Urology Grand Urology Grand RoundsRounds

Saleh A. BinsalehSaleh A. Binsaleh

MD, FRCS(C)MD, FRCS(C)

Case PresentationCase Presentation

• 55 years old male55 years old male• PMH: Diverticulitis, recent flare PMH: Diverticulitis, recent flare

treated conservatively with treated conservatively with antibiotics(ciprofloxacin)antibiotics(ciprofloxacin)

• Flue, few months earlier, treated Flue, few months earlier, treated with ciprofloxacin.with ciprofloxacin.

• Referred to urology due to a high Referred to urology due to a high PSA level on routine screening.PSA level on routine screening.

• PSA : 6.1 (confirmed on repeat test).PSA : 6.1 (confirmed on repeat test).

Case PresentationCase Presentation

• No irritative or obstructive urinary No irritative or obstructive urinary symptoms.symptoms.

• No Family history of prostate No Family history of prostate cancer.cancer.

• Examination was unremarkable Examination was unremarkable including normal feeling prostate on including normal feeling prostate on DRE.DRE.

Case PresentationCase Presentation

• Next step:Next step:

Booked for TRUS prostate biopsy.Booked for TRUS prostate biopsy.

TRUSTRUS• Pt had pre procedure ciprofloxacin antibiotic Pt had pre procedure ciprofloxacin antibiotic

prophylaxis (500 mg P.O one tab. nightprophylaxis (500 mg P.O one tab. night before and before and one in the morning of procedure, and BID after.)one in the morning of procedure, and BID after.)

• Pt was prescribed 500 mg but took own supply of Pt was prescribed 500 mg but took own supply of 250 mg.250 mg.

• No bowel prep.No bowel prep.• No pre op. U\A, culture available.No pre op. U\A, culture available.• Infiltrated with lidocaine LA.Infiltrated with lidocaine LA.• TRUS: normal.TRUS: normal.• Predicted max. PSA:19Predicted max. PSA:19• 10 cores obtained.10 cores obtained.• Uneventful procedure.Uneventful procedure.

Post Procedure CoursePost Procedure Course

• Post procedure, C\O increasing Post procedure, C\O increasing frequency,hematuria, was feeling unwell.frequency,hematuria, was feeling unwell.

• Told to increase ciprofloxacin to 500mg Told to increase ciprofloxacin to 500mg BID.BID.

• 2 days post procedure, spiked temp., with 2 days post procedure, spiked temp., with chills.chills.

• Next morning on the way to the hospital: Next morning on the way to the hospital: became agitated, confused, and pale.became agitated, confused, and pale.

In ERIn ER

• T: 42.3 C, BP: 89/60, PR: 118.T: 42.3 C, BP: 89/60, PR: 118.• BP further dropped to 76/40.BP further dropped to 76/40.• Intubated, started on Intubated, started on

Ampicillin,Gentamycin, and Timintin.Ampicillin,Gentamycin, and Timintin.• P/A: soft, no guarding, no masses.P/A: soft, no guarding, no masses.• DRE ?!: painful (pt was grimacing DRE ?!: painful (pt was grimacing

while on Propafol), no fluctuation while on Propafol), no fluctuation felt.felt.

• Transferred to ICU. Transferred to ICU.

InvestigationsInvestigations

• WBC: 5.5WBC: 5.5• Creatinine: 117Creatinine: 117• CK:115CK:115• LFT,Amylase:NLFT,Amylase:N• CXR: NCXR: N• CT abdomen & pelvis:CT abdomen & pelvis:- no fluid collection.no fluid collection.- Prostate very non-homogenous, measuring Prostate very non-homogenous, measuring

6.6 x 6.3 cm.6.6 x 6.3 cm.- Mild bladder wall thickening.Mild bladder wall thickening.

ICU courseICU course

• Kept on antibiotics.Kept on antibiotics.• Required vasoactive inotropes for BP Required vasoactive inotropes for BP

support for 24 hours.support for 24 hours.• Blood culture: E coli.(S\T: everything, Blood culture: E coli.(S\T: everything,

Cipro. not tested)Cipro. not tested)• Urine culture: negative.Urine culture: negative.• Extubated, off inotropes after 24 hours.Extubated, off inotropes after 24 hours.• Discharged to the ward after 3 days.Discharged to the ward after 3 days.

In the Medical WardIn the Medical Ward

• Kept on levaquine orally for 4 weeks.Kept on levaquine orally for 4 weeks.• Repeated blood and urine cultures: Repeated blood and urine cultures:

negative.negative.• Pathology report: Pathology report: high grade PINhigh grade PIN..

cores 3 to 7.cores 3 to 7.

IssuesIssues

Complicated prostatitis,septicemia, Complicated prostatitis,septicemia, and septic shock.and septic shock.

• ? Ciprofloxacin resistance.? Ciprofloxacin resistance.• ? Inadequate antibiotic dose.? Inadequate antibiotic dose.• ? Unusual E.coli strain.? Unusual E.coli strain.• ? How will this pt high grade PIN ? How will this pt high grade PIN

followed up.followed up.

ReviewReview

Antibiotic Prophylaxis ForAntibiotic Prophylaxis For

Transrectal Prostate BiopsyTransrectal Prostate Biopsy

(TPB)(TPB)

ReviewReview

• Do they need prophylactic Do they need prophylactic antibiotics?antibiotics?

• Which antibiotic(s)?Which antibiotic(s)?• Antibiotic duration?Antibiotic duration?• Do we need to add Metronidazole?Do we need to add Metronidazole?• Enemas?Enemas?• Lidocaine infiltration?Lidocaine infiltration?

IntroductionIntroduction

• Infective complications after TRUS Infective complications after TRUS prostate biopsy(TPB) are well known, and prostate biopsy(TPB) are well known, and potentially fatal.potentially fatal.

• Six reported cases of Six reported cases of fatalfatal sepsis post TPB. sepsis post TPB. - Brewster et al, Br J Urol 1993;77:977-8.- Borer et al, J Infect 1999;38:128-9.

• Theoretically, an adequate prophylactic Theoretically, an adequate prophylactic antibiotic active against both urinary and antibiotic active against both urinary and colorectal flora, and reaches high tissue colorectal flora, and reaches high tissue concentrations within the prostate should concentrations within the prostate should be taken peri-procedure.be taken peri-procedure.

IntroductionIntroduction

• However, the agent to be used, However, the agent to be used, route and duration of prophylaxis route and duration of prophylaxis are yet to be determined.are yet to be determined.

• Similarly, there is no agreement on Similarly, there is no agreement on the role of enemas in preventing the role of enemas in preventing infective complications after TPB.infective complications after TPB.

Do they need Do they need prophylactic prophylactic antibioticsantibiotics

??

Q-1Q-1

Enlunde Enlunde et alet al, BJU 1997; 79(5):777-80., BJU 1997; 79(5):777-80.• evaluate prospectively the incidence of evaluate prospectively the incidence of

complications following TPB without complications following TPB without prophylactic antibiotic therapy.prophylactic antibiotic therapy.

• 415 patients.415 patients.• Febrile UTI in 3%. ( treated with PO Abx)Febrile UTI in 3%. ( treated with PO Abx)• TPB does not provoke the need for prophylactic TPB does not provoke the need for prophylactic

antibiotic therapy.antibiotic therapy. • RecommendedRecommended to counsel patients before biopsy to counsel patients before biopsy

and to monitor the infection rate.and to monitor the infection rate.

Q-1Q-1

Kapoor Kapoor et alet al, Urology , Urology 1998;52:552-8.1998;52:552-8.

• Prospective randomized DB multicenter Prospective randomized DB multicenter study comparing TPB with and without study comparing TPB with and without antibiotic prophylaxis (single dose cipro. antibiotic prophylaxis (single dose cipro. 500mg).500mg).

• 537 patients included.537 patients included.• TPB with no ABX was associated with:TPB with no ABX was associated with:- 5% more rate of clinical UTI.- 5% more rate of clinical UTI.- 2% more rate of hospitalization due to - 2% more rate of hospitalization due to

febrile UTI.febrile UTI.

Q-1Q-1

Aron Aron et alet al, BJU Int.2000;85:682-5., BJU Int.2000;85:682-5.• 231 pts randomized to cirpro 500mg 231 pts randomized to cirpro 500mg

x1, cipro 500mg BID x3 D, or Placebo.x1, cipro 500mg BID x3 D, or Placebo.• 19% rate of bacteriuria and 7% rate of 19% rate of bacteriuria and 7% rate of

pyrexia in pts undergoing TPB with no pyrexia in pts undergoing TPB with no prophylactic antibiotics (vs. 6%, 8% prophylactic antibiotics (vs. 6%, 8% respectively).respectively).

• No difference between single dose or 3 No difference between single dose or 3 days course prophylaxis.days course prophylaxis.

Q-1Q-1

Dennis Dennis et alet al, Infect Urol , Infect Urol 2003;16(1):3-122003;16(1):3-12..

• Literature review for all reported Literature review for all reported preparations before prostate biopsy, preparations before prostate biopsy, and the associated infectious and the associated infectious complications.complications.

• Also cost-effectiveness was reviewed.Also cost-effectiveness was reviewed.• Between 1975-2002.Between 1975-2002.• 33 studies reviewed.33 studies reviewed.

ResultsResults

• Without antibiotic prophylaxis, the Without antibiotic prophylaxis, the infection rate (bacteriuria,fever,persistent infection rate (bacteriuria,fever,persistent dysuria,UTI, prostatitis and sepsis) dysuria,UTI, prostatitis and sepsis) ranged from 0-87%ranged from 0-87%

• With Abx use: 0-20%.With Abx use: 0-20%.• Fluroquinolones were the most commonly Fluroquinolones were the most commonly

used antibiotic for prophylaxis.used antibiotic for prophylaxis.• Infectious rate with the use of Infectious rate with the use of

fluroquinolones alone:0-11%.fluroquinolones alone:0-11%.

Q-1Q-1 Puig Puig et alet al, Eur Radiol. 2006;16(4):939-43., Eur Radiol. 2006;16(4):939-43. • Retrospective review of the infective Retrospective review of the infective

complications after TPB with/without complications after TPB with/without prophylactic Abx.prophylactic Abx.

• 1018 pts included (614 without Abx proph.)1018 pts included (614 without Abx proph.)• Infectious complications occurred in 10.3% Infectious complications occurred in 10.3%

procedures without antibiotic prophylaxis and procedures without antibiotic prophylaxis and in 3.7% of those with antibiotic prophylaxis.in 3.7% of those with antibiotic prophylaxis.

• 41 major infectious complications, of these 41 major infectious complications, of these 75.6% occurred in procedures without 75.6% occurred in procedures without antibiotic prophylaxis versus 24.4% in those antibiotic prophylaxis versus 24.4% in those with prophylaxis. with prophylaxis.

Which antibioticWhich antibiotic??

Q-2Q-2

• No agreement on which antibiotic to use.No agreement on which antibiotic to use. A survey of 25 urology and radiology A survey of 25 urology and radiology

departments in the UK showed 19 different departments in the UK showed 19 different regimens for pts undergoing TPB.regimens for pts undergoing TPB.

Brewster et al, BJU 1995;76:351.

A survey of 568 practicing American A survey of 568 practicing American urologists randomly selected showed 11 urologists randomly selected showed 11 different antibiotics were used, with 20 different antibiotics were used, with 20 different doses and 23 different timing-different doses and 23 different timing-duration regimens.duration regimens.

Shandera et al, Urology. 1998;52(4):644-6.Shandera et al, Urology. 1998;52(4):644-6.

Q-2Q-2

• Quinolones, tinidazole, co-trimoxazole, cephalosporins, carbenicillin, pipericillin, tazobactam, metronidazole and netilmycin have all been shown to be effective, either alone or in combination, and in various dose regimes.

• Floroquinolones, particularly ciprofloxacin, are Floroquinolones, particularly ciprofloxacin, are widely used due to their broad spectrum of widely used due to their broad spectrum of action, adequacy for common colorectal and action, adequacy for common colorectal and urinary flora, high concentration within urinary flora, high concentration within prostatic tissue, and ease of oral prostatic tissue, and ease of oral administration.administration.

Q-2Q-2

• Failure of cipro. Prophylaxis is expected Failure of cipro. Prophylaxis is expected to increase because of the excessive use, to increase because of the excessive use, and the emerging phenomenon of and the emerging phenomenon of multiresistant enterobacteriaceae. multiresistant enterobacteriaceae.

Gilad et al J Urol 1999;161:222. Ena et al J Urol 1995;153:117.

• Prophylaxis with broad spectrum agents Prophylaxis with broad spectrum agents such as pipracillin-tazobactum, or such as pipracillin-tazobactum, or carbapenem, should be strongly carbapenem, should be strongly considered in any pt undergoing TPB, considered in any pt undergoing TPB, with a history of recent exposure to with a history of recent exposure to multiple antibiotics.multiple antibiotics.

Emerging Emerging Ciprofloxacin Ciprofloxacin Resistance!Resistance!

Zhonghua Nan Ke Xue. Zhonghua Nan Ke Xue. 2003 Dec;9(9):690-22003 Dec;9(9):690-2

Shao et al,Shao et al,• From China.From China.• Distribution and resistance trends of Distribution and resistance trends of

pathogens from UTI and impact on pathogens from UTI and impact on management.management.

• High resistance rates to High resistance rates to ciprofloxacin(56%) observed among ciprofloxacin(56%) observed among E.coli UTI.E.coli UTI.

Clin. Microbiol. Infect. Clin. Microbiol. Infect. 2004 Jan;10(1):75-782004 Jan;10(1):75-78

Chaniotaki et al,Chaniotaki et al,• Study from GreeceStudy from Greece• Quinolone resistance among E.coli strains Quinolone resistance among E.coli strains

from community-acquired UTI.from community-acquired UTI.• 36% resistance to ciprofloxacin.36% resistance to ciprofloxacin.• Previous exposure to quinolones and Previous exposure to quinolones and

underlying chronic disease were underlying chronic disease were independent risk factors for infection by independent risk factors for infection by quinolone-resistant E.coli strains.quinolone-resistant E.coli strains.

J Antimicrob Chemother. J Antimicrob Chemother. 2003 Dec;52(6):1005-102003 Dec;52(6):1005-10

Kahlmeter et al,Kahlmeter et al,• Study from Sweden.Study from Sweden.• Non-hospital antimicrobial usage and Non-hospital antimicrobial usage and

resistance in community-acquired E.coli UTI.resistance in community-acquired E.coli UTI.• From 14 European countries in 1997-2000.From 14 European countries in 1997-2000.• A statistically significant correlation between A statistically significant correlation between

consumption of penicillins and quinolones consumption of penicillins and quinolones and resistance to ciprofloxacin.and resistance to ciprofloxacin.

Abx DurationAbx Duration??

Q-3Q-3

• Doubts remain about the duration of Doubts remain about the duration of prophylaxis.prophylaxis.

- one prospective study showed no advantage one prospective study showed no advantage of a 3 days course over a single dose of oral of a 3 days course over a single dose of oral ciprofloxacin. ciprofloxacin.

Aron et al,BJU Int.2000;85:682-5.

- another prospective study showed a one another prospective study showed a one week course of norfloxacin orally provided a week course of norfloxacin orally provided a significant reduction(4.9% Vs 11%) in significant reduction(4.9% Vs 11%) in infective complications over a one day infective complications over a one day course. course.

Aus et al,BJU 1996;77:851-5.

Q-3Q-3 Sabbagh Sabbagh et alet al, Can J Urol. , Can J Urol.

2004;11(2):2216-9.2004;11(2):2216-9.• Montreal.Montreal.• Prospective randomized study to compare the Prospective randomized study to compare the

incidence of infection between 1 day and 3 days incidence of infection between 1 day and 3 days of fluroquinolone antibiotic prophylaxis for TPB.of fluroquinolone antibiotic prophylaxis for TPB.

• 363 pts.363 pts.• Two (0.55%) of the 363 patients, one in each Two (0.55%) of the 363 patients, one in each

group, had an episode of sepsis.group, had an episode of sepsis.• There is no clinically nor statistically significant There is no clinically nor statistically significant

difference between a 1 day and 3 day antibiotic difference between a 1 day and 3 day antibiotic prophylaxis regimen for patients undergoing prophylaxis regimen for patients undergoing TPB. TPB.

Q-3Q-3 Lindstedt Lindstedt et alet al, Eur Urol. 2006;50(4):832-7., Eur Urol. 2006;50(4):832-7.• Prospective randomized study to assess the level Prospective randomized study to assess the level

of infectious complications and the impact of of infectious complications and the impact of timing of a timing of a singlesingle, prophylactic, oral dose of , prophylactic, oral dose of ciprofloxacin 750 mg given either 2 hours before ciprofloxacin 750 mg given either 2 hours before or in conjunction with the biopsy of the prostate.or in conjunction with the biopsy of the prostate.

• 1157 patients.1157 patients.• Twelve (0.9%) cases of febrile UTI.Twelve (0.9%) cases of febrile UTI.• Administrating the drug 2 hours before or at the Administrating the drug 2 hours before or at the

time of biopsy (p > 0.5) showed no statistical time of biopsy (p > 0.5) showed no statistical difference.difference.

Do we need to addDo we need to add Metronidazole Metronidazole

??

Q-4Q-4

• The nature of fecal composition is mostly The nature of fecal composition is mostly anaerobic bacteria.anaerobic bacteria.

• 30-50% of fecal matter is composed of 30-50% of fecal matter is composed of B.fragilis.B.fragilis.

• Fluroquinolones do not provide coverage Fluroquinolones do not provide coverage for anaerobes.for anaerobes.

• Role of Cleansing enemas in this setting?.Role of Cleansing enemas in this setting?.• No randomized studies that compare the No randomized studies that compare the

use of Flagyl with either placebo or a use of Flagyl with either placebo or a fluoroquinolone in a prostate biopsy fluoroquinolone in a prostate biopsy setting.setting.

Other Other ControversiesControversies

Enemas?Enemas?

• Does enema reduce the incidence of Does enema reduce the incidence of infective complications after TPB?infective complications after TPB?

• Overall, they were found to be Overall, they were found to be ineffective in reducing infective ineffective in reducing infective complications.complications.

Enemas?Enemas?

• Carey JM et alCarey JM et al, Transrectal ultrasound , Transrectal ultrasound guided biopsy of the prostate. Do enemas guided biopsy of the prostate. Do enemas decrease clinically significant complications?, decrease clinically significant complications?, J Urol. 2001; 166: 82–85.J Urol. 2001; 166: 82–85.

• Lindert KA et alLindert KA et al, Bacteremia and bacteriuria , Bacteremia and bacteriuria after transrectal ultrasound guided prostate after transrectal ultrasound guided prostate biopsy, J Urol. 2000; 164: 76–80.biopsy, J Urol. 2000; 164: 76–80.

• Terris MKTerris MK, Re: Transrectal ultrasound , Re: Transrectal ultrasound guided biopsy of the prostate. Do enemas guided biopsy of the prostate. Do enemas decrease clinically significant complications?, decrease clinically significant complications?, J Urol. 2002; 167: 2145–2146.J Urol. 2002; 167: 2145–2146.

Lidocaine infiltration?Lidocaine infiltration?

• Does periprostatic local anesthesia Does periprostatic local anesthesia for prostate biopsy increase the risk for prostate biopsy increase the risk of infective complications?of infective complications?

• It may.It may.• Not well studied.Not well studied.

Lidocaine infiltration?Lidocaine infiltration? Obek Obek et alet al, J Urol. 2002;168(2):558-61., J Urol. 2002;168(2):558-61.• Prospective randomized trial to assess the Prospective randomized trial to assess the

infectious or hemorrhagic complications infectious or hemorrhagic complications associated with periprostatic local anesthesia associated with periprostatic local anesthesia for prostate biopsy.for prostate biopsy.

• 100 pts.100 pts.• High fever (greater than 37.8C) was more High fever (greater than 37.8C) was more

frequent in the nerve block group and 2 frequent in the nerve block group and 2 patients in this group required patients in this group required rehospitalization. Bacteriuria in post-biopsy rehospitalization. Bacteriuria in post-biopsy urine cultures was significantly more common urine cultures was significantly more common in the anesthesia group. in the anesthesia group.

Lidocaine infiltration?Lidocaine infiltration?

Nambirajan Nambirajan et alet al, Surgeon. , Surgeon. 2004;2(4):221-4.2004;2(4):221-4.

• Prospective randomized study to assess Prospective randomized study to assess the efficacy and safety of periprostatic the efficacy and safety of periprostatic lidocaine injection Vs Placebo in TPB.lidocaine injection Vs Placebo in TPB.

• 96 pts.96 pts.• The complication rates were not The complication rates were not

significantly different between the two significantly different between the two groups.groups.

ConclusionConclusion

• TPB has been reported in the literature TPB has been reported in the literature since 1973.since 1973.

• Routine antibiotics prophylaxis for the Routine antibiotics prophylaxis for the procedure effectively decreases the procedure effectively decreases the infection rates.infection rates.

• No agreements on which Abx to use, nor No agreements on which Abx to use, nor the prophylaxis duration.the prophylaxis duration.

• To date, only one prospective randomized To date, only one prospective randomized double-blind multicenter trial supporting double-blind multicenter trial supporting fluoroquinolone as cost-effective fluoroquinolone as cost-effective antimicrobial agent for prostate biopsy. antimicrobial agent for prostate biopsy.

ConclusionConclusion

• Caution should be taken in pts with recent Caution should be taken in pts with recent exposure to ciprofloxacin.exposure to ciprofloxacin.

• Prophylaxis with broad spectrum agents Prophylaxis with broad spectrum agents such as pipracillin-tazobactum, or such as pipracillin-tazobactum, or carbapenem, should be strongly considered carbapenem, should be strongly considered in any pt undergoing TPB, with a history of in any pt undergoing TPB, with a history of recent exposure to multiple antibiotics.recent exposure to multiple antibiotics.

• Still uncertain whether the addition of Still uncertain whether the addition of metronidazole to the regimen is warranted.metronidazole to the regimen is warranted.

ThanksThanks

Faculty of Medicine- KKUH- Faculty of Medicine- KKUH- RiyadhRiyadh