Urology Grand Rounds

1. Urology Grand Rounds Saleh A. Binsaleh MD, FRCS(C)

2. Case Presentation 55 years old male PMH: Diverticulitis, recent flare treated conservatively with antibiotics(ciprofloxacin) Flue, few months earlier, treated with ciprofloxacin. Referred to urology due to a high PSA level on routine screening. PSA : 6.1 (confirmed on repeat test).

3. Case Presentation No irritative or obstructive urinary symptoms. No Family history of prostate cancer. Examination was unremarkable including normal feeling prostate on DRE.

4. Case Presentation Next step: Booked for TRUS prostate biopsy.

5. TRUS Pt had pre procedure ciprofloxacin antibiotic prophylaxis (500 mg P.O one tab. night before and one in the morning of 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.

6. 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: became agitated, confused, and pale.

7. In ER T: 42.3 C, BP: 89/60, PR: 118. BP further dropped to 76/40. Intubated, started on Ampicillin,Gentamycin, and Timintin. P/A: soft, no guarding, no masses. DRE ?!: painful (pt was grimacing while on Propafol), no fluctuation felt. Transferred to ICU.

8. 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.

9. ICU course Kept on antibiotics. Required vasoactive inotropes for BP support for 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.

10. 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.

11. Issues Complicated prostatitis,septicemia, and septic shock. ? Ciprofloxacin resistance. ? Inadequate antibiotic dose. ? Unusual E.coli strain. ? How will this pt high grade PIN followed up.

12. Review Antibiotic Prophylaxis For Transrectal Prostate Biopsy (TPB)

13. Review Do they need prophylactic antibiotics? Which antibiotic(s)? Antibiotic duration? Do we need to add Metronidazole? Enemas? Lidocaine infiltration?

14. Introduction Infective complications after TRUS prostate biopsy(TPB) are well known, and potentially fatal. Six reported cases of fatal 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 antibiotic active against both urinary and colorectal flora, and reaches high tissue concentrations within the prostate should be taken peri-procedure.

15. Introduction However, the agent to be used, route and duration of prophylaxis are yet to be determined. Similarly, there is no agreement on the role of enemas in preventing infective complications after TPB.

16. Do they need prophylactic antibiotics?

17. Q-1 Enlunde et al, BJU 1997; 79(5):777-80. evaluate prospectively the incidence of complications following 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.

18. Q-1 Kapoor et al, Urology 1998;52:552-8. Prospective randomized DB multicenter study comparing 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.

19. Q-1 Aron et al, BJU Int.2000;85:682-5. 231 pts randomized to cirpro 500mg x1, cipro 500mg BID x3 D, or Placebo. 19% rate of bacteriuria and 7% rate of pyrexia in pts undergoing TPB with no prophylactic antibiotics (vs. 6%, 8% respectively). No difference between single dose or 3 days course prophylaxis.

20. Q-1 Dennis et al, Infect Urol 2003;16(1):3-12. Literature review for all reported preparations before prostate biopsy, and the associated infectious complications. Also cost-effectiveness was reviewed. Between 1975-2002. 33 studies reviewed.

21. Results Without antibiotic prophylaxis, the infection rate (bacteriuria,fever,persistent dysuria,UTI, prostatitis and sepsis) 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%.

22. Q-1 Puig et al, Eur Radiol. 2006;16(4):939-43. Retrospective review of the infective complications after 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 those with antibiotic prophylaxis. 41 major infectious complications, of these 75.6% occurred in procedures without antibiotic prophylaxis versus 24.4% in those with prophylaxis.

23. Which antibiotic?

24. Q-2 No agreement on which antibiotic to use. A survey of 25 urology and radiology departments in the UK showed 19 different regimens for pts undergoing TPB. Brewster et al, BJU 1995;76:351. A survey of 568 practicing American urologists randomly 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.

25. Q-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 widely used due to their broad spectrum of action, adequacy for common colorectal and urinary flora, high concentration within prostatic tissue, and ease of oral administration.

26. Q-2 Failure of cipro. Prophylaxis is expected to increase because of the excessive use, and the emerging phenomenon 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 as pipracillin-tazobactum, or carbapenem, should be strongly considered in any pt undergoing TPB, with a history of recent exposure to multiple antibiotics.

27. Emerging Ciprofloxacin Resistance!

28. 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.

29. Clin. Microbiol. Infect. 2004 Jan;10(1):75-78 Chaniotaki et al, Study from Greece Quinolone resistance among E.coli strains from community-acquired UTI. 36% resistance to ciprofloxacin. Previous exposure to quinolones and underlying chronic disease were independent risk factors for infection by quinolone-resistant E.coli strains.

30. J Antimicrob Chemother. 2003 Dec;52(6):1005-10 Kahlmeter 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 and resistance to ciprofloxacin.

31. Abx Duration?

32. Q-3 Doubts remain about the duration of prophylaxis. one prospective study showed no advantage of a 3 days course over a single dose of oral ciprofloxacin. Aron et al,BJU Int.2000;85:682-5. another prospective study showed a one week course of norfloxacin orally provided a significant reduction(4.9% Vs 11%) in infective complications over a one day course. Aus et al,BJU 1996;77:851-5.

33. 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 of fluroquinolone 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 antibiotic prophylaxis regimen for patients undergoing TPB.

34. Q-3 Lindstedt et al, Eur Urol. 2006;50(4):832-7. Prospective randomized study to assess the level of infectious complications and the impact of timing of a single, prophylactic, oral dose of ciprofloxacin 750 mg given either 2 hours before or in conjunction with the biopsy 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.

35. Do we need to add Metronidazole?

36. Q-4 The nature of fecal composition is mostly anaerobic bacteria. 30-50% of fecal matter is composed of B.fragilis. Fluroquinolones do not provide coverage for anaerobes. Role of Cleansing enemas in this setting?. No randomized studies that compare the use of Flagyl with either placebo or a fluoroquinolone in a prostate biopsy setting.

37. Other Controversies

38. Enemas? Does enema reduce the incidence of infective complications after TPB? Overall, they were found to be ineffective in reducing infective complications.

39. Enemas? Carey JM et al, Transrectal ultrasound guided biopsy of the prostate. Do enemas decrease clinically significant complications?, J Urol. 2001; 166: 82�85. Lindert KA et al, Bacteremia and bacteriuria after transrectal ultrasound guided prostate biopsy, J Urol. 2000; 164: 76�80. Terris MK, Re: Transrectal ultrasound guided biopsy of the prostate. Do enemas decrease clinically significant complications?, J Urol. 2002; 167: 2145�2146.

40. Lidocaine infiltration? Does periprostatic local anesthesia for prostate biopsy increase the risk of infective complications? It may. Not well studied.

41. Lidocaine infiltration? Obek et al, J Urol. 2002;168(2):558-61. Prospective randomized trial to assess the infectious or hemorrhagic complications associated with periprostatic local anesthesia for prostate biopsy. 100 pts. High fever (greater than 37.8C) was more frequent in the nerve block group and 2 patients in this group required rehospitalization. Bacteriuria in post-biopsy urine cultures was significantly more common in the anesthesia group.

42. Lidocaine infiltration? Nambirajan et al, Surgeon. 2004;2(4):221-4. Prospective randomized study to assess the efficacy and safety of periprostatic lidocaine injection Vs Placebo in TPB. 96 pts. The complication rates were not significantly different between the two groups.

43. Conclusion TPB has been reported in the literature since 1973. Routine antibiotics prophylaxis for the procedure effectively decreases the infection rates. No agreements on which Abx to use, nor the prophylaxis duration. To date, only one prospective randomized double-blind multicenter trial supporting fluoroquinolone as cost-effective antimicrobial agent for prostate biopsy.

44. Conclusion Caution should be taken in pts with recent exposure to ciprofloxacin. Prophylaxis with broad spectrum agents such as pipracillin-tazobactum, or carbapenem, should be strongly considered in any pt undergoing TPB, with a history of recent exposure to multiple antibiotics. Still uncertain whether the addition of metronidazole to the regimen is warranted.

45. Thanks Faculty of Medicine- KKUH- Riyadh