MedPath

Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.

Phase 4
Completed
Conditions
Infection
Complication
Prostate Cancer
Interventions
Drug: Trimethoprim/Sulfamethoxazole
Drug: Pivmecillinam/augmentin
Registration Number
NCT03228108
Lead Sponsor
Radboud University Medical Center
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
1538
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Targeted antimicrobial prophylaxisCiprofloxacinMen 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.
Targeted antimicrobial prophylaxisTrimethoprim/SulfamethoxazoleMen 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.
Targeted antimicrobial prophylaxisPivmecillinam/augmentinMen 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.
Targeted antimicrobial prophylaxisFosfomycinMen 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.
Routine empirical prophylaxisCiprofloxacinCiprofloxacin 500 mg orally 2 hours before and 12 hours after transrectal prostate biopsy.
Primary Outcome Measures
NameTimeMethod
Any registered clinical infectious complication after prostate biopsywithin 7 days post-biopsy

Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis

Secondary Outcome Measures
NameTimeMethod
Cost of carewithin 30 days after prostate biopsy

Difference of costs between the intervention and the control group

Prevalence of ciprofloxacin-resistant gram negative bacilli in local rectal florarectal swabs are taken 14 days before biopsy

Assessed through microbiological rectal swab cultures

Positive microbiological resultswithin 7 and 30 days after prostate biopsy

Urine or blood culture results

Any registered clinical infectious complication after prostate biopsywithin 7 and 30 days after prostate biopsy

Urinary tract infection, pyelonephritis, sepsis, fever, acute prostatitis, acute epididymitis

Hospitalization after prostate biopsywithin 30 days after prostate biopsy

Any hospital admission, including ICU admission

Overall mortalitywithin 30 days after prostate biopsy

Mortality of any cause

Overall antibiotic use after prostate biopsywithin 30 days after prostate biopsy

Number of antibiotic prescriptions

Side effects of used antibioticswithin 30 days after prostate biopsy

All side effects mentioned in the Summary of Product Characteristics (SPC)

Trial Locations

Locations (11)

Zuyderland Hospital

🇳🇱

Sittard, Netherlands

Amphia Hospital

🇳🇱

Breda, Netherlands

Radboud University Medical Center

🇳🇱

Nijmegen, Netherlands

Jeroen Bosch Hospital

🇳🇱

's-Hertogenbosch, Netherlands

Catharina Hospital

🇳🇱

Eindhoven, Netherlands

Rijnstate

🇳🇱

Arnhem, Netherlands

Isala

🇳🇱

Zwolle, Netherlands

Bravis

🇳🇱

Roosendaal, Netherlands

Canisius Wilhelmina Hospital

🇳🇱

Nijmegen, Netherlands

Bernhoven Hospital

🇳🇱

Uden, Netherlands

Elisabeth Tweesteden Hospital

🇳🇱

Tilburg, Netherlands

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