1. No category

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.
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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
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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
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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.
REFERENCES AND RECOMMENDED READINGS
(*of special interest, **of outstanding interest)
*1. Moreno Alarcón C, López González PA, López
Cubillana P, Doñate Iñiguez G, Ruíz Morcillo JC,
Olarte Barragán EH et al. Morbilidad y factores
de riesgo de la biopsia transrectal prostática. Actas Urol Esp. 2010; 34(6):531-536.
2. Bosquet Sanz M, Gimeno Argente V, Arlandis
Guzmán S, Bonillo García MA, Trassierra Villa
M, Jiménez Cruz JF. Estudio comparativo entre
Tobramicina y Tobramicina más Ciprofloxacino como profilaxis para la biopsia transrectal de
próstata. Actas Urol Esp. 2006: 30(9): 866-870.
**3. Muñoz Vélez D, Vicens Vicens A, Ozonas Moragues M. Profilaxis antibiótica en la biopsia
transrectal de próstata. Actas Urol Esp. 2009;
33(8):853-859.
4. Luján Galán M, Páez Bordá A, Fernández González I, Romero Cajigal I, Gómez de Vicente JM,
Berenguer Sánchez A. Efectos adversos de la
biopsia prostática transrectal. Un análisis de 303
procedimientos. Actas Urol Esp. 2001; 25 (1): 4649.
5. Santos Arrotes D, Luján Galán M, Pascual Mateo C, Chiva Robles V, Fernández González I,
Berenguer Sánchez A. Análisis descriptivo de los
efectos adversos de la biopsia transrectal prostático en 603 procedimientos. Arch. Esp. Urol. 2004;
57(6): 601-605.
6. Rodríguez-Patrón Rodríguez R, Mayayo Dehesa
T, Zucharino L, González Galán A, Peral Amorós
M. Complicaciones de la biopsia transrectal ecodirigida prostática y tolerancia según el paciente y
el realizador. Estudio de 305 pacientes. Arch. Esp.
Urol., 2002; 55(5): 509-521.
*7. Feltes Ochoa JA, Passas Martínez J, Felip Santamaría N, Romero Otero J, Rodríguez Antolín A,
Leiva Galvis O. La anestesia local mejora significativamente la tolerancia de la biopsia prostática.
Arch. Esp. Urol., 2006; 59(4):407-414.
8. Grabe M. Controversies in antibiotic prophylaxis
in urology. Int J Antimicrob Agents 2004 Mar; 23
suppl 1:S17-23.
*9. Horcajada JP, Bustos M, Grau S, Sorlí L, Terradas R, Salvadó M et al. High prevalence of
extended-spectrum
Beta-lactamase-producing
enterobacteriaceae in bacteremia after transrectal ultrasound-guided prostate biopsy: a need of
changing preventive protocol. Urol 2009; 74(6):
1195-1199.