By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
SYNOPSIS: A randomized clinical trial found a similar rate of infection between patients given antibiotics for transperineal prostate biopsy compared to those not given antibiotics. It may be possible to omit antibiotics in certain patients undergoing transperineal prostate biopsy.
SOURCE: Jacewicz M, Günzel K, Rud E, et al. Antibiotic prophylaxis versus no antibiotic prophylaxis in transperineal prostate biopsies (NORAPP): A randomised, open-label, non-inferiority trial. Lancet Infect Dis 2022;22:1465-1471.
The incidence of prostate cancer is increasing worldwide, along with a corresponding number of prostate biopsies. Urologists have two methods for performing prostate biopsies: transrectal and transperineal. Transrectal is the more traditional and common approach, although transperineal (which has a lower risk of infection, a similar cancer detection rate, and can be done under local anesthetic in outpatient settings) has been gaining popularity. After primary care physicians, urologists are the second largest group of physician prescribers of antibiotics in the United States. Jacewicz and colleagues sought to determine whether antibiotic prophylaxis can be omitted in patients undergoing transperineal biopsy.
The study was a randomized, open-label, noninferiority trial with patients referred for a prostate biopsy at two medical centers in Norway and Germany from November 2019 to February 2021. Inclusion criteria were elevated or increasing prostate specific antigen (PSA), patients with prostate cancer under active surveillance, an abnormal rectal examination, suspicion of recurrent cancer following radiation treatment, or follow-up biopsy after ultrasound treatment. Patients were excluded who had an active urinary tract infection (UTI) or were diagnosed with one in the preceding month, had an indwelling urinary catheter, were immunodeficient, had a high risk for infective endocarditis (IE), or had a history of thromboembolic disease. All of these conditions were considered to be high-risk for post-biopsy infection.
Patients were randomized 1:1 to receive a single dose of intramuscular (IM) or intravenous (IV) cefuroxime 1.5 g 30 minutes before the biopsy (control group) or no prophylaxis (experimental group). The perineal skin was sterilized using swabs soaked in chlorhexidine, followed by approximately 20 mL of local anesthesia. Target biopsies of the prostate then were obtained by freehand technique using an ultrasound probe for guidance. The primary outcome of the study was the difference in the rate of urosepsis or UTI requiring hospitalization up to two months following biopsy between the experimental and control groups. The study needed at least 516 patients to be enrolled to be 90% sure that the upper limit of a one-sided 97.5% confidence interval (CI) would show the rate of infections in patients not receiving antibiotic therapy would be no more than 4% worse than patients treated with antibiotic prophylaxis.
There were 555 patients randomized in the study: 277 to the control group and 276 to the experimental group. The median number of biopsies per patient was 10. The rate of urosepsis or UTIs requiring hospitalization was 0% (0 out of 277 patients; 95% CI, 0 to 1.37) in the control group and 0% (0 out of 276 patients; 95% CI, 0 to 1.37) in the experimental group. The rate of UTIs not requiring hospitalization was 0.36% (1 out of 277; 95% CI, 0.01 to 2.00) in the control group and 1.09% (3 out of 276; 95% CI, 0.37 to 3.15) in the experimental group. Infections occurred seven to 21 days after biopsy and all were treated with oral antibiotics in an outpatient setting. Urinary culture results were reported for two patients: one grew Escherichia coli and the other grew Citrobacter freundii.
COMMENTARY
Overprescribing antibiotics is the biggest promoter of antimicrobial resistance (AMR) worldwide. Thus, reducing antibiotic prescribing would have major societal and public health benefits. The study by Jacewicz and colleagues is important because it provides evidence that patients at low risk for infection do not need antibiotic prophylaxis when undergoing transperineal prostate biopsy. The threshold for determining what constitutes increased risk needs further elucidation, along with risk factors for developing infection following transperineal biopsy. Indeed, there is no valid scientific evidence for omitting antibiotic prophylaxis in high-risk patients.
Of the four patients in the study who developed an infection, one used intermittent transurethral catheterization and was treated for a UTI shortly before the biopsy. Therefore, he should not have been included in the study because of his high risk for infection.
Despite the robust study design, there were a couple of limitations worth mentioning. First, the study was conducted in two European countries, so the results might not be generalizable to other geographic areas or patient populations. Second, 30% (237/792) of the patients referred for biopsy were not included before randomization, mainly because they were high risk for infection or were unwilling to participate. How or if this high exclusion rate affected the results is unknown. Finally, given the extremely low rate of infection in the study, it might have been more appropriate to have chosen the non-inferiority rate between the two groups to be closer to zero rather than 4%. However, having a lower non-inferiority rate would have required a much larger sample size, so this criticism must be balanced against pragmatic concerns regarding study design.
Are the results of the study by Jacewicz and colleagues enough to change clinical practice? Previous observation studies also have found a low rate of infectious complications after transperineal biopsy when antibiotics were withheld. Thus, it seems reasonable to conclude that continued use of antibiotic prophylaxis in patients at low risk of infection following transperineal biopsy likely will lead to more harm than good.
