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TitleA retrospective study of patients with post-TRPB (transrectalprostate biopsy) bacteraemia

Author(s) Chan, Shuk-wun; –s Ñ ›

Citation

Issued Date 2010

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

Rights Creative Commons: Attribution 3.0 Hong Kong License

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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

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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:

Date:

16th Dec, 2010

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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.

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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%

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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.

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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

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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.

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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 Authority’s 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.

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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 non-

insulin 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 pre-

TRPB 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).

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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 patient’s 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.

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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 beta-

lactamse- producing E coli, which is slightly lower than that of 43% reported by Ozeden et

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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

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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 patient’s 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.

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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 patient’s outcomes.

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Levofloxacin resistant Escherichia coli sepsis following an ultrasound-guided transrectal

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Table and figures

Table 1: Summary of patient characteristics, clinical presentation, bacteriology and outcomesPatient 1 2 3

Biopsy date 2004/2/18 2004/8/16 2005/11/23

Age(y) 64 67 62

Medical History BPH Left RCC withradical nephrectomydone in private 2003

BPH DM on gliclazide

Hypertension on pravachol and Napamid Hypercholesteraemia

Biopsy Indication Elevated PSA Abnormal finding on PR

exam

Elevated PSA

Any previous antibioticexposure

No No No

Antibiotic indication forantibiotic exposure

N/A N/A N/A

Antibiotic prophylaxis Ciprofloxacin 500mg POonce + metronadiazole400mg PO once

Ciprofloxacin 500mg POonce + metronadiazole400mg PO once

Cipofloxacin 500mg PO once + metronadiazoPO once

Bowel preparation Feet enema Feet enema Feet enema

Time interval of antibiotic prophylaxis and OT

4 hour 30 minutes Same morning(OT timenot available)

2.5 hours

Pre-biopsy urine culture Not done Not done Not done

Interval to presentation (d)of symptoms

1 2 Immediate PU bleeding

Symptoms Fever, chills, rigors,haematuria, dysuria

Fever, dysuria,hamaturia, dysuria

Fresh bleeding immediate post biopsy, fever (op), chills, rigors

Temperature (degreeCelsius)

39 38.2 39.2

Heart rate (bpm) 95 110 110

BP (mmHg) 125/86 155/75 155/75

WBC Normal 18.4 17.4

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Interval(from biopsy date)

to collection of positive

blood culture(d)

5 2 1 2

Blood isolate Escherichia coli Escherichia coli ESBL + Escherichia coli ESBL + Escheri

Blood sensitivity Ampicillin SAugmentin S

Cefuroxime(oral) ICefuroxime(parenteral) SCiprofloxacin RGentamicin SLevofloxacin RTimentin S

Ampicillin RAugmentin S

Cefuroxime(oral) ICefuroxime(parenteral) SCiprofloxacin SGentamicin RTimentin SSulperozon S

Ampicillin RAugmentin I

Cefotaxime RCeftazidime RCeftriaxone RCefuroxime(oral) RCefuroxime(parenteral) RCiprofloxacin R

Gentamicin SSulperazon S

Tazocin S

Timentin I

Amikicin SAmpicillin R

Augmentin SCeftazidime RCefuroxime(oralCefuroxime(parCiprofloxacin RGentamicin S

Tazocin STimentin S

Any previous isolates ofESBL+ organisms

No No No

Empirical antibiotics Levofloxacin,metronidazole

Cefuroxime(parenteral),then sulperazon

Levofloxacin + metronidazole, then sulperazometronidazole

Definitive treatment Cefuroxime, thenaugmentin

Augmentin Augmentin

Hospital course Fever down on D2admission, haematuria clearon D3, no more dysuria,

discharge with oralaugmentin.

Patient developed feveron D2 post-TRPB, giveniv cefuroxime but

temperature on up goingtrend, switched to

sulperazon and fever was

down on D1 sulperazon.Later switched toaugmentin anddischarged

Develop fresh PU bleeding immediately afterfever day 1 post-biopsy, started iv levofloxacimetronidazole, fever persist. Develop chills, r

confusion on day 2, tachycardia (HR 140bpmswitched to sulperazon and consulted ICU. Fe

on D3 sulperazon, condition stable, switched

augmentin on D4 and discharge.

LOS (d) 5 7 8

History of biopsy 1st 1st 1st

Pathology – anymalignancy

adenocarcionma No No

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Patient 5 6 7 8

Biopsy date 2007/4/2 2007/6/13 2008/3/12 2008/7/23 Age(y) 81 60 69 70

Medical History Senile cataract with

extra capsularextraction of lens and

replacement 4/2002 BPH

Good Past Health Senile cataract with

phacoemulsificationdone 1999

EmphysematousCXR with apicalfibrosis

Acute retention ofurine 4/2005

Hyperten DM

Biopsy Indication Elevated PSA Elevated PSA Elevated PSA Elevated PSA

Any previous antibioticexposure

No No Yes - Ciprofloxacin andmetronidazole(13 months

before current TRPB)

Yes - Ciproflometronidazole

before currentAntibiotic indication forantibiotic exposure

N/A N/A Antibiotic prophylaxisfor his previous TRPB

Antibiotic profor his previou

Antibiotic prophylaxis Ciprofloxacin 500mg POonce + metronadiazole

400mg PO once

Ciprofloxacin 500mg PO once+ metronadiazole 400mg PO

once

Ciprofloxacin 500mg POonce + metronadiazole

400mg PO once

Ciprofloxacinonce + metron

400mg PO onc

Bowel preparation Feet enema Feet enema Feet enema Feet enema

Time interval ofantibiotic prophylaxis

and OT

Same morning(OT timenot available)

Same morning(OT time notavailable)

Same morning(OT timenot available)

Same morningnot available)

Pre-biopsy urine culture Not done Not done Not done Not done

Interval to presentation

(d) of symptoms

2 3 1 1

Symptoms Fever, chills, rigors,

frequency, dysuria,haematuria, alsocomplained of increasedcough and sputum

Fever, chills, rigors, dysuria,

vomiting

Fever, chills, rigors,

dysuria, haematuria

Fever, chills, r

dysuria, haemvomiting


41.3 39.2 40 39.7

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Heart rate (bpm) 105 126 115 129

BP (mmHg) 125/57 115/61 153/84 91/55

WBC 27.4l 1.9 13.1 3.4 Interval(from biopsydate) to collection of

positive bloodculture(d)

20 3 1 20

Blood isolate ESBL+ Escherichia coli Escherichia coli Escherichia coli Escherichia co

Blood sensitivity Amikacin S

Ampicillin RAugmentin ICeftazidine RCeftriaxone RCefuroxime(oral) RCefuroxime(parenteral) R

Ciprofloxacin RGentamicin SSulperazon I

Tazocin STimentin I

Ampicillin R

Augmentin SCefuroxime(oral) SCefuroxime(parenteral) SCiprofloxacin RGentamicin RTazocin S

Timentin S

Amikacin S

Ampicillin RAugmentin SCefuroxime(oral) ICefuroxime(parenteral) SCiprofloxacin RGentamicin R

Timentin S

Amikacin S

Ampicillin RAugmentin SCefotaxime SCeftazidime SCeftriaxone SCefuroxime(o

Cefuroxime(pSCiprofloxacin

Gentamicin RImipenem SMeropenem SSulperazon STazocin STimentin S

Any previous isolates ofESBL+ organisms

No No No No

Empirical antibiotics Cefuroxime(parenteral) +

metronidazol

Cefuroxime(parenteral)Tienam,

then tazocin

Cefuroxime(parenteral),

levofloxacin thensulperazon

Ciprofloxacin

Definitive treatment Tazocin, then augemntin Augmentin Augmentin Ciprofloxacin

Hospital course Started zinacef, fever downon D4 zinacef, ST resultshown resistant to zinacef,sensitive to gentamicine

Fever, chills and rigors D3 post-biopsy, given zinacef.Develop septic shockhypotension to 80/65 D1

Given gentamicin 160mgstat once together withzinacef 750mg Q8H ivifor 1 dose then switch to

TRPB perform2008/7/23, admAED on 2008/ because of fev

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and tazocin. Switched to

tazocin. Developed acute

renal insufficiency with Cr334(baseline 157), foleyinserted, added gentamicinivi 80mg once, fever downand urine clear 2 daysafterwards, then switch

antibiotics to augmentinand was discharged on D20

admission, tachycardia

105bpm, consulted ICU and

requires fluid resuscitation anddopamine, antibiotic switchedto tazocin. ST result available:sensitive to augmentin,switched to augmentin, fevergradually down and stable,

discharge D7.

1g Q12H for 2 doses.

Stepped down to

levofloxacin, developspike of high fever 40.3degree Celsius. Restartsulperazon then switchedto augmentin. Feverdown and discharge on

D5

haematuria, bl

culture on adm

shown no grow2008/7/28: no Treated with cfever down andischarged 5 dafterwards wit

cefuroxime fo

Follow up in c2008/8/12, fou persistent fevedysuria despitweek course o

cefuroxime, adsame day and ciprofloxacin,

subsided and pdischarged onciprofloxacin total

Blood culture available, grew

ciprofloxacin coli

Patient visiteddoctor and wawith other anti

LOS (d) 20 7 5 8(5+3)

History of biopsy 1st 1st 2nd 4th


Yes - adenocarcionma No No No

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Patient 10 11

Biopsy date 2009/10/15 2009/11/18Age(y) 62 51

Medical History Hypertension Diabetes mellitus Old pulmonary TB HBV carrier Pancreatits with laparotomy

done 30+ years back

BPH

Biopsy Indication Elevated PSA Elevated PSA, prostate nodule onDRE

Any previous antibioticexposure(within 24months)

No No

Antibiotic indication forantibiotic exposure

N/A N/A

Antibiotic prophylaxis Ciprofloxacin 500mg PO once +metronadiazole 400mg PO once

Ciprofloxacin 500mg PO once +metronadiazole 400mg PO once

Bowel preparation Feet enema Feet enema

Time interval of antibiotic prophylaxis and OT

1 hour 15 min before OT 2 hour 40 min

Pre-biopsy urine culture Not done Not done

Interval to presentation (d)of symptoms

3 1

Symptoms Fever, chills, rigors, haematuria Fever, chills, rigors


38 38.5

Heart rate (bpm) 70 136

BP (mmHg) 130/70 96/57

WBC 11.3 2.7

Interval(from biopsy date)to collection of positive blood culture(d)

6 1

Blood isolate Klebsiella pneumoniae ESBL + Escherichia coli

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Blood sensitivity Amikacin S

Ampicillin R

Augmentin SCefepime SCefotaxime SCeftazidime SCeftriaxone SCefuroxime(oral) S

Cefuroxime(parenteral) SCiprofloxacin S

Ertapenem SGentamicin SImipenem SMeropenem SSulperazon S

Tazocin STimentin S

Amikicin S

Ampicillin R

Augmentin SCefepime RCefotaxime RCeftazidime RCeftriaxone RCefuroxime(oral) R

Cefuroxime(parenteral) RCiprofloxacin S

Ertapenem SGentamicin SImipenem SMeropenem SSulperazon S

Tazocin STimentin S

Any previous isolates of

ESBL+ organisms

No No

Empirical antibiotics Tienam, gentamicine Tienam

Definitive treatment Ciprofloxacin Augmentin

Hospital course Started tienem, still high swinging

fever, desaturation D1 admission,low BP on gelofusin. CT pelvisshown L prostate haematoma with peripherial zone abscess, laterdevelop sepsis induced atrial

fibrillation.

Fever down with tienem, later

switched to augmentin anddischarged

LOS (d) 10 5

History of biopsy 1st 1st


No No

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28

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

symptoms(range)

2.5(0-3)

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 Resistant

Penicillins:

AmpicillinAmpicillin/clavulanate

Ticarcillin/clavulanate

Piperacillin/tazobactam

Cephalosporins:

Cefuroxime(parenteral)

Ceftazidime

Cefotaxime

Cefoperazone/sulbactam

Carbapenems:

Imipenem

Aminoglycosides:Gentamicin

Amikacin

Fluoroquinolones

Ciprofloxacin

8.375

83.3

100

66.7

66.7

66.7

91.6

100

58.3

100

33.3

025

16.7

0

0

0

0

8.3

0

0

0

0

91.70

0

0

33.3

33.3

33.3

0

0

41.7

0

66.7

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29

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

Ciprofloxacin

27.3%(3)

18.2%(2)

2. Cephalosporins:

Cefuroxime(parenteral) 45.5%(5)

3. Cefoperazon/sulbactam 27.3%(3)

4. Imipenem 18.2%(2)

5. Piperacillin/tazobactam 9.09%(1)

6. Ampicillin/clavulanate 0%(0)

7. Ticarcillin/clavulanate 0%(0)

Table 5- Appropriateness of empirical antibiotics prescribed and patients’ outcomePts No

LOS(days)

Hospital course MeanLOS(days)

MedianLOS(days)

Appropriate(empirical antibiotic prescribed could

cover pathogeninvolved)

2 7 Uneventful 6.4 7

4 3 Uneventful

6 7 Septic shock with BP

80/55 on D1 admissionrequiring ICUconsultation.

Shown good response totazocin and later switched

to augmentin

10 10 Diagnosis: prostate abscess.Fever down and discharged,

patient well on oral antibiotics

11 5 Uneventful

Inappropriate(empiricalantibiotics

prescribed could notcover pathogeninvolved)

1 5 Uneventful 8.2 6.5

3 8 Fever persisted, patientdeveloped confusion and

tachycardia, requiringICU consultation duringthe period of

inappropriate empiricalantibiotic (levofloxacin

given, later ciprofloxacinresistant blood isolates

cultured). Condition improves with

sulperazon and then

augmentin5 20 Developed acute renal

insufficiency, Cr raised to

335(Cr 157 on admission)

7 5 Spike of high fever whileempirical 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 2004-2009

7.4 7

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Figure 1

two-tailed P value = 0.8528

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