ランダム化非盲検試験：経直腸的前立腺針生検の抗菌薬予防vsなし

Antibiotic prophylaxis versus no antibiotic prophylaxis in transperineal prostate biopsies (NORAPP): a randomised, open-label, non-inferiority trial

Lancet infectious diseases, 2022 

ポイント：

・高リスク群を除く患者555名で、経直腸的前立腺針生検の抗菌薬予防vsなしを評価

・ノルウェーの大学病院（Oslo University Hospital）でランダム化非盲検試験

・予防的抗菌薬では1名で感染(0.35%)、抗菌薬なしでは3名(1.1%)で感染

要約：

経直腸前立腺生検アプローチでは抗菌薬処方はゴールドスタンダードであり、感染率は5-7%。但し近年の報告で、抗菌薬なしで0.0-0.1%の報告あり。システミックレビューでも有効性は確認されず、欧州泌尿器科学会ガイドラインでは抗菌薬投与を推奨するもランダム化試験の必要性について記述

2019-2021でノルウェーの大学病院（Oslo University Hospital）でランダム化非盲検試験：経直腸的前立腺針生検の抗菌薬予防vsなし

除外：尿路感染症（1か月以内を含む）、免疫不全、尿道カテーテル留置、感染性心内膜炎高リスク、血栓性疾患歴、

予防的抗菌薬：Cefuroxime 

プライマリエンドポイントは2か月までの感染

792名が対象候補となり、555名でランダム化（279, 276）

予防的抗菌薬グループでは1名で感染(0.35%)、抗菌薬なしグループでは3名(1.1%)で感染

：低リスク群では予防的抗菌薬の有効性は高くないと論文中で記載

Background

The benefit of antibiotic prophylaxis is uncertain when performing transperineal prostate biopsies. Judicious use of antibiotics is required as antimicrobial resistance increases worldwide. We aimed to assess whether antibiotic prophylaxis can be omitted when performing transperineal prostate biopsies under local anaesthesia as an outpatient procedure.

Methods

In this randomised, open-label, non-inferiority trial, we aimed to enrol all patients with a suspicion of prostate cancer undergoing transperineal prostate biopsies at two hospitals in Norway and Germany. Patients with a high risk of infection or ongoing infection were excluded. Patients were randomised (1:1) to receive intramuscular (in Norway) or intravenous (in Germany) 1·5 g cefuroxime antibiotic prophylaxis or not. Follow-up assessments were done after 2 weeks and 2 months. The primary outcome was rate of sepsis or urinary tract infections requiring hospitalisation within 2 months. The secondary outcome was the rate of urinary tract infections not requiring hospitalisation. These outcomes were assessed in all eligible randomly allocated participants with a prespecified non-inferiority margin of 4%. Biopsies were performed using an MRI–transrectal ultrasound fusion transperineal technique under local anaesthesia. Patients with a positive MRI underwent 2–4 biopsies per target; in addition, 8–12 systematic biopsies were performed in biopsy naive and MRI-negative patients. This study is registered with ClinicalTrials.gov, NCT04146142.

Findings

Between Nov 11, 2019, and Feb 23, 2021, 792 patients were referred for biopsy, of whom 555 (70%) were randomly allocated to treatment groups. 277 (50%) patients received antibiotic prophylaxis and 276 (50%) did not; two (<1%) patients were excluded after randomisation because of unknown allergy to study drug. Sepsis or urinary tract infections requiring hospitalisation occurred in no patients given antibiotic prophylaxis (0%, 95% CI 0 to 1·37) or not given antibiotic prophylaxis (0%, 0 to 1·37; difference 0% [95% CI –1·37 to 1·37]). Urinary tract infections not requiring hospitalisation occurred in one patient given antibiotic prophylaxis (0·36%, 95% CI 0·01 to 2·00) and three patients not given antibiotic prophylaxis (1·09%, 0·37 to 3·15; difference 0·73% [95% CI –1·08 to 2·81]). The number needed to treat with antibiotic prophylaxis to avoid one infection was 137.

Interpretation

The non-inferiority margin of 4% was not exceeded, suggesting rates of infections were not higher in patients not receiving antibiotic prophylaxis before transperineal prostate biopsy than in those receiving it. Therefore, antibiotic prophylaxis might be omitted in this population.