Clinical trial NCT03228108: Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.
Official title: The Effect of Rectal Swab Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy on Infectious Complications and Cost of Care: A Randomized Controlled Trial in the Netherlands.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Complication
Infection
Prostate Cancer
Keywords: Culture-guided
Targeted prophylaxis
Prostate biopsy
Antibiotic prophylaxis
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: ZonMw: The Netherlands Organisation for Health Research and Development
First posted: 2017-07-24
Enrollment: 1538
Sex: MALE
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study aims to assess the effectiveness and cost-effectiveness of rectal swab culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Half of participants will receive routine empirical prophylaxis with oral ciprofloxacin (control group), while the other half will receive rectal culture-guided oral antibiotic prophylaxis (intervention group). In the intervention group, men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prophylaxis, comparable to the control group. In case of ciprofloxacin-resistant bacteria an alternative oral antibiotic based on the culture results will be prescribed (trimethoprim/sulfamethoxazole, fosfomycin or pivmecillinam/augmentin).

The investigators hypothesise that the targeted prophylaxis group (intervention group) will have a lower rate of post-biopsy infectious complications compared to the control group.

Detailed description: Several classes of antibiotics are proven effective for prophylaxis during transrectal prostate biopsy, reducing infectious complications to less than 1% in case of susceptible rectal flora. Ciprofloxacin has been best studied and is recommended as first choice prophylaxis in urology guidelines. However, due to increasing fluoroquinolone resistance in gram negative bacilli (currently more than 20% in E.coli), a significant increase up to 6% in infectious complications after transrectal prostate biopsy was recently noticed. Antibiotic treatment of these infections and hospitalization may account for increased health care associated costs and will contribute to the further development of antibiotic resistance.

Besides, in urology guidelines no clear recommendations are made on the duration of prophylaxis. In the Netherlands, therefore, various prophylactic ciprofloxacin schedules are used, of which 2 to 3 day regimens are most common. Prolonged duration of prophylaxis during prostate biopsy is not proven to be more effective than a 1-day regimen, but it is more likely to select more fluoroquinolone (FQ) resistance.

This study aims to assess the effectiveness and cost-effectiveness of rectal culture-guided antimicrobial prophylaxis to reduce infectious complications after transrectal prostate biopsy. Also, duration of antibiotic prophylaxis will be minimized to 24 hours, thereby controlling further development of resistant bacteria.

The culture method used in this study with four phenotypic screening agars to support the choice of one of the oral prophylactic antibiotics is innovative. Culture results become available rapidly, within 48 hours, the method is simple, relatively inexpensive, as it does not need full susceptibility testing of separate colonies, and useful in daily practice.

Eligibility criteria: Inclusion Criteria:

* Subject is able and willing to sign the Informed Consent Form.
* Subject undergoes a transrectal prostate biopsy as part of the standard care in the Radboudumc (Nijmegen), Canisius Wilhelmina hospital (Nijmegen) or Catharina hospital (Nijmegen) (because of suspicion of prostate cancer).

Exclusion Criteria:

* Inability to receive ciprofloxacin (e.g. documented history of sensitivity to medicinal products or excipients similar to those found in the antibiotic prophylaxis, relevant history or presence of cardiovascular disorders)
* Inability to receive either co-trimoxazole, fosfomycin and pivmecillinam/augmentin prophylaxis for any reason (e.g. documented history of sensitivity to medicinal products or excipients similar to those found in the antibiotic prophylaxis)
* Inability to understand the nature of the trial and the procedures required.
* Individuals with an urinary tract infection or acute prostatitis within 14 days prior to intervention.
* Individuals who receive antibiotics within 14 days before prostate biopsy.
* Individuals who fail to send a rectum swab to the microbiology laboratory.
* Individuals whose rectal swab shows no growth on a (growth) control MacConkey agar without antibiotics.

Primary outcomes:
measure: Any registered clinical infectious complication after prostate biopsy
timeFrame: within 7 days post-biopsy
Secondary outcomes:
measure: Cost of care
timeFrame: within 30 days after prostate biopsy
measure: Positive microbiological results
timeFrame: within 7 and 30 days after prostate biopsy
measure: Any registered clinical infectious complication after prostate biopsy
timeFrame: within 7 and 30 days after prostate biopsy
measure: Hospitalization after prostate biopsy
timeFrame: within 30 days after prostate biopsy
measure: Overall mortality
timeFrame: within 30 days after prostate biopsy
measure: Side effects of used antibiotics
timeFrame: within 30 days after prostate biopsy
measure: Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora
timeFrame: rectal swabs are taken 14 days before biopsy
measure: Overall antibiotic use after prostate biopsy
timeFrame: within 30 days after prostate biopsy
Other outcomes:
Locations:
city: 's-Hertogenbosch
country: Netherlands
facility: Jeroen Bosch Hospital
city: Arnhem
country: Netherlands
facility: Rijnstate
city: Bergen Op Zoom
country: Netherlands
facility: Bravis
city: Breda
country: Netherlands
facility: Amphia Hospital
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Heerlen
country: Netherlands
facility: Zuyderland Hospital
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Hospital
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
city: Roosendaal
country: Netherlands
facility: Bravis
city: Sittard
country: Netherlands
facility: Zuyderland Hospital
city: Tilburg
country: Netherlands
facility: Elisabeth Tweesteden Hospital
city: Uden
country: Netherlands
facility: Bernhoven Hospital
city: Zwolle
country: Netherlands
facility: Isala
Study officials:
affiliation: Radboud University Medical Center
name: Heiman Wertheim, Prof. dr.
role: STUDY_DIRECTOR
References: