showed that compromised host to be significant risk factors to the prcedures for Ethics approval and consent to participate