Antibiotic prophylaxis in urologic interventions: Who,when,where?

Abstract

Background:

Periprocedural prophylaxis in medicine encompasses the set of measures (physical, chemical, and pharmacological) used to reduce the risk of infection. Antibiotic prophylaxis (AP) refers to the administration of a short-term regimen of antibiotics shortly before a medical procedure to reduce the risk of infectious complications that can result from diagnostic and therapeutic interventions. The outspreading growth of multidrug-resistant bacterial species and changes in the bacterial local ecosystem have impeded the development of a unique scheme of AP in urology.

Objectives:

To review the literature and current guidelines regarding AP for urological diagnostic and therapeutic procedures, and to define agents, timing, and occasions when administering pharmacological prophylaxis. Secondly, according to current literature, to open new scenarios where AP can be useful or useless.

Results:

Major gaps in evidence still exist in this field. AP appears useful in many invasive procedures and some sub-populations at risk of infectious complications. AP is not routinely recommended for urodynamic exams, diagnostic cystoscopy, and extracorporeal shock-wave lithotripsy. The available data regarding the use of AP during the transperineal prostate biopsy are still unclear; conversely, in the case of the transrectal approach AP is mandatory. AP is still considered the gold standard for the prevention of postoperative infective complications in the case of ureteroscopy, percutaneous nephrolithotomy, endoscopic resection of bladder tumor, endoscopic resection of the prostate, and prosthetic or major surgery.

Conclusion:

The review highlights the complexity of determining the appropriate candidates for AP, emphasizing the importance of considering patient-specific factors such as comorbidities, immunocompetence, and the nature of the urologic intervention. The evidence suggests that a one-size-fits-all approach may not be suitable, and a tailored strategy based on the specific procedure and patient characteristics is essential.

Keywords

Antibiotic prophylaxis urologic procedures infections antibiotic resistance healthcare-acquired infections

Introduction

According to the Center for Disease Control and Prevention (CDC), healthcare-acquired infections (HAIs) are defined as any infection that arises in an inpatient or outpatient setting and appears 48 h after hospitalization or within 30 days after receiving healthcare assistance.¹

HAIs represent the sixth cause of death worldwide (100,000 deaths per year).^2,3 Surgical site infections (SSIs) are defined as every type of infection that hits the patient at or near the surgical wound within 30 days of an operative procedure or within 1 year since device implantation. They can be divided into superficial incisional, deep incisional, and organ/space incisional.² Urinary tract infections (UTIs) and SSIs cause most HAIs.⁴

Periprocedural prophylaxis in medicine, specifically in urology, represents the ensemble of measures (physical, chemical, and pharmacological) used to reduce the risk of infection. Non-antibiotic measures must be performed during the hospitalization and convalescence period to improve the effectiveness and reduce the complication rate of a urological treatment.^5–7

Antibiotic prophylaxis (AP) consists of administering a short-term regime of antibiotics before or at the beginning of a medical procedure to reduce the risk of infectious complications resulting from diagnostic or therapeutic interventions. Even if AP does not eliminate microorganisms, it reduces the microbial burden at surgical sites, allowing the host’s immune system to manage any remaining bacteria.⁸

The absence of well-conducted and statistically significant studies, especially in the cases of endoscopic procedures, has impeded the development of a proper scheme of AP in urology. This lack of strength led to divergences regarding the definition and evaluation of risk factors and substantial disparities in treatment protocols and therapy selections. Rigorous scientific evidence-based recommendations are strongly required in this domain. In the last 20 years, urologic surgery reduced surgical invasiveness (from open to endoscopic, laparoscopic, and robotic surgery) while the patients’ mean age and frailty increased. These changes may have an impact on AP policies.⁹

AP is not designed to treat any post-procedural infections. The ideal approach is to administer specific therapy with appropriate dosages using antibiotics based on factors such as the type of infection, the patient’s clinical characteristics, and the epidemiological context, particularly in the case of nosocomial infection.¹⁰

Although the rationale for using antibiotics in prophylaxis is widely acknowledged, inappropriate use can have detrimental effects on the patient (unexpected side effects, increased risk of infection), on the environment (increased resistance), and on the health system (waste of financial resources).⁹ It is crucial to emphasize that AP represents a supplement to a good surgical technique in an aseptic setting and good hygiene, not their replacement. An effective strategy for controlling acquired infections must include prevention as one of its key elements.

This literature review aims to highlight the value of AP in urologic diagnostic and therapeutic procedures and to examine the following main elements of this topic:

Who requires AP?

When should prophylaxis be administered? In what precise window of time?

Where should it be administrated? What is the ideal setting?

Materials and methods

A literature review was conducted in October 2023, and no temporal limits were adopted. The search was performed on Pubmed and Web of Science databases, using the following keywords (title and abstract): “antibiotic prophylaxis” and “urologic surgery” or “urologic procedures” or “urologic interventions” or “urology” or “urodynamics” or “cystoscopy” or “stent removal” or “ureteral stent” or “urinary catheter” or “urethral catheterization” or “prostate biopsy” or “transrectal prostate biopsy” or “transperineal prostate biopsy” or “extracorporeal shock wave lithotripsy” or “ureteroscopy” or “percutaneous nephrolithotomy” or “TURB” or “TURBT” or “bladder resection” or “TURP” or “prostatectomy” or “nephrectomy” or “cystectomy” or “artificial urinary sphincter” or “penile prosthesis” or “sling” or “urological prosthetic device.” References of retrieved articles were also manually searched for other relevant citations. In addition, European Association of Urology (EAU) and American Urological Association (AUA) guidelines were consulted to identify specific recommendations for each urologic procedure. Evidence was pooled and compared with the results of articles, meta-analyses, and randomized trials. The evidence synthesis was conducted descriptively.

Aims and principles of antibiotic prophylaxis

The main purpose of AP is to reduce the risk of infections and to decrease antibiotic overuse, reducing postoperative complications and controlling the spread of antibiotic resistance.¹¹ AP can be useful, but it can also lead to adverse events, multidrug resistance, and more dangerous community-acquired infections.^12,13

AP does not eliminate microorganisms from tissues but decreases microbial burden at the surgical site to a level that the host’s immune system can effectively manage. Bacterial contamination at the surgical site is inevitable due to the patient’s colonization and the surrounding environmental bacterial flora.¹⁴

Different antibiotics should be administered when designing a prophylactic treatment depending on skin wound risk of infection, local pathogen prevalence, local resistance profiles and rates, patient drug-related allergies, and comorbidities. Ideally, pharmacological agents designed for AP should not be the same used to treat the possible after-treatment infection.¹⁴

Risk factors

In some cases, due to factors linked to the patient, the microorganism, or environmental factors, the risk of contracting HAIs is high. Overall, risk factors can be classified into three different groups:

Patient’s condition according to the American Society of Anesthesiologists (ASA) score [from ASA-1 to ASA-6];

Patient’s general risk factors according to age, diabetes mellitus, immune-compromisation, malnutrition, altered weight (obesity or underweight);

Exogenous or endogenous risk factors: history of urological infections, use of a permanent urinary catheter, presence of bacteriuria and its urinary load, previous operations, genetic factors, urinary anatomic malformations.

The type of urological procedure can also be linked to an increased risk of infection. The National Nosocomial Infections Surveillance (NNIS) System risk score combines the ASA score, the duration of the surgical procedure, and the Altemeier classification (used to stratify the surgical procedures and wound infectious risk¹⁵) to establish the postoperative infectious risk.¹⁶

As the SSIs risk varies largely depending on multiple factors, it is extremely difficult to build a universal infection risk score and to build reliable recommendations for reducing the infection rate.

Recently, numerous scores have been proposed as indicators of the SSIs risk in every surgical area, to minimize the abuse of antibiotics, stop the spreading of antibiotic resistance, and identify the right patient to treat.^17–19

Transurethral procedures are risk factors for postoperative infections themselves, moreover, urines are not considered sterile. As a result, the EAU guidelines classify every endoscopic procedure with a transurethral approach as “clean-contaminated.”^20,21

Antibiotic selection and administration route

No clear indications are given in current EAU guidelines regarding agents used in AP. Ideally, the antibiotic agent used for AP should differ from those required for the treatment of the infections.²¹

Target AP represents a topic of current debate. This process of care has been formally indicated in the case of transrectal ultrasound prostate biopsy^22,23 while has not been assessed prior to other urological procedures. In high-risk patients, it would be useful to perform a preoperative urine culture to direct the AP.

When selecting an antibiotic for prophylaxis, attention should be given to adverse effects and allergy profiles. All antibiotics have the potential to cause an allergic reaction. β-Lactam allergies are some of the most frequent drug-related reactions.²⁴

Nowadays, the use of fluoroquinolones (FQs) in AP is becoming wider thanks to an undemanding oral and intravenous administration, a favorable oral bioavailability and safety profile, relatively low cost, and high penetration into the genitourinary (GU) system. On the other hand, their overuse has increased the resistance rate worldwide, especially among typical urologic pathogens like Escherichia Coli.^25,26

The evaluation of local bacteria epidemiology and susceptibility profile is of utmost importance and should be performed in all healthcare facilities to identify the correct agent to administer.^27,28

When the risk of negative outcomes in the case of SSIs is low or minimal, despite the presence of scant data on the topic, a good choice can be represented by an aminoglycoside or a second-generation cephalosporin, as an alternative.^29,30

No pieces of advice are given in European guidelines about the type of drug to use in high-risk procedures. Regarding the administration route, if an antibiotic agent possesses adequate bioavailability, it can be administered either orally or intravenously; no differences in efficacy are shown.¹¹

Timing and duration

According to the current EAU guidelines, AP should be administered 1–2 h before the procedure when recurring to an orally administered drug, while it can be given at the time of induction of anesthesia if administered intravenously.³¹

Duration should be reduced to the minimum, and continuing AP after the end of surgery should be avoided. Although a single dose of AP is preferred, duration should be administered depending on the procedure’s duration, the antibiotic’s half-life, and if significant blood loss occurs during surgery.^14,32,33

Diagnostic procedures

Urodynamics

A urodynamic study is a diagnostic, minimally invasive procedure used to investigate low urinary tract symptoms (LUTS) or pelvic floor dysfunction.³⁴ Using transurethral and rectal catheters, it measures the vesical volume and compliance, both abdominal and vesical pressures, and uroflow parameters. The occurrence of postoperative UTIs (symptomatic or asymptomatic) is variable, depending on several factors, ranging from 1.5% to 36%.³⁵

In a systematic review published in 2008, the administration of AP reduced the risk of significant bacteriuria when compared with no treatment [OR 0.39, 95% CI 0.24–0.61].³⁶

According to a recent Cochrane review that compares the administration of AP with a placebo, no significant difference was observed regarding the risk of UTIs [RR 0.73, 95% CI 0.52–1.03], while the overall risk of asymptomatic bacteriuria (ASB) decreased in the treatment group [RR 0.35, 95% CI 0.22–0.56].³⁷

Accordingly, Benseler et al. reported that AP could reduce the risk of bacteriuria but not clinical UTIs following urodynamic studies in women.³⁸

Conversely, a recent meta-analysis shows that AP usage, when compared with the placebo or no treatment, has a statistically significant impact in preventing not only ASB [RR 0.42, 95% CI 0.30–0.60] but also symptomatic UTIs [RR 0.65, 95% CI 0.48–0.88]. In addition, there was no statistically significant difference in the risk of adverse events between the AP group and no treatment group [RR 4.93, 95% CI 0.61–40.05].³⁹

According to the most up-to-date EAU and AUA guidelines, AP should not be performed for simple outpatient urodynamics procedures.^21,40

AUA guidelines mentioned some factors that appeared to increase the SSIs risk of urodynamic procedure (relevant GU anomalies, diabetics, prior GU surgery, a history of recurrent UTIs, post-menopausal women, recently hospitalized patients, patients with cardiac valvular disease, nutritional deficiencies, or obesity). The investigators, with low levels of evidence, suggested that there was an increased risk of infection for patients with neurogenic lower urinary tract dysfunction, outlet obstruction or an elevated post-void residual volume, frailty, indwelling catheters, or on clean intermittent catheterization.⁴⁰ AP in these higher-risk settings should consider trimethoprim-sulfamethoxazole. Alternatives include first- or second-generation cephalosporins, amoxicillin/clavulanate, or an aminoglycoside ± ampicillin. When indicated, a single oral dose given within an hour before the procedure is sufficient, although it depends on the agent’s oral pharmacokinetics. Oral dose was the route chosen in nearly all reviewed studies.⁴⁰

Cystoscopy

Cystoscopy is a common diagnostic procedure that involves the insertion of a thin (16–22 Ch), flexible, or rigid tube with a camera (cystoscope) into the bladder through the urethra. It is routinely performed to investigate hematuria, recurrent UTIs, LUTS, and for bladder tumor surveillance.⁴¹ A working channel allows interventions such as bladder biopsies and diathermy. Additional applications include ureteral stent insertion and removal, as well as therapeutic interventions such as botulinum toxin injections.⁴²

Several past studies demonstrated the presence of ASB after cystoscopy in rates ranging from 2.7% to 7.5%.^43,44 Some more recent meta-analyses measured the rate of symptomatic UTIs between the AP group compared with placebo or no treatment group. Results showed the reduction of symptomatic UTI episodes in the AP group (both in Carey et al. ’s [RR 0.34, 95% CI 0.27–0.47]⁴⁵ and Garcia-Perdomo et al. study [RR 0.53, 95% CI 0.31–0.90]⁴⁶).

In addition, Zeng et al.⁴⁷ evaluated the outcome of systemic UTI, showing no effect of AP compared with placebo or no treatment [RR 1.12, 95% CI 0.38–3.32]. The increased antibiotic resistance was observed as a secondary outcome [RR 1.73, 95% CI 1.04–2.87], with a very low level of evidence.

According to EAU and AUA guidelines, no use of AP is required in the case of routinary cystoscopy in the absence of infectious signs and symptoms.^21,40

Stent removal and catheterization

After stone surgical treatments, indwelling ureteral stents are frequently used to ensure adequate drainage. Finally, they are extracted cystoscopically within a few weeks.⁴⁸ There is still considerable disagreement on using single-dose AP in cases involving indwelling catheters and stents beyond the immediate perioperative period. So far, limited high-quality literature is available.

The administration of AP during catheter removal has been a cornerstone in urological practice.^49,50 A meta-analysis revealed that patients may benefit from AP at the time of catheter removal, as the incidence of symptomatic UTIs was much lower. The calculated number needed to treat was 17, indicating a favorable outcome in preventing UTIs.⁵¹ In most of the analyzed studies the risk of selection and attrition bias was high, and the quality of evidence was inconsistent. However, as demonstrated by a study of renal transplant recipients, AP should be performed in high-risk sub-populations.⁵²

In contrast with the former statements, the AUA guidelines did not recommend AP for catheterization or catheter substitutions.⁴⁰

Given the high prevalence rate of carriers of multidrug-resistant bacteria (such as E. coli ESBL+), investigations based on local population and ecology should be used to determine the true cost-benefit profile. The uncontrolled use of AP in case of catheter or stent removal would have detrimental consequences on resistance selection and adverse effects.

Antimicrobials are not indicated for the reduction of SSIs in case of catheterization during the postoperative period as they do not reduce the risk of catheter-associated urinary tract infection.⁴⁰

AP may be considered at the time of clinical procedures such as ureteral stent or nephrostomy tube placement, especially when risk factors are present.

When intraoperative circumstances change and a wound is considered contaminated, a shift up in AP coverage should occur. For example, if purulence is discovered at the time of a routinary stent exchange, then cultures should be obtained, and the antimicrobial agent(s) should continue until the culture results are known.⁴⁰

A Randomized Controlled Trial (RCT) of 58 patients by Bradshaw et al. found a low risk of infectious complications during cystoscopic stent removal, regardless of the use of AP. Urine culture positivity rate before stone surgery (16.7% vs 11.8%, p = 0.819) and at the time of stent removal (16.0% vs 11.1%, p = 0.648) was not significantly different in treatment versus control groups, respectively. The postprocedural infection risk profiles would seem to change intuitively from more invasive cystourethroscopic procedures to the minimally disruptive nature of stent removal.⁴⁸ However, this study had a very small sample size and therefore represents a low level of evidence. EAU guidelines do not provide recommendations regarding catheterization, ureteral stent, and nephrostomy tube management.²¹

Further studies are needed to clarify the role of AP in these urological settings.

Prostate biopsy

Biopsy of the prostate is a urological procedure used to definitively diagnose the presence of a prostatic tumor. It can be performed using a transrectal or transperineal approach.⁵³

According to EAU guidelines,²¹ the transrectal approach should be abandoned in favor of the transperineal approach, as in the case of transrectal biopsy the risk of infection [RR 2.48, 95% CI 1.47–4.20] and the sepsis rates (transrectal 0.9% vs transperineal 0.1%) increase significantly.^54,55

Beyond these guidelines, global consensus is missing in this topic. During the annual AUA meeting in April 2023, results from the first RCT showed no differences in terms of composite infections rate over 30 days and noninfectious complications between transrectal and transperineal arms [RR 1.06, 95% CI 0.43–2.65].⁵⁶

However, there is still a hot debate on this topic and for a stronger recommendation it is necessary to wait for the results of ongoing RCTs (NCT04815876; NCT05179694).^57,58

Transrectal prostate biopsy

During the transrectal prostate biopsy, the needle is inserted in the rectum, approaching the prostate from behind. This procedure allows bacteria to migrate from the lower intestine to the urinary tract, resulting in an increased risk of infection and sepsis. Even if its use is not recommended, it is still performed.

Regarding the non-pharmacologic prophylaxis, rectal povidone-iodine preparation before the biopsy is mandatory to reduce by half the rate of infectious complications [RR 0.47, 95% CI 0.36–0.61].^59,60

No differences were found in terms of risk of infection regarding needle guide type, needle type, needle size, or number of anesthetic injections for nerve-blockage.⁵⁴

Rectal culture should be performed to avoid infective complications following the procedure and a targeted prophylactic treatment should be started. In the study of Tops et al.⁶¹ patients were divided in a control group (who took ciprofloxacin empirically) and in a treatment group (antibiotic choice was based on the preoperative rectal culture and antibiogram). Patients who underwent a rectal culture sample collection showed a statistically significant reduction in infectious complication rates when compared to empirically treated patients [OR 0.52, 95% CI 0.27–0.99].

According to the literature, AP should be performed in case of transrectal prostate biopsy, allowing the patient to reduce the risk of serious infections and systemic sepsis.⁶² Whereas FQs are considered the prophylactic gold standard in the case of prostate biopsy, a recent South Korean study showed that fosfomycin has a similar impact on preventing an infectious onset.⁶³

EAU guidelines recommend the use of target prophylaxis based on rectal swabs or stool culture for transrectal biopsy. An alternative is augmented prophylaxis (two or more different classes of antibiotics) without FQs or alternative antibiotics (e.g. fosfomycin trometamol, cephalosporin, aminoglycoside). The use of FQs should be avoided in favor of other antibiotic classes as a result of the European Commission decision on EMEA/H/A-31/1452.²¹

According to the AUA guidelines, the risk of SSIs and sepsis in healthy individuals is considerable with transrectal prostate biopsy; as such, AP is mandatory. No further information is provided by the American panel.⁴⁰

Transperineal prostate biopsy

A recent study by Castellani et al.⁶⁴ showed no association between AP and reduction of infectious complications [RR 2.09, 95% CI 0.54–8.10].

Accordingly, a randomized, open-label, non-inferiority trial directed by Jacewicz et al. demonstrated that AP could be omitted in patients undergoing transperineal prostate biopsy; however, high-risk patients were not included in the study.⁶⁵

A smaller RCT in 85 patients showed no differences in terms of UTI or sepsis rates when performing or not performing AP before transperineal prostate biopsy.⁶⁶

These results are in line with another meta-analysis that showed no differences in terms of post-procedural infections between patients who received AP and patients who did not.⁶⁷

Differently, Benli et al. demonstrated that AP, especially when targeted and based on a rectal swab performed some days before the biopsy, could effectively prevent infective complications following transperineal prostate biopsy.⁶⁸

Interestingly, research on single-dose antibiotic prophylaxis performed before transperineal biopsies showed that it could lead to changes in gut microbiota composition.⁶⁹

According to EAU guidelines, prostatic biopsy should be performed using a transperineal approach due to the lower risk of infective complications. Routine surgical disinfection of perineal skin should be performed. Although several studies reveal that AP may not be required when performing the transperineal prostate biopsy, the EAU Panel chose to wait for other ongoing RCTs on the topic before elaborating a statement. No clear evidence is reported about the use of target prophylaxis based on rectal swabs or stool culture.²¹

The AUA guidelines provide no recommendations regarding AP in transperineal biopsy.⁴⁰

Therapeutic procedures

Extracorporeal Shock-Wave Lithotripsy

The extracorporeal Shock-Wave Lithotripsy (ESWL) is a non-invasive option for treating renal lithiasis. Several studies investigated the effect of AP in patients undergoing this procedure, either with or without preoperative bacteriuria.⁷⁰

In the study of Lu et al., no association was found between AP and the rate of fever [RR 0.36, 95% CI 0.07–2.36], rate of positive urine culture [RR 0.77, 95% CI 0.54–1.11], the incidence of UTIs [RR 0.54, 95% CI 0.29–1.01] in patients with pre-procedural sterile urines.⁷¹ Mrkobrada et al. showed no evidence of an association between AP and the risk of post-procedural UTIs [RR 0.76, 95% CI 0.39–1.48] and indicated that, according to the Canadian Urological Association (CUA) Guidelines Committee, AP could be considered in patients at high risk of infectious complications.⁷² Hsieh et al. evidenced that no benefits in terms of postoperative pyuria, bacteriuria, and symptomatic UTIs were shown in patients who took levofloxacin orally as a prophylactic agent.⁷³

In conclusion, no study showed a benefit in performing AP in patients undergoing ESWL. No AP is needed before or during this procedure according to EAU guidelines.²¹ According to the AUA guidelines, ESWL does not require AP if the pre-procedure urine culture is negative.^40,74,75

Ureteroscopy and endoscopic lithotripsy

Ureteroscopy is an endoscopic procedure that allows the surgeon to investigate and treat different conditions at the level of the ureter and renal pelvis. It can be used as a diagnostic or a treatment procedure, either for lithiasis and urothelial tumors of the upper urinary tract (UTUC).

A meta-analysis by Deng et al.⁷⁶ evidenced that AP could have an impact on pyuria [OR 0.42, 95% CI 0.25–0.69], and ASB [OR 0.25, 95% CI 0.11–0.58], but it does not affect UTIs [OR 1.00 95% CI 0.26–3.88].

When comparing FQs and fosfomycin as prophylactic agents, two RCTs showed similar effects on the risk of systemic inflammatory response syndrome (SIRS).^77,78 In both articles, a benefit regarding the risk of infection was observed in the group that recurred to AP.

Due to the lack of high-quality papers regarding the use of AP in ureteroscopy, the recommendation about AP in EAU’s latest guidelines is weak.²¹ More data should be collected.

In the AUA guidelines ureteroscopy is considered a clean contaminated procedure and no benefit of AP has been demonstrated. Selective use of AP for higher-risk individuals is encouraged.⁴⁰

Urine culture is not mentioned in European Guidelines. Its role in the prevention of UTIs has been analyzed by El-Agamy et al.⁷⁹ A randomized comparison was performed between standard AP and enhanced prophylactic measures using urine cultures and targeted pharmacological therapy. Results demonstrated that an antibiotic-culture-based therapy could significantly reduce the risk of UTIs in patients undergoing ureteroscopy when compared with a traditional empirical antibiotic.

Percutaneous nephrolithotomy

Percutaneous nephrolithotomy (PCNL) is currently the gold standard treatment for kidney stones larger than 2 cm.⁸⁰ Despite its efficacy, PCNL is associated with complications including urinary leakage, blood transfusion, postoperative fever, and sepsis,⁸¹ and shares the same risk factors for infectious complications with therapeutic ureteroscopy.

Charton et al.⁸² observed that: bacteriuria developed in 35% of cases and fever without bacteriuria developed in 10% of patients post-PCNL who did not receive AP. They also showed that 32% of patients required postoperative antibiotic therapy due to increased transitory fever, and 3.5% developed sepsis with the need for antibiotic therapy.

In their two RCTs, Fourcade⁸³ and Doğan et al.⁸⁴ compared patients who underwent AP with those untreated. Findings revealed a substantial reduction in infectious complications among patients who were offered AP, regardless of the choice of antibiotic.

Several RCTs comparing different antibiotic regimes are available: no differences in SIRS or sepsis rates were observed between patients receiving sulbactam/ampicillin versus cefuroxime⁸⁵; or ceftriaxone versus ceftriaxone plus an oral third-generation cephalosporin⁸⁶; or ceftriaxone versus cefazolin⁸⁷; or ciprofloxacin versus cefotaxime.⁸⁸

A large meta-analysis of 13 comparative studies (1549 patients)⁸⁹ revealed that a single dose of AP administrated before surgery significantly decreased postoperative sepsis and fever rates [OR 0.31, 95% CI 0.20–0.50 and OR 0.26, 95% CI 0.14–0.48, respectively]. Additionally, preoperative AP reduced the rate of positive pelvic urine cultures and positive stone cultures. No difference in sepsis rate between patients receiving or not receiving postoperative prophylaxis was observed.⁸⁹

Jung et al. in a meta-analysis of 10 articles, found no significant differences between single-dose and extended-dose of antibiotics regarding the rate of fever [OR = 0.96, 95% CI 0.44–2.13]. On the other hand, the incidence of SIRS was lower in the extended-dose group compared to the single-dose group, especially in high-risk patients [OR = 1.81, 95% CI 1.30–2.53]. The impact of therapy duration was not assessed and in the included studies the duration varied too much.⁹⁰

Danilovic et al.⁹¹ showed in a recent meta-analysis that a one-week preoperative cycle of oral antibiotics was a protective factor from developing SIRS/sepsis [OR = 0.37, 95% CI 0.23–0.53]. Patients who received preoperative antibiotic therapy had lower positive intraoperative urine culture and stone culture than the control group.

These studies moderately evidenced that a single dose of antibiotics can be effective and sufficient, however, in patients at high risk for post-PCNL infections, the use of extended doses may be required.

According to the EAU and AUA guidelines, only a single-dose AP is strongly recommended to reduce the rate of clinical UTIs.^21,40

Transurethral resection of the prostate

Transurethral resection of the prostate (TURP) is widely recognized as the gold-standard surgical intervention for the management of benign prostatic hyperplasia. Infectious complications are particularly increased in males with preoperative bacteriuria.⁹² Postoperative UTIs and urosepsis represent common complications, with incidence rates ranging from 6% to 13% and 4% to 12%, respectively.^93,94

Berry and Barratt⁹⁵ systematically reviewed 32 RCTs (4260 patients), demonstrating that AP use in patients with preoperative sterile urine undergoing TURP significantly decreased the bacteriuria incidence from 26% to 9% [RR reduction 65%, 95% CI 56–73] and the clinical septicemia incidence from 4.4% to 0.7% [RR reduction 77%, 95% CI 55–88].

Qiang et al.,⁹⁶ in a systematic review including 28 RCTs (4694 patients) showed similar results. Specifically, AP was significantly more effective than placebo in reducing postoperative TURP complications such as bacteriuria, high-degree fever, and bacteremia. Both reviews showed that short-term prophylaxis lasting more than 72 h is more effective than a single dose but less effective than therapy administered for a week.

Dahm and Dmochowski⁹⁷ confirmed the abovementioned results in a systematic review of 39 RCTs. The use of AP compared to placebo showed a RR reduction for sepsis [RR 0.51, 95% CI 0.27–0.96], for fever [RR 0.64, 95% CI 0.55–0.75], and for bacteriuria [0.37, 95% CI 0.32–0.41].

Postoperative bacteriuria may be prevented by careful hemostasis, prevention of postoperative catheter disconnections, and limitation of the duration of postoperative catheterization.⁹⁸ In summary, there is significant evidence acquired from high-quality research indicating that AP for TURP effectively decreases the rate of postoperative bacteriuria, fever, and sepsis.

EAU guidelines recommended the use of AP to reduce the rate of infectious complications in males undergoing TURP.²¹

A single dose of AP is also indicated in the AUA guidelines, and, in addition, the antibiotic agent choice requires knowledge of the urine culture results, the local antibiogram, and the patient’s associated risks.⁴⁰

Transurethral resection of bladder tumor

Transurethral resection of bladder (TURB) tumor is one of the most frequently performed urological procedures. Despite its widespread use, there is a lack of high-quality evidence evaluating AP in TURB.

Bausch et al.,⁹⁹ in a meta-analysis including seven studies (1725 patients), showed no significant effect of AP on postoperative UTIs incidence [OR 1.55, 95% CI 0.73–3.31] and ASB [OR 0.43, 95% CI 0.18–1.04]. Age, preoperative pelvic radiation, preoperative ASB, and pyuria have been identified as risk factors for UTIs following TURB.

In an RCT conducted by Yang et al.,¹⁰⁰ the efficacy of a single oral dose of fosfomycin 3 g administered the night before surgery was compared to the intravenous administration of 2 g of cefoxitin, given 30 min pre- and 24 h post-surgery. The oral single dose of fosfomycin was found to be non-inferior to intravenous administration of cefoxitin in the prevention of post-TURB UTIs, even in patients considered high-risk.

Baten et al.,¹⁰¹ in a multi-centered RCT, investigated the safety of omitting AP in TURB in patients without a preoperative indwelling catheter/double-J/nephrostomy and with a negative preoperative urinary culture. They found no significant differences between groups for developing postoperative fever (p = 0.44).

Kohada et al.,¹⁰² in a retrospective study, demonstrated that AP was effective for patients who underwent TURB; history of pelvic radiotherapy, high age, preoperative hospital stay, and large tumor size were risk factors as well as pyuria and postoperative bacteriuria.

In high-risk patients undergoing TURB (large or necrotic tumors and prolonged operation time), the EAU guidelines recommendations reflect the low level of evidence and provide a weak recommendation in favor of AP.²¹ The AUA guidelines state that AP may not be necessary for simple bladder biopsies performed with periprocedural uninfected urine. No more indications are given.⁴⁰

Slings and prosthetic device implantation

The use of AP in incontinence surgery remains a topic with limited available research.

One systematic review and meta-analysis¹⁰³ was performed on UTIs prevention after synthetic midurethral slings implantation in women. Only one of the seven analyzed studies assessed AP for midurethral sling surgery and was halted early due to a low rate of infectious events. No statistically significant differences between Cefazolin and placebo group regarding wound infections [1 (3.3%) and 0 (0%)] or bacteriuria [3 (10%) and 1 (3.5%)], were found.

A registry-based cohort study¹⁰⁴ of 28,687 women undergoing midurethral sling implantation showed that AP led to a reduction in the occurrence of postoperative infections and extended pain after surgery but did not offer protection against tape exposure. However, the variations in the success rate were minimal and likely not significant from a clinical perspective. The authors concluded that if a slight increase in surgical site infections is considered acceptable, it may be possible to avoid the use of AP.

AUA guidelines⁴⁰ recommend AP targeting common skin flora, such as coagulase-negative staphylococci, and other gram-negative bacteria, such as Pseudomonas species, for implantation of prosthetic device surgery.

It is worth noting that recent research^105,106 has indicated a decline in the overall incidence of prosthetic infections. Nevertheless, when infections do occur, relatively higher rates of anaerobic infections, methicillin-resistant Staphylococcus aureus (MRSA), and fungal infections are potentially identified.

The effectiveness of periprocedural non-pharmacological prophylactic measures has an impact on reducing colonization and the presence of positive postoperative cultures after the placement of artificial urinary sphincters. However, establishing a clear correlation with periprocedural infectious complications is challenging due to the low prevalence of SSIs.¹⁰⁷

Currently, there is a substantial lack of standardized practice in terms of AP for prosthetic devices and the existing evidence is relatively limited.⁴⁰ While the majority of the authors use an extended AP in this setting, other authors reported similar results with a single-dose administration for both sling and artificial urinary sphincter in males.^108,109

Urgent studies are required to fill these gaps, as the risk associated with extended antibiotic courses and the use of vancomycin is notably higher compared to short-course first-generation cephalosporins. Similarly, the efficacy of wound irrigation in the absence of prosthetic infection or erosion is being actively investigated, along with methods to reduce biofilm formation.¹⁰⁶

Major surgery

No RCTs evidenced the role of AP in major urological surgery.¹¹⁰ So far, the knowledge about AP in urology comes from other surgical specialties. The pieces of evidence about this topic should be deepened. The infectious risk is linked to the procedure:

In clean procedures involving non-infected tissues, AP is not recommended¹¹¹;

In clean-contaminated procedures involving non-infected opened urological structures (e.g.: radical prostatectomy, pieloureteroplasty), preoperative AP is recommended when risk factors are present^112,113;

In contaminated procedures, for example, in case of intestinal manipulation during radical cystectomy, AP is mandatory.¹¹⁴

Consensus exists about the minor incidence of infective complications in the case of laparoscopic or robotic procedures when compared to traditional open procedures.¹¹⁵

No specific recommendations are available in the EAU and AUA guidelines regarding major surgery procedures (in which AP represents common practice).

Conclusions

AP plays a critical role in reducing the risk of HAIs in urological diagnostic and therapeutic procedures; however, scientific evidence remain scant and antibiotic resistance is a major issue.

The European CDC¹⁴ identified five modalities that should be used when creating local policies for antibiotic prophylaxis use. All these five key points, shown in Table 1, support the harmonization of the administration of AP and increase awareness in hospitals, which would eventually lead to a decrease in antibiotic use and antibiotic resistance.

Table 1.

Perioperative antibiotic prophylaxis modality. Reproduced and adapted from European Centre for Disease Prevention and Control Technical Report on perioperative antibiotic prophylaxis.¹⁴

Perioperative antibiotic prophylaxis (PAP) modality	Indicators for each modality
Modality #1: Multidisciplinary antimicrobial management (AM) teams
Hospitals should establish a multidisciplinary AM team who should develop and implement a protocol of appropriate PAP.	The presence of a multidisciplinary AM team which is responsible for developing, implementing, and regularly updating the PAP protocol; in charge of regularly updating the local antibiotic protocol; and responsible for regularly analyzing and auditing compliance with appropriate PAP.
Modality #2: Responsibility for appropriate timing of perioperative antibiotic prophylaxis
To ensure appropriate timing, PAP should be the responsibility of the anesthesiologist.	Measurement of the presence of an anesthesiologist or another designated professional at surgery who is responsible for applying PAP.
Modality #3: Timing of perioperative antibiotic prophylaxis
PAP should be administered within 60 min before incision (except when administering vancomycin or fluoroquinolones), ideally at the time of anesthetic induction.	Rate of compliance with the administration of PAP within 60 min.
Modality #4: Dosing and duration of perioperative antibiotic prophylaxis
Although a single dose of PAP is preferred, subsequent doses should be given depending on the duration of the procedure and the half-life of the antibiotic, and if significant blood loss occurs during surgery.	Rate of compliance with indication, selection and dosage of PAP according to protocol.
Modality #5: Duration and termination of perioperative antibiotic prophylaxis
Continuing antibiotic prophylaxis after the end of surgery is not recommended	Rate of compliance with discontinuation of PAP within 24 h after initiation of surgery.

Single-dose AP is suggested before undergoing any procedure for treating benign prostatic hyperplasia, TURB, open and laparoscopic/robotic stone surgery, PCNL, endoscopic stone removal, and prostate transrectal biopsy. Currently, no strong scientific evidence supports the use of multiple doses of antibiotics when there is no symptomatic infection before surgery. Furthermore, several RCTs with moderate-quality evidence do not demonstrate any advantages in extending AP beyond the time of the surgery’s completion.¹¹⁶ Table 2 summarizes evidence and recommendations for peri-procedural prophylaxis and the suggested regimes for each kind of urological procedure according to EAU guidelines. Table 3 summarizes the principal studies that were examined during the drafting of this review.

Table 2.

Suggested regimes for antibiotic prophylaxis prior to urological procedures. Reproduced and adapted from EAU guidelines.²¹

Procedure	Pathogens (expected)	Prophylaxis suggested	Antibiotic	Remarks
Diagnostic procedures
Urodynamics	Enterobacteriaceae Enterococci Staphylococci	No		Consider host’s risk factors
Cystoscopy	Enterobacteriaceae Enterococci Staphylococci	No		Consider host’s risk factors
Transrectal prostate biopsy	Enterobacteriaceae	Yes	FosfomycinTMP+SMXTargeted alternativeFluoroquinoles (AUA)	Targeted prophylaxis – based on rectal swab/stool culture
Transperineal prostate biopsy	Enterobacteriaceae	N/A	FosfomycinTMP+SMXTargeted alternative	More RCTs are needed
Endourological surgery or non-invasive treatments
External Shock-Wave Lithotripsy (ESWL)	Enterobacteriaceae Enterococci	No		Only if risk factors are present (AUA)
Ureteroscopy	Enterobacteriaceae Enterococci Staphylococci	Yes	TMP+SMXCephalosporin II generationAminopenicillin+β lactamase inhibitor	Weak recommendation Consider it especially in high-risk patients
Percutaneous nephrolithotomy (PCNL)	Enterobacteriaceae Enterococci Staphylococci	Yes	TMP+SMXCephalosporin II generationAminopenicillin+β lactamase inhibitor	Single-dose
Transurethral resection of the prostate (TURP)	Enterobacteriaceae Enterococci	Yes	TMP+SMXCephalosporin II or III generationAminopenicillin+β lactamase inhibitor
Transurethral resection of the bladder (TURB)	Enterobacteriaceae Enterococci	Yes	TMP+SMXCephalosporin II or III generationAminopenicillin+β lactamase inhibitor	Weak recommendation Especially in high-risk patients
Major surgery (open or laparoscopic surgery)
Clean procedures	Skin-related and catheter-associated pathogens	No		Considered it in high-risk patients
Clean-contaminated procedures	Enterobacteriaceae Enterococci Staphylococci	Recommended	TMP+SMXCephalosporin II or III generationAminopenicillin+β lactamase inhibitor	In case of risk factors
Contamined procedures	Enterobacteriaceae Enterococci AnaerobesSkin-related bacteria	Yes	Cephalosporin II or III generationMetronidazole
Implant of prothesic devices	Skin-related bacteria	Yes (EAU)Likely not required (AUA)	Cephalosporin II or III generationPenicillin

Table 3.

Resuming principal articles on AP in urological procedures.

Author	Study design	Population number	Main results	Notes
Urodynamics
UTI incidence 1.5%−36%.^36,37
Latthe et al.	Meta-analysis	995 patients	ASB ↓ 40% (OR 0.39; 95% CI 0.24–0.61)	AP versus no treatment
Foon et al.	Cochrane review	973 patients	ASB ↓ 4% vs 12% (RR 0.35; 95% CI 0.22–0.56)UTI ↓ 20% vs 28% (RR 0.73; 95% CI 0.52–1.03)	AP versus Placebo
Wu et al.	Meta-analysis	1828 patients	ASB ↓ (RR 0.42; 95% CI 0.30–0.60)UTI ↓ (RR 0.65; 95% CI 0.48–0.88)	AP versus Placebo/No treatmentNo adverse effects
Cystoscopy
UTI incidence 2.7%−35% (of which septicemia 10%−16%).^43,117
Carey et al.	Meta-analysis	5107 patients	UTI ↓ (RR 0.34; 95% CI 0.27–0.47)	AP versus Placebo/No treatment
Garcia-Perdomo el at.	Meta-analysis	3038 patients	ASB ↓ (RR 0.28; 95% CI 0.20–0.39)UTI ↓ (RR 0.53; 95% CI 0.31–0.90)	AP versus Placebo
Zeng et al.	Cochrane review	7711 patients	No systemic UTI ↓ (RR 1.12; 95% CI 0.38–3.32)Localized UTI ↓ (RR 0.49; 95% CI 0.28–0.86)*Bacterial resistance ↓ (RR 1.73; 95% CI 1.04–2.87)	AP versus Placebo/No treatment
Transrectal prostate biopsy
UTI incidence 4%–7%.^118,119
Park et al.	Monocentric interventional study	481 patients	UTI ↓ (RR 0.47; 95% CI 0.36–0.61)	Povidone iodine preparation versus no treatment in patients all receiving AP
Tops et al.	Multicentered randomized trial	1288 patients	UTI ↓ (OR 0.52; 95% CI 0.27–0.99)	Rectal culture-based versus empirical (ciprofloxacin) AP
Transperineal prostate biopsy
UTI incidence 0.1%–3%.^64,120,121
Castellani et al.	Meta-analysis	3662 patients	No UTI ↓ (RR 1.02; 95% CI 0.54–8.10)	AP versus no treatment
Basourakos et al.	Meta-analysis	42,577 patients	No UTI ↓ (1.35% vs 1.22%; p = 0.8)	AP versus no treatment
Benli et al.	Prospective randomized control trial	140 patients	Bacteremia/Sepsis ↓ [3 (4.3%) vs 7 (9.9%); p = 0.012]	Rectal swab-based versus empirical (ciprofloxacin) AP
ESWL
UTI incidence 1%–14%.⁷¹
Lu et al.	Meta-analysis	1364 patients	No UTI ↓ (RR 0.54; 95% CI 0.29–1.01)	AP versus no treatment
Mrkobrada et al.	Meta-analysis	3599 patients	No UTI ↓ (RR 0.76; 95% CI 0.39–1.48)	AP versus no treatment
Ureteroscopy and endoscopic lithotripsy
UTI incidence 1%–10%.⁸¹
Deng et al.	Meta-analysis	4591 patients	ASB ↓ (OR 0.25; 95% CI 0.11–0.58)No UTI ↓ (OR 1; 95% CI 0.26–3.88)	AP versus no treatment
PCNL
UTI incidence 10.8%¹²²
Yu et al.	Meta-analysis	1549 patients	Sepsis ↓ (OR 0.31; 95% CI 0.20–0.50)	AP versus no treatment
Jung et al.	Meta-analysis	1456 patients	No fever ↓ (OR 0.96; 95% CI 0.44–2.13)SIRS ↓ (OR 1.81; 95% CI 1.30–2.53)	Extended-dose versus single-dose AP
TURP
UTI incidence 6%−13%.^{93,94,123,124}
Berry et al.	Meta-analysis	4260 patients	ASB ↓ (RR 0.35; 95% CI 0.56–0.73)	AP versus no treatment
TURB
UTI incidence 3.1%−3.4%.^102,125
Bausch et al.	Meta-analysis	1725 patients	No ASB ↓ (OR 0.43; 95% CI 0.18–1.04)No UTI ↓ (OR 1.55; 95% CI 0.73–3.31)	AP versus no treatment
Baten et al.	Multi-centered RCT	459 patients	No post-operative fever ↓ [6/202 (2.9%) vs 8/257 (3.1%); p = 0.44]	AP versus no treatment
Midurethral slings and prosthetic device implantation
UTI incidence 34%.¹²⁶
Svenningsen et al.	Multi-centered cohort study	28,687 patients	SSIs ↓ (0.6% vs 1.2%; p < 0.01)	AP versus no treatment

Future research should focus on refining AP guidelines and individualizing prophylactic approaches to ensure effective infection prevention while minimizing the risks of antibiotic overuse and resistance. In this regard, the DEEP-URO (DEEscalation of antibiotic Prophylaxis in UROlogical procedures) study was set in motion during the EAU23 Congress in Milan with the aim to generate high-level evidence for the appropriate use of AP in urology.¹²⁷ It aims to increase our understanding of rates and risk factors for infectious complications in urology and to determine the actual need for AP in urological procedures. The primary objective is to identify the limits of AP de-escalation by comparing 30-day infection rates (deep tissue, skin, urinary tract, and sepsis) relative to contemporary intensive AP protocols.

In summary, this review encourages a nuanced and patient-centered perspective on AP, underscoring the evidence gaps in the field and advocating for a judicious use of antibiotics to minimize the risk of infections while simultaneously addressing concerns related to antibiotic resistance.

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Filippo Marino

Francesco Rossi

Emilio Sacco

References

Siegel

Rhinehart

Jackson

, et al.; Health Care Infection Control Practices Advisory Committee. 2007 Guideline for isolation precautions: preventing transmission of infectious agents in health care settings. Am J Infect Control 2007; 35(10 Suppl 2): S65–164.

Klevens

Edwards

Richards

Jr , et al. Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Rep 2007; 122(2): 160–166.

Liu

Dickter

. Nosocomial infections: a history of hospital-acquired infections. Gastrointest Endosc Clin N Am 2020; 30(4): 637–652.

Iacovelli

Gaziev

Topazio

, et al. Nosocomial urinary tract infections: a review. Urologia 2014; 81(4): 222–227.

Tanner

Dumville

Norman

, et al. Surgical hand antisepsis to reduce surgical site infection. Cochrane Database Syst Rev 2016; 2016(1): CD004288.

Webster

Osborne

. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. Cochrane Database Syst Rev 2015; 2015(9): CD004985.

Güenaga

Matos

Wille-Jørgensen

. Mechanical bowel preparation for elective colorectal surgery. Cochrane Database Syst Rev 2011; 2011(9): CD001544.

Bootsma

Laguna Pes

Geerlings

, et al. Antibiotic prophylaxis in urologic procedures: a systematic review. Eur Urol 2008; 54(6): 1270–1286.

Recupero

Bientinesi

Foschi

, et al. La profilassi antibiotica in Urologia [Antibiotic prophylaxis in urology]. Urologia 2014; 81(4): 209–217.

10.

Grabe

. Perioperative antibiotic prophylaxis in urology. Curr Opin Urol 2001; 11(1): 81–85.

11.

Mirone

Franco

. Clinical aspects of antimicrobial prophylaxis for invasive urological procedures. J Chemother 2014; 26(Suppl 1): S1–S13.

12.

Sutter

Rüegg

Tschudin-Sutter

. Seizures as adverse events of antibiotic drugs: a systematic review. Neurology 2015; 85(15): 1332–1341.

13.

van Hecke

Wang

Lee

, et al. Implications of antibiotic resistance for patients' recovery from common infections in the community: a systematic review and meta-analysis. Clin Infect Dis 2017; 65(3): 371–382.

14.

European Centre for Disease Prevention and Control. Systematic review and evidence-based guidance on peri-operative antibiotic prophylaxis. Stockholm: ECDC, 2013. https://www.ecdc.europa.eu/en/publications-data/systematic-review-and-evidence-based-guidance-peri-operative-antibiotic

15.

Onyekwelu

Yakkanti

Protzer

, et al. Surgical wound classification and surgical site infections in the orthopaedic patient. J Am Acad Orthop Surg Glob Res Rev 2017; 1(3): e022.

16.

Emori

Culver

Horan

, et al. National nosocomial infections surveillance system (NNIS): description of surveillance methods. Am J Infect Control 1991; 19(1): 19–35.

17.

Bustamante-Munguira

Herrera-Gómez

Ruiz-álvarez

, et al. A new surgical site infection risk score: Infection Risk Index in Cardiac Surgery. J Clin Med 2019; 8(4): 480.

18.

Zhang

Xue

Liu

, et al. Risk factors and prediction model for inpatient surgical site infection after elective abdominal surgery. World J Gastrointest Surg 2023; 15(3): 387–397.

19.

Toumpoulis

Anagnostopoulos

Swistel

, et al. Does EuroSCORE predict length of stay and specific postoperative complications after cardiac surgery? Eur J Cardiothorac Surg 2005; 27(1): 128–133.

20.

Grabe

. Controversies in antibiotic prophylaxis in urology. Int J Antimicrob Agents 2004; 23: S17–S23.

21.

EAU Guidelines. Edn. presented at the EAU Annual Congress Milan, Italy 2023. https://uroweb.org/guidelines/urological-infections (2023, accessed 15 November 2023).

22.

Concepcion

Schaeffer

Shore

, et al. The effect of local antibiogram-based augmented antibiotic prophylaxis on infection-related complications following prostate biopsy. Rev Urol 2019; 21(2-3): 93–101.

23.

Taylor

Zembower

Nadler

, et al. Targeted antimicrobial prophylaxis using rectal swab cultures in men undergoing transrectal ultrasound guided prostate biopsy is associated with reduced incidence of postoperative infectious complications and cost of care. J Urol 2012; 187(4): 1275–1279.

24.

Shenoy

Macy

Rowe

, et al. Evaluation and management of penicillin Allergy: a Review. JAMA 2019; 321(2): 188–199.

25.

Zaytoun

Vargo

Rajan

, et al. Emergence of fluoroquinolone-resistant Escherichia coli as cause of postprostate biopsy infection: implications for prophylaxis and treatment. Urology 2011; 77(5): 1035–1041.

26.

Araújo

MRB

Sant'Anna

Santos

NNCD

, et al. Monitoring fluoroquinolone resistance among ESBL-positive and ESBL-negative Escherichia coli strains isolated from urinary tract infections: an alert for empirical treatment. Rev Soc Bras Med Trop 2023; 56: e0513.

27.

Gavi

Fiori

Gandi

, et al. Prevalence and antimicrobial resistance patterns of hospital acquired infections through the COVID-19 pandemic: real-word data from a tertiary urological centre. J Clin Med 2023; 12(23): 7278.

28.

Vittori

D'Addessi

Sasso

, et al. Microbiological follow-up of nosocomial infections in a single urological center. Urologia 2012; 79: 147–151.

29.

Antibacterial prophylaxis in surgery: 2–Urogenital, obstetric and gynaecological surgery. Drug Ther Bull 2004; 42(2): 9–13.

30.

Marino Sabo

Stern

. Approach to antimicrobial prophylaxis for urology procedures in the era of increasing fluoroquinolone resistance. Ann Pharmacother 2014; 48(3): 380–386.

31.

Classen

Evans

Pestotnik

, et al. The timing of prophylactic administration of antibiotics and the risk of surgical-wound infection. N Engl J Med 1992; 326(5): 281–286.

32.

Rando

Giovannenze

Murri

, et al. A review of recent advances in the treatment of adults with complicated urinary tract infection. Expert Rev Clin Pharmacol 2022; 15(9): 1053–1066.

33.

Bientinesi

Murri

Sacco

. Efficacy and safety of levofloxacin as a treatment for complicated urinary tract infections and pyelonephritis. Expert Opin Pharmacother 2020; 21(6): 637–644.

34.

Yokoyama

Nozaki

Nose

, et al. Tolerability and morbidity of urodynamic testing: a questionnaire-based study. Urology 2005; 66(1): 74–76.

35.

Payne

Mckenning

Pead

, et al. Microbiological look at urodynamic studies. Lancet 1988; 332(8620): 1123–1126.

36.

Latthe

Foon

Toozs-Hobson

. Prophylactic antibiotics in urodynamics: a systematic review of effectiveness and safety. Neurourol Urodyn 2008; 27(3): 167–173.

37.

Foon

Toozs-Hobson

Latthe

. Prophylactic antibiotics to reduce the risk of urinary tract infections after urodynamic studies. Cochrane Database Syst Rev 2012; 10: CD008224.

38.

Benseler

Anglim

Zhao

, et al. Antibiotic prophylaxis for urodynamic testing in women: a systematic review. Int Urogynecol J 2021; 32(1): 27–38.

39.

Cheng

, et al. Prophylactic antibiotics for urinary tract infections after urodynamic studies: a meta-analysis. Biomed Res Int 2021; 2021.

40.

Lightner

Wymer

Sanchez

, et al. Best practice statement on urologic procedures and antimicrobial prophylaxis. J Urol 2020; 203: 351–356.

41.

Grasso

Beaghler

Bagley

, et al. Actively deflectable, flexible cystoscopes: no longer solely a diagnostic instrument. J Endourol 1993; 7(6): 527–530.

42.

Cohen

Rivera

Barboglio

, et al. Safety and tolerability of sedation-free flexible cystoscopy for intradetrusor botulinum toxin-A injection. J Urol 2007; 177(3): 1006–1010.

43.

Almallah

Rennie

Stone

, et al. Urinary tract infection and patient satisfaction after flexible cystoscopy and urodynamic evaluation. Urology 2000; 56(1): 37–39.

44.

Clark

Higgs

. Urinary infection following out-patient flexible cystoscopy. Br J Urol 1990; 66(5): 503–505.

45.

Carey

Zreik

Fenn

, et al. Should we use antibiotic prophylaxis for flexible cystoscopy? A systematic review and meta-analysis. Urol Int 2015; 95(3): 249–259.

46.

Garcia-Perdomo

Jimenez-Mejias

Lopez-Ramos

. Efficacy of antibiotic prophylaxis in cystoscopy to prevent urinary tract infection: a systematic review and meta-analysis. Int Braz J Urol 2015; 41(3): 412–424.

47.

Zeng

Zhang

Bai

, et al. Antimicrobial agents for preventing urinary tract infections in adults undergoing cystoscopy. Cochrane Database Syst Rev 2019; 2(2): CD012305.

48.

Bradshaw

Bechis

, et al. Antibiotics are not necessary during routine cystoscopic stent removal: A randomized controlled trial at UC San Diego. Urol Ann 2020; 12(4): 373–378.

49.

Wazait

van der Meullen

Patel

, et al. Antibiotics on urethral catheter withdrawal: a hit and miss affair. J Hosp Infect 2004; 58(4): 297–302.

50.

Musco

Giammò

Savoca

, et al. How to prevent catheter-associated urinary tract infections: a reappraisal of Vico's theory—is history repeating itself? J Clin Med 2022; 11(12): 3415.

51.

Marschall

Carpenter

Fowler

, et al.; CDC Prevention Epicenters Program. Antibiotic prophylaxis for urinary tract infections after removal of urinary catheter: meta-analysis. BMJ 2013; 346.

52.

Wolters

Palmes

Lordugin

, et al. Antibiotic prophylaxis at urinary catheter removal prevents urinary tract infection after kidney transplantation. Transplant Proc 2014; 46(10): 3463–3465.

53.

Wagenlehner

van Oostrum

Tenke

, et al.; GPIU investigators. Infective complications after prostate biopsy: outcome of the global prevalence study of infections in Urology (GPIU) 2010 and 2011, a prospective multinational multicentre prostate biopsy study. Eur Urol 2013; 63(3): 521–527.

54.

Pradere

Veeratterapillay

Dimitropoulos

, et al. Nonantibiotic strategies for the Prevention of infectious complications following prostate biopsy: A systematic review and meta-analysis. J Urol 2021; 205(3): 653–663.

55.

Bennett

Roberts

Doi

, et al. The global burden of major infectious complications following prostate biopsy. Epidemiol Infect 2016; 144(8): 1784–1791.

56.

Mian

Feustel

Aziz

, et al. Complications following transrectal and transperineal prostate biopsy: results of the ProBE-PC randomized clinical trial. J Urol 2024; 211(2): 205–213.

57.

PReclude Infection EVEnts With No Prophylaxis Transperineal Biopsy 2 (PREVENT2). ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT04815876 (accessed 15 November 2023).

58.

The TRANSLATE Trial. ClinicalTrials.gov. https://clinicaltrials.gov/study/NCT05179694 (accessed 15 November 2023).

59.

Park

Lee

, et al. Simple use of the suppository type povidone-iodine can prevent infectious complications in transrectal ultrasound-guided prostate biopsy. Adv Urol 2009; 2009.

60.

Ergani

Çetin

Yalçın

, et al. Effect of rectal mucosa cleansing on acute prostatitis during prostate biopsy: A randomized prospective study. Turk J Urol 2020; 46(2): 159–164.

61.

Tops

SCM

Kolwijck

Koldewijn

, et al. Rectal culture-based versus empirical antibiotic prophylaxis to prevent infectious complications in men undergoing transrectal prostate biopsy: A randomized, nonblinded Multicenter Trial. Clin Infect Dis 2023; 76(7): 1188–1196.

62.

Pilatz

Dimitropoulos

Veeratterapillay

, et al. Antibiotic prophylaxis for the prevention of infectious complications following prostate biopsy: A systematic review and meta-analysis. J Urol 2020; 204(2): 224–230.

63.

Chung

, et al. Fosfomycin for antibiotic prophylaxis in men undergoing a transrectal prostate biopsy: a systematic review and meta-analysis. Medicina 2023; 59(5): 911.

64.

Castellani

Pirola

Law

YXT

, et al. Infection rate after transperineal prostate biopsy with and without prophylactic antibiotics: results from a systematic review and meta-analysis of comparative studies. J Urol 2022; 207(1): 25–34.

65.

Jacewicz

Günzel

Rud

, et al. Antibiotic prophylaxis versus no antibiotic prophylaxis in transperineal prostate biopsies (NORAPP): a randomised, open-label, non-inferiority trial. Lancet Infect Dis 2022; 22(10): 1465–1471.

66.

Chernysheva

Popov

Orlov

, et al. The first experience of transperineal prostate biopsy without antibiotic prophylaxis. Cancer Urol 2021; 17(2): 46–52.

67.

Basourakos

Alshak

Lewicki

, et al. Role of prophylactic antibiotics in transperineal prostate biopsy: a systematic review and meta-analysis. Eur Urol Open Sci 2022; 37: 53–63.

68.

Benli

Yuce

Cirakoglu

, et al. Effect of targeted prophylaxis with rectal swab on complications after prostate biopsy: prospective randomized study. Ir J Med Sci 2022; 191(3): 1147–1152.

69.

JKM

Wang

Lau

BSY

, et al. Oral antibiotics perturbation on gut microbiota after prostate biopsy. Front Cell Infect Microbiol 2022; 12.

70.

D’Addessi

Vittori

Racioppi

, et al. Complications of extracorporeal shock wave lithotripsy for urinary stones: to know and to manage Them—A review. Sci World J 2012; 2012. 6: 19820.

71.

Tianyong

Ping

, et al. Antibiotic prophylaxis for shock wave lithotripsy in patients with sterile urine before treatment may be unnecessary: a systematic review and meta-analysis. J Urol 2012; 188(2): 441–448.

72.

Mrkobrada

Ying

Mokrycke

, et al. CUA guidelines on antibiotic prophylaxis for urologic procedures. Can Urol Assoc J 2015; 9(1-2): 13–22.

73.

Hsieh

Yang

Chang

. The effectiveness of prophylactic antibiotics with oral levofloxacin against post-shock wave lithotripsy infectious complications: a randomized controlled trial. Surg Infect 2016; 17(3): 346–351.

74.

Assimos

Krambeck

Miller

, et al. Surgical management of stones: American Urological Association/Endourological Society guideline, PART I. J Urol 2016; 196(4): 1153–1160.

75.

Assimos

Krambeck

Miller

, et al. Surgical management of stones: American Urological Association/Endourological Society guideline, PART II. J Urol 2016; 196(4): 1161–1169.

76.

Deng

Liu

Duan

, et al. Antibiotic prophylaxis in ureteroscopic lithotripsy: a systematic review and meta-analysis of comparative studies. BJU Int 2018; 122(1): 29–39.

77.

Qiao

Chen

Lin

, et al. Evaluation of perioperative prophylaxis with fosfomycin tromethamine in ureteroscopic stone removal: an investigator-driven prospective, multicenter, randomized, controlled study. Int Urol Nephrol 2018; 50: 427–432.

78.

Zhao

Fan

Sun

, et al. Recommended antibiotic prophylaxis regimen in retrograde intrarenal surgery: evidence from a randomised controlled trial. BJU Int 2019; 124(3): 496–503.

79.

El-Agamy

Elhelaly

Abouelgreed

, et al. Randomized comparison of effect of standard antibiotic prophylaxis versus enhanced prophylactic measures on rate of urinary tract infection after flexible ureteroscopy. Arch Ital Urol Androl 2023; 95(1): 11084.

80.

Geraghty

Davis

Tzelves

, et al. Best practice in interventional management of Urolithiasis: an Update from the European Association of Urology Guidelines Panel for Urolithiasis 2022. Eur Urol Focus 2023; 9(1): 199–208.

81.

Seitz

Desai

Häcker

, et al. Incidence, prevention, and management of complications following percutaneous nephrolitholapaxy. Eur Urol 2012; 61(1): 146–158.

82.

Charton

Vallancien

Veillon

, et al. Urinary tract infection in percutaneous surgery for renal calculi. J Urol 1986; 135(1): 15–17.

83.

Fourcade

; the Cefotaxime Cooperative Group. Antibiotic prophylaxis with cefotaxime in endoscopic extraction of upper urinary tract stones: a randomized study. J Antimicrob Chemother 1990; 26(Suppl A): 77–83.

84.

Doğan

Sahin

Cetinkaya

, et al. Antibiotic prophylaxis in percutaneous nephrolithotomy: prospective study in 81 patients. J Endourol 2002; 16(9): 649–653.

85.

Seyrek

Binbay

Yuruk

, et al. Perioperative prophylaxis for percutaneous nephrolithotomy: randomized study concerning the drug and dosage. J Endourol 2012; 26(11): 1431–1436.

86.

Tuzel

Aktepe

Akdogan

. Prospective comparative study of two protocols of antibiotic prophylaxis in percutaneous nephrolithotomy. J Endourol 2013; 27(2): 172–176.

87.

Taken

Aşık

Eryılmaz

, et al. Comparison of ceftriaxone and cefazolin sodium antibiotic prophylaxis in terms of SIRS/Urosepsis rates in patients undergoing percutaneous nephrolithotomy. J Urol Surg 2019; 6(2): 111–117.

88.

Omar

Selim

El Sherif

, et al. Ciprofloxacin infusion versus third generation cephalosporin as a surgical prophylaxis for percutaneous nephrolithotomy: a randomized study. Cent Eur J Urol 2019; 72(1): 57–61.

89.

Guo

, et al. Antibiotic prophylaxis in perioperative period of percutaneous nephrolithotomy: a systematic review and meta-analysis of comparative studies. World J Urol 2020; 38(7): 1685–1700.

90.

Jung

Cho

Moon

, et al. Antibiotic prophylaxis for percutaneous nephrolithotomy: an updated systematic review and meta-analysis. PLoS One 2022; 17(4).

91.

Danilovic

Talizin

Torricelli

FCM

, et al. One week pre-operative oral antibiotics for percutaneous nephrolithotomy reduce risk of infection: a systematic review and meta-analysis. Int Braz J Urol 2023; 49(2): 184–193.

92.

Nicolle

Gupta

Bradley

, et al. Clinical practice guideline for the management of asymptomatic bacteriuria: 2019 update by the Infectious Diseases Society of americaa. Clin Infect Dis 2019; 68(10): 1611–1615.

93.

Cafferkey

Falkiner

Gillespie

, et al. Antibiotics for the prevention of septicaemia in urology. J Antimicrob Chemother 1982; 9(6): 471–477.

94.

Murphy

Stassen

Carr

, et al. Bacteraemia during prostatectomy and other transurethral operations: influence of timing of antibiotic administration. J Clin Pathol 1984; 37(6): 673–676.

95.

Berry

Barratt

. Prophylactic antibiotic use in transurethral prostatic resection: a meta-analysis. J Urol 2002; 167(2 Pt 1): 571–577.

96.

Qiang

Jianchen

MacDonald

, et al. Antibiotic prophylaxis for transurethral prostatic resection in men with preoperative urine containing less than 100,000 bacteria per ml: a systematic review. J Urol 2005; 173(4): 1175–1181.

97.

Dahm

Dmochowski

(eds). Evidence-based urology. 2nd ed. Hoboken, NJ: Wiley-Blackwell, 2018. pp.616.

98.

Colau

Lucet

Rufat

, et al. Incidence and risk factors of bacteriuria after transurethral resection of the prostate. Eur Urol 2001; 39(3): 272–276.

99.

Bausch

Halbeisen

Aghlmandi

, et al. Antimicrobial prophylaxis for postoperative urinary tract infections in transurethral resection of bladder tumors: a systematic review and meta-analysis. J Urol 2021; 205(4): 987–998.

100.

Yang

Zhang

Zhou

, et al. Prospective, randomized controlled study of the preventive effect of fosfomycin tromethamine on post-transurethral resection of bladder tumor urinary tract infection. Int J Urol 2018; 25(10): 894–895.

101.

Baten

Van der Aa

Goethuys

, et al. A randomized trial regarding antimicrobial prophylaxis (AMP) in transurethral resection of bladder tumor (TURB). World J Urol 2021; 39(10): 3839–3844.

102.

Kohada

Goriki

Yukihiro

, et al. The risk factors of urinary tract infection after transurethral resection of bladder tumors. World J Urol 2019; 37(12): 2715–2719.

103.

Sanaee

Hutcheon

Larouche

, et al. Urinary tract infection prevention after midurethral slings in pelvic floor reconstructive surgery: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 2019; 98(12): 1514–1522.

104.

Svenningsen

Kulseng-Hanssen

Kråkenes

EBC

, et al. Is antibiotic prophylaxis necessary in mid-urethral sling surgery? Int Urogynecol J 2021; 32(3): 629–635.

105.

Gross

Phillips

Carrasquillo

, et al. Multicenter investigation of the micro-organisms involved in penile prosthesis infection: an analysis of the efficacy of the AUA and EAU Guidelines for penile prosthesis prophylaxis. J Sex Med 2017; 14(3): 455–463.

106.

Faller

Kohler

. The status of biofilms in penile implants. Microorganisms 2017; 5(2): 19.

107.

Magera

Inman

Elliott

. Does preoperative topical antimicrobial scrub reduce positive surgical site culture rates in men undergoing artificial urinary sphincter placement? J Urol 2007; 178(4 Pt 1): 1328–1332.

108.

Sacco

Gandi

Marino

, et al. Artificial urinary sphincter significantly better than fixed sling for moderate post-prostatectomy stress urinary incontinence: a propensity score-matched study. BJU Int 2021; 127(2): 229–237.

109.

Sacco

Marino

Gandi

, et al. Transalbugineal artificial urinary sphincter: A refined implantation technique to improve surgical outcomes. J Clin Med 2023; 12(8): 3021.

110.

Wolf

Bennett

Dmochowski

, et al.; Urologic Surgery Antimicrobial Prophylaxis Best Practice Policy Panel. Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol 2008; 179(4): 1379–1390.

111.

Swartz

Morgan

Krieger

. Complications of scrotal surgery for benign conditions. Urology 2007; 69(4): 616–619.

112.

Terai

Ichioka

Kohei

, et al. Antibiotic prophylaxis in radical prostatectomy: 1-day versus 4-day treatments. Int J Urol 2006; 13(12): 1488–1493.

113.

Richter

Lang

Zur

, et al. Infected urine as a risk factor for postprostatectomy wound infection. Infect Control Hosp Epidemiol 1991; 12(3): 147–149.

114.

Hara

Kitamura

Saito

, et al. Perioperative antibiotics in radical cystectomy with ileal conduit urinary diversion: efficacy and risk of antimicrobial prophylaxis on the operation day alone. Int J Urol 2008; 15(6): 511–515.

115.

Steiner

Traue

Schubert

. Perioperative Antibiotikaprophylaxe bei transperitonealer Tumornephrektomie. Kann sie die Rate klinisch signifikanter postoperativer Infektionen senken? [Perioperative antibiotic prophylaxis in transperitoneal tumor nephrectomy: does it lower the rate of clinically significant postoperative infections?]. Urologe A 2003; 42(1): 34–37.

116.

Global Guidelines for the Prevention of Surgical Site Infection. https://www.ncbi.nlm.nih.gov/books/NBK536404/ (2018, accessed 15 November 2023).

117.

Olson

Cookson

. Do antimicrobials have a role in preventing septicaemia following instrumentation of the urinary tract? J Hosp Infect 2000; 45(2): 85–97.

118.

Loeb

Vellekoop

Ahmed

, et al. Systematic review of complications of prostate biopsy. Eur Urol 2013; 64(6): 876–892.

119.

Wagenlehner

Pilatz

Waliszewski

, et al. Reducing infection rates after prostate biopsy. Nat Rev Urol 2014; 11(2): 80–86.

120.

Huang

Kang

Lee

, et al. Comparisons of cancer detection rate and complications between transrectal and transperineal prostate biopsy approaches - a single center preliminary study. BMC Urol 2019; 19(1): 101.

121.

Ding

Luan

, et al. Risk factors for infection complications after transrectal ultrasound-guided transperineal prostate biopsy. World J Urol 2021; 39(7): 2463–2467.

122.

Türk

Petřík

Sarica

, et al. EAU guidelines on interventional treatment for urolithiasis. Eur Urol 2016; 69(3): 475–482.

123.

Grabe

Forsgren

Hellsten

. The effect of a short antibiotic course in transurethral prostatic resection. Scand J Urol Nephrol 1984; 18(1): 37–42.

124.

Grabe

Forsgren

Björk

, et al. Controlled trial of a short and a prolonged course with ciprofloxacin in patients undergoing transurethral prostatic surgery. Eur J Clin Microbiol 1987; 6(1): 11–17.

125.

Yokoyama

Fujii

Yoshida

, et al. Discarding antimicrobial prophylaxis for transurethral resection of bladder tumor: a feasibility study. Int J Urol 2009; 16(1): 61–63.

126.

Anger

Litwin

Wang

, et al. Complications of sling surgery among female Medicare beneficiaries. Obstet Gynecol 2007; 109(3): 707–714.

127.

European Urology Today. Vol. 35 No. 2 - April/May 2023 by European Association of Urology (EAU) - Issuu. https://issuu.com/uroweb/docs/eau-european-urology-today-eut-edition-april-may-2 (accessed 15 November 2023).