Antibiotic Prophylaxis for Transrectal Prostate Biopsy
Article information
Abstract
Transrectal prostate biopsy (TRPB) is widely used for the diagnosis of prostate cancer but carries a clinically meaningful risk of infectious complications due to inoculation and translocation of rectal flora into the urinary tract and bloodstream. Antibiotic prophylaxis remains central to preventing febrile urinary tract infection and sepsis; however, increasing antimicrobial resistance—particularly fluoroquinolone-resistant Enterobacterales—has reduced the reliability of conventional empirical regimens in many regions. In this narrative review, we searched PubMed/MEDLINE, Embase, and Scopus for relevant literature published through February 2026 and synthesized current guideline positions and selected clinical evidence on prophylactic regimens, resistance-adapted regimen selection, and adjunctive measures for TRPB. Cumulative evidence indicates that the efficacy of fluoroquinolone monotherapy has significantly declined in regions with high-resistance prevalence. Alternative or augmented strategies (e.g., cephalosporin- or fosfomycin-based approaches) may reduce infectious complications in selected settings, although their performance appears context-dependent and may be accompanied by shifts in pathogen distribution. Rectal swab-guided targeted prophylaxis can individualize antibiotic selection; however, its effectiveness varies across studies because of methodological heterogeneity and imperfect prediction of clinical outcomes. Technique-based prevention, most notably transperineal biopsy, may reduce infectious risk while decreasing reliance on broad-spectrum prophylaxis. Taken together, infection prevention after prostate biopsy should be individualized according to local susceptibility patterns and patient-level risk while integrating antimicrobial stewardship and selecting adjunctive or technique-based measures when feasible.
HIGHLIGHTS
Rising antimicrobial resistance has reduced the reliability of conventional fluoroquinolone prophylaxis for transrectal prostate biopsy. Infection prevention should be individualized using local resistance patterns, patient risk, targeted or alternative regimens, and adjunctive rectal antisepsis. When feasible, transperineal biopsy offers a technique-based prevention that can reduce infectious risk and reliance on broad-spectrum antibiotics.
INTRODUCTION
Prostate biopsy remains essential for histologic confirmation of prostate cancer. Transrectal prostate biopsy (TRPB) has been widely adopted because it is technically straightforward and cost-effective, but traversal of the rectal mucosa introduces a persistent risk of infectious complications, ranging from asymptomatic bacteriuria to febrile urinary tract infection (UTI) and life-threatening sepsis [1,2]. Antibiotic prophylaxis is therefore routinely used; however, rising antimicrobial resistance—particularly fluoroquinolone-resistant Escherichia coli and other Enterobacterales—has increasingly undermined the effectiveness of traditional empirical regimens [3,4]. In parallel, targeted prophylaxis guided by rectal cultures, adjunctive rectal antisepsis, and alternative biopsy techniques such as transperineal biopsy (TPB) have emerged as strategies to reduce infections while limiting unnecessary broad-spectrum antibiotic exposure [5,6]. This review summarizes (1) the epidemiology and clinical spectrum of post-TRPB infections, (2) evidence for commonly used and resistance-adapted prophylactic regimens, and (3) targeted, adjunctive, and technique-based approaches to minimize infectious complications in the era of increasing antimicrobial resistance.
We performed a targeted search of PubMed/MEDLINE, Embase, and Scopus for studies published through February 2026 using combinations of keywords related to TRPB, antibiotic prophylaxis, and postbiopsy infection. We prioritized clinical guidelines, randomized trials, systematic reviews/meta-analyses, and representative observational studies reporting infectious outcomes and resistance-adapted strategies. Evidence was selected to reflect heterogeneity across resistance ecologies and practice settings, with interpretation focused on clinical applicability and antimicrobial stewardship. Reference lists of key guidelines and landmark randomized trials were reviewed to identify additional relevant studies.
INFECTIOUS COMPLICATIONS AFTER TRPB
1. Spectrum, Incidence, and Pathogenesis
Infectious complications after TRPB span asymptomatic bacteriuria, febrile UTI, prostatitis, bacteremia, and sepsis [1,2]. Because bacterial inoculation occurs during needle passage through the rectal wall, the pathogenesis is closely linked to transfer of rectal flora into the prostate, urinary tract, and bloodstream. E. coli remains the most frequently isolated pathogen, although other gram-negative organisms and polymicrobial infections are increasingly reported in some regions [2].
2. Resistance Trends and Clinical Implications
Fluoroquinolones have historically been favored for prophylaxis because of oral bioavailability and prostatic penetration, but the emergence and spread of fluoroquinolone-resistant E. coli have reduced the effectiveness of conventional fluoroquinolone-based prophylaxis [3]. High background resistance, including extended-spectrum beta-lactamase (ESBL) production in some settings, further complicates empirical regimen selection and is associated with higher rates of postbiopsy infection and sepsis [4].
PRINCIPLES OF ANTIBIOTIC PROPHYLAXIS
1. Goals and Stewardship Considerations
Professional society guidelines (e.g., the American Urological Association and European Association of Urology) recommend prophylaxis for TRPB and emphasize risk-adapted selection aligned with local resistance patterns and antimicrobial stewardship [5,7].
The primary goal of prophylaxis is to reduce the bacterial burden of rectal flora and prevent bacterial translocation during biopsy while minimizing adverse effects and selective pressure for resistance. Optimal regimens provide effective coverage against likely pathogens—especially E. coli—achieve adequate exposure at the time of biopsy, and avoid unnecessarily broad spectrum or prolonged duration [2,5].
2. Pharmacokinetic and Timing Considerations
Prophylactic success depends on aligning dosing with pharmacokinetic and pharmacodynamic properties so that peak tissue and serum concentrations coincide with the biopsy procedure [1,2]. Intravenous agents (e.g., third-generation cephalosporins, aminoglycosides) provide predictable early systemic exposure, whereas oral agents require sufficient lead time to ensure adequate concentrations. In the setting of resistance, optimizing exposure is necessary but may not overcome pharmacodynamic failure when organisms are nonsusceptible [5].
COMMON PROPHYLACTIC REGIMENS
1. Fluoroquinolones
Ciprofloxacin (CIP) and levofloxacin have been widely used as monotherapy, but rising resistance has diminished their reliability as empirical prophylaxis in many regions [3,5]. Where local resistance prevalence is high, guidelines increasingly discourage routine fluoroquinolone monotherapy and favor resistance-adapted or alternative strategies [5].
2. Cephalosporins
Third-generation cephalosporins such as ceftriaxone are commonly used either alone or as part of augmented regimens to broaden coverage against fluoroquinolone-resistant organisms [1,2]. Although some centers extend prophylaxis beyond a single periprocedural dose in high-risk settings, prolonged courses may increase selective pressure; therefore, duration should be minimized whenever adequate protection can be achieved with shorter regimens [5].
3. Aminoglycoside Augmentation
Single-dose aminoglycosides (e.g., gentamicin or amikacin) are sometimes added to fluoroquinolones to enhance activity against resistant gram-negative organisms. However, evidence from Asian settings with high fluoroquinolone resistance suggests that incremental benefit may be limited: a Korean multicenter trial found no significant reduction in infectious complications with amikacin plus CIP compared with CIP alone, and a Japanese randomized trial similarly reported no advantage of adding amikacin to levofloxacin prophylaxis [8,9]. Potential explanations include limited tissue penetration and timing or exposure mismatches during the brief window of bacterial translocation. In contrast, observational studies have reported reductions in postbiopsy infection and septicemia after the addition of amikacin to fluoroquinolone-based prophylaxis [10,11]. These conflicting findings suggest that the effectiveness of aminoglycoside augmentation may depend on study design, local resistance patterns, dosing, and timing of administration.
4. Fosfomycin-Based Strategies
Fosfomycin (FOS) has been evaluated as an alternative or augmented prophylactic option because of activity against multidrug-resistant (MDR) E. coli and convenient oral dosing [12,13]. A systematic review and meta-analysis reported lower postbiopsy infection rates with FOS-based prophylaxis compared with fluoroquinolone-only regimens [14]. Observational data from Korea and Canada suggest that FOS augmentation (e.g., CIP plus FOS) may reduce infectious complications in settings with high fluoroquinolone resistance [15-17]. Nevertheless, effectiveness appears context-dependent, and pathogen shifts toward non–E. coli gram-negative organisms such as Klebsiella species have been reported in some cohorts, underscoring the need to consider local epidemiology when adopting FOS-based strategies [15]. In the Korean multicenter cohort, culture-confirmed breakthrough infections after FOS monotherapy frequently involved non–E. coli gram-negative organisms, with multiple Klebsiella spp. isolates reported among infected cases [16]. Practical interpretation is therefore regimen-and ecology-specific: if baseline fluoroquinolone (FQ) resistance is high and local postbiopsy infections are dominated by CIP-resistant E. coli, CIP/FOS augmentation is a reasonable stewardship-conscious option; if local breakthrough infections show increasing non–E. coli gram-negative pathogens (e.g., Klebsiella spp.), FOS monotherapy should be used cautiously and protocols should be revised based on pathogen-specific surveillance.
TARGETED AND ADJUNCTIVE APPROACHES
1. Rectal Swab-Guided Targeted Prophylaxis
Prebiopsy rectal swab cultures can identify colonization with fluoroquinolone-resistant organisms and enable individualized antibiotic selection. Some studies have reported reduced infectious complications with targeted prophylaxis [18], whereas others have shown inconsistent benefit compared with empirical strategies, particularly in settings with high multidrug resistance [19]. Limitations include lack of standardized sampling and culture methods, incomplete representation of the rectal microbiome, and residual infections despite in vitro susceptibility, likely reflecting host factors, inoculum effects, and exposure dynamics. In routine practice, implementation is further constrained by laboratory turnaround time, coordination with biopsy scheduling, and incremental costs of culture and susceptibility testing; therefore, targeted prophylaxis may be most useful when applied selectively to high-risk patients or in centers with established prebiopsy workflows and microbiology support.
2. Rectal Antisepsis and Other Nonantibiotic Measures
Adjunctive rectal preparation aims to reduce bacterial load at the biopsy site without adding antibiotic selective pressure. Rectal cleansing with povidone-iodine has been associated with lower infectious complications when used with standard prophylaxis and is particularly attractive in regions with high fluoroquinolone resistance [4,20]. Japanese perioperative infection guidance also endorses tailored prophylaxis and rectal preparation in selected settings [21]. Evidence for probiotics remains limited and insufficient to recommend routine use for TRPB infection prevention [2].
TECHNIQUE-BASED PREVENTION: TRANSPERINEAL BIOPSY
TPB avoids traversal of the rectal mucosa and therefore markedly reduces exposure to rectal flora. Randomized trials have shown comparable cancer detection between TPB and TRPB, while infection outcomes have ranged from significantly lower rates with TPB to no significant between-group difference [6,22-24]. Reflecting these data, European guidance increasingly favors TPB when feasible as a strategy that can reduce reliance on broad-spectrum prophylaxis in the resistance era [5,25]. Barriers to widespread adoption include training, equipment, and anesthesia requirements, although advances in local anesthesia techniques have improved outpatient feasibility [2].
Recent randomized trials provide contemporary direct comparisons of TPB versus TRPB. In PREVENT, TPB performed without prophylactic antibiotics resulted in 0 of 372 (0%) infections versus 6 of 370 (1.6%) with TRPB using rectal culture-guided prophylaxis (difference, -1.6%; 95% confidence interval [CI], -3.5 to -0.3; p=0.02) [6]. In ProBE-PC, 30-day composite infectious complications were similar between arms (2.6% TRPB vs. 2.7% TPB; odds ratio, 1.06; 95% CI, 0.43–2.65; p=0.99), with no sepsis reported in either group [22]. The magnetic resonance imaging-targeted PERFECT trial likewise reported no significant differences in grade ≥2 adverse events (35.7% TP vs. 40.5% TR, p=0.426) and documented one grade 3 sepsis event in the TR arm (0.8%) [26]. Collectively, these trials support TPB as a technique-based option to reduce infectious risk and reliance on broader prophylaxis, while underscoring that event rates and endpoint definitions vary across studies (Table 1).
Key randomized trials comparing transperineal and transrectal biopsy routes and infectious outcomes
PRACTICAL RECOMMENDATIONS FOR INFECTION PREVENTION
A pragmatic approach is to stratify patients and choose prophylaxis based on (1) local resistance prevalence, (2) individual risk factors (e.g., recent fluoroquinolone exposure, prior postbiopsy infection, recent hospitalization, long-term care facility (LTC) residence, indwelling catheter, immunosuppression), and (3) procedural feasibility of a technique-based option. When a TPB is feasible, it can be considered to minimize infection risk and broad-spectrum antibiotic exposure. If a transrectal approach is used, consider rectal povidone- iodine preparation and select an empirical or targeted regimen aligned with local susceptibility data; reserve augmented or alternative regimens (e.g., cephalosporin- or FOS-based strategies) for high-risk patients or settings with high fluoroquinolone resistance. Antibiotic duration should be minimized to the shortest effective periprocedural course to support antimicrobial stewardship. An overview of a practical, risk-adapted workflow is provided in Fig. 1.
Practical algorithm to reduce infectious complications after prostate biopsy. TP, transperineal; TR, transrectal; UTI, urinary tract infection; LTC, long-term care facility; MDR, multidrug-resistant; ESBL, extended-spectrum beta-lactamase; FQ, fluoroquinolone.
(1) Consider TPB when feasible; otherwise use transrectal biopsy with a prevention bundle (e.g., rectal antisepsis and optimized prophylaxis).
(2) Use culture-guided targeted prophylaxis selectively when logistics allow and resistance prevalence is high.
(3) Tailor empirical regimens to local ecology; avoid routine prolonged courses and reassess institutional protocols periodically.
Representative supporting evidence is summarized in Table 2.
Key evidence by strategy to reduce infectious complications after prostate biopsy
Clinical recommendations (pragmatic, ecology-aware)
• Low-risk patients in low-resistance settings: single-dose, narrowest effective prophylaxis; avoid extended courses.
• High baseline fluoroquinolone resistance or prior antibiotic exposure: avoid routine FQ monotherapy; consider augmented regimens (e.g., CIP/FOS) or non‑FQ pathways aligned with local antibiograms.
• High-risk patients (recent hospitalization/LTC, catheter, immunosuppression, prior postbiopsy infection, known MDR/ESBL): prioritize targeted prophylaxis (rectal swab-guided) when feasible and add adjunctive rectal antisepsis for TRPB workflows.
• Where TPB is feasible: consider TPB as a technique-based strategy to reduce infection risk and dependence on escalating prophylaxis; tailor antibiotics per institutional policy and patient risk.
• Track outcomes and pathogen distribution: routinely audit postbiopsy infections (severity, pathogens, resistance) and update local protocols accordingly.
LIMITATIONS OF THE EVIDENCE
First, infectious endpoints vary across studies (definitions, severity thresholds, and follow-up windows), limiting direct comparison of absolute event rates. Second, prophylaxis protocols in comparator arms differ (drug choice, timing, duration, and cointerventions such as rectal antisepsis), introducing clinical heterogeneity. Third, many antibiotic-regimen studies are observational and may be confounded by center practice changes over time, baseline risk, and admission thresholds. Fourth, severe outcomes such as sepsis are rare; several trials may be underpowered for high-grade infection endpoints. Finally, effectiveness is ecology-dependent—local resistance prevalence and pathogen distribution may limit generalizability across regions and healthcare systems.
CONCLUSION
Infectious complications after TRPB remain clinically significant, and increasing antimicrobial resistance has reduced the reliability of traditional empirical prophylaxis in many regions. A practical near-term approach is risk-adapted prophylaxis that incorporates local susceptibility patterns and selective use of adjunctive measures (e.g., povidone-iodine rectal cleansing) while minimizing unnecessary spectrum and duration. In the longer term, technique-based prevention and workflow changes—including TPB where feasible—may further reduce infectious risk and may help limit escalation to broader prophylactic regimens.
Notes
Funding/Support
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conflict of Interest
The authors have nothing to disclose.
Author Contribution
Conceptualization: SIJ, DGL; Data curation: DGL; Methodology: SIJ, DGL; Project administration: SIJ; Visualization: DGL; Writing-original draft: DGL; Writing review & editing: SIJ, DGL.