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A retrospective study of patients with post-TRPB (transrectal


prostate biopsy) bacteraemia

Chan, Shuk-wun;

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2010

http://hdl.handle.net/10722/173731

Creative Commons: Attribution 3.0 Hong Kong License

A retrospective study of patients with post-TRPB (transrectal prostate biopsy) bacteraemia:


implications on choice of empirical antibiotics

By

Chan Shuk Wun

This work is submitted to


Faculty of Medicine of The University of Hong Kong
In partial fulfillment of the requirements for
The Postgraduate Diploma in Infectious Diseases, PDipID (HK)

Date: 16th Dec, 2010

Supervisor: Dr. Susanna Lau

Declaration

I, Chan Shuk Wun, declare that this dissertation represents my own work and that it has not
been submitted to this or other institution in application for a degree, diploma or any other
qualifications.
I, Chan Shuk Wun also declare that I have read and understand the guideline on What is
plagiarism?

published

by

The

University

of

Hong

Kong

(available

at

http://www.hku.hk/plagiarism/) and that all parts of this work complies with the guideline.

Candidate: Chan Shuk Wun


Signature:
16th Dec, 2010
Date:

Acknowledgement
Special thanks to my supervisor, Dr. Susanna Lau, for her invaluable enlightenment,
guidance and support; and Dr. TK Ng, consultant microbiologist of Princess Margaret
Hospital, for his permission and advice on data collection for my project dissertation and
presentation.

Background
Transrectal ultrasound-guided needle biopsy of the prostate is a standard procedure
to investigate patients with elevated serum prostate-specific antigen or abnormal findings
on a digital rectal examination. Antibiotic prophylaxis is prescribed before the procedure
to reduce the infective complication. Yet, a minority of patients still suffered from
bacteraemia afterwards. Big gums antibiotics are commonly prescribed under such
situation, but there is no universal recommendation on the appropriate choice of antibiotics
for such patients.
Objective
To study the incidence, demographic data, pathogenic bacteria, appropriate
antibiotics choices and outcome for patients suffered from post-TRPB bacteraemia
Method
The medical records of Urology in-patients who and had undergone TRPB in
Princess Margaret Hospital from 2004-2009 and developed post-TRPB bacteraemia were
reviewed retrospectively. The indications for biopsy were generally elevated serum
prostate specific antigen, abnormal findings on a digital rectal examination, or both. All
biopsies were performed with the patient hospitalized. Ciprofloxacin and metronidazole
was administered as antibiotic prophylaxis. The incidence, demographic data, time to
positive blood culture, antibiotic prophylaxis, empirical antibiotics and definitive antibiotic
prescribed for post-TRPB bacteraemia, pathogenic bacteria and antibiotics susceptibility
profile in blood culture and urine culture results were evaluated.
Results
2540 patients undergone TRPB in the study period and 11 patients (0.43%)
developed bacteraemia within 30 days of biopsy. Among a total of 12 blood culture
isolates, 66.7% were fluoroquinolone resistant pathogens, 83.3% were sensitive to
ticarcillin/ clavulanate, 75% isolates were sensitive to ampicillin/ clavulanate, and 100%

were sensitive to imipenem and amikacin. Prevalence of extended spectrum lactamase


producing E. coli was 33.3%
Conclusion
The management of bacteraemia complicating transrectal prostate biopsy depends on
the recognition of its clinical features, the usual pathogenic organisms and their
antimicrobial susceptibility. When patients present with post-prostate biopsy infective
symptoms with bacteraemia, nearly 70% were associated with fluoroquinolone resistant
pathogens. The recommended empirical treatment for patients receiving ciprofloxacin and
metronidazole as antibiotic prophylaxis includes timentin, augmentin or amikacin.
Cabapenems could be considered if patients are clinically unstable or do not response to
the empirical antibiotics, before the availability of culture results. Cephalosporins are not
recommended due to the low susceptibility of isolates observed.

Background
In 1937, Astraldi first described prostate biopsy by transrectal route [1]. Ultrasound
guided transrectal prostate biopsy was first introduced in the 1980s [2]. Transrectal
ultrasound-guided needle biopsy of the prostate is the standard procedure for diagnosis of
prostate cancer [3, 4]. With the widespread availability of serum prostate specific antigen
testing and increasing awareness of prostate cancer, an ultrasound guided transrectal
prostate biopsy is among one of the most common urological procedure and is considered a
safe procedure. However, complications including pain, urinary retention, hematuria,
hematospermia, rectal bleeding and infectious complications are occasional encountered.
Infectious complications include urinary tract infection, acute bacterial prostatitis,
orchiepididymitis, pyelonephritis, local abscess and urosepsis which could be fatal.
Transrectal biopsy of the prostate (TRPB) was one of the most extensively studied
subject in urology regarding the use of antibiotic prophylaxis.[5] Six RCTs comparing
antibiotic prophylaxis with the use of a placebo or no antibiotic prophylaxis were included
[6-11]. They show a significant decrease of bacteriuria after prostate biopsy with the use of
antibiotic prophylaxis compared with no antibiotics prophylaxis. The Fluoroquinolones are
the most commonly used because of their broad spectrum of action against gram-positive
and gram-negative bacteria, can achieve high concentration in the prostate and ease of oral
administration. Borer et al [12] recommended the addition of prophylactic anti-anaerobe
drugs after report of three cases of fatal anaerobic sepsis after a transrectal biopsy of
prostate.
In Princess Margaret Hospital, all patients were given ciprofloxacin 500mg PO once,
metrondiazole 400mg PO once and feet enema in the morning before transrectal prostate
biopsy. Yet, a minority of patients still suffered from bacteraemia afterwards despite
adequate antibiotics prophylaxis. Big gums antibiotics are commonly prescribed under
such situation. In recent years, urologists in our institute tend to treat patients complicated
with post-TRPB fever with tienem according to their protocol, in case patient had known
6

allergy to penicillin, then amikicin would be used. Although the choices of antibiotics
prophylaxis for patients undergoing TRPB were extensively studied, there are no published
studies on the appropriate empirical antibiotics for patients who develop bacteraemia
despite adequate antibiotic prophylaxis. Therefore, it becomes essential to have a clear
understanding of the pathogenic bacteria, antibiotics susceptibility profile and clinical
course to guide appropriate management.
In this study, the incidence, demographic data, clinical feature, pathogenic bacteria,
antibiotic profile, appropriate antibiotics choices and outcome for patients suffered from
post-TRPB bacteraemia in Princess Margaret Hospital were investigated.

Methodology
All patients with positive blood culture result form year 2004 to 2009 in our institute
were obtained and the operation/ procedure records of each patient were revealed from the
Hospital Authoritys Clinical Management System (CMS). Only patients with bacteraemia
within 30 days after transrectal prostate biopsy was included, such period was used as a
cutoff to capture only infections that may have been related to prostate biopsy. Any events
more than one month after prostate biopsy were unlikely related to the procedure itself.
A total of 11 patients fulfill the above criteria and the medical records for each
patient were reviewed from case notes and CMS. Blood cultures were taken on admission;
the culture results, pathogenic organism and antibiotic sensitivity profile were obtained.
The hospital course, mean hospital stay and pathology results were recorded.
Age, past medical history and co-morbidities, history of biopsy, indication of biopsy,
antibiotic prophylaxis were noted. Previous history of antibiotic exposure within 24
months was recorded, including the period before prostate biopsy and indication. Any
urinary culture obtained within 2 weeks before transrectal biopsy was noted. Any previous
isolates of resistant organism was recorded. The time to onset of symptoms, clinical
presentations, temperature, blood pressure, and pulse rate on admission was noted.
The number of transrectal biopsy of prostate in our institute from 2004-2009 was
recorded. This was used to estimate the incidence of post-TRPB bacteraemia. The
estimate of incidence was retrospective and assumed that all patients with blood stream
infection was presented to and treated in public sector. Statistical analysis was performed
by using the Mann-Whitney U test, two-tailed P value of <0.05 is considered as significant.

Results
There was 2540 transrectal biopsy of prostate performed between Jan 2004 to Dec
2009. 11 patients developed infective symptoms with positive blood culture within 30 days
after biopsy. Incidence of post-TRPB in our institute is 0.43 %.
The mean age of the 11 patients was 65.5 years (range 51-81). 3 patients had noninsulin dependent diabetes mellitus. 1 had a significant urological history, with left renal
cell carcinoma and radical nephrectomy done. 1 had significant surgical history, with
pancreatitis and laparotomy done. Regarding the indication for transrectal biopsy of
prostate, 10 had elevated prostate specific antigen, 1 got abnormal findings in digital rectal
examination. 3 patients had history of transrectal biopsy. 3 patients had had exposure to
antibiotics within 24 months before biopsy. All were cases of repeated transrectal prostate
biopsy and had been given oral ciprofloxacin and metronidazole as antibiotic prophylaxis
for previous biopsies.
All patients received oral ciprofloxacin 500mg and metronidazole 400mg as
antibiotic prophylaxis, together with feet enema on the morning of transrectal prostate
biopsy. Exact interval time between antibiotics prophylaxis and procedure could not be
determinate in most cases as the operation time was not documented in OT record. For
those with documentation, antibiotic prophylaxis was given 1 hour 30 minutes to 4 hour 30
minutes before transrectal biopsy of prostate. None of the patients experienced infective
symptoms e.g. pyuria before the prostate biopsy. 1 patient had early morning urine for
AFB culture 1 day before the TRPB, as patient complained of haemospermia and was
clinically suspicious of TB infection. The urine culture was not intended to test as a preTRPB urine culture. It shown overgrown with contaminants and was not repeated. No
routine pre-TRPB urine cultures were performed for all the 11 patients. The duration of
procedure ranged from 5-15 minutes, all were eventful except 1 developed fresh PU
bleeding immediately after biopsy.
All patients developed infective symptoms within 3 days after biopsy. All
complained of fever, 9 complained of chills and 7 of rigors. Other symptoms included
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haematuria, dysuria, frequency, urgency, vomiting and dizziness. One patient had prostatic
tenderness suggestive of prostatic abscess and was subsequently confirmed by CT pelvis.
The temperature on admission was 38.0 41.3 degree celsius. The heart rate at
presentation was 70-140 bpm (no patient on beta blocker). None of the patients was
hypotensive on admission. 6 out of 11 patients had leukocytosis.
All patients had one set of blood culture performed on admission and were positive.
Patient no. 3 had another set of positive blood culture 1 day after admission as he shown
clinical deterioration with disorientation and tachycardia. There are total of 12 isolates for
these 11 patients. 11 isolates were E. coli. 1 was K. pneumoniae. 4 (33.3%) isolates were
tested positive for extended spectrum beta lactamase (ESBL) production. All 11 patients
did not have previous isolates of ESBL positive organisms or other resistant organisms
according to the CMS. Table 1 and 2 illustrates a more comprehensive list of patients
parameter and bacteriology.
8 isolates (66.7%) were resistant to Ciprofloxacin, 4 (33.3%) was sensitive. Of the
aminoglycosides, the best drug was amikacin, all tested (100%) isolates were sensitive,
while only 7 (58.3%) isolates were susceptible to gentamicin, 5 (41.7%) were resistant. 11
isolates are resistant to ampicillin (91.7%), 1 was sensitive (8.3%). For sensitivity toward
augmentin, 9 were sensitive (75%) and 3 were intermediate (25%). For timentin, 10
(83.3%) were sensitive and 2 (16.7%) were intermediate. For cefuroxime (intravenous),
8(66.7%) isolates were sensitive, 4 (33.3%) were resistant. All isolates resistant to
cefuroxime (intravenous) were ESBL positive, and therefore are also resistant to the third
generation and forth cephalospirins tested namely cefotaxime, ceftazidime, cetriaxone and
cefepime. For the remaining 8 ESBL negative isolates were all (100%) sensitive to
cefuroxime (intravenous).
Regarding the sensitivity towards big gums, 1 isolated were tested intermediate to
sulperazon, all other remaining tested isolated were sensitive. Sensitivity towards
imipenem and tazocin were 100% susceptible (Table 3).

10

For empirical treatment of post-TRPB bacteraemia before the sensitivity test became
available, fluoroquinolones and cefuroxime were most commonly prescribed. 5(45.5%)
patients were prescribed fluoroquniolones - levofloxacin were used in 3 patients,
ciprofloxacin in 2 patients. Cefuroxime (intravenous) was used in 5 patients. Imipenem in
2 patients. 3 patients were later switched to sulperazon (2 from cefuroxime, 1 from
levofloxacin). None of the patients received augmentin or timentin as empirical treatment
(table 4).
For definitive treatment, augmentin was chosen in 7(63.6%) patients. These include
2 patients in which isolates were tested intermediate to augmentin and ESBL positive.
Both were switched to augmentin because patients clinical condition was stable. 3 have
ciprofloxacin as definitive treatment (although 2 of these patients later have blood culture
results turned out to be ciprofloxacin resistant isolates. 1 patient was likely to suffered
from transient bacteraemia. He could still clear the infection, shown good clinical response
and was discharged before culture result available. Another patients visited private doctor
after discharged and was finally treated with another antibiotic.) and none required
carbapenems.
The average length of hospital stay was 7.4 days (range 3-20 days), one patient with
repeated admission for post-TRPB fever. 2 patients developed hypotension after admission
requiring isotropic support. 1 developed disorientation and tachycardia. 1 with desaturation
and sepsis induced atrial fibrillation. 1 developed acute renal insufficiency. 2 required
intensive care unit consultation. The pathologic examination revealed malignancy
(adenocarcinoma) in 2 patients. All patients recovered from the post-TRPB sepsis.
The mean length of hospital stay (LOS) for patients with appropriate empirical
antibiotics prescribed was 6.4 days, compared with 8.2 days among patients who received
inappropriate empirical antibiotic (table 5). The two-tailed P value is 0.8528, considered
not significant. One patient had an exceptionally long LOS of 20 days in the group of
inappropriate empirical antibiotics (Figure 1). Median LOS was 7 days and 6.5 days for
patients receiving appropriate and inappropriate empirical antibiotics respectively.
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Appropriate empirical antibiotic was defined here as antibiotics with adequate coverage for
the pathogen involved.

12

Discussion
Transrectal ultrasound guided prostate biopsy is the standard procedure by urologist
for the histological diagnosis of prostate cancer. There has been increasing awareness
among the public regarding the importance of early detection of prostate cancer, resulting
in the increased number of men undergoing digital rectal examination, PSA testing and
subsequent prostate biopsy. Infectious complication of such procedure, from bacteruria to
the most severe complication of sepsis, has been significantly reduced by the antibiotic
prophylaxis [13]. The estimated incidence of bacteraemia in our study is 0.43%, similar to
the estimated rate of sepsis (presented with fever and blood culture positive) of 0.1-0.9%
by Young et al [2].
Bacteria is apparently introduced into the urine and/or blood from the rectum via the
biopsy needle [14]. In the study by Feliciano et al from 2004 to 2006[15], they stratified
the incidence of fluoroquinolone resistance infection after prostate biopsy by year and
reported that the pathogens are adapting and developing resistance to fluoroquinolone
prophylaxis with an increasing trend observed. 66.7 % of the isolates are fluoroquinolone
resistant compared to 83% in their study.
Previous studies have demonstrated a wide range of pathogens, including aerobic
gram negative bacteria (Escherichia coli, Kiebsiella pneumoniae), aerobic gram positive
bacteria (Enterococcus, other Streptococcus speciesm, Staphylococcus epidimidis and
others) and anaerobes(acteroides fragilis, prptostreptococcus species, Petococcus species,
Eubactacterium species and others). [9, 13, 16, 17]. However, drugs other than
fluoroquinolones e.g. trimethoprim-sulfamethoxazole were used for prophylaxis in these
studies. Few studies which specified the pathogens under fluoroquinolne prophylaxis. Isen
et al [9] reported 2 positive cultures under fluoroquinolones prophylaxis, including 1 that
yielded E.coli and 1 that yielded coagulase-negative Staphylococcus aureus, which could
possibly be a contaminant. Tal et al [18] reported the isolates of 6 positive blood cultures,
all were E coli. Feliciano et al [15] reported 19 isolates (urine or blood culture) under
levofloxacin or gatifloxacin prophylaxis, 17 were E. coli (89.5%), 1 were E. cloacae, 1
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were S. epidermidis. In our report, all the pathogenic bacteria were Escherichia coli except
one isolate of Kiebsiella pneumoniae. This study establishes that the chief pathogen
involved in bacteraemia complicating prostate biopsy under fluoroquinolone prophylaxis is
still E. coli.
There are very few studies to describe the susceptibility pattern of bacteria isolated
from patients with infective symptoms after transrectal prostate biopsy. A pubMud search
yields no reports specifically address the antimicrobial profile in patient with bacteraemia
complicating prostate biopsy. From the literature review, there are several studies on the
susceptibility profile specifically for patients received fluoroquinolones prophylaxis but
still developed infective complications after prostate biopsy, and the results would be
compared with the current study.
In the study conducted from 2000 to 2001 by Tal et al[18] empirical management
of urinary tract infections complicating transrectal ultrasound guided prostate biopsy, they
observed the susceptibility of urine/blood isolates to 2nd and 3rd generation cephalosporins
(cefuroxime, cefotaxime and ceftriaxone), amikacin, tazocin and carbapenems were 100%.
Based on the above results, they recommended the use of these drugs in management of
urinary tract infections complicating transrectal biopsy. From their data, susceptibility to
ampicillin/clavulanate was 93.3%
On the other hand, study by Ferrandino et al [15] also reached similar conclusion.
They recommended that fluoroquinolones are still effective as antibiotic prophylaxis for
prostate biopsies but there was an increase in infective complications and fluoroquinolone
resistance. Empirical treatment with ceftrixone, ceftazidime or amikacin should be initiated
until culture specific therapy can be implemented. Form their study, 100% of isolates were
susceptible to cefotaxime, ceftazidime, ceftriaxone and amikicin. The sensitivity to
ampicillin/clavulanate was not tested but only 45% of isolates were susceptible to
apmicillin/ sulbactam in their study. Susceptibility of ticarcillin/clavulanate was 95%.
In a third study by Young et al [2], they included 5 patients presented with fever and
positive blood culture after prostate needle biopsy with pre-procedure fluoroquinolone
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antimicrobial prophylaxis from 2006-2008. From their findings, all 5 isolates were E. coli.
In addition, 3 out of 5 were ESBL producing and resistant to cephalosporins. Other
antibiotics including amikacin, imipenem and augmentin were not tested in most of the
isolates.
Miura et al reported 4 cases of levofloxacin resistance E. coli sepsis in patients who
received oral levofloxacin prophylaxis and underwent transretal prostate biopsy from 2002
to 2006 in their institute [19]. All 4 isolates were sensitive to ceftazidime, amikacin and
imipenem. Testing of isolates against ESBL production was not mentioned. They
recommended that antimicrobial therapy for sepsis following a TRPB is intravenous
carbapenems because of their susceptibility results. However, only levofloxacin, ampicillin,
piperacillin, cefazolin, cefmetazole, ceftazidime, amiklacin, minocycline and imipenem
were tested in their study. Augmentin or timentin were not tested. In addition, the author
quote that 3 cases of fatal anaerobic sepsis after a TPB have been reported by Borer et al
[12], and Miura et al explained that carbapenems are highly active against anaerobic
bacteria.
Looking into the study by Borer et al, a case of C. sordellii ischio-rectal abscess with
rapidly fatal septicaemia is described which complicated ultrasound-guided transrectal
biopsy of the prostate, despite ciprofloxacin prophylaxis. They recommended that the
addition of prophylactic anti-anaerobe drugs should be strongly considered until an optimal
prophylactic regimen will be defined by randomized controlled trials, instead of treating
patients with carbapenem. In our institute, metrondiazole coupled with ciprofloxacin was
used as antibiotic prophylaxis. In addition, narrower spectrum antibiotics including
augmentin and timentin offers good coverage to anaerobes as well.
Regarding this study, the susceptibility profile agreed with that of Tal and
Ferrandino et al concerning the 100% susceptibility of amikacin and imipenem. However,
testing of ESBL production was not mentioned in their studies. We reported 33.3% of the
isolated from patients with post-TRPB bacteraemia were extended-spectrum betalactamse- producing E coli, which is slightly lower than that of 43% reported by Ozeden et
15

al regarding their study of the incidence of acute prostatitis caused by extended-spectrum


beta-lactamse- producing Escherichia coli after transrectal prostate biopsy[20]. From our
study, most of the patients who harbored ESBL producing E coli did not have history of
repeated hospitalization, previous board spectrum antibiotic exposure nor previous culture
of multi-resistance isolates. Based on the findings of current study, 33.3% of isolates were
resistant to cephalosporins. Isolates resistant to cefuroxime are also resistant to cefotaxime,
ceftazidine, ceftriaxone and cefepime. Therefore, in contrast to the previous studies,
cephalosporins are not recommended. Escalation from 2nd to 3rd/4th generation
cephaolospoins in case of poor clinical response do not give additional benefits.
Prevalence of ESBL organisms, even in the absence of risk factors, shall not be overlooked.
In fact, ampicillin/ clavulanate and ticarcillin/ clavulanate were not frequently tested
in other studies but were demonstrated to give good susceptibility profile. From our data,
75% isolates were sensitive to ampicillin/ clavulanate and 25% were intermediate. For
ticarcillin/ clavulanate, 10 (83.3%) were sensitive and 2 (16.7%) were intermediate.
Therefore, timentin and augmentin are recommended as empirical therapy. However, in
case of severe clinical condition eg. septic shock or poor response to empirical antibiotics,
cabapenems could be considered as empirical treatment but stepped down according to the
sensitivity result and clinical condition.
Another unexplained occurrence is the infection in 4(33.3%) patients who received
ciprofloxacin prophylaxis and got post-TRPB bacteraemia with isolates sensitive to
ciprofloxacin. The compliance of one of these patients with the recommendation of
antibiotic prophylaxis was questionable, as it was documented in case notes that oral
ciprofloxacin and metronidazole were prescribed but suspected not taken by patient.
Another possible explanation was the administration of antibiotic prophylaxis was given
too early before the procedure (4 hours for patient no. 4, 2 hour 40 min for patient no. 11),
although for patient number 10, the oral antibiotics were given 1hr 15 min before OT, he
still got post-TRPB fever with ciprofloxacin susceptible isolates. Following the
administration of single dose of oral ciprofloxacin, the time to peak serum concentration
16

are attained within 0.78 - 0.33 hours[21]. Therefore, measures to increase


compliance(eg, clear explanation and directions to patient concerning purpose of
administration of prophylactic antibiotics or nursing staffs might observe the patients
taking medications as most patients were admitted to ward in the same morning of prostate
biopsy) and special attention to time of oral prophylaxis administration. Prophylaxis is
effective only if administrated appropriately.
5 patients were prescribed fluoroquinolones as empirical treatment, suggesting
fluoroquinolones is still a popular choice among doctors treating post-TRPB fever.
However, clinicians should be aware that fluroquinolones should not be prescribed as
empirical treatment in such cases as the patients had taken fluoroquinolones as prophylaxis.
This is because nearly 70% of these blood isolates would turned out to be fluoroquinolone
resistant due to antibiotic selection pressure (unless patients compliance to or
administration of antibiotics prophylaxis was in doubt).
This study demonstrates the importance of appropriate empirical antibiotic use.
Inappropriate empirical antibiotics could result in repeated hospitalization and acute renal
insufficiency, especially among TRPB patients with history of BPH/ chronic outflow
obstruction. In addition, a difference in mean LOS of 1.8 days were observed between the
2 groups of patients(8.2 days compared with mean of 6.4 days in patients with appropriate
empirical antibiotics prescribed).The difference in mean LOS is not statistically significant
(two-tailed P value is 0.8528) in our study. This could be due to the small sample size. On
the other hand, one patient in the group of inappropriate empirical antibiotics had an
exceptionally long stay of 20 days which might result in an apparent difference in LOS
between the 2 groups (figure 1). The Median LOS of patients with appropriate empirical
antibiotics was 7 compared to that of 6.5 days in those with inappropriate empirical
antibiotics. We cannot conclude whether appropriate empirical antibiotic use is associated
with shorter LOS. Hence, larger scale studies are required to minimize bias and determine
whether appropriate empirical antibiotic use associates with better outcomes.
17

One limitation of the current study was the retrospective nature of data collection.
The estimated incidence shall be interpreted with caution, as it was assumed that the
patients reported to the public hospitals. Also, the sample size of the group was limited
because of the low incidence of symptomatic bacteraemia after transrectal prostate biopsy
with adequate antibiotic prophylaxis.
Conclusion
Fluroquinolones are among the most commonly prescribed antibiotic prophylaxis
before transrectal resection of prostate. Patient with post-TRPB bactaeamia after
ciprofloxacin prophylaxis would most likely harbor ciprofloxacin resistance pathogens,
although possibility of poor compliance or inappropriate administration of antibiotic
prophylaxis still have to be considered. Escherichia coli are still the chief pathogens in this
group of patients. Prevalence of ESBL E. coli could not be overlooked even in patient with
no previous board spectrum antibiotic exposure, or frequent hospitalization. Augmentin or
timentin is recommended as empirical treatment for patients with post-TRPB bacteraemia
who are clinically stable. Cephalosprins are not recommended and escalation form 2nd to
3rd/4th generation cephalosporins does not show additional benefits. Carbapenems should
be reserved as empirical treatment for patients with clinically severe infection
complications or poor response to augmentin or timentin. Larger scale studies are required
to investigate the impact of empirical antibiotics on patients outcomes.

18

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20

Table and figures


Table 1: Summary of patient characteristics, clinical presentation, bacteriology and outcomes
Patient
1
2
3
Biopsy date
2004/2/18
2004/8/16
2005/11/23
Age(y)
64
67
62
Medical History
BPH
Left RCC with
Hypertension on pravachol and Napamide
radical nephrectomy Hypercholesteraemia
done in private 2003
BPH
DM on gliclazide
Biopsy Indication
Elevated PSA
Abnormal finding on PR
Elevated PSA
exam
Any previous antibiotic
No
No
No
exposure
Antibiotic indication for
antibiotic exposure
Antibiotic prophylaxis

Bowel preparation
Time interval of antibiotic
prophylaxis and OT
Pre-biopsy urine culture
Interval to presentation (d)
of symptoms
Symptoms
Temperature (degree
Celsius)
Heart rate (bpm)
BP (mmHg)
WBC

4
2006/6/12
59
BPH

Elevated PSA

Feet enema
2.5 hours

Yes ciprofloxacin and


metronidazole(20 months
before current TRPB)
Antibiotic prophylaxis for
his first TRPB in 2004
Ciprofloxacin 500mg PO
once + Metronadiazole
400mg PO once
Feet enema
4 hours

Not done

Not done

Immediate PU bleeding

Fever, chills, rigors,


haematuria, dysuria
39

Fever, dysuria,
hamaturia, dysuria
38.2

Fresh bleeding immediate post biopsy, fever (D1 postop), chills, rigors
39.2

Fever, chills haematuria,


vomiting
39.2

95
125/86
Normal

110
155/75
18.4

110
155/75
17.4

127
127/60
14.5

N/A

N/A

N/A

Ciprofloxacin 500mg PO
once + metronadiazole
400mg PO once
Feet enema
4 hour 30 minutes

Cipofloxacin 500mg PO once + metronadiazole 400mg


PO once

Not done

Ciprofloxacin 500mg PO
once + metronadiazole
400mg PO once
Feet enema
Same morning(OT time
not available)
Not done

21

Interval(from biopsy date)


to collection of positive
blood culture(d)
Blood isolate
Blood sensitivity

Escherichia coli
Ampicillin S
Augmentin S
Cefuroxime(oral) I
Cefuroxime(parenteral) S
Ciprofloxacin R
Gentamicin S
Levofloxacin R
Timentin S

Escherichia coli
Ampicillin R
Augmentin S
Cefuroxime(oral) I
Cefuroxime(parenteral) S
Ciprofloxacin S
Gentamicin R
Timentin S
Sulperozon S

ESBL + Escherichia coli


Amikicin S
Ampicillin R
Augmentin S
Ceftazidime R
Cefuroxime(oral) R
Cefuroxime(parenteral) R
Ciprofloxacin R
Gentamicin S
Tazocin S
Timentin S

Escherichia coli
Ampicillin R
Augmentin S
Cefuroxime(oral) I
Cefuroxime(parenteral) S
Ciprofloxacin S
Gentamicin R
Timentin S

Any previous isolates of


ESBL+ organisms
Empirical antibiotics

No

No

ESBL + Escherichia coli


Ampicillin R
Augmentin I
Cefotaxime R
Ceftazidime R
Ceftriaxone R
Cefuroxime(oral) R
Cefuroxime(parenteral) R
Ciprofloxacin R
Gentamicin S
Sulperazon S
Tazocin S
Timentin I
No

Levofloxacin,
metronidazole
Cefuroxime, then
augmentin
Fever down on D2
admission, haematuria clear
on D3, no more dysuria,
discharge with oral
augmentin.

Cefuroxime(parenteral),
then sulperazon
Augmentin

Levofloxacin + metronidazole, then sulperazon +


metronidazole
Augmentin

Patient developed fever


on D2 post-TRPB, given
iv cefuroxime but
temperature on up going
trend, switched to
sulperazon and fever was
down on D1 sulperazon.
Later switched to
augmentin and
discharged
7
1st
No

Develop fresh PU bleeding immediately after biopsy,


fever day 1 post-biopsy, started iv levofloxacin and
metronidazole, fever persist. Develop chills, rigors,
confusion on day 2, tachycardia (HR 140bpm),
switched to sulperazon and consulted ICU. Fever down
on D3 sulperazon, condition stable, switched to
augmentin on D4 and discharge.

Definitive treatment
Hospital course

LOS (d)
History of biopsy
Pathology any
malignancy

5
1st
adenocarcionma

8
1st
No

No
Cefuroxime (parenteral) +
metronidazole
Cipofloxacin +
metronidazole
Haematuria cleared D2
admission, fever day and
discharged on D3

3
2nd
No

22

Patient
Biopsy date
Age(y)
Medical History

5
2007/4/2
81
Senile cataract with
extra capsular
extraction of lens and
replacement 4/2002
BPH

6
2007/6/13
60
Good Past Health

Biopsy Indication
Any previous antibiotic
exposure

Elevated PSA
No

Elevated PSA
No

Antibiotic indication for


antibiotic exposure
Antibiotic prophylaxis

N/A

N/A

Ciprofloxacin 500mg PO
once + metronadiazole
400mg PO once
Feet enema
Same morning(OT time
not available)

Bowel preparation
Time interval of
antibiotic prophylaxis
and OT
Pre-biopsy urine culture
Interval to presentation
(d) of symptoms
Symptoms

Temperature (degree
Celsius)

8
2008/7/23
70
Hypertension
DM

9
2008/6/4
75
Hypertension
BPH with TURP
done in private
1992

Elevated PSA
Yes - Ciprofloxacin and
metronidazole(3 months
before current TRPB)
Antibiotic prophylaxis
for his previous TRPB
Ciprofloxacin 500mg PO
once + metronadiazole
400mg PO once
Feet enema
Same morning(OT time
not available)

Elevated PSA
No

Ciprofloxacin 500mg PO once


+ metronadiazole 400mg PO
once
Feet enema
Same morning(OT time not
available)

7
2008/3/12
69
Senile cataract with
phacoemulsification
done 1999
Emphysematous
CXR with apical
fibrosis
Acute retention of
urine 4/2005
Elevated PSA
Yes - Ciprofloxacin and
metronidazole(13 months
before current TRPB)
Antibiotic prophylaxis
for his previous TRPB
Ciprofloxacin 500mg PO
once + metronadiazole
400mg PO once
Feet enema
Same morning(OT time
not available)

Not done

Not done

Not done

Not done

Not done

Fever, chills, rigors,


frequency, dysuria,
haematuria, also
complained of increased
cough and sputum
41.3

Fever, chills, rigors, dysuria,


vomiting

Fever, chills, rigors,


dysuria, haematuria

Fever, chills, rigors,


dysuria, haematuria,
vomiting

Fever, chills, rigors,


dysuria, haematuria

39.2

40

39.7

39.7

No
Ciprofloxacin 500mg PO
once + metronadiazole
400mg PO once
Feet enema
Same morning(OT time
not available)

23

Heart rate (bpm)


BP (mmHg)
WBC
Interval(from biopsy
date) to collection of
positive blood
culture(d)
Blood isolate
Blood sensitivity

105
125/57
27.4l
20

126
115/61
1.9
3

115
153/84
13.1
1

129
91/55
3.4
20

129
91/55
3.4
3

ESBL+ Escherichia coli


Amikacin S
Ampicillin R
Augmentin I
Ceftazidine R
Ceftriaxone R
Cefuroxime(oral) R
Cefuroxime(parenteral) R
Ciprofloxacin R
Gentamicin S
Sulperazon I
Tazocin S
Timentin I

Escherichia coli
Ampicillin R
Augmentin S
Cefuroxime(oral) S
Cefuroxime(parenteral) S
Ciprofloxacin R
Gentamicin R
Tazocin S
Timentin S

Escherichia coli
Amikacin S
Ampicillin R
Augmentin S
Cefuroxime(oral) I
Cefuroxime(parenteral) S
Ciprofloxacin R
Gentamicin R
Timentin S

Escherichia coli
Amikacin S
Ampicillin R
Augmentin S
Cefotaxime S
Ceftazidime S
Ceftriaxone S
Cefuroxime(oral) S
Cefuroxime(parenteral)
S
Ciprofloxacin R
Gentamicin R
Imipenem S
Meropenem S
Sulperazon S
Tazocin S
Timentin S

Escherichia coli
Amikacin S
Ampicillin R
Augmentin I
Cefotaxime S
Ceftazidime S
Ceftriaxone S
Cefuroxime(oral) I
Cefuroxime(parenteral)
S
Ciprofloxacin R
Gentamicin S
Imipenem S
Meropenem S
Sulperazon S
Tazocin S
Timentin I

Any previous isolates of


ESBL+ organisms
Empirical antibiotics

No

No

No

No

No

Cefuroxime(parenteral) +
metronidazol

Cefuroxime(parenteral)Tienam,
then tazocin

Ciprofloxacin

Ciprofloxacin +
metronidazole

Definitive treatment

Tazocin, then augemntin

Augmentin

Cefuroxime(parenteral),
levofloxacin then
sulperazon
Augmentin

Ciprofloxacin

Hospital course

Started zinacef, fever down


on D4 zinacef, ST result
shown resistant to zinacef,
sensitive to gentamicine

Fever, chills and rigors D3


post-biopsy, given zinacef.
Develop septic shock
hypotension to 80/65 D1

Given gentamicin 160mg


stat once together with
zinacef 750mg Q8H ivi
for 1 dose then switch to

TRPB performed on
2008/7/23, admitted
AED on 2008/7/26
because of fever and

Ciprofloxacin +
metronidazole
Diagnosis: UTI. Fever
down D2 admission.
Able to self void,
haematuria cleared by
24

and tazocin. Switched to


tazocin. Developed acute
renal insufficiency with Cr
334(baseline 157), foley
inserted, added gentamicin
ivi 80mg once, fever down
and urine clear 2 days
afterwards, then switch
antibiotics to augmentin
and was discharged on D20

admission, tachycardia
105bpm, consulted ICU and
requires fluid resuscitation and
dopamine, antibiotic switched
to tazocin. ST result available:
sensitive to augmentin,
switched to augmentin, fever
gradually down and stable,
discharge D7.

1g Q12H for 2 doses.


Stepped down to
levofloxacin, develop
spike of high fever 40.3
degree Celsius. Restart
sulperazon then switched
to augmentin. Fever
down and discharge on
D5

haematuria, blood
culture on admission
shown no growth, MSU
2008/7/28: no growth.
Treated with cefuroxime,
fever down and
discharged 5 days
afterwards with
cefuroxime for 1 week

D3 admission

Follow up in clinic
2008/8/12, found
persistent fever and
dysuria despite having 1
week course of
cefuroxime, admitted
same day and given iv
ciprofloxacin, fever
subsided and patient
discharged on D3 with
ciprofloxacin 2 weeks in
total
Blood culture later
available, grew
ciprofloxacin resistant E
coli

LOS (d)
History of biopsy
Pathology any
malignancy

20
1st
Yes - adenocarcionma

7
1st
No

5
2nd
No

Patient visited a private


doctor and was treated
with other antibiotic
8(5+3)
4th
No

3
1st
No

25

Patient
Biopsy date
Age(y)
Medical History

Biopsy Indication
Any previous antibiotic
exposure(within 24
months)
Antibiotic indication for
antibiotic exposure
Antibiotic prophylaxis
Bowel preparation
Time interval of antibiotic
prophylaxis and OT
Pre-biopsy urine culture
Interval to presentation (d)
of symptoms
Symptoms
Temperature (degree
Celsius)
Heart rate (bpm)
BP (mmHg)
WBC
Interval(from biopsy date)
to collection of positive
blood culture(d)
Blood isolate

10
2009/10/15
62
Hypertension
Diabetes mellitus
Old pulmonary TB
HBV carrier
Pancreatits with laparotomy
done 30+ years back
Elevated PSA

11
2009/11/18
51
BPH

No

Elevated PSA, prostate nodule on


DRE
No

N/A

N/A

Ciprofloxacin 500mg PO once +


metronadiazole 400mg PO once
Feet enema
1 hour 15 min before OT

Ciprofloxacin 500mg PO once +


metronadiazole 400mg PO once
Feet enema
2 hour 40 min

Not done

Not done

Fever, chills, rigors, haematuria


38

Fever, chills, rigors


38.5

70
130/70
11.3
6

136
96/57
2.7
1

Klebsiella pneumoniae

ESBL + Escherichia coli


26

Blood sensitivity

Amikacin S
Ampicillin R
Augmentin S
Cefepime S
Cefotaxime S
Ceftazidime S
Ceftriaxone S
Cefuroxime(oral) S
Cefuroxime(parenteral) S
Ciprofloxacin S
Ertapenem S
Gentamicin S
Imipenem S
Meropenem S
Sulperazon S
Tazocin S
Timentin S

Amikicin S
Ampicillin R
Augmentin S
Cefepime R
Cefotaxime R
Ceftazidime R
Ceftriaxone R
Cefuroxime(oral) R
Cefuroxime(parenteral) R
Ciprofloxacin S
Ertapenem S
Gentamicin S
Imipenem S
Meropenem S
Sulperazon S
Tazocin S
Timentin S

Any previous isolates of


ESBL+ organisms
Empirical antibiotics
Definitive treatment
Hospital course

No

No

Tienam, gentamicine
Ciprofloxacin
Started tienem, still high swinging
fever, desaturation D1 admission,
low BP on gelofusin. CT pelvis
shown L prostate haematoma with
peripherial zone abscess, later
develop sepsis induced atrial
fibrillation.
10
1st
No

Tienam
Augmentin
Fever down with tienem, later
switched to augmentin and
discharged

LOS (d)
History of biopsy
Pathology any
malignancy

5
1st
No

27

Table 2 Patient characteristics, clinical manifestations of infective complications and


bacteriology
No. patients undergone TRPB 2004-2009
2540
Total no. of patients with symptomatic bacteraemia
11
% with symptomatic bacteraemia
0.43%
Mean age(range)
65.5(51-81)
Infective symptoms:
% fever
100%
% chills
81.8%
% rigors
63.6%
% haematuria
72.7%
% dysuria
63.6%
Mean days since biopsy to presentation of
2.5(0-3)
symptoms(range)
Mean (degree celcuis) fever
39.3
Mean hospital stay(range)
7.4(3-20)
% Bacteriology(No.)
E. coli
91.7(11)
K. pneumoniae
8.3(1)
% ESBL producing organisms(No.)
33.3%(4)
Ciprofloxacin resistance(No.)
66.7%(8)
Table 3 Bacterial susceptibility to antibiotics
Drug
% Cultured Bacteria
Susceptible
Intermediate
Penicillins:
Ampicillin
8.3
0
Ampicillin/clavulanate
75
25
Ticarcillin/clavulanate
83.3
16.7
Piperacillin/tazobactam
100
0
Cephalosporins:
Cefuroxime(parenteral)
66.7
0
Ceftazidime
66.7
0
Cefotaxime
66.7
0
Cefoperazone/sulbactam
91.6
8.3
Carbapenems:
Imipenem
100
0
Aminoglycosides:
Gentamicin
58.3
0
Amikacin
100
0
Fluoroquinolones
Ciprofloxacin
33.3
0

Resistant
91.7
0
0
0
33.3
33.3
33.3
0
0
41.7
0
66.7

28

Table 4 Prescription of empirical antibiotics (in descending order of frequency)


Ciprofloxacin resistance among isolates(No)
66.7%(8)
Empirical antibiotics used
1 Fluoroquinolones:
45.5%(5)
Levofloxacin
27.3%(3)
Ciprofloxacin
18.2%(2)
2. Cephalosporins:
Cefuroxime(parenteral)
3. Cefoperazon/sulbactam
4. Imipenem
5. Piperacillin/tazobactam
6. Ampicillin/clavulanate
7. Ticarcillin/clavulanate

45.5%(5)
27.3%(3)
18.2%(2)
9.09%(1)
0%(0)
0%(0)

Table 5- Appropriateness of empirical antibiotics prescribed and patients outcome


Pts
No
2
4
6

LOS
(days)
7
3
7

Hospital course

Uneventful
Uneventful

Septic shock with BP


80/55 on D1 admission
requiring ICU
consultation.

Shown good response to


tazocin and later switched
to augmentin
10
10
Diagnosis: prostate abscess.
Fever down and discharged,
patient well on oral antibiotics
11
5
Uneventful
1
5
Uneventful
Inappropriate
3
8

Fever persisted, patient


(empirical
developed confusion and
antibiotics
tachycardia, requiring
prescribed could not
ICU consultation during
cover pathogen
the period of
involved)
inappropriate empirical
antibiotic (levofloxacin
given, later ciprofloxacin
resistant blood isolates
cultured).

Condition improves with


sulperazon and then
augmentin
5
20
Developed acute renal
insufficiency, Cr raised to
335(Cr 157 on admission)
7
5
Spike of high fever while
empirical antibiotics switched
from cefuroxime(susceptible)
to levofloxacin(resistant)
8
8
Persistent post-TRPB fever,
requiring 2 hospital admissions.
(Eventually treated in private
sector)
9
3
Uneventful(remarks: possibly
transient bacteraemia only)
Remarks: Mean LOS of all patients with post-TRPB bacteraemia 20042009

Appropriate

(empirical antibiotic
prescribed could
cover pathogen
involved)

Mean
LOS(days)
6.4

Median
LOS(days)
7

8.2

6.5

7.4

29

Figure 1

two-tailed P value = 0.8528

30