Risk Factors for Acute Prostatitis after Transrectal Biopsy of the Prostate

Transrectal ultrasound-guided needle biopsy of the prostate is generally accepted as the standard diagnostic procedure for detecting prostate cancer [1-4]. Although transrectal ultrasound-guided prostate biopsy is generally considered to be a safe procedure, complications are occasionally encountered. These include minor complications such as hematuria, hemospermia, and rectal bleeding as well as clinically significant, major complications such as acute prostatitis and urosepsis, which may be fatal [5-8].

Antibiotic prophylaxis before transrectal prostate biopsy is generally accepted to reduce the infection-related complications. Fluoroquinolones, which are known to be delivered at high concentrations in the prostate, are considered to be effective in lowering the incidence of infective complications [9-12]. However, there are recent reports of the development of fluoroquinolone-resistant infections after transrectal prostate biopsy [13-16].

The number of prostate biopsies is bound to progressively increase with the advent of prostate-specific antigen (PSA) screening and increasing awareness of prostate cancer. Therefore, it becomes essential to have a clear understanding of the morbidity of transrectal prostate biopsy to allow for more appropriate patient counseling and management.

In this study, we investigated the incidence, clinical features, pathogenic bacteria, and risk factors associated with acute prostatitis after transrectal prostate biopsy.

We retrospectively reviewed the medical records of 923 prostate biopsies, including 77 repeated biopsies, performed in 878 patients at our institution from June 2004 to May 2009. The indications for prostate biopsy were serum PSA elevation or abnormal findings on a digital rectal examination or transrectal ultrasonography. All prostate biopsies were performed transrectally under ultrasound guidance by a radiologist. An automatic biopsy gun with an 18-gauge needle was used to obtain the biopsy specimens. Either 10- or 12-core biopsies were sampled depending on the time period during which the biopsy was performed. Ten-core biopsies were performed from June 2004 to April 2008, and 12-core biopsies were performed since May 2008. As a rule, acetylsalicylic acid or oral anticoagulant agents were stopped 7 days before prostate biopsy with the approval of the prescribing physician. Urine samples were obtained for urinalysis before prostate biopsy in all cases except 5 and for urine culture in all cases except 10.

All prostate biopsies were performed with the patient hospitalized except for 10 patients who refused to be hospitalized. In patients who were hospitalized, 200 mg ciprofloxacin was injected intravenously before and after the biopsy. All hospitalized patients received a cleansing enema before biopsy. They were discharged from the hospital on the following morning after the biopsy and received 250 mg ciprofloxacin orally twice daily for 7 days. Patients who underwent the biopsy on an outpatient basis did not receive a cleansing enema or parenteral injections of ciprofloxacin. These patients received 250 mg ciprofloxacin orally twice daily for 7 days, beginning on the morning before biopsy. If symptoms of acute prostatitis, such as fever, chills, and voiding difficulty, developed after prostate biopsy, the patient was readmitted for treatment including intravenous antibiotics.

The incidence, clinical features, and pathogenic bacteria of acute prostatitis after prostate biopsy were investigated. Variables such as the patient's age, past medical history, prostate volume, biopsy core numbers, number of biopsy sessions, cleansing enema, and urinalysis and urine culture findings before biopsy were also assessed.

Statistical analysis was performed by using the chisquare test or independent t-test with SPSS version 13.0 (SPSS Inc., Chicago, USA). Values of p<0.05 were considered to be statistically significant in all of the analyses.

Of the 923 prostate biopsy cases, acute prostatitis developed in 18 (2.0%) cases after prostate biopsy. Among these 18 cases, 9 (1.0%) had bacteremia as confirmed by positive blood culture, and 2 (0.2%) showed clinical features of sepsis. The patients developed infective symptoms a median of 1 day (mean, 2.8 days; range, 1-25 days) after prostate biopsy.

Of the 18 cases with acute prostatitis, 13 (72.2%) cases had positive urine and/or blood cultures, including E. coli in 11, Klebsiella pneumoniae in 1, and Citrobacter freundii in 1. Of the total 50 urine or blood specimens sent for culture study, 27 (54.0%) specimens showed positive cultures, including E. coli in 25, Klebsiella pneumoniae in 1, and Citrobacter freundii in 1. Among the 27 culture-positive specimens, 26 (96.3%) yielded ciprofloxacin-resistant pathogens, including E. coli in 24, Klebsiella pneumoniae in 1, and Citrobacter freundii in 1. However, these pathogens were sensitive to cephalosporins and aminoglycosides (Table 1).

TABLE 1
Susceptibility of ciprofloxacin-resistant E. coli to antibiotics in 24 urine and blood culture specimens

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When stratified by year, there was no statistically significant difference in the annual rates of acute prostatitis that developed after prostate biopsy (p=0.904) (Table 2).

TABLE 2
Annual rates of acute prostatitis that developed after prostate biopsy

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The mean age of the patients who underwent prostate biopsy was 65.4 years (range, 20-95 years). The mean ages of the patients who developed acute prostatitis and of those who did not were 59.3±13.0 years and 65.5±11.0 years, respectively, which showed no statistically significant difference (p=0.063) (Table 3).

TABLE 3
Patient's age and prostate volume in relation to acute prostatitis

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The mean prostate volume of the patients who underwent prostate biopsy was 50.2 cc (range, 12.2-383.3 cc). The mean prostate volumes of the patients who developed acute prostatitis and of those who did not were 44.7±20.1 cc and 50.3±29.3 cc, respectively, which showed no statistically significant difference (p=0.261) (Table 3).

Among the other potential risk factors for acute prostatitis after prostate biopsy, biopsy performed as an outpatient procedure without a cleansing enema (p=0.001) and past history of cerebrovascular accident (p=0.048) were statistically significant (Table 4).

TABLE 4
Potential risk factors and rates of acute prostatitis after prostate biopsy

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Although a few studies have demonstrated that antibiotic prophylaxis may not be required for transrectal prostate biopsy [17], antibiotic prophylaxis before transrectal prostate biopsy is generally accepted to decrease the rate of infective complications [9-12]. However, there is much variability in the type, dosage, and duration of antibiotic prophylaxis [18, 19].

Fluoroquinolones are the most frequently used antibiotics for prophylaxis before transrectal prostate biopsy because of their broad spectrum of action, which is adequate for common urinary and colorectal flora; their high concentration within the prostatic tissue; and the ease of oral administration [20]. Numerous studies have demonstrated a decrease in infective complications with fluoroquinolone use to rates of less than 1% to 4% [9, 10, 12-14, 21]. In our study, the rate of acute prostatitis was 2.0%, which is consistent with the previously reported rates. This means that fluoroquinolone is effective as an antibiotic prophylaxis for transrectal prostate biopsy in most cases.

However, recent reports have shown that fluoroquinolone-resistant infections following transrectal prostate biopsy are emerging [9, 10, 13-16, 21]. Shigehara et al reported that all of the urine cultures of patients with acute prostatitis that developed after transrectal prostate biopsy yielded levofloxacin-resistant E. coli [9]. Feliciano et al showed that 61% of the patients with infective complications after transrectal prostate biopsy had positive urine and/or blood cultures. Of the positive cultures, those from 89% of patients yielded E. coli and 90% were fluoroquinolone-resistant. The incidence of infective complications and fluoroquinolone-resistant infections in 2006 were 3 times and 3.3 to 4.3 times higher than in 2004 and 2005, respectively [13]. Özden et al reported that 61% of the patients with acute prostatitis after transrectal prostate biopsy had positive cultures, with E. coli being the most common pathogen (82%). Among the patients infected with E. coli, 93% showed fluoroquinolone resistance and 43% harbored extended-spectrum β-lactamase-producing E. coli [16]. In our study, 72.2% of cases with acute prostatitis after transrectal prostate biopsy had positive urine and/or blood cultures. Of the positive cultures, 96.3% were resistant to ciprofloxacin. However, in contradiction to the findings by Feliciano et al, there was no significant difference in the annual rates of acute prostatitis after prostate biopsy [13].

Özden et al suggested that the increasing fluoroquinolone resistance might be due to the previous wide use of these drugs [16]. Shigehara et al considered that the previous use of levofloxacin might cause bacterial selection in the rectum, and levofloxacin-resistant E. coli might then appear in the rectum for a certain period [9]. In their reports, acute prostatitis developed more frequently after repeat biopsy than after the first biopsy [9, 16]. However, in our study, the rate of acute prostatitis did not differ according to the number of biopsy sessions, and all cases of acute prostatitis occurred after the first biopsy.

Because our results showed that ciprofloxacin-resistant pathogens were sensitive to cephalosporins and aminoglycosides, empirical treatment with cephalosporins or aminoglycosides is recommended in patients with acute prostatitis that develops after transrectal prostate biopsy until culture-specific therapy can be implemented.

The impact of cleansing enemas before transrectal prostate biopsy on the infective complications is still controversial. Whereas some studies have shown that a cleansing enema is not required or recommended before biopsy [22, 23], others have suggested that a cleansing enema before biopsy may decrease bacteremia and bacteriuria after prostate biopsy [24, 25]. A cleansing enema has the advantage of producing a superior acoustic window for prostate imaging by decreasing the amount of feces in the rectum. Furthermore, a cleansing enema and an empty rectal vault may reduce bacterial seeding of the prostate [26].

In our series of 923 prostate biopsy cases, all patients except 10 (1.1%) received a cleansing enema. Acute prostatitis developed more frequently in cases without a cleansing enema than in those with a cleansing enema before biopsy, and this difference was statistically significant. Because only 1.1% of our cases did not receive a cleansing enema, however, a large, prospective randomized study will be needed to clarify the impact of a cleansing enema on infective complications.

In our study, biopsy performed as an outpatient procedure without a cleansing enema and past history of cerebrovascular accident were statistically significant risk factors for acute prostatitis after transrectal prostate biopsy. Pyuria and positive urine culture before biopsy were not significant risk factors, which is consistent with the findings of Ecke et al that positive microbiology in urine before prostate biopsy is not a risk factor for a higher infection rate [27]. Chiang et al suggested that patients with a larger prostate (>45 ml) had a significantly higher risk of developing acute prostatitis and acute urinary retention after prostate biopsy than did those with a smaller prostate (<45 ml) [28]. However, in our study, prostate volume was not a significant risk factor for acute prostatitis after prostate biopsy.

In our study, patient's age, diabetes mellitus, hypertension, and number of biopsy cores were not significant risk factors for acute prostatitis after prostate biopsy, which is consistent with the results of a study by Chiang et al [28]. Past history of cerebrovascular accident was a statistically significant risk factor for acute prostatitis after prostate biopsy in our study, but not in the report by Chiang et al [28]. The possible explanation is that the patients with a history of cerebrovascular accident may have altered bowel function and constipation [29, 30], which may result in a change in the bacterial flora in the rectum. They also could have consumed fluoroquinolones before prostate biopsy. These combined might lead to the appearance of fluoroquinolone-resistant pathogens in the rectum and an increase in infective complications after transrectal prostate biopsy.

A limitation of our study is that it was retrospective in nature, and the sample size of the groups was limited because of the low incidence of acute prostatitis after transrectal prostate biopsy. All patients except 10 (1.1%) were hospitalized and received a cleansing enema before transrectal prostate biopsy. Further prospective studies will be necessary to confirm the impact on infective complications of a cleansing enema before transrectal prostate biopsy.

Fluoroquinolone is effective as an antibiotic prophylaxis for transrectal prostate biopsy in most cases. The incidence of acute prostatitis after transrectal prostate biopsy was 2.0%, and almost all cases were caused by fluoroquinolone-resistant E. coli. A cleansing enema is recommended before transrectal prostate biopsy. Empirical treatment with cephalosporins or aminoglycosides should be initiated for patients with acute prostatitis after transrectal prostate biopsy until culture-specific therapy can be implemented.