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.

Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.

Sponsors

Lead sponsor: Radboud University

Collaborator: ZonMw: The Netherlands Organisation for Health Research and Development

Source Radboud University
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.

Overall Status Recruiting
Start Date April 3, 2018
Completion Date February 2021
Primary Completion Date November 2020
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Any registered clinical infectious complication after prostate biopsy within 7 days post-biopsy
Secondary Outcome
Measure Time Frame
Cost of care within 30 days after prostate biopsy
Positive microbiological results within 7 and 30 days after prostate biopsy
Any registered clinical infectious complication after prostate biopsy within 7 and 30 days after prostate biopsy
Hospitalization after prostate biopsy within 30 days after prostate biopsy
Overall mortality within 30 days after prostate biopsy
Side effects of used antibiotics within 30 days after prostate biopsy
Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora rectal swabs are taken 14 days before biopsy
Overall antibiotic use after prostate biopsy within 30 days after prostate biopsy
Enrollment 1618
Condition
Intervention

Intervention type: Drug

Intervention name: Ciprofloxacin

Description: see study arms.

Other name: Ciproxin

Intervention type: Drug

Intervention name: Trimethoprim/Sulfamethoxazole

Description: see study arms.

Arm group label: Targeted antimicrobial prophylaxis

Other name: Co-trimoxazole

Intervention type: Drug

Intervention name: Fosfomycin

Description: see study arms.

Arm group label: Targeted antimicrobial prophylaxis

Other name: Monuril

Intervention type: Drug

Intervention name: Pivmecillinam/augmentin

Description: see study arms.

Arm group label: Targeted antimicrobial prophylaxis

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.

Gender: Male

Gender based: Yes

Minimum age: 18 Years

Maximum age: 90 Years

Healthy volunteers: No

Overall Official
Last Name Role Affiliation
Heiman Wertheim, Prof. dr. Study Director Radboud University
Overall Contact

Last name: Eva Kolwijck, Dr.

Phone: +31243614356

Email: [email protected]

Location
facility status contact investigator
Jeroen Bosch Hospital | 's-Hertogenbosch, Netherlands Recruiting Paul Veenboer, Dr. Rob Schipper, Dr. Principal Investigator
Rijnstate | Arnhem, Netherlands Not yet recruiting Michael van Balke, Dr.
Bravis | Bergen Op Zoom, Netherlands Not yet recruiting Sander van Leeuwen, Dr.
Amphia Hospital | Breda, Netherlands Not yet recruiting Deric van der Schoot, Dr.
Catharina Hospital | Eindhoven, Netherlands Recruiting Evert Koldewijn, Dr.
Zuyderland Hospital | Heerlen, Netherlands Recruiting Filip Delaere, Dr.
Canisius Wilhelmina Hospital | Nijmegen, Netherlands Recruiting Rik Somford, Dr.
Radboud University Medical Center | Nijmegen, Netherlands Recruiting Eva Kolwijck, Dr. +31243614356 [email protected] Michiel Sedelaar Principal Investigator
Bravis | Roosendaal, Netherlands Not yet recruiting Sander van Leeuwen, Dr.
Zuyderland Hospital | Sittard, Netherlands Recruiting Filip Delaere, Dr.
Elisabeth Tweesteden Hospital | Tilburg, Netherlands Recruiting Anton Breeuwsma, Dr.
Bernhoven Hospital | Uden, Netherlands Recruiting Thijn de Vocht, Dr.
Isala | Zwolle, Netherlands Recruiting Martijn Steffens, Dr.
Location Countries

Netherlands

Verification Date

September 2019

Responsible Party

Responsible party type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Arm group label: Targeted antimicrobial prophylaxis

Arm group type: Experimental

Description: Men whose rectal swabs do not show ciprofloxacin-resistant bacteria will receive ciprofloxacin prior to biopsy (equal to the active comparator arm), and men whose swabs do show ciprofloxacin-resistant bacteria will receive alternative oral antibiotics, based on culture results, in the following order: trimethoprim/sulfamethoxazole (SXT) 960 mg orally 2 hours before and 12 hours after prostate biopsy, or fosfomycin 3 g orally 2 hours before prostate biopsy, or pivmecillinam/augmentin respectively 400 mg and 500/125 mg 2 hours before prostate biopsy followed by 2 days with three divided doses each day after prostate biopsy.

Arm group label: Routine empirical prophylaxis

Arm group type: Active Comparator

Description: Ciprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy.

Acronym pro-SWAP
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Primary purpose: Prevention

Masking: None (Open Label)

Source: ClinicalTrials.gov