Thurnheer et al conducted a randomized, single-center, nonblinded, noninferiority trial to evaluate outcomes of a 24-hour course of perioperative antibiotic prophylaxis compared with an extended course (>48 hours) of antibiotics for patients undergoing cystectomy and urinary diversion. The median extended course of prophylactic antibiotics was 8 days. The authors found that the overall rate of surgical site infections in the 24-hour prophylaxis group was not significantly different from the rate in the extended prophylaxis group, implying noninferiority of the 24-hour regimen. In addition, there was no difference in all-cause mortality, febrile urinary tract infection, or length of stay. The authors noted significantly higher rates of asymptomatic bacteriuria and treatment for it in the 24-hour prophylaxis group, although the difference was no longer apparent once perioperative antibiotic prophylaxis was completed.

Antibiotic stewardship initiatives involving surgical and procedural interventions are an emerging and important field of study. There is inherent risk associated with prolonged antibiotic use, especially in hospitalized surgical oncology patients, ranging from Clostridioides difficile infection to creation of multidrug-resistant organisms. Finding the balance between maximizing prophylaxis benefit and minimizing antibiotic adverse events is paramount and is the focus of this study. In the inpatient setting, antibiotic stewardship initiatives improve clinical outcomes while reducing antimicrobial resistance, adverse events, hospital cost, and length of stay.

Historically, patients undergoing cystectomy and urinary diversion received extended courses of intravenous antibiotics given the notoriously high infectious complication rate. However, on the basis of studies from other clean-contaminated open abdominal surgical procedures, perioperative antibiotic practices for cystectomy now recommend a shorter perioperative antibiotic duration. In our practice, we adhere to American Urological Association (AUA) guidelines, which recommend single-dose cefazolin for cystectomy with small-bowel urinary diversion (alternative agents include single-dose clindamycin and aminoglycoside, second-generation cephalosporin, or aminopenicillin and β-lactamase inhibitor and metronidazole). These guidelines highlight an evidence-based approach to perioperative antibiotic utilization, because they consider recommendations from the National Surgical Infection Prevention Project, Centers for Disease Control and Prevention, and JAMA. Notably, the European Association of Urology makes no recommendations for specific agents or duration of perioperative antibiotics for cystectomy and leaves the decision to the clinician. Despite best practice statements and guidelines, perioperative antibiotic prophylaxis practices for cystectomy and urinary diversion remain highly heterogeneous. Thurnheer et al propose that this is due to the lack of high-quality randomized data to support optimal duration of antibiotic prophylaxis for cystectomy. Thus, this Swiss randomized clinical trial fills a large gap in the literature supporting the recommendation for shorter course prophylaxis.

One of the overarching goals of antibiotic stewardship initiatives is to strike the balance between preventing infection and de-escalating antibiotic coverage when safe to do so. Therefore, we would like to note the broad antibiotics used in this study. The authors selected a combination of tobramycin, metronidazole, and amoxicillin-clavulanate (with vancomycin instead of amoxicillin-clavulanate if patients were allergic to penicillin or β-lactam antibiotics). This combination of antibiotics provides high-level gram-negative and anaerobic coverage, dissimilar to the AUA guidelines. Given that a large proportion of surgical site infections are caused by gram-positive skin flora, it is unclear to what extent gram-negative coverage is required for surgical site prophylaxis. However, as the authors note, other infectious complications of cystectomy are caused by gram-negative or anaerobic bacteria. The authors of this study did not find a difference in febrile urinary tract infection rate, for example, when using the antibiotic prophylaxis regimen described above. Further randomized studies are needed to determine the extent of antimicrobial coverage needed to prevent surgical site infection vs other procedure-specific infectious complications, considering the risk of more devastating complications as the spectrum of antibiotics broadens.

A recent retrospective study of a prospectively maintained database of patients undergoing robotic-assisted radical cystectomy at a single institution compared AUA guideline recommendations of single-dose cephalosporin for perioperative antibiotic prophylaxis with a modified protocol based on the hospital's antibiogram (ampicillin-sulbactam, gentamicin, and fluconazole for 24 hours). The study found that patients who received the antibiogram-based prophylaxis protocol had significantly lower rates of urinary tract infection and wound infection at 30 days compared with those who received the single-dose cephalosporin. Unfortunately, the 2 groups received different durations of antibiotics, leaving the question of single-dose vs 24 hours of antibiotics unanswered. Regardless, this study supports a patient-specific and population-specific perioperative antibiotic prophylaxis protocol for cystectomy, which we believe may provide the best means of infection prevention while selecting the narrowest antibiotic coverage possible. As an extension of this, we hypothesize that a standardized preoperative urine culture-based prophylaxis protocol may also be useful in reducing urinary tract and wound infection.

Finally, we would like to make note of the authors' inclusion and focus on asymptomatic bacteriuria in this study. Asymptomatic bacteriuria is expected following urinary diversion. It is unclear why urine cultures were routinely obtained postoperatively. In addition, the authors state that although neither specified nor recommended by the protocol, antibiotic treatments for asymptomatic bacteriuria were prescribed at the discretion of the treating practitioner at their institution. There was no significant difference in rates of febrile urinary tract infection between the 24-hour and extended prophylaxis groups, despite the higher rate of asymptomatic bacteriuria in the 24-hour prophylaxis group. This further supports the well-established recommendation to refrain from treatment of asymptomatic bacteriuria. In our practice, we refrain from antibiotics unless there are clinical signs and symptoms of infection, which would most typically include fever, flank pain, and/or leukocytosis.

In summary, on the basis of current evidence, patients undergoing cystectomy with urinary diversion should receive perioperative antibiotic prophylaxis for 24 hours or less, because longer courses have not been shown to provide superior benefit and are associated with increasing adverse events. Overall, the study is informative and relevant, and the authors should be commended for successfully conducting a randomized trial in this space. One should note that routine postoperative urine cultures and treatment of asymptomatic bacteriuria are not recommended unless infectious signs and symptoms are present.

Corresponding Author: Peyton A. Skupin, MD, Department of Urology, Division of Health Services Research, University of Pittsburgh Medical Center, 3471 Fifth Ave, Ste 700, Pittsburgh, PA 15213 ([email protected]).

Conflict of Interest Disclosures: Dr Jacobs reported receiving grants from Shadyside Hospital Foundation during the conduct of the study. No other disclosures were reported.