Culture-guided Antimicrobial Prophylaxis in Men Undergoing Prostate Biopsy.

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Complication, Infection, Prostate Cancer

Intervention / Treatment
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* Drug: Ciprofloxacin
* Drug: Trimethoprim/Sulfamethoxazole
* Drug: Fosfomycin
* Drug: Pivmecillinam/augmentin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Culture-guided, Targeted prophylaxis, Prostate biopsy, Antibiotic prophylaxis