BERKELEY, CA (UroToday.com) - Flexible urethrocystoscopy is a diagnostic outpatient technique used in daily clinical practice in urology.
Usually it is well tolerated, but its main and most frequent disadvantage is urinary tract infection (UTI). The impact of this complication has not been well studied: some studies show percentages from 2 -7.5%,[1, 2, 3] but values may be higher.[4] To reduce the risk of UTI, urologists turn to antibiotic prophylaxis, but there is not a unified approach about indication, dosage and duration, route of administration, and kind of antibiotic.[4, 5, 6, 7, 8, 9, 10, 11, 12] Prophylaxis antibiotic must fulfill: a prolonged elimination half-life, no hepatic biotransformation, high renal elimination, no cross-resistance, not active against special pathogens, no toxicity, and low cost.[13] A priori, fosfomycin trometamol could be considered ideal for prophylaxis praxis, however there is not yet any study about the use of this antibiotic in UTI chemoprophylaxis after flexible urethrocystoscopy.[14]
Our clinical experience in patient management and monitoring with diagnosis by urethrocystoscopy, together with an exhaustive bibliographic review,[4, 5, 7, 10, 11] leads us to consider that additional administration of a prophylactic antibiotic does not clinically reduce the UTI risk, providing adequate pre-intervention aseptic measures in patients without additional risk factors. To test this hypothesis, we have carried out an experimental study to assess chemoprophylaxis effectiveness with three grams of fosfomycin trometamol to prevent bacteriuria post-urethrocystoscopy.
An unblinded, randomized, controlled study has been conduced to compare the incidence of post-urethocystoscopy bacteriuria in a control group vs. a patients group that received three grams of fosfomycin trometamol previous to the procedure.
Our population sample was comprised of the first 60 patients, without any of exclusion criteria, and who gave us informed consent to participate in our study. The 60 patients were distributed in 2 groups by random assignment in units n=four, until all of them were assigned (a sequence of sixty assignments in fifteen units). This sequence was kept hidden to the person responsible for the assignments until just before the moment of intervention. Group 1 was the “control” (30 patients), and did not receive any dose of antibiotics after the test. Group 2, or “treatment” (N=30) was given antibiotic prophylaxis: 3 grams as oral single-dose of fosfomycin trometamol, during the first 2 hours prior to the test.
Previous to urethrocystoscopy, and ten days after, a urine culture and urinalysis were checked in all 60 patients. Bacteriuria was considered when more than 105 CFU/ml were recorded in urinalysis, pyuria for more than 5 leukocytes/high power field, and microhematuria for three or more red cells/field. Three of sixty patients in the treated group did not produce a urine culture. One month later, a telephone questionnaire was initiated to evaluate lower urinary tract symptoms, regardless of bacteriuria. Patients were classified according to symptoms as: asymptomatic, mild symptoms (stranguria, mild hematuria, less than 24 hours), moderate symptoms (dysuria, urinary frequency, moderate hematuria, and urinary frequency and urgency less than a week), and severe symptoms (dysuria, severe hematuria, urinary frequency and urgency more than a week, pyelonephritis, prostatitis). They were also asked if they had gone to a general practitioner because of symptoms. We could not contact five patients (2 in the control group, and 3 in the treated group).
In the statistical analysis, first of all, distribution of all variables was compared (baseline and outcomes) between two groups by “t Student” test to age, and Chi Square to the rest of the variables. We estimated bacteriuria, Pyuria, and micro hematuria cumulative incidence in both groups, and the corresponding 95% confidence intervals (CI). We alternated between two strategies, per protocol and intention to treat analysis, and we considered statistically significant values from p < 0.05.
No statistically significant differences were observed regarding the distribution of most baseline variables between both groups. The only significant statistical difference found, among patients’ personal history in group of intervention, was the higher frequency of patients without any urological history but with chronic or metabolic disease (43.4% compared to 10% in control group).
No statistically significant differences were found between both groups for any outcome variable. Control patients had values of 10%, 23.3%, and 26.7% respectively, while the values of treated patients differed depending on the type of analysis. The incidence considering only the twenty-seven patients that provided results was 11.1%, 37%, and 29.6% respectively. If the three patients without results are included their results are considerd as negatives for the analysis, the results would come down to 10%, 33.3%, and 26.7% respectively. Finally, if they were included as positives, then incidences raise to 20%, 43.3% and 36.7%. In any of three cases, differences are not statistically significant, so in any scenario, differences between groups were statistically significant.
Six positive cultures were obtained (three in each group): Escherichia coli grown in three samples (two in control group), klebsiella pneumoniae in two samples (both into treatment group), and Serratia liquefaciens grown in one culture of control group.
Regarding the appearance of symptoms post-cystoscopy, ten patients (33.3%) in the control group had no symptoms (there was one positive culture among these patients), another ten patients had mild symptoms, and eight (26.7%) moderate symptoms (two positive cultures were checked). None of the patients in this group had severe symptoms. In the treatment group, 6 patients (20%) had no symptoms, 14 (46.7%) had mild symptoms (2 of them with positive culture), 7 (23.3%) had moderate symptoms (one with positive culture) and 2 (6.7%) had severe symptoms. All cases of bacteriuria, except one in the control group, were associated with the presence of groups.
With regard to primary care consultations, no patients in the control group had to consult with a general practitioner for treatment of any symptom. However3 patients (10%) in the treatment group (two of them with Klebsiella pneumoniae-positive culture, and one with severe symptoms) had to go.
In spite of the fact the sample size is clearly insufficient to obtain statistically clinical differences if they exist (N=60, the power of the study is only 20% to detect the maximum difference found in the proportion of positive cultures between both groups -10%), results clearly indicate that no clinically relevant differences exist after the administration of chemoprophylaxis with fosfomycin trometamol.
One of our main problems is that literature is limited, and based on relatively small samples of patients (except for the studies of Jiménez Cruz et al.,[8] and Johnson et al.,[6] with 2 284 and 2 481 patients respectively), which makes the choice of our strategy more difficult.
To minimize selection bias, we decided to implement 3 alternative strategies of analysis. Assuming that the 3 patients in the intervention group, who did not provide urine culture, had negative culture is the most plausible alternative. According with this assumption, bacteriuria incidence would have been 10% in both groups.
Finally, another aspect to consider is the external validity of our outcomes. Our criteria of exclusion allowed us to select a target population with low risk of infection post-test. Therefore, it is necessary to be cautious when assessing the indication of chemoprophylaxis in patients whose risk of infection is higher (lower urinary system malformations or other personal circumstances). Anyway, we believe that a high homogeneity of the target population, achieved through the application of the exclusion criteria mentioned above, guarantees the validity of the results and compensates for the reduced generalization of our outcomes.
In conclusion, this study suggests that antibiotic chemoprophylaxis does not result in a clinically relevant reduction of incidence of UTI after flexible urethrocystoscopy, providing that adequate aseptic conditions are fulfilled. Nevertheless, a higher sample size is necessary to reach definitive conclusions, both from clinical and statistical points of view.
References:
- Burke DM, Shackley DC, O´Reilly PH. The community-based morbidity of flexible cystoscopy. BJU Int 2002; 89: 347-49.
- Thompson A, Pearce I, Robinson E, Ladds TJ, Payne SR. Bacteriological safety and cost-effectiveness of a non-refluxing valve in the irrigation system during outpatient flexible cystoscopy. BJU Int 2000; 85: 1019-22.
- Clark KR, Higgs MJ. Urinary infection following outpatient flexible cystoscopy. Br J Urol<>/ 1990; 66: 503-5.
- Cundiff GW, McLennan MT, Bent AE. Randomized trial of antibiotic prophylaxis for combined urodynamics and cystourethroscopy. Obstet Gynecol. 1999; 93: 749-52.
- Almallah YZ, Rennie CD, Stone J, Lancashire MJ. Urinary tract infection and patient satisfaction after flexible cystoscopy and urodynamic evaluation. Urology. 2000; 56: 37-9.
- Johnson MI, Merrilees D, Robson WA, Lennon T, Masters J, Orr KE, et al. Oral ciprofloxacin or trimethoprim reduces bacteriuria after flexible cystoscopy. BJU Int. 2007; 100: 826-9.
- Karmouni T, Bensalah K, Alva A, Patard JJ, Lobel B, Guillé F. Place de I´antibioprophylaxie lors d´une cystoscopie en ambulatoire. Prog Urol. 2001; 11: 1239-41.
- Jiménez Cruz JF, Sanz Chinesta S, Otero G, Díaz González R, Álvarez Ruiz, Flores N, et al. Antimicrobial prophylaxis in urethrocystoscopy. Comparative study. Actas Urol Esp 1993; 17: 172-175.
- Wilson L, Ryan J, Thelning C, Masters J, Tuckey J. Is antibiotic prophylaxis required for flexible cystoscopy? A truncated randomized double-blind controlled trial. J Endourol. 2005; 19: 1006-8.
- Manson AL. Is antibiotic administration indicated after outpatient cystoscopy. J Urol. 1988; 140: 316-7.
- Tsugawa M, Monden K, Nasu Y, Kumon H, Ohmori H. Prospective randomized comparative study of antibiotic prophylaxis in urethrocystoscopy and urethrocystography. Int J Urol. 1998; 5: 441-3.
- Rane A, Cahill D, Saleemi A, Montgomery B, Palfrey E. The issue of prophylactic antibiotics prior to flexible cystoscopy. Eur Urol 2001; 39: 212-4.
- Dalet F, Del Rio G. Profilaxis antibiótica en Urología. Infecciones Urinarias, Barcelona 1997: 445-475.
- Andreu A, Planeéis I, Grupo cooperativo español para el estudio de la sensibilidad antimicrobiana de los patógenos urinarios. Etiology of community-acquired lower urinary infections and antimicrobial resistance of Escherichia coli: a national surveillance study. Med Clin (Barc) 2008; 130: 481-6.
Written by:
Antonio Jimenez-Pacheco as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Randomized clinical trial on antimicrobial prophylaxis for flexible urethrocystoscopy - Abstract
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