Abstract
Purpose
To analyze the impact of long-term postoperative antibiotic prophylaxis following urethral reconstruction on perioperative outcomes, postoperative urine cultures, and the emergence of multidrug-resistant bacteria.
Methods
In this retrospective review of patients undergoing urethral reconstruction with a single surgeon from 2019 to 2023, patients either received long-term prophylactic postoperative antibiotics for 3–4 weeks while indwelling catheters were in place or they did not receive prophylactic antibiotics. Preoperative and postoperative urine cultures were obtained on all patients. The primary outcome measure was the association of prophylactic antibiotics with the presence of multidrug-resistant bacteria in postoperative urine cultures. Secondary outcomes included differences in perioperative outcomes.
Results
Of 166 patients undergoing urethral reconstruction, 147 met all inclusion criteria. Of these, 84 received antibiotic prophylaxis and 63 did not. The number of multidrug-resistant organisms in postoperative urine cultures was significantly different between cohorts indicating a harmful effect of antibiotic prophylaxis (P <.01). There were no significant differences in perioperative outcomes including positive urine cultures, clinical urinary tract infections, wound complications, or recurrence.
Conclusion
These data show that the administration of postoperative prophylactic antibiotics does not influence perioperative outcomes but does heighten the risk of encountering multidrug-resistant bacteria. This novel finding should discourage the routine use of antibiotic prophylaxis in patients undergoing urethral reconstruction.
Keywords: Urethral stricture, Multidrug resistance, Antibiotic prophylaxis, Patient outcome assessment, Reconstructive surgical procedure
Introduction
Urethral reconstruction remains the gold standard treatment in the management of recurrent urethral stricture disease (USD) [1–2]. Urethral reconstruction frequently requires the use of indwelling foley catheters, suprapubic tubes, or both during the perioperative period to ensure comprehensive drainage while the patient heals from the reconstruction. While a single dose of preoperative antibiotics is recommended for patients undergoing urethral reconstruction, currently there remains a lack of well-established guidelines for postoperative prophylactic antibiotic use [3]. The primary objective of antibiotic prophylaxis is to reduce the incidence of adverse postoperative outcomes, such as clinically significant urinary tract infections while indwelling catheters are in place. However, there is substantial variability in clinical practice among genitourinary reconstructive surgeons. Some surgeons administer long-term prophylactic antibiotics postoperatively for 3–4 weeks while indwelling catheters are in place, while others refrain from giving any [4]. There is a need for high quality evidence to address this heterogeneity in practice patterns.
Current evidence fails to demonstrate the clinical benefit of postoperative antibiotics, with multiple studies showing no clinical disparity in infection rates or wound complications [5]. Moreover, inappropriate antibiotic usage contradicts the principles of antibiotic stewardship and may contribute to the development of multidrug-resistant (MDR) bacteria [6–7]. There is paucity in the literature regarding the potential harmful effects of long-term perioperative antibiotic use after urethral reconstruction. Our current study stands out as the first to present postoperative urine culture data from an all-comer urethral reconstruction cohort, split into patients who received long-term perioperative antibiotic prophylaxis, and those who did not. Our aim is to shed light on the impact of antibiotic prophylaxis on perioperative outcomes, postoperative urine cultures, and the emergence of MDR bacteria. We hypothesize that long-term antibiotic prophylaxis would not only fail to demonstrate improved perioperative outcomes but also result in an increase in MDR organisms.
Materials and methods
Patient selection and study design
We conducted a retrospective review of patients who underwent urethral reconstruction by a single surgeon at our institution between 2019 and 2023. All study participants have provided written consent or informed consent for participation in this study. Patients with USD were engaged in a patient-centered approach and counseled on the risks and benefits of urethral reconstruction. Inclusion criteria included all patients over the age of 16 years old undergoing urethral reconstruction. We excluded any patient who only had a meatoplasty or extended meatotomy (as indwelling catheters are not typically left in place for a long period of time at our facility), patients who had incomplete pre- or postoperative culture data, or those who did not comply with our follow-up protocol.
Stricture characteristics were assessed through cystoscopy, retrograde urethrogram or voiding cystourethrogram [8], with specific details on the length and location of strictures recorded. Preoperative urine cultures were obtained on all patients, with antibiotic treatment given if necessary. Additionally, all patients were given a single dose of intravenous preoperative antibiotics which was cefazolin and gentamicin for > 90% of both cohorts, unless preoperative urine cultures required a different antibiotic based on specificity. The first cohort received prophylactic antibiotics postoperatively for 3–4 weeks while indwelling catheters were in place, which was standard protocol at our facility from 2019 to 2022. Normally, patients received nitrofurantoin; however, in cases where preoperative cultures revealed resistance, trimethoprim/sulfamethoxazole was administered instead, accounting for 7.1% of patients.
The second cohort of patients undergoing urethral reconstruction from 2022 to 2023 did not receive routine long-term prophylactic antibiotics. Patients were assigned to cohorts based solely on the timing of their surgery, with prophylactic antibiotics administered to all patients before a specific cut-off date, and none administered thereafter. Postoperative urine cultures were still obtained from all patients 10–14 days after surgery to guide short term antibiotic administration at the time of catheter removal. In cases where postoperative cultures were positive, patients received a short course (3 days) of nitrofurantoin at the time of catheter removal unless postoperative cultures showed resistance, in which case trimethoprim/sulfamethoxazole was given (only 3 patients). Figure 1 illustrates the management protocol of all patients included in this study.
Fig. 1.
Flow diagram detailing management of patients undergoing urethral reconstruction with a comparison of the differences between cohorts
Follow-Up protocol
Follow-up protocol included obtaining a voiding cystourethrogram 3–4 weeks after surgery, cystoscopy 4 months after surgery to assess early success, and then subsequent annual symptom and post-void residual assessment. Technical success was defined as the easy passage of a 16 French flexible cystoscope through the entire anterior urethra at the time of 4-month cystoscopy.
Statistical analysis
Our primary end point was the association of prophylactic antibiotics with the presence of MDR bacteria in postoperative urine cultures. MDR bacteria were defined as bacteria exhibiting acquired nonsusceptibility to at least one agent in three or more antimicrobial categories [9]. Secondary end points included analyzing the association of prophylactic antibiotics with perioperative outcomes. These included the incidence of symptomatic urinary tract infections (UTIs), wound complications, and recurrence. Patients with UTIs were defined as those who exhibited classic symptoms, including pain, fevers, malaise, and bladder spasms refractory to anticholinergics, with corresponding positive urine cultures. Asymptomatic patients with positive postoperative urine cultures were considered colonized but not classified as having a UTI. Continuous variables were presented as mean and standard deviation, and categorical and binary variables were presented as counts and percentages. Comparative analysis was performed using Chi-square analysis for categorical variables, Fisher’s exact test for categorical variables with > 20% of expected cell counts less than 5, and two-sample independent t-Test for parametric continuous variables. For all outcomes, P-values were 2-sided and statistical significance was predefined at P <.05.
Results
A total of 166 patients underwent urethral reconstruction at our institution, but only 147 patients met all inclusion criteria for this study. The patients’ characteristics are shown in Table 1. Most of the patients had a urethral stricture in the bulbar urethra with a mean (standard deviation) stricture length of 3.1 (3.0) cm. The most prevalent etiology of urethral stricture was idiopathic with the majority of patients having undergone prior management. The most frequent procedure type among patients was anastomotic urethroplasty. There were 53 positive preoperative urine cultures (36.1%) and 76 (51.7%) positive postoperative urine cultures. Patients were followed after their surgery for an average of 406.9 days.
Table 1.
Demographics and urethral characteristics of patients undergoing Urethral Reconstruction
| Variable | n (%) or mean (st dev) |
|---|---|
| Patients | 147 |
| Age | 47.2 (16.4) |
| Comorbidities | |
| Hypertension | 44 (29.9) |
| Hyperlipidemia | 10 (6.8) |
| Diabetes | 27 (18.4) |
| Heart Disease | 6 (4.1) |
| Smoking | 42 (28.6) |
| Follow-up length, days | 406.9 (414.3) |
| Stricture Length (cm) | 3.1 (3.0) |
| Stricture Location | |
| Meatus/Fossa navicularis | 3 (2.0) |
| Penile urethra | 24 (16.3) |
| Bulbar urethra | 83 (56.5) |
| Membranous urethra | 8 (5.4) |
| Panurethral | 29 (19.7) |
| Etiology | |
| Idiopathic | 63 (42.9) |
| Iatrogenic | 32 (21.8) |
| Hypospadias | 14 (9.5) |
| Trauma | 32 (21.8) |
| Lichen sclerosus | 6 (4.1) |
| Prior management | 118 (80.3) |
| Dilation | 60 (50.8) |
| DVIUa | 32 (27.1) |
| Previous urethral reconstruction | 30 (25.4) |
| Suprapubic catheter | 61 (51.7) |
| Procedure | |
| Urethroplasty with graft | 48 (32.7) |
| Anastomotic urethroplasty | 72 (49.0) |
| Urethroplasty with flap | 8 (5.4) |
| Staged urethroplasty | 5 (3.4) |
| Perineal urethrostomy | 14 (9.5) |
| Positive urine cultures | |
| Preoperative | 53 (36.1) |
| Postoperative | 76 (51.7) |
Abbreviations: aDirect Vision Internal Urethrotomy
Comparing patients by long-term antibiotic management (Table 2), there were 84 patients who received antibiotics and 63 who did not. No statistically significant differences were found concerning age, comorbidities, location, stricture length, etiology, prior management, or type of procedure. Predictably, the average follow up length did vary significantly between cohorts as a result of our sequential protocol (P <.01).
Table 2.
Comparison of prophylactic antibiotics and no prophylactic antibiotics of patients undergoing Urethral Reconstruction
| Variable | Prophylactic Antibiotics (n = 84) |
No Prophylactic Antibiotics (n = 63) |
P |
|---|---|---|---|
| n (%) or mean (st dev): | |||
| Age | 46.5 (16.2) | 48.2 (16.7) | 0.54 |
| Comorbidities | |||
| Hypertension | 23 (27.4) | 21 (33.3) | 0.44 |
| Hyperlipidemia | 6 (7.1) | 4 (6.3) | 0.99 |
| Diabetes | 14 (16.7) | 13 (20.7) | 0.54 |
| Heart Disease | 3 (3.6) | 3 (4.8) | 0.99 |
| Smoking | 28 (33.3) | 14 (22.2) | 0.14 |
| Follow-up length, days | 537.3 (486.1) | 232.9 (184.5) | < 0.01 |
| Stricture Length (cm) | 2.9 (2.7) | 3.3 (3.4) | 0.43 |
| Stricture Location | 0.38 | ||
| Meatus/Fossa navicularis | 3 (3.6) | 0 (0.0) | |
| Penile urethra | 16 (19.0) | 8 (12.7) | |
| Bulbar urethra | 43 (51.2) | 40 (63.5) | |
| Membranous urethra | 5 (6.0) | 3 (4.8) | |
| Panurethral | 17 (20.2) | 12 (19.0) | |
| Etiology | 0.32 | ||
| Idiopathic | 31 (37.0) | 32 (50.8) | |
| Iatrogenic | 23 (27.4) | 9 (14.3) | |
| Hypospadias | 8 (9.5) | 6 (9.5) | |
| Trauma | 18 (21.4) | 14 (22.2) | |
| Lichen sclerosus | 4 (4.8) | 2 (3.2) | |
| Prior management | 64 (76.2) | 54 (85.7) | 0.45 |
| Dilation | 28 (33.3) | 32 (50.8) | |
| DVIU | 17 (20.2) | 15 (23.9) | |
| Previous urethroplasty | 19 (22.6) | 11 (17.5) | |
| Suprapubic catheter | 35 (41.7) | 26 (41.3) | |
| Procedure | 0.21 | ||
| Urethroplasty with graft | 28 (33.3) | 20 (31.7) | |
| Anastomotic urethroplasty | 39 (46.4) | 33 (52.4) | |
| Urethroplasty with flap | 2 (2.4) | 5 (7.9) | |
| Staged urethroplasty | 3 (3.6) | 2 (3.2) | |
| Perineal urethrostomy | 12 (14.3) | 3 (4.8) |
Bold text indicates significant P value
Abbreviations: aDirect Vision Internal Urethrotomy
When comparing perioperative outcomes (Table 3), there were no significant differences in the number of preoperative urine cultures (P =.43) or postoperative urine cultures (P =.42). There were also no significant differences in the number of UTIs, wound complications, or recurrences between groups (P =.51, P =.61, P =.82, respectively). However, patients who received antibiotic prophylaxis had a significantly greater presence of MDR organisms (43.9%) compared to patients who did not receive antibiotics (17.1%, P <.01).
Table 3.
Perioperative outcomes comparing Antibiotic Management
| Variable | Prophylactic Antibiotics | No Prophylactic Antibiotics | P |
|---|---|---|---|
| n (%) | n (%) | n (%) | |
| Positive urine cultures | |||
| Preoperative | 28 (33.3) | 25 (39.7) | 0.43 |
| Postoperative | 41 (48.8) | 35 (55.6) | 0.42 |
| Multidrug resistance | 18 (43.9) | 6 (17.1) | 0.01 |
| Clinical UTIsa | 9 (10.7) | 9 (14.3) | 0.51 |
| Wound complications | 7 (8.3) | 3 (4.8) | 0.61 |
| Recurrence | 6 (7.1) | 3 (4.8) | 0.82 |
Bold text indicates significant P value
Abbreviations: aUrinary tract infections
Discussion
Urethral reconstruction is widely considered the standard of care for urethral stricture disease with a high success rate [10–11]. However, unlike less definitive endoscopic management, urethral reconstruction has the increased burden of longer term (2–3 week) indwelling foley catheters or suprapubic tubes to allow for healing [12]. Each day with a catheter in place increases the opportunity for bacterial colonization, but there is unclear evidence that such colonization is clinically significant [13]. At this time there is not a best practice statement on long-term antibiotic prophylaxis following urethral reconstruction, with significant heterogeneity in practice patterns. Additionally, there have been no studies demonstrating that antibiotic prophylaxis is clinically beneficial. Our study is uniquely significant because we are the first study to date to report postoperative urine culture data in all patients even in the absence of symptoms [14–15].
Our results add to the growing literature suggesting that there is no additional clinical benefit with the administration of antibiotic prophylaxis in this context [16]. A retrospective study involving 900 patients undergoing urethroplasty or perineal urethrostomy found no disparity in infection rates, wound complications, or recurrences between prolonged postoperative antibiotic regimens and no postoperative antibiotics [5]. Another review involving 120 patients found no significant difference in UTI or wound infection rates following urethroplasty between long-term postoperative antibiotic prophylaxis and a decreased course (3 days around catheter removal) [17]. Our results support the previous findings that long term antibiotic prophylaxis does not result in differences in perioperative outcomes. We found that 51.7% of patients who underwent urethral reconstruction had a positive postoperative urine culture. However, there is no statistical difference in the number of patients with positive postoperative cultures between the two cohorts, suggesting that there is no association with antibiotic prophylaxis. Likewise, there is no association between clinically significant symptomatic UTIs, wound complications, and recurrence rates with antibiotic prophylaxis.
However, this report has revealed a noteworthy association between the administration of postoperative prophylactic antibiotics and the presence of MDR bacteria in patients undergoing urethral reconstruction. This finding underscores a critical aspect of antimicrobial stewardship, shedding light on the unintended consequences of unnecessary antibiotic use in this setting. Such organisms pose a threat to local microbiomes, and can lead to prolonged hospital stays, increased healthcare costs, and are responsible for millions of deaths each year [18]. It has been estimated in one study that the occurrence of antimicrobial resistant infections has an attributable mortality rate of 6.5% and also results in a cost of more than $21,000 per patient [19]. Also, the limited availability of effective antibiotics against MDR bacteria further exacerbate the problem, leaving clinicians with fewer options for managing patients. The finding of MDR organisms further discourages the use of antibiotic prophylaxis following urethral reconstruction, especially given that prophylaxis does not appear to confer any clinical benefit.
Several similar studies have examined the use of prolonged antibiotic prophylaxis in patients with indwelling urinary catheters following prostatectomy. A 2023 study found no statistically significant difference in UTI rates between long-term and short-term antibiotic prophylaxis in such patients [20]. Additionally, Banks et al. prospectively analyzed urine cultures collected at the time of urinary catheter removal following prostatectomy in men receiving prophylactic antibiotics and found that 27.7% of patients with positive cultures were resistant to ciprofloxacin [21]. These findings emphasize the importance of limiting excessive antibiotic use, further supporting the conclusions of our study.
Our findings hold substantial implications for clinical practice. The use of prophylactic antibiotics following urethroplasty has been common practice by a large percentage of urologists to prevent surgical site infections and UTIs [3–4]. However, we challenged this approach by highlighting the association between prophylactic antibiotics and the emergence of MDR bacteria. Based on the findings of this study, the authors have continued to refrain from administering long-term antibiotic prophylaxis in patients undergoing urethral reconstruction.
Our study has several limitations including its retrospective nature. However, this limitation is mitigated by the fact that usage of prophylactic antibiotics was based solely on the timing of surgery, rather than due to other clinical factors, ensuring a more balanced comparison. Furthermore, due to the sequential nature of our study, there were differences in the average follow-up time per cohort. Lastly, this was a single-institution and single surgeon study. Despite such limitations, the findings show that long-term antibiotic prophylaxis fails to provide a clinical benefit and also may be harmful due to the emergence of MDR organisms.
Conclusions
This retrospective review of patients undergoing urethral reconstruction shows that the administration of postoperative prophylactic antibiotics does not influence perioperative outcomes but does heighten the risk of encountering MDR bacteria. The amplified prevalence of MDR bacteria in patients receiving prophylactic antibiotics emphasizes the urgency of reevaluating antibiotic practice patterns in the setting of urethral reconstruction. These results discourage the routine use of prophylactic antibiotics in patients undergoing urethral reconstruction. Ultimately, our findings should inform evidence-based practice guidelines in an effort to mitigate the threat of MDR bacteria and enhance the quality of care for patients undergoing urethral reconstruction.
Acknowledgements
None.
Author contributions
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Will Hoover, Jena Deitrick, and James Furr. The first draft was prepared by Will Hoover and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
Funding
This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Data availability
The data sets generated or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethical approval
This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. IRB approval was obtained for this protocol, IRB #11377.
Consent to participate
All study participants have provided written consent or informed consent for participation in this study.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data sets generated or analyzed during the current study are available from the corresponding author on reasonable request.