Infectious complications after transrectal prostate biopsy in Algeria: A prospective study in a high-resistance setting

Abstract

Background

The aim of this study was to assess infectious outcomes and safety of fosfomycin trometamol compared with ciprofloxacin for the prevention of infectious complications following transrectal ultrasound–guided prostate biopsy (TRPB) in a local setting characterized by high fluoroquinolone resistance.

Material and methods

This prospective single-center cohort study included 423 consecutive patients undergoing TRPB between February 2023 and December 2025. An initial comparative phase involved 200 patients receiving either ciprofloxacin (n=83) or fosfomycin trometamol (n=117). Fosfomycin was subsequently adopted as the standard prophylactic regimen in an additional 223 patients. Infectious complications occurring within 30 days were recorded. A univariate analysis was performed to explore factors associated with infectious complications.

Results

The overall rate of infectious complications was 8.3% (35/423), mainly transient isolated fever (5.2%). Five patients (1.2%) required hospitalization for acute prostatitis. No statistically significant association with infectious complications was observed in the univariate analysis. In the initial comparative phase, no significant difference was observed between ciprofloxacin and fosfomycin regarding infectious outcomes.

Conclusions

In a context of high fluoroquinolone resistance, single-dose fosfomycin trometamol may represent a pragmatic prophylactic option, although comparative efficacy cannot be concluded from the present design.

Level of Evidence

Level 2.

1. Introduction

Prostate cancer is the second most frequently diagnosed malignancy in men worldwide and represents a major cause of cancer-related mortality. In 2022, nearly 1.5 million new cases were reported, with approximately 396,000 deaths worldwide.¹ In Algeria, its incidence has steadily increased over recent years; it represents the most common urological cancer and one of the most frequent cancers in men, accounting for approximately 12% of all diagnosed cancers.²

Transrectal ultrasound–guided prostate biopsy (TRPB) remains, in many countries, the most widely used technique to confirm the diagnosis. However, this approach is associated with a non-negligible risk of infectious complications, which may be severe. Despite the systematic use of antibiotic prophylaxis,^3,4 clinically significant infections are still reported, with an incidence ranging from 1% to 7.6%, including severe presentations such as acute prostatitis and sepsis.^{5, 6, 7}

Recent guidelines such as those of the European Association of Urology (EAU), as well as recent literature,^{8, 9, 10} favor the transperineal approach, for which routine antibiotic prophylaxis is generally not recommended because of the low risk of infection. Nevertheless, TRPB remains widely performed in our setting, making the issue of antibiotic prophylaxis still highly relevant.

Fluoroquinolones, particularly ciprofloxacin, have long been considered the reference prophylactic regimen. However, the emergence of bacterial resistance, especially among Escherichia coli, has significantly limited their current effectiveness. According to the Algerian Network for Antimicrobial Resistance Surveillance (20th report, 2019; updated in 2021), resistance rates of E. coli to ciprofloxacin reach 27.29% among hospitalized patients and 22.84% among outpatients. In contrast, resistance rates to fosfomycin in the same population remain considerably lower, at 2.55% and 2.18%, respectively.¹¹

In this context, fosfomycin trometamol appears to be a promising alternative, owing to its broad antimicrobial spectrum and the low prevalence of resistance. Several studies have suggested its effectiveness in preventing infectious complications following TRPB.^12,13

The aim of this prospective study was to assess infectious outcomes and safety of fosfomycin trometamol compared with ciprofloxacin in preventing post-TRPB infectious complications in a local setting characterized by high fluoroquinolone resistance. In a second step, we evaluated the feasibility of adopting fosfomycin as the standard prophylactic regimen in our clinical practice.

2. Patients and methods

2.1. Study design and population

This prospective cohort study was conducted in our department and consecutively included all patients who underwent TRPB between February 2023 and December 2025, for a total of 423 patients.

The study was conducted in two successive phases according to a predefined protocol established before patient inclusion. The initial comparative phase aimed to evaluate the incidence of infectious complications under two empirical antibiotic prophylaxis regimens. According to the study protocol, fosfomycin trometamol was to be adopted as the standard regimen if comparable results were observed relative to ciprofloxacin.

2.2. Comparative phase

The first 200 included patients were analyzed. During this period, antibiotic prophylaxis was not yet standardized and depended on the prescribing practices of individual urologists. Eighty-three patients received ciprofloxacin 1000 mg orally as a single dose (two 500-mg tablets) administered two hours before TRPB (group 1), and 117 received fosfomycin trometamol 3 g orally as a single dose administered two hours before TRPB (group 2). No postbiopsy antibiotic dose was given. Baseline characteristics of the two groups were compared using appropriate statistical tests to assess comparability prior to analysis of infectious outcomes.

2.3. Standardization phase

Following the initial comparative period and in the absence of increased infectious complications with fosfomycin, fosfomycin trometamol was adopted as the standard prophylactic regimen in our department.

The study was then continued prospectively with the inclusion of 223 additional patients, all of whom received a single 3-g oral dose of fosfomycin trometamol administered two hours before TRPB, in order to confirm safety and tolerability outcomes in a larger cohort.

Prebiopsy urinalysis and urine culture were not performed routinely in our practice in the absence of a specific recommendation for systematic screening before TRPB in asymptomatic patients. Patients with clinical suspicion of urinary tract infection were not scheduled for immediate TRPB and were managed before any biopsy procedure.

2.4. Follow-up and outcomes

All patients attended a follow-up visit 30 days after TRPB. Infectious complications occurring during this interval, including those managed in other healthcare facilities, were recorded based on patient reports and available medical documentation.

The diagnosis of infectious complications was based on clinical data documented in medical records and information collected at follow-up. Microbiological investigations, when performed as part of routine clinical care, were not systematically available and were therefore not included in the analysis. In particular, patients who developed postbiopsy prostatitis were often managed in external medical facilities, sometimes far from our department due to our regional referral setting, and the corresponding microbiological documentation was not consistently available at follow-up.

Infectious complications included symptomatic urinary tract infection, postbiopsy fever (temperature ≥38°C), acute prostatitis, orchiepididymitis, and sepsis.

2.5. Data collection and statistical analysis

Data were prospectively collected from medical records and follow-up visits. Analyzed variables included demographic, clinical, and procedural data such as age, prostate-specific antigen (PSA) level, history of previous prostate biopsy, the number of biopsy cores, prostate cancer detection, and relevant comorbidities.

Continuous variables were expressed as mean ± standard deviation or median with interquartile range (IQR) according to their distribution. Categorical variables were expressed as counts and percentages.

Comparisons were performed using the Chi-square test or Fisher’s exact test for categorical variables and Student t test or the Mann–Whitney U-test for continuous variables.

A univariate logistic regression analysis was conducted to identify factors associated with post-TRPB infectious complications. Statistical significance was defined as a P value <0.05. All analyses were performed using SPSS software (IBM Corp., Armonk, NY, USA) (version 20.0).

2.6. Ethical considerations

The study was conducted in accordance with applicable ethical principles and local regulatory requirements. All patients provided written informed consent prior to inclusion. Given the purely observational nature of the study and the absence of any modification to standard clinical practice, formal ethical committee approval was not required under institutional regulations.

3. Results

The initial comparative phase included the first 200 consecutively enrolled patients. Among them, 83 (41.5%) received ciprofloxacin prophylaxis and 117 (58.5%) received fosfomycin trometamol, according to nonstandardized prescribing practices. Baseline characteristics were comparable between the two groups, with no statistically significant differences in age, PSA level, number of biopsy cores, or overall complications, including infectious events (Table 1). In accordance with the predefined protocol, fosfomycin trometamol was adopted in our department as the standard prophylactic regimen after the initial phase showed no increase in infectious complications compared with ciprofloxacin [10/117 (8.5%) vs. 9/83 (10.8%), P = 0.585].

Table 1.

Baseline patient characteristics according to antibiotic prophylaxis regimen

Variables	Ciprofloxacin n°:83 (41,5%)	Fosfomycin n°: 117 (58,5%)	Total 200 (100%)	P
Age (years), mean ± SD	71.57 ± 6.68	70.96 ± 7.88	71.21 ± 7.4	0.567
PSA (ng/mL), median (IQR)	17.78 (10.5–50.9)	13.83 (9.0–33.5)	15.65 (9.53–54.49)	0.245
Number of biopsy cores, median (IQR)	14 (12–16)	16 (14-16)	15 (12–16)	0.117
Prostate cancer, n (%)	52 (62.7%)	67 (57.3%)	119 (59.5%)	0.445
Overall complications, n (%)	35 (42.2%)	56 (47.9%)	91 (45.5%)	0.426
Infectious complications, n (%)	9 (10.8%)	10 (8.5%)	19 (9.5%)	0.585

Quantitative variables are expressed as mean ± SD or median (IQR), depending on distribution. Comparisons were performed using Student t test or Mann–Whitney U-test. Categorical variables were compared using the χ² test or Fisher’s exact test.

IQR, interquartile range; PSA, prostate-specific antigen; SD, standard deviation.

The final analysis included 423 prospectively enrolled patients. Mean age was 71.2 ± 7.3 years, and median PSA was 15.65 ng/mL (IQR: 9.53–54.49). Prostate adenocarcinoma was diagnosed in 276 patients (65.2%). Noninfectious complications were observed in 203 patients (48%).

Overall, infectious complications occurred in 35 patients (8.3%). These included isolated febrile episodes in 22 patients (5.2%), acute prostatitis, and one case of orchiepididymitis. Five patients (1.2%) required hospitalization for acute prostatitis, four of whom had received fosfomycin prophylaxis.

One death occurred beyond the predefined 30-day follow-up period. It was related to multiorgan failure in a patient with metastatic prostate adenocarcinoma.

The overall characteristics of the cohort and the detailed distribution of infectious complications are presented in Table 2.

Table 2.

Overall cohort characteristics and infectious complications observed (n = 423)

Variables	Data
Age (years), mean ± SD	71.16 ± 7.34
PSA (ng/mL), median (IQR)	14.29 (9.07–36)
Number of biopsy cores, median (IQR)	15 (13–16)
Prostate cancer, n (%)	276 (65.2%)
Infectious complications, n (%)	35 (8.3%)
Fever	22 (5.2%)
Prostatitis	12 (2.8%)
Epididymo-orchitis	1 (0.2%)
Hospitalization for infection, n (%)	5 (1.2%)

IQR, interquartile range; PSA, prostate-specific antigen; SD, standard deviation.

Finally, no statistically significant association with infectious complications was observed in the univariate analysis (Table 3).

Table 3.

Univariate analysis of factors associated with infectious complications.

Variables	P
Age	0.821
PSA	0.553
Number of biopsy cores	0.209
Antibioprophylaxis	0.343
Prostate cancer	0.976
ISUP grade	0.560
Diabetes	0.653
Cardiovascular diseases	0.297
Hypertension and respiratory disease	0.851
Previous prostate biopsy	1.000
Digital rectal exam positivity	0.749

PSA, prostate-specific antigen; ISUP, International Society of Urological Pathology.

4. Discussion

In this prospective observational study conducted in a high bacterial resistance setting, single-dose fosfomycin trometamol was associated with an acceptable rate of infectious complications after TRPB. The overall infection rate observed in our cohort was 8.3%, with a low hospitalization rate (1.2%), suggesting a satisfactory safety profile in our practice. These findings are broadly consistent with those reported in the literature.¹⁴

Nevertheless, infectious complications after TRPB remain a significant concern despite systematic antibiotic prophylaxis. Clinically significant infections are generally reported with an incidence ranging from 1% to 7.6%,^{5, 6, 7} whereas some series using broader definitions (including isolated fever or bacteriuria) have described rates up to 17.5%, with hospitalization rates for severe infections ranging between 0.5% and 6.9%.¹²

In our cohort, most events consisted of transient febrile episodes that resolved spontaneously, which may explain an overall infection rate slightly higher than that reported in studies applying stricter definitions. We were not able to formally distinguish transient bacteremia from systemic inflammatory response syndrome¹⁵ in the absence of systematic microbiological documentation, particularly when these episodes were only reported during follow-up consultation.

Overall, our findings suggest that fosfomycin trometamol may represent a pragmatic prophylactic option in settings with high fluoroquinolone resistance.

In the context of increasing and sometimes inappropriate antibiotic use, a prophylactic strategy adapted to the local epidemiological situation is required. The emergence of antimicrobial resistance has become a major global public health issue.^16,17 It is estimated that in emergency and primary care settings, 20% to 50% of antibiotic prescriptions are either unnecessary or inappropriate.^18,19 According to the United Nations, antimicrobial resistance could become one of the leading causes of death worldwide by 2050, with more than 10 million deaths per year.^20,21

Algeria is not spared by this phenomenon. Despite available national surveillance data,¹¹ the absence of standardized local recommendations complicates the optimization of prophylactic strategies, particularly in the setting of prostate biopsy.

These concerns are also reflected in recent international recommendations. The European Medicines Agency,²² as well as scientific societies such as the EAU,⁸ have advised against the routine use of ciprofloxacin for TRPB prophylaxis. To address this issue, several alternatives have been evaluated, including single agents or combination regimens.^{23, 24, 25} Some antibiotic combinations have demonstrated efficacy, notably fosfomycin–ciprofloxacin,^23,26 fluoroquinolones combined with trimethoprim–sulfamethoxazole or ceftriaxone, as well as gentamicin–ciprofloxacin.^27,28 Other approaches have proposed targeted prophylaxis based on rectal-swab cultures, although current recommendations do not systematically support this strategy.⁸ A systematic review and meta-analysis of randomized controlled trials also highlighted the effectiveness of certain prolonged regimens (≥3 days).²⁹

However, these conclusions may appear contradictory to several recent studies demonstrating the efficacy of single-dose monotherapy prophylaxis. The effectiveness of fosfomycin trometamol for post-TRPB prophylaxis was confirmed by an international consensus statement published in 2022, emphasizing its favorable tolerance profile, low resistance rates, and ability to achieve effective intraprostatic concentrations.³⁰ These elements, combined with the low resistance levels observed in our country, motivated the present study.

Other prospective randomized trials have confirmed these findings. A study conducted between 2021 and 2023 including 204 patients found no significant difference between a single-dose regimen and a protocol including a second dose at 48 hours.¹⁴ Another prospective randomized trial also confirmed the efficacy of a single 3-g dose administered the day before biopsy.³¹

This study nevertheless has certain limitations. The absence of systematic microbiological confirmation represents a major limitation as it prevented precise identification of causative pathogens in confirmed infections and limited our ability to formally distinguish transient bacteremia from noninfectious inflammatory syndromes, as discussed earlier. In addition, the single-center design and the lack of strict randomization during the initial comparative phase may limit the generalizability of the findings. Furthermore, the initial comparison between ciprofloxacin and fosfomycin should be considered exploratory only, owing to the nonrandomized design, urologist-dependent treatment allocation, and the subsequent temporal transition to a fosfomycin-only strategy. Accordingly, no formal comparative or equivalence inference can be drawn from our data. Finally, the relatively small number of infectious events may have reduced the statistical power of the analysis. Moreover, because only univariate analyses were performed, residual confounding cannot be excluded, and the absence of statistically significant associations should not be interpreted as evidence that no predictive factors exist.

5. Conclusion

In a high fluoroquinolone-resistance setting, single-dose fosfomycin trometamol was associated with acceptable clinical outcomes after transrectal prostate biopsy, with a low rate of hospitalization. These findings suggest that it may represent a pragmatic prophylactic option in regions with a high prevalence of antimicrobial resistance. However, given the nonrandomized design, the limited number of infectious events, and the absence of systematic microbiological confirmation, no formal comparative efficacy inference can be drawn from our data. Further multicenter randomized studies are warranted to confirm these findings.

Conflicts of Interest

The author declares no conflict of interest.