Oncological Urology Arch. Esp. Urol. 2011; 64 (7): 605-610 INFECTIOUS COMPLICATIONS AFTER TRANSRECTAL ULTRASOUND-GUIDED PROSTATIC BIOPSY. ANALYSIS OF OUR EXPERIENCE Natalia Miranda Utrera, Maria Blanco Alvarez1, Jose Medina Polo, Angel Tejido Sanchez, Juan Passas Martinez y Rafael Diaz Gonzalez. Urology Department. Hospital Universitario 12 de Octubre. Madrid. Spain. 1 Urology Department. Hospital Txagorritxu. Vitoria. Pais Vasco. Spain. Summary.- OBJECTIVES: To establish the rate of infectious complications derived from the use of transrectal ultrasound-guided prostate biopsy (TRUS), identify its microbiological proﬁle and related risk factors. METHODS: We designed a prospective non-randomized study in which we enrolled 220 patients undergoing TRUS biopsy at our centre between April and September 2008. The inclusion criteria were: suspicious digital rectal examination, PSA >10 ng/ml, and free/total ratio of PSA is assessed in patients with PSA 4-10 ng/ ml. The exclusion criteria were: having an indwelling @ urinary catheter, the administration of antibiotic treatment in the week before the needle biopsy, manipulation of the urinary tract in the month prior to the needle biopsy, allergy to quinolones and risk of endocarditis, failure to comply with the antibiotic prophylaxis regimen and loss to follow-up. We analyzed the relationship between diabetes, immunodepression, previous UTI or prostatitis and positive prebiopsy urine culture with the appearance of fever, dysuria or bacteriuria following needle biopsy. RESULTS: Mean age was 69.5 years (+/-7.9), mean total PSA 12.7ng/ml (+/-28.7), mean prostate volume 50.6 cc (+/-29.6) and mean number of cores obtained by needle biopsy 13.5 (+/-1.7). 25% of the patients had dysuria following needle biopsy, 3.2% fever and 4.5% bacteriuria. E.coli was the pathogen most frequently found in pre- and post-biopsy urine cultures. No statistically signiﬁcant relationship was found between the appearance of dysuria and fever and being diabetic, having immunosuppression, previous UTI or prostatitis, prostate volume and number of cores obtained in the biopsy. CORRESPONDENCE Natalia Miranda Utrera Servicio de Urología Hospital Universitario 12 de Octubre Avda. de Córdoba s/n 28041 Madrid (Spain). [email protected] Accepted for publication: Jamuary 4th, 2011 Only the existence of a positive pre-biopsy urine culture and biopsy with more than 14 cores proved to have a statistically signiﬁcant association with the existence of bacteriuria following biopsy, p=0.007 and p= 0.018, respectively. CONCLUSIONS: Our rate of infectious complications was similar to that described in other series. The existence of a positive prebiopsy urine culture and obtaining more than 14 cores per biopsy was related, with statistical signiﬁcance, to the existence of bacteriuria following the biopsy. E.coli was the most frequently isolated pathogen. 606 N. Miranda Utrera, M. Blanco Álvarez, J. Medina Polo, et al. Keywords: Antibiotic prophylaxis. Ultrasoundguided transrectal prostate biopsy. Complications. Resumen.- OBJETIVO: Establecer la tasa de complicaciones infecciosas derivadas de la realización de una biopsia prostática transrectal ecodirigida (BPTRE), identiﬁcar su perﬁl microbiológico y los factores de riesgo relacionados. MÉTODOS: Diseñamos un estudio prospectivo no aleatorizado donde se incluyeron 220 pacientes sometidos a BPTRE en nuestro centro entre Abril y Septiembre de 2008. Los criterios de inclusión fueron: tacto rectal sospechoso, PSA >10ng/ml y en aquellos con PSA 4-10 ng/ml se tiene valora el cociente PSA libre/total. Los criterios de exclusión empleados fueron: ser portador de catéter urinario, administración de tratamiento antibiótico la semana previa a la realización de la biopsia, manipulación de la vía urinaria en el mes previo a la biopsia, alergia a quinolonas y riesgo de endocarditis, incumplimiento de la pauta de proﬁlaxis antibiótica y pérdida de seguimiento. Analizamos la relación entre ser diabético, inmunodeprimido, ITU o prostatis previas y urocultivo prebiopsia positivo con la aparición de ﬁebre, disuria o bacteriuria tras la biopsia. RESULTADOS: La edad media fue de 69,5 años (+/7,9), el PSA total medio 12,7ng/ml (+/-28,7), el volumen prostático medio 50,6cc (+/-29,6) y el número medio de cilindros obtenidos por biopsia 13,5 (+/1,7). El 25% de los pacientes tenía disuria tras la biopsia, el 3,2% ﬁebre, el 4,5% bacteriuria. El E.coli fue el patógeno más frecuentemente hallado en los urocultivos pre y post biopsia. No encontramos relación estadísticamente signiﬁcativa entre la aparición de disuria y la ﬁebre con la condición de diabético, inmunosupresión, ITU o prostatitis previas, volumen prostático y número de cilindros obtenidos en la biopsia. Únicamente la existencia de un urocultivo prebiopsia positivo y una biopsia con más de 14 cores, demostraron tener asociación estadísticamente signiﬁcativa con la existencia de bacteriuria tras la biopsia, p=0,007 y p= 0,018 respectivamente. CONCLUSIONES: Nuestra tasa de complicaciones infecciosas fue similar a la descrita para otras series. La existencia de un urocultivo prebiopsia positivo y obtener más de 14 cilindros por biopsia demostró tener relación estadísticamente signiﬁcativa con la existencia de bacteriuria tras la biopsia. El E-coli fue el patógeno más frecuentemente aislado. Palabras clave: Proﬁlaxis antibiótica. Biopsia prostática transrectal ecodirigida. Complicaciones. INTRODUCTION Since the introduction of the prostate speciﬁc antigen (PSA) in the nineteen-eighties, and its use in screening campaigns, the detection of prostate cancer has increased considerably, particularly in earlier and potentially curable stages. The transrectal ultrasound-guided prostate biopsy (TRUS) is a safe and regular procedure in the urologist’s daily practice, albeit not free of complications (1,2). A review of the literature shows that although the American Urological Association, in 2008, recommended, with a Ib level of evidence, the use of ﬂuoroquinolones as the most suitable antibiotic prophylaxis for the prevention of TRUS-derived infectious complications, many groups continue to use their own prophylactic regimen. Similarly, we also observed divergences regarding the most suitable pre-biopsy analgesic and intestinal preparation protcols (3). The objectives of this study are: 1) To establish our rate of TRUS-derived infectious complications. 2) To identify the risk factors associated with the development of infectious complications. 3) To identify the microbiological proﬁle of postprostate biopsy infections. MATERIAL AND METHODS We designed a prospective non-randomised study enrolling patients undergoing an ambulatory TRUS at our centre (Hospital Universitario 12 de Octubre, Madrid) between April and September 2008. In our department all patients with suspicious digital rectal examination, PSA >10 ng/ml are currently indicated for biopsy, and free/total ratio of PSA is assessed in patients with PSA 4-10 ng/ml. The exclusion criteria were: being a urinary catheter carrier, administration of antibiotic treatment in the week before the biopsy, manipulation of the urinary tract in the month prior to the needle biopsy, allergy to quinolones and risk of endocarditis (both criteria due to being unable to follow our regular antibiotic regimen), failure to comply with the antibiotic prophylaxis regimen and loss to follow-up. INFECTIOUS COMPLICATIONS AFTER TRANSRECTAL ULTRASOUND-GUIDED PROSTATIC BIOPSY. ANALYSIS OF OUR EXPERIENCE Our usual pre-biopsy clinical procedure consists of intestinal preparation by means of conventional enema, anxiolytic medication (Bromazepam 1.5 mg) and antibiotic prophylaxis (Ciproﬂoxacin 500 mg) on the morning of the exploration. Following the biopsy, two tablets of Ciproﬂoxacin 500 mg are given 12 and 24 hours after the ﬁrst tablet. For the study, a spontaneous sample was taken for urine culture prior to the TRUS (pre-biopsy urine culture) and a second urine sample on the seventh day post-biopsy (post-biopsy urine culture). With the patient in the lithotomy position and with local anaesthesia (1% Mepivacaine). Between 6 and 8 cores were taken from each prostate lobe and a further two from hypoechoic areas or suspicious nodes. The urologist performing the needle biopsy collects data of interest for the study: number of previous biopsies, possible risk factors predisposing to infection (diabetes mellitus, immunodepression, history of prostatitis or urinary infection (UTI) and the existence of exclusion criteria. A telephone survey on the seventh day after the biopsy was used to identify possible complications related to infection (dysuria and fever), and the patient was questioned on the conditions in which the post-biopsy urine culture was taken and whether the sample was taken at the same time as the infection symptoms (fever or dysuria), with the administration of antibiotic treatment, or if the patient had to go to the emergency room for this reason. A descriptive analysis of the series was performed and contingency tables (Chi-square test) was used to assess the combination between possible risk factors and complications found, considering p<0.05 as the level of statistical signiﬁcance. RESULTS A total of 260 patients were enrolled, 220 of whom fulﬁlled the inclusion criteria, and 40 were excluded. Mean age was 69.5 years (+/-7.9), total mean PSA 12.7ng/ml (+/-28.7), mean prostate volume 50.6 cc (+/-29.6) and mean number of cores obtained by needle biopsy 13.5 (+/-1.7)(Table I). In 76.8% patients the biopsy was performed for the ﬁrst time, 17.7% had already had one and 607 in 5% it was the third time they were undergoing the procedure (Table I). With regard to the pathological anatomy of the biopsy, we found 57.5% without evidence of malignancy or with foci of prostatitis, 38.2% were diagnosed with acinar adenocarcinoma and 4.1% of patients had atypias or high-grade PIN (Table I). The 17.3% of patients had some kind of risk factor for infection: 13.2% diabetics, 1.4% on immunosuppressive treatment and 3.6% with a history of prostatitis or previous UTI (Table I). 82.7% patients collected the pre-biopsy urine culture and 90.5% collected the post-biopsy urine culture. Of the former, 91.2% of the samples were sterile, 3.8% were contaminated and 4.9% were positive (2% E.coli, 0.9% E. faecalis, 0.5% Klebsiella, 1.5% others). Of the post-biopsy urine cultures, 89.9% were sterile, 8.5% were positive (4.6% E.coli, 1.9% Enterococci, 0.9% Pseudomona, 1.1% other) and 1.4% were contaminated (Table I). Of the patients that delivered the sample on the seventh day after the procedure, 7.8% presented symptoms at the time the sample was taken. 75% of the patients did not present voiding symptoms when they were polled. Mild dysuria was present in 24.1% of patients and 0.9% presented intense dysuria that required treatment. We found 4.5% of symptom-free bacteriuria. 94.5% of the patients polled were fever-free over the ﬁrst week after the procedure, although 3.2% patients had to go to the emergency room for fever. We only identiﬁed one case of hospitalisation for a serious procedure-derived infectious complication (0.5%) (Table I). The existence of fever during the ﬁrst week after the procedure was not statistically signiﬁcantly associated with: diabetes (p=0.36), immunodepression (p=0.88), history of UTI or prostatitis (p=0.73), number of cores biopsied (p=0.27), prostate size (p=0.08) and previous positive urine culture (p=0.9) (Table II). Neither was the presence of dysuria during the ﬁrst week post-procedure related in a statistically signiﬁcant way to the existence of a previous positive urine culture (p=0.21), the number of cores biopsied (p=0.93), prostate volume (p=0.36), diabetes (p=0.76), immunodepression (p=0.92) and history of UTI or prostatitis (p=0.64) (Table II). A positive post-biopsy urine culture was not related to diabetes (p=0.06), immunodepression (p=0.7), UTI or previous prostatitis (p=0.55) or with 608 N. Miranda Utrera, M. Blanco Álvarez, J. Medina Polo, et al. TABLE I. CHARACTERISTIC OF OUR SERIE. Number of patients Age (years) PSA (ng/ml) Number of cores Prostatic volume (cc) Number of biopsies: • First biopsy • Second biopsy • Third biopsy • Fourth biopsy Histopathology: • NEM or Prostatitis • Adenocarcinoma 220 69,5 (7,9)* 12,7 (28,7)* 13,5 (1,7)* 50,6 (29,6)* • PIN o Atypias Prebiopsy urine culture: • Sterile • Positive • Contaminated Postbiopsy urine culture: • Sterile • Positive • Contaminated Microorganisms: • Prebiopsy urine culture: E.coli 9 (4,1%) 182 (82,7%) 166 (91,2%) 9 (4,9%) 7 (3,8%) 199 (90,5%) 179 (89,9%) 17 (8,5%) 3 (1,4%) 169 (76,8%) 39 (17,7%) 11 (5%) 1 (0,5%) 127 (57,5%) 84 (38,2%) 2% E. faecalis Klebsiella Others • Postbiopsy urine culture: E.coli 0,9% 0,5% 1,5% 4,6% Enterococcus Pseudomona Others Risk factors: • Diabetes mellitus • Inmunodepression • Prostatitis o previous UTI Complications related with infection: • Disuria • Fever • Bacteriuria postbiopsy • Hospitalisation 1,9% 0,9% 1,1% 29 (13,2%) 3 (1,4%) 8 (3,6%) 53 7 9 1 (24,1%) (3,2%) (4,5%) (0,5%) *mean (Standard desviation) PSA = Prostate Speciﬁc Antigen NEM = No Evidence of Malignacy PIN = Prostatic Intraepithelial Neoplasia UTI = Urinary Tract Infection INFECTIOUS COMPLICATIONS AFTER TRANSRECTAL ULTRASOUND-GUIDED PROSTATIC BIOPSY. ANALYSIS OF OUR EXPERIENCE prostate volume (p=0.31). However, the existence of a positive pre-biopsy urine culture and biopsy with more than 14 cores proved to have a statistically signiﬁcant association with the existence of bacteriuria following the biopsy, p=0.007 and p= 0.018, respectively (Table II). DISCUSSION Serum determination of PSA, digital rectal examination and TRUS are currently basic tools for the early detection of prostate cancer (4). TRUS is a safe and regular procedure in the urologist’s daily practice, although it is not free of complications which, while mostly frequent and mild, may become very serious (1,2). The minor complications include: haematuria (10-74%), haemospermia (9-78%), rectal bleeding (1-40%) and dysuria. And as major complications: pain (9-30%), fever (0.6-4.2%), bacteremia (100%), bacteriuria. (13-36%), symptomatic UTI (13-20%), AUR (0-4.6%) and hospitalisation (0-1.6%) (1-6). A review of the literature shows that although the American Urological Association, in 2008, recommended, with a Ib level of evidence, the use of ﬂuoroquinolones as the most suitable antibiotic prophylaxis for the prevention of TRUS-derived infectious complications, many groups continue to use their own prophylactic regimen. Similarly, we have also observed divergences in terms of the most suitable pre-biopsy analgesic and intestinal preparation protcols (3). 609 In many centres a local anaesthetic is not commonly used. In our Department we inject 10 ml of 1% mepivacaine into the vesicoprostatic angles to achieve peripheral nerve blockade, which is conducive to good tolerance of prostate biopsy (7). There is insufﬁcient scientiﬁc evidence on the use of enemas and disposable kits to support their role in infection prevention (3). In our centre the administration of a conventional enema and the use of disposable kits are routine practice. There is scientiﬁc evidence that the use of antibiotic prophylaxis reduces the rates of bacteriuria, febrile genitourinary infection and postTRUS sepsis to less than 5% (8). The choice of the antibiotic and its efﬁcacy will depend fundamentally on its bioavailability and the sensitivity of the target microorganism. The ﬂuoroquinolones provide good coverage against urinary pathogens and reach high concentrations in urine and in prostate tissue. Single doses, more economical, and short oral regimens are preferred in patients without risk factors. Longer regimens (more than 4 days) might be justiﬁed in high-risk patients (diabetics, concomitant steroid consumption, immunodeﬁciency, pre-existing bacteriuria, history of prostatitis and prostates > 75 cc) (3). However, in our study we could not demonstrate that diabetes, immunosuppression, history of UTI or prostatitis and prostate volume are signiﬁcantly related to a greater incidence of infection-related events. Only one statistically signiﬁcant relationship was demonstrated between a positive pre-biopsy urine TABLE II. RELATIONSHIPS BETWEEN VALUABLES. Risk factors Complications after biopsy Fever Disuria Positive postbiopsy urine culture *Contingency table. Diabetes mellitus Inmunodepression UTI or previous prostatitis Prostatic volume (> 45cc) Number of cores (>14) Positive prebiopsy urine culture p=0,36 p=0,76 p=0,88 p=0,92 p=0,73 p=0,64 p=0,08 p=0,36 p=0,27 p=0,93 p=0,9 p=0,21 p=0,06 p=0,7 p=0,55 p=0,31 p=0,018 p=0,007 UTI= Urinary Tract Infection 610 N. Miranda Utrera, M. Blanco Álvarez, J. Medina Polo, et al. culture and obtaining more than 14 cores by needle biopsy with the existence of bacteriuria following the needle biopsy. In our series, as occurs in the literature, the most frequently isolated pathogen is Escherichia coli, followed by gram-negative bacilli (Klebsiella, Pseudomonas) and enterococci (2,3). Our rate of complications related to infectious processes is similar to that which has been described by other authors: dysuria 24.1%, asymptomatic bacteriuria 4.5%, fever 3.2% and hospitalisation for sepsis (0.5%). Therefore, and despite the fact that the percentage of resistances for quinolones in Spain is estimated at 40%, it seems that our clinical procedure and our short antibiotic prophylaxis regimen are sufﬁcient to prevent infectious complications, although a comparative study with another antibiotic regimen would be necessary to determine superiority. CONCLUSIONS Our rate of infectious complications is within the ranges described in different series in the literature. The existence of a positive pre-biopsy urine culture and obtaining more than 14 cores per biopsy was related, with statistical signiﬁcance, to the existence of bacteriuria following the biopsy. The microbiological proﬁle of our series shows that infection by E.coli is the most frequent. 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