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Urology Grand RoundsSaleh A. Binsaleh
MD, FRCS(C)
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Case Presentation
55 years old male
PMH: Diverticulitis, recent flare treatedconservatively with antibiotics(ciprofloxacin)
Flue, few months earlier, treated withciprofloxacin.
Referred to urology due to a high PSA level on
routine screening. PSA : 6.1 (confirmed on repeat test).
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Case Presentation
No irritative or obstructive urinary symptoms.
No Family history of prostate cancer.
Examination was unremarkable includingnormal feeling prostate on DRE.
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Case Presentation
Next step:
Booked for TRUS prostate biopsy.
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TRUS
Pt had pre procedure ciprofloxacin antibiotic prophylaxis
(500 mg P.O one tab. nightbefore and one in the morningof procedure, and BID after.)
Pt was prescribed 500 mg but took own supply of 250 mg.
No bowel prep.
No pre op. U\A, culture available.
Infiltrated with lidocaine LA.
TRUS: normal.
Predicted max. PSA:19
10 cores obtained.
Uneventful procedure.
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Post Procedure Course
Post procedure, C\O increasing frequency,hematuria,was feeling unwell.
Told to increase ciprofloxacin to 500mg BID.
2 days post procedure, spiked temp., with chills.
Next morning on the way to the hospital: becameagitated, confused, and pale.
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Investigations
WBC: 5.5
Creatinine: 117
CK:115
LFT,Amylase:N CXR: N
CT abdomen & pelvis:
- no fluid collection.- Prostate very non-homogenous, measuring 6.6 x 6.3
cm.
- Mild bladder wall thickening.
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ICU course
Kept on antibiotics.
Required vasoactive inotropes for BP supportfor 24 hours.
Blood culture: E coli.(S\T: everything, Cipro.not tested)
Urine culture: negative. Extubated, off inotropes after 24 hours.
Discharged to the ward after 3 days.
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In the Medical Ward
Kept on levaquine orally for 4 weeks.
Repeated blood and urine cultures: negative.
Pathology report: high grade PIN.cores 3 to 7.
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Issues
Complicated prostatitis,septicemia, and septicshock.
? Ciprofloxacin resistance.
? Inadequate antibiotic dose.
? Unusual E.coli strain.
? How will this pt high grade PINfollowed up.
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ReviewAntibiotic Prophylaxis For
Transrectal Prostate Biopsy(TPB)
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Review
Do they need prophylactic antibiotics?
Which antibiotic(s)?
Antibiotic duration? Do we need to add Metronidazole?
Enemas?
Lidocaine infiltration?
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Introduction
However, the agent to be used, route andduration of prophylaxis are yet to bedetermined.
Similarly, there is no agreement on the role ofenemas in preventing infective complicationsafter TPB.
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Do they needprophylactic antibiotics
?
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Q-1
Enlunde et al, BJU 1997; 79(5):777-80.
evaluate prospectively the incidence of complicationsfollowing TPB without prophylactic antibiotic therapy.
415 patients.
Febrile UTI in 3%. ( treated with PO Abx)
TPB does not provoke the need for prophylactic
antibiotic therapy. Recommended to counsel patients before biopsy and to
monitor the infection rate.
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Q-1
Kapoor et al, Urology 1998;52:552-8.
Prospective randomized DB multicenter studycomparing TPB with and without antibiotic prophylaxis
(single dose cipro. 500mg). 537 patients included.
TPB with no ABX was associated with:
- 5% more rate of clinical UTI.
- 2% more rate of hospitalization due to febrile UTI.
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Q-1
Aron et al, BJU Int.2000;85:682-5.
231 pts randomized to cirpro 500mg x1, cipro500mg BID x3 D, or Placebo.
19% rate of bacteriuria and 7% rate of pyrexia inpts undergoing TPB with no prophylacticantibiotics (vs. 6%, 8% respectively).
No difference between single dose or 3 dayscourse prophylaxis.
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Q-1
Dennis et al, Infect Urol 2003;16(1):3-12.
Literature review for all reported preparationsbefore prostate biopsy, and the associated
infectious complications. Also cost-effectiveness was reviewed.
Between 1975-2002.
33 studies reviewed.
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Results
Without antibiotic prophylaxis, the infection rate(bacteriuria,fever,persistent dysuria,UTI, prostatitis andsepsis) ranged from 0-87%
With Abx use: 0-20%. Fluroquinolones were the most commonly used
antibiotic for prophylaxis.
Infectious rate with the use of fluroquinolones alone:0-11%.
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Q-1
Puig et al, Eur Radiol. 2006;16(4):939-43.
Retrospective review of the infective complicationsafter TPB with/without prophylactic Abx.
1018 pts included (614 without Abx proph.) Infectious complications occurred in 10.3% procedures
without antibiotic prophylaxis and in 3.7% of thosewith antibiotic prophylaxis.
41 major infectious complications, of these 75.6%occurred in procedures without antibiotic prophylaxis
versus 24.4% in those with prophylaxis.
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Which antibiotic
?
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Q-2
No agreement on which antibiotic to use.
A survey of 25 urology and radiology departments inthe UK showed 19 different regimens for pts
undergoing TPB.Brewster et al, BJU 1995;76:351.
A survey of 568 practicing American urologistsrandomly selected showed 11 different antibiotics were
used, with 20 different doses and 23 different timing-duration regimens.
Shandera et al, Urology. 1998;52(4):644-6.
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Q-2
Quinolones, tinidazole, co-trimoxazole, cephalosporins,carbenicillin, pipericillin, tazobactam, metronidazoleand netilmycin have all been shown to be effective,
either alone or in combination, and in various doseregimes.
Floroquinolones, particularly ciprofloxacin, are widelyused due to their broad spectrum of action, adequacy
for common colorectal and urinary flora, highconcentration within prostatic tissue, and ease of oraladministration.
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Q-2
Failure of cipro. Prophylaxis is expected to increasebecause of the excessive use, and the emergingphenomenon of multiresistant enterobacteriaceae.
Gilad et al J Urol 1999;161:222.
Ena et al J Urol 1995;153:117.
Prophylaxis with broad spectrum agents such aspipracillin-tazobactum, or carbapenem, should bestrongly considered in any pt undergoing TPB, with a
history of recent exposure to multiple antibiotics.
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Zhonghua Nan Ke Xue. 2003
Dec;9(9):690-2
Shao et al,
From China.
Distribution and resistance trends of pathogens
from UTI and impact on management. High resistance rates to ciprofloxacin(56%)
observed among E.coli UTI.
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Clin. Microbiol. Infect. 2004
Jan;10(1):75-78Chaniotaki et al,
Study from Greece
Quinolone resistance among E.coli strains from
community-acquired UTI. 36% resistance to ciprofloxacin.
Previous exposure to quinolones and underlyingchronic disease were independent risk factors for
infection by quinolone-resistant E.coli strains.
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J Antimicrob Chemother. 2003
Dec;52(6):1005-10Kahlmeter et al,
Study from Sweden.
Non-hospital antimicrobial usage and resistance in
community-acquired E.coli UTI. From 14 European countries in 1997-2000.
A statistically significant correlation between
consumption of penicillins and quinolones andresistance to ciprofloxacin.
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Abx Duration
?
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Q-3
Doubts remain about the duration of prophylaxis.
- one prospective study showed no advantage of a 3days course over a single dose of oral ciprofloxacin.
Aron et al,BJU Int.2000;85:682-5.
- another prospective study showed a one weekcourse of norfloxacin orally provided a significantreduction(4.9% Vs 11%) in infective complications
over a one day course.Aus et al,BJU 1996;77:851-5.
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Q-3
Sabbagh et al, Can J Urol. 2004;11(2):2216-9. Montreal. Prospective randomized study to compare the
incidence of infection between 1 day and 3 days offluroquinolone antibiotic prophylaxis for TPB.
363 pts. Two (0.55%) of the 363 patients, one in each group,
had an episode of sepsis. There is no clinically nor statistically significant
difference between a 1 day and 3 day antibioticprophylaxis regimen for patients undergoing TPB.
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Q-3
Lindstedt et al, Eur Urol. 2006;50(4):832-7.
Prospective randomized study to assess the level ofinfectious complications and the impact of timing of asingle, prophylactic, oral dose of ciprofloxacin 750 mggiven either 2 hours before or in conjunction with thebiopsy of the prostate.
1157 patients.
Twelve (0.9%) cases of febrile UTI. Administrating the drug 2 hours before or at the time
of biopsy (p > 0.5) showed no statistical difference.
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Do we need to addMetronidazole
?
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Q-4
The nature of fecal composition is mostly anaerobicbacteria.
30-50% of fecal matter is composed of B.fragilis.
Fluroquinolones do not provide coverage foranaerobes.
Role of Cleansing enemas in this setting?.
No randomized studies that compare the use of Flagyl
with either placebo or a fluoroquinolone in a prostatebiopsy setting.
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Other Controversies
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Enemas?
Does enema reduce the incidence of infectivecomplications after TPB?
Overall, they were found to be ineffective inreducing infective complications.
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Enemas?
Carey JM et al, Transrectal ultrasound guided biopsyof the prostate. Do enemas decrease clinicallysignificant complications?, J Urol. 2001; 166: 8285.
Lindert KA et al, Bacteremia and bacteriuria aftertransrectal ultrasound guided prostate biopsy, J Urol.2000; 164: 7680.
Terris MK, Re: Transrectal ultrasound guided biopsyof the prostate. Do enemas decrease clinicallysignificant complications?, J Urol. 2002; 167: 21452146.
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Lidocaine infiltration?
Does periprostatic local anesthesia for prostatebiopsy increase the risk of infectivecomplications?
It may.
Not well studied.
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Lidocaine infiltration?
Obeket al, J Urol. 2002;168(2):558-61.
Prospective randomized trial to assess the infectious orhemorrhagic complications associated withperiprostatic local anesthesia for prostate biopsy.
100 pts.
High fever (greater than 37.8C) was more frequent inthe nerve block group and 2 patients in this group
required rehospitalization. Bacteriuria in post-biopsyurine cultures was significantly more common in theanesthesia group.
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Lidocaine infiltration?
Nambirajan et al, Surgeon. 2004;2(4):221-4.
Prospective randomized study to assess theefficacy and safety of periprostatic lidocaineinjection Vs Placebo in TPB.
96 pts.
The complication rates were not significantlydifferent between the two groups.
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Conclusion
TPB has been reported in the literature since 1973.
Routine antibiotics prophylaxis for the procedureeffectively decreases the infection rates.
No agreements on which Abx to use, nor theprophylaxis duration.
To date, only one prospective randomized double-blindmulticenter trial supporting fluoroquinolone as cost-
effective antimicrobial agent for prostate biopsy.
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Conclusion
Caution should be taken in pts with recent exposure tociprofloxacin.
Prophylaxis with broad spectrum agents such as
pipracillin-tazobactum, or carbapenem, should bestrongly considered in any pt undergoing TPB, with ahistory of recent exposure to multiple antibiotics.
Still uncertain whether the addition of metronidazole to
the regimen is warranted.
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Thanks
Faculty of Medicine- KKUH- Riyadh