Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy. (pro-SWAP)

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.

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.

Study Overview

• Status: Completed
• Conditions: Prostate Cancer; Infection; Complication
• Intervention / Treatment: Drug: Ciprofloxacin; Drug: Trimethoprim/Sulfamethoxazole; Drug: Fosfomycin; Drug: Pivmecillinam/augmentin

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.

• Study Type: Interventional
• Enrollment (Actual): 1538
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • 's-Hertogenbosch, Netherlands
    • Jeroen Bosch Hospital
  • Arnhem, Netherlands
    • Rijnstate
  • Bergen Op Zoom, Netherlands
    • Bravis
  • Breda, Netherlands
    • Amphia Hospital
  • Eindhoven, Netherlands
    • Catharina Hospital
  • Heerlen, Netherlands
    • Zuyderland hospital
  • Nijmegen, Netherlands
    • Radboud University Medical Center
  • Nijmegen, Netherlands
    • Canisius Wilhelmina Hospital
  • Roosendaal, Netherlands
    • Bravis
  • Sittard, Netherlands
    • Zuyderland hospital
  • Tilburg, Netherlands
    • Elisabeth Tweesteden Hospital
  • Uden, Netherlands
    • Bernhoven Hospital
  • Zwolle, Netherlands
    • Isala

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Targeted antimicrobial prophylaxis; 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.	Drug: Ciprofloxacin; see study arms.; Other Names: Ciproxin; Drug: Trimethoprim/Sulfamethoxazole; see study arms.; Other Names: Co-trimoxazole; Drug: Fosfomycin; see study arms.; Other Names: Monuril; Drug: Pivmecillinam/augmentin; see study arms.; Other Names: Selexid; Amoxicillin/clavulanic acid
Active Comparator: Routine empirical prophylaxis; Ciprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy.	Drug: Ciprofloxacin; see study arms.; Other Names: Ciproxin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Any registered clinical infectious complication after prostate biopsy	Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis	within 7 days post-biopsy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cost of care	Difference of costs between the intervention and the control group	within 30 days after prostate biopsy
Positive microbiological results	Urine or blood culture results	within 7 and 30 days after prostate biopsy
Any registered clinical infectious complication after prostate biopsy	Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis	within 7 and 30 days after prostate biopsy
Hospitalization after prostate biopsy	Any hospital admission, including ICU admission	within 30 days after prostate biopsy
Overall mortality	Mortality of any cause	within 30 days after prostate biopsy
Side effects of used antibiotics	All side effects mentioned in the Summary of Product Characteristics (SPC)	within 30 days after prostate biopsy
Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal flora	Assessed through microbiological rectal swab cultures	rectal swabs are taken 14 days before biopsy
Overall antibiotic use after prostate biopsy	Number of antibiotic prescriptions	within 30 days after prostate biopsy

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: ZonMw: The Netherlands Organisation for Health Research and Development
• Investigators: Study Director: Heiman Wertheim, Prof. dr., Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2018
• Primary Completion (Actual): September 26, 2021
• Study Completion (Actual): September 26, 2021

Study Registration Dates

• First Submitted: July 18, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (Actual): July 24, 2017

Study Record Updates

• Last Update Posted (Actual): May 10, 2022
• Last Update Submitted That Met QC Criteria: May 9, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: Antibiotic prophylaxis; Prostate biopsy; Culture-guided; Targeted prophylaxis
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Cytochrome P-450 CYP1A2 Inhibitors; beta-Lactamase Inhibitors; Anti-Dyskinesia Agents; Anti-Infective Agents, Urinary; Renal Agents; Cytochrome P-450 CYP2C8 Inhibitors; Ciprofloxacin; Amoxicillin; Trimethoprim; Sulfamethoxazole; Trimethoprim, Sulfamethoxazole Drug Combination; Clavulanic Acid; Clavulanic Acids; Amoxicillin-Potassium Clavulanate Combination; Fosfomycin; Amdinocillin Pivoxil
• Other Study ID Numbers: pro-SWAP104622

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No