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Prevalence of ciprofloxacin-resistant Enterobacteriaceae in the intestinal flora of patients undergoing trans-rectal prostate biopsy in Norwich, UKMarcelino Yazbek Hanna1*, Catherine Tremlett2, Gurvir Josan1, Robert Mills1, Mark Rochester1, David M Livermore3.1Urology and 2Microbiology Departments. Norfolk and Norwich University Hospital. Colney Lane Norwich. UK NR4 7UYand 3Norwich Medical School, University of East Anglia, Norwich NR4 7TJmarcelino.yazbekhanna@nnuh.nhs.uk,catherine.tremlett@nnuh.nhs.uk, gurvir.josan@nnuh.nhs.uk,robert.mills@nnuh.nhs.uk, mark.rochester@nnuh.nhs.uk, d.livermore@uea.ac.ukKeywords: Prostate biopsy, sepsis, infection, rectal swabs, fluoroquinolone.Running head: TRUS, ciprofloxacin prophylaxis and sepsis*Corresponding authorAbstractObjective. To determine the efficacy of fluoroquinolone prophylaxis in patients undergoing trans-rectal ultrasound scan (TRUS)-guided biopsy of the prostate in the Norwich population, and its correlation with ciprofloxacin resistance in the faecal flora. We also aimed to determine the usefulness of a pre-biopsy rectal screen for resistant bacteria in these patients.Patients and methods The incidence and microbiology of sepsis after TRUS-guided prostate biopsies between 2007 and 2011 was audited retrospectively. Subsequently, in 2012, a prospective study was performed, collecting the same data but also culturing rectal swabs from all patients undergoing TRUS biopsy, with a post-biopsy follow-up period of 6 months. All patients were given prophylactic oral ciprofloxacin, as per Trust policy (750 mg 1 hour pre-biopsy, followed by 250 mg q12h for 3 subsequent days). Results: Between 2007 and 2011, 3600 patients underwent TRUS biopsy. Among these, 11 (0.3%) were admitted to hospital for post-biopsy related sepsis but only 4 (0.1%) had ciprofloxacin-resistant Escherichia coli confirmed from blood cultures: three had ciprofloxacin-susceptible Enterobacteriaceae, and four had no ciprofloxacin susceptibility data. In 2012, 10 (3.7%) of 267 patients sampled pre-biopsy had ciprofloxacin-resistant E. coli recovered on rectal swab culture but none of these men presented with post-biopsy sepsis; during the 6-month follow-up period, seven patients were diagnosed with urinary tract infections.Conclusion: Ciprofloxacin-resistant Enterobacteriaceae remain rare in the intestinal flora of the Norwich TRUS population, meaning that the drug remains adequate as prophylaxis. Pre-biopsy rectal swabs may be useful for individual departments to periodically assess their own populations and to ensure their antibiotic policy remains valid. In populations where resistance is known to be highly prevalent, pre-biopsy rectal swabs can help guide addition of further antibiotics to prevent post-biopsy septicaemia.IntroductionTrans-rectal Ultrasound (TRUS)-guided prostate biopsy is a common procedure in the diagnosis of prostate cancer, performed on approximately 75,000 men every year in the UK alone ADDIN PAPERS2_CITATIONS <citation><uuid>C307AB96-D1F6-42A0-A80E-5D29B08C77BA</uuid><priority>0</priority><publications><publication><uuid>24ACA983-DD2D-4332-A985-6D8C4144BB05</uuid><volume>68</volume><doi>10.1093/jac/dks401</doi><startpage>247</startpage><publication_date>99201302001200000000220000</publication_date><url> national burden of infections after prostate biopsy in England and Wales: a wake-up call for better prevention.</title><location>&lt;html>&lt;head>&lt;meta http-equiv="content-type" content="text/html; charset=utf-8"/>&lt;title>Sorry...&lt;/title>&lt;style> body { font-family: verdana, arial, sans-serif; background-color: #fff; color: #000; }&lt;/style>&lt;/head>&lt;body>&lt;div>&lt;table>&lt;tr>&lt;td>&lt;b>&lt;font face=times color=#0039b6 size=10>G&lt;/font>&lt;font face=times color=#c41200 size=10>o&lt;/font>&lt;font face=times color=#f3c518 size=10>o&lt;/font>&lt;font face=times color=#0039b6 size=10>g&lt;/font>&lt;font face=times color=#30a72f size=10>l&lt;/font>&lt;font face=times color=#c41200 size=10>e&lt;/font>&lt;/b>&lt;/td>&lt;td style="text-align: left; vertical-align: bottom; padding-bottom: 15px; width: 50%">&lt;div style="border-bottom: 1px solid #dfdfdf;">Sorry...&lt;/div>&lt;/td>&lt;/tr>&lt;/table>&lt;/div>&lt;div style="margin-left: 4em;">&lt;h1>We're sorry...&lt;/h1>&lt;p>... but your computer or network may be sending automated queries. To protect our users, we can't process your request right now.&lt;/p>&lt;/div>&lt;div style="margin-left: 4em;">See &lt;a href="">Google Help&lt;/a> for more information.&lt;br/>&lt;br/>&lt;/div>&lt;div style="text-align: center; border-top: 1px solid #dfdfdf;">&amp;copy; 2009 Google - &lt;a href="">Google Home&lt;/a>&lt;/div>&lt;/body>&lt;/html></location><institution>Department of Urology, Northwick Park Hospital, Watford Road, London HA1 3UJ, UK. deepakbatura@</institution><number>2</number><subtype>400</subtype><endpage>249</endpage><bundle><publication><title>Journal of Antimicrobial Chemotherapy</title><type>-100</type><subtype>-100</subtype><uuid>101E02B3-9D38-4FA7-9756-0565F655EB57</uuid></publication></bundle><authors><author><firstName>Deepak</firstName><lastName>Batura</lastName></author><author><firstName>Guduru</firstName><lastName>Gopal Rao</lastName></author></authors></publication></publications><cites></cites></citation>(1).The procedure is relatively safe, except for the risk of infection, in particular bacteraemia ADDIN PAPERS2_CITATIONS <citation><uuid>9DE30FE3-A075-4D7D-8521-E5CC4553975F</uuid><priority>1</priority><publications><publication><volume>31</volume><publication_date>99199900001200000000200000</publication_date><number>5</number><doi>10.1023/A:1007168823851</doi><startpage>681</startpage><title>Multiple transrectal ultrasound guided prostatic biopsies: morbidity and tolerance</title><uuid>7E1767B1-ED37-49EE-AED4-5B4DBE261FD3</uuid><subtype>400</subtype><endpage>686</endpage><type>400</type><url> Urology and Nephrology</title><type>-100</type><subtype>-100</subtype><uuid>DFF5749F-78C6-4206-81B7-EBB789EDCB34</uuid></publication></bundle><authors><author><firstName>Ch</firstName><lastName>Deliveliotis</lastName></author><author><firstName>V</firstName><lastName>John</lastName></author><author><firstName>G</firstName><lastName>Louras</lastName></author><author><firstName>S</firstName><lastName>Andreas</lastName></author><author><firstName>E</firstName><lastName>Alargof</lastName></author><author><firstName>F</firstName><lastName>Sofras</lastName></author><author><firstName>N</firstName><lastName>Goulandris</lastName></author></authors></publication><publication><volume>71</volume><publication_date>99199304001200000000220000</publication_date><number>4</number><doi>10.1111/j.1464-410X.1993.tb15993.x</doi><startpage>460</startpage><title>Multiple Transrectal Ultrasound-Guided Prostatic Biopsies-True Morbidity and Patient Acceptance</title><uuid>3FBD0304-67ED-44CA-8865-79EC899B9FD3</uuid><subtype>400</subtype><endpage>463</endpage><type>400</type><url> journal of urology</title><type>-100</type><subtype>-100</subtype><uuid>4456EB7A-2B03-4342-86F6-EE920A1D6882</uuid></publication></bundle><authors><author><firstName>G</firstName><middleNames>N</middleNames><lastName>Collins</lastName></author><author><firstName>S</firstName><middleNames>N</middleNames><lastName>Lloyd</lastName></author><author><firstName>M</firstName><lastName>Hehir</lastName></author><author><firstName>G</firstName><middleNames>B</middleNames><lastName>McKELVIE</lastName></author></authors></publication></publications><cites></cites></citation>(2,3). Several studies have shown the benefits of antibiotic prophylaxis in reducing infective complications, and fluoroquinolones are the preferred agents owing to good penetration into the prostatic cytosol ADDIN PAPERS2_CITATIONS <citation><uuid>6AF5160A-6F13-4112-BD43-C2547260071C</uuid><priority>2</priority><publications><publication><uuid>CEA9CC5F-6C10-4625-A605-009138F67608</uuid><volume>85</volume><doi>10.1046/j.1464-410x.2000.00576.x</doi><subtitle>ANTIBIOTIC PROPHYLAXIS FOR NEEDLE BIOPSY OF THE PROSTATE</subtitle><startpage>682</startpage><publication_date>99200112241200000000222000</publication_date><url> prophylaxis for transrectal needle biopsy of the prostate: a randomized controlled study</title><number>6</number><subtype>400</subtype><endpage>685</endpage><bundle><publication><title>British journal of urology</title><type>-100</type><subtype>-100</subtype><uuid>4456EB7A-2B03-4342-86F6-EE920A1D6882</uuid></publication></bundle><authors><author><firstName>M</firstName><lastName>Aron</lastName></author><author><firstName>T</firstName><middleNames>P</middleNames><lastName>Rajeev</lastName></author><author><firstName>N</firstName><middleNames>P</middleNames><lastName>Gupta</lastName></author></authors></publication><publication><type>400</type><publication_date>99199700001200000000200000</publication_date><title>Antibiotic prophylaxis in ultrasound guided transrectal prostate biopsy</title><url> Journal of …</title><type>-100</type><subtype>-100</subtype><uuid>118140E5-D0DE-45E4-AB96-B302B62DDB26</uuid></publication></bundle><authors><author><firstName>F</firstName><middleNames>M</middleNames><lastName>Rommel</lastName></author><author><firstName>V</firstName><middleNames>E</middleNames><lastName>Agusta</lastName></author><author><firstName>J</firstName><middleNames>A</middleNames><lastName>Breslin</lastName></author><author><firstName>H</firstName><middleNames>W</middleNames><lastName>Huffnagle</lastName></author></authors></publication><publication><type>400</type><publication_date>99199800001200000000200000</publication_date><title>Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy</title><url>;(4-6). A randomised control study by Aron et al. (3) observed a significant decrease in post-biopsy infection when fluoroquinolones were used compared with placebo (8% vs 25%) whilst other studies reported reductions to 1% ADDIN PAPERS2_CITATIONS <citation><uuid>60503C64-7F4D-427F-A708-3DFF5B74D679</uuid><priority>3</priority><publications><publication><type>400</type><publication_date>99199700001200000000200000</publication_date><title>Antibiotic prophylaxis in ultrasound guided transrectal prostate biopsy</title><url> Journal of …</title><type>-100</type><subtype>-100</subtype><uuid>118140E5-D0DE-45E4-AB96-B302B62DDB26</uuid></publication></bundle><authors><author><firstName>F</firstName><middleNames>M</middleNames><lastName>Rommel</lastName></author><author><firstName>V</firstName><middleNames>E</middleNames><lastName>Agusta</lastName></author><author><firstName>J</firstName><middleNames>A</middleNames><lastName>Breslin</lastName></author><author><firstName>H</firstName><middleNames>W</middleNames><lastName>Huffnagle</lastName></author></authors></publication></publications><cites></cites></citation>(5) and 0.5% ADDIN PAPERS2_CITATIONS <citation><uuid>8B75BFF2-7852-481A-9CAA-35B48544B045</uuid><priority>4</priority><publications><publication><type>400</type><publication_date>99201200001200000000200000</publication_date><title>Increasing Risk of Infectious Complications After Transrectal Ultrasound–Guided Prostate Biopsies: Time to Reassess Antimicrobial Prophylaxis?</title><url> Association of Urology</publisher><title>European Urology</title><type>-100</type><subtype>-100</subtype><uuid>2D4624D7-3859-4C07-9E9C-8F000D852594</uuid></publication></bundle><authors><author><firstName>A</firstName><lastName>Carignan</lastName></author><author><firstName>J</firstName><middleNames>F</middleNames><lastName>Roussy</lastName></author><author><firstName>V</firstName><lastName>Lapointe</lastName></author><author><firstName>L</firstName><lastName>Valiquette</lastName></author></authors></publication></publications><cites></cites></citation>(7). Such findings led both the American Urological Association (AUA) and European Association of Urology (EAU) to recommend fluoroquinolones as routine prophylactic antibiotics for TRUS biopsy ADDIN PAPERS2_CITATIONS <citation><uuid>DDF88217-4980-4A26-A99D-206EBB8820EB</uuid><priority>5</priority><publications><publication><type>400</type><publication_date>99201200001200000000200000</publication_date><title>Increasing Risk of Infectious Complications After Transrectal Ultrasound–Guided Prostate Biopsies: Time to Reassess Antimicrobial Prophylaxis?</title><url> Association of Urology</publisher><title>European Urology</title><type>-100</type><subtype>-100</subtype><uuid>2D4624D7-3859-4C07-9E9C-8F000D852594</uuid></publication></bundle><authors><author><firstName>A</firstName><lastName>Carignan</lastName></author><author><firstName>J</firstName><middleNames>F</middleNames><lastName>Roussy</lastName></author><author><firstName>V</firstName><lastName>Lapointe</lastName></author><author><firstName>L</firstName><lastName>Valiquette</lastName></author></authors></publication><publication><type>400</type><publication_date>99200800001200000000200000</publication_date><title>Management of urinary and male genital tract infections</title><url>;(7,8). This strategy is however being undermined by the international proliferation of fluoroquinolone-resistant faecal Enterobacteriaceae, which are carried into the bloodstream by the biopsy procedure. These are widely reported as agents of post-biopsy bacteraemias ADDIN PAPERS2_CITATIONS <citation><uuid>BE610835-0F73-48E7-B7A3-3D1326C49CF6</uuid><priority>6</priority><publications><publication><uuid>7ED054B4-6427-4E77-9565-87D204C500E4</uuid><volume>106</volume><doi>10.1111/j.1464-410X.2010.09294.x</doi><subtitle>ANTIMICROBIAL RESISTANCE IN INTESTINAL FLORA OF PATIENTS UNDERGOING PROSTATIC BIOPSY</subtitle><startpage>1017</startpage><publication_date>99201009141200000000222000</publication_date><url> of antimicrobial resistance in intestinal flora of patients undergoing prostatic biopsy: implications for prophylaxis and treatment of infections after biopsy</title><number>7</number><subtype>400</subtype><endpage>1020</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Deepak</firstName><lastName>Batura</lastName></author><author><firstName>G</firstName><middleNames>Gopal</middleNames><lastName>Rao</lastName></author><author><firstName>Peder</firstName><middleNames>Bo</middleNames><lastName>Nielsen</lastName></author></authors></publication><publication><uuid>E1BE1439-48F9-4D84-94E2-1195832EC89D</uuid><volume>183</volume><doi>10.1016/j.juro.2009.11.043</doi><startpage>963</startpage><publication_date>99201003001200000000220000</publication_date><url> Hospital Admission Rates for Urological Complications After Transrectal Ultrasound Guided Prostate Biopsy</title><publisher>Elsevier</publisher><number>3</number><subtype>400</subtype><endpage>969</endpage><bundle><publication><publisher>Elsevier</publisher><title>The Journal of Urology</title><type>-100</type><subtype>-100</subtype><uuid>D4D5E358-F6AE-4FCD-915A-A11572E308A9</uuid></publication></bundle><authors><author><firstName>Robert</firstName><middleNames>K</middleNames><lastName>Nam</lastName></author><author><firstName>Refik</firstName><lastName>Saskin</lastName></author><author><firstName>Yuna</firstName><lastName>Lee</lastName></author><author><firstName>Ying</firstName><lastName>Liu</lastName></author><author><firstName>Calvin</firstName><lastName>Law</lastName></author><author><firstName>Laurence</firstName><middleNames>H</middleNames><lastName>Klotz</lastName></author><author><firstName>D</firstName><middleNames>Andrew</middleNames><lastName>Loblaw</lastName></author><author><firstName>John</firstName><lastName>Trachtenberg</lastName></author><author><firstName>Aleksandra</firstName><lastName>Stanimirovic</lastName></author><author><firstName>Andrew</firstName><middleNames>E</middleNames><lastName>Simor</lastName></author><author><firstName>Arun</firstName><lastName>Seth</lastName></author><author><firstName>David</firstName><middleNames>R</middleNames><lastName>Urbach</lastName></author><author><firstName>Steven</firstName><middleNames>A</middleNames><lastName>Narod</lastName></author></authors></publication><publication><type>400</type><publication_date>99201000001200000000200000</publication_date><title>Multi-drug resistant E.coli urosepsis in physicia... 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These experiences led us to review both TRUS outcomes and carriage of resistant Escherichia coli in Norwich, UK, a relatively isolated city with a population of 213,166 some, 118 miles north of London. Material and Methods Case review 2007-11All patients who underwent TRUS biopsy of the prostate between 2007 and 2011 at the Norfolk and Norwich University Hospital were retrospectively audited. The Trust antibiotic policy for TRUS biopsy remained unchanged, including oral administration of 750 mg ciprofloxacin 1 hour before the biopsy followed by 250 mg q12h for 3 subsequent days. A review of subsequent sepsis cases resulting in hospital admission was made, including any microbiological data for E. coli or other Enterobacteriaceae recovered.Prospective study, 2012For the 9 months from April to December 2012 (inclusive), rectal swabs were taken immediately prior to the TRUS biopsy from 267 men who presented to our prostate specific antigen (PSA) one-stop clinic. Ciprofloxacin prophylaxis continued to be given to all patients as above. Patient details including age, race, medical history, medications and past history infections were recorded, as well as any history of recent hospitalisations, procedures, travel and antibiotic treatments in the previous year.Swabs were cultured onto CLED agar with a 1-?g ciprofloxacin disc applied on the first set of streaks after the primary inoculum. Colonies that grew within the ciprofloxacin zone were recovered, identified, and confirmed as ciprofloxacin resistant by BSAC disk diffusion testing or using the Vitek 2 (bioMerieux, La Balme les Grottes, France). Patients’ hospital admissions within 31 days of the biopsy were recorded and correlated to the swab result. All patients were followed up, for a period of 6 months (by enquiring about urinary tract infections though general practitioners and tracking hospital admission due to related symptoms), to identify post-biopsy infective complications. Any urine cultures received by the hospital laboratory during this period were reviewed, with identification of the reason for culture submission, the culture results, and the antibiotic resistance of any organism grown. ResultsFrom the 3600 TRUS procedures done between 2007 and 2011, 18 patients were hospitalised due to biopsy-related complications, and 11 (0.3%) of these involved sepsis. Microbiology for the corresponding blood and urine cultures was available for nine patients (Fig 1): four had ciprofloxacin-resistant E. coli recovered from blood whereas two had ciprofloxacin-susceptible E. coli, one had a ciprofloxacin-susceptible Enterobacter cloacae and two had isolates that were not tested with ciprofloxacin. One patient with bacteraemia due to a ciprofloxacin-resistant E. coli was known to be long-colonised with this organism (previous bacteriuria), whereas the patient with the Ent. cloacae bacteraemia suffered a further bacteraemia with the same species 2 months later, followed by two episodes of bacteraemia with ciprofloxacin-resistant E. coli, 4 and 7 months post-TRUS. One patient had vascular surgery a month after readmission and grew Bacteroides spp. from pus and aortic tissue, possibly seeded by the TRUS procedure.Only 10 (3.7%) of the 267 patients sampled pre-biopsy in 2012 had ciprofloxacin-resistant E. coli recovered from the swab cultures. Five of the 267 (1.87%) were admitted to the hospital within 31 days of the procedure with complications, comprising haematuria (n=1) and urinary retention (n=4); none had infection. The mean (SD) age of the 10 patients carrying ciprofloxacin-resistant Enterobacteriaceae from the 2012 series was 68.7 (SD, 9.2) years vs. 68 (SD=6.8) for the rest of the cohort. Three of the ten patients with ciprofloxacin-resistant isolates had a possible risk factor (2 travel abroad, 1 with previous antibiotic treatment) as shown in Table 1. Full antimicrobial susceptibility patterns of the 10 ciprofloxacin-resistant isolates are shown in Table 2: meropenem retained activity against all 10 isolates as did ertapenem, amikacin and tigecycline, with gentamicin active against 9/10 tested..Within the 6-month follow-up period, seven patients were diagnosed with uncomplicated urinary tract infections. None of these patients had ciprofloxacin-resistant Enterobacteriaceae in their original rectal swabs. Five grew Enterobacteriaceae on urine culture but none of these showed multiple resistance; the remaining two patients yielded heavy mixed growth, meaning that infection was not microbiologically confirmed (Table 3).DiscussionCiprofloxacin is widely used as the prophylactic antibiotic of choice for TRUS biopsy ADDIN PAPERS2_CITATIONS <citation><uuid>9AB63888-CF27-4BA2-A2AC-F9EFD04C4C56</uuid><priority>7</priority><publications><publication><uuid>736B9B4D-2F27-4061-956F-C82423F6E3F3</uuid><volume>101</volume><doi>10.1111/j.1464-410X.2008.07554.x</doi><startpage>1201</startpage><publication_date>99200805001200000000220000</publication_date><url> after prostate biopsy and antibiotic resistance.</title><institution>Department of Radiology, St. George's Hospital, London, UK. uday.patel@stgeorges.nhs.uk</institution><number>10</number><subtype>400</subtype><endpage>1202</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Uday</firstName><lastName>Patel</lastName></author><author><firstName>Roger</firstName><lastName>Kirby</lastName></author></authors></publication></publications><cites></cites></citation>(14), reflecting its efficacy and good prostatic penetration. However reports of increasing resistance to the drug, and a rise in Clostridium difficile infections linked to fluoroquinolone use ADDIN PAPERS2_CITATIONS <citation><uuid>D7E50A3F-22FE-47FF-8491-311FCE74D7CB</uuid><priority>8</priority><publications><publication><volume>54</volume><publication_date>99200409291200000000222000</publication_date><number>5</number><doi>10.1093/jac/dkh448</doi><startpage>952</startpage><title>Antibiotic resistance of faecal Escherichia coli from healthy volunteers from eight developing countries</title><uuid>2F6884D1-21C3-41DA-B559-6882A19E69FB</uuid><subtype>400</subtype><endpage>955</endpage><type>400</type><url> of Antimicrobial Chemotherapy</title><type>-100</type><subtype>-100</subtype><uuid>101E02B3-9D38-4FA7-9756-0565F655EB57</uuid></publication></bundle><authors><author><firstName>S</firstName><lastName>Nys</lastName></author></authors></publication><publication><uuid>B295B543-8618-4F82-B9C1-2D1C2872ADA8</uuid><volume>106</volume><doi>10.1111/j.1464-410X.2010.09294.x</doi><subtitle>ANTIMICROBIAL RESISTANCE IN INTESTINAL FLORA OF PATIENTS UNDERGOING PROSTATIC BIOPSY</subtitle><startpage>1017</startpage><publication_date>99201009141200000000222000</publication_date><url> of antimicrobial resistance in intestinal flora of patients undergoing prostatic biopsy: implications for prophylaxis and treatment of infections after biopsy</title><number>7</number><subtype>400</subtype><endpage>1020</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Deepak</firstName><lastName>Batura</lastName></author><author><firstName>G</firstName><middleNames>Gopal</middleNames><lastName>Rao</lastName></author><author><firstName>Peder</firstName><middleNames>Bo</middleNames><lastName>Nielsen</lastName></author></authors></publication><publication><publication_date>99200500001200000000200000</publication_date><title>A Large Outbreak of Clostridium difficile‐Associated Disease With an Unexpected Proportion of Deaths and Colectomies at a Teaching Hospital Following Increased Fluoroquinolone Use</title><uuid>F0B69331-CBBE-407B-800F-8B7E2132D0B3</uuid><subtype>400</subtype><publisher> The University of Chicago Press </publisher><type>400</type><url>; The University of Chicago Press </publisher><url> A Muto</lastName></author><author><firstName>MPH</firstName><middleNames>BS CIC</middleNames><lastName>Marian Pokrywka</lastName></author><author><firstName>M</firstName><middleNames>S</middleNames><lastName>Kathleen Shutt</lastName></author><author><firstName>PhD</firstName><lastName>Aaron B Mendelsohn</lastName></author><author><firstName>MPH</firstName><middleNames>RN BSN CIC</middleNames><lastName>Kathy Nouri</lastName></author><author><firstName>MPH</firstName><middleNames>BS CIC</middleNames><lastName>Kathy Posey</lastName></author><author><firstName>BS</firstName><middleNames>CIC</middleNames><lastName>Terri Roberts</lastName></author><author><firstName>BS</firstName><middleNames>CIC</middleNames><lastName>Karen Croyle</lastName></author><author><firstName>MPH</firstName><middleNames>MS CIC</middleNames><lastName>Sharon Krystofiak</lastName></author><author><firstName>B</firstName><middleNames>S</middleNames><lastName>Sujata Patel Brown</lastName></author><author><firstName>ScD</firstName><lastName>A William Pasculle</lastName></author><author><firstName>M</firstName><middleNames>D</middleNames><lastName>David L Paterson</lastName></author><author><firstName>M</firstName><middleNames>S</middleNames><lastName>Melissa Saul</lastName></author><author><firstName>M</firstName><middleNames>D</middleNames><lastName>Lee H Harrison</lastName></author></authors></publication></publications><cites></cites></citation>(15-17), have led some hospitals to replace or supplement ciprofloxacin with other antibiotics, though not always successfully. In Cambridge, 56 miles from Norwich, the incidence of post-TRUS infections rose to 12.9% among patients receiving amoxicillin-clavulanate plus gentamicin as prophylaxis compared with 2.4% among those receiving ciprofloxacin in the immediately previous period. This finding led to the re-adoption of the ciprofloxacin regimen ADDIN PAPERS2_CITATIONS <citation><uuid>5F8B8CB7-9C6F-45AD-8A48-D8F145161F71</uuid><priority>9</priority><publications><publication><uuid>0DEDFA80-263C-4D2C-AC5D-BBEA76B3D09A</uuid><volume>108</volume><doi>10.1111/j.1464-410X.2011.10160.x</doi><subtitle>INFECTIVE COMPLICATIONS AFTER PROSTATE BIOPSY’</subtitle><startpage>1597</startpage><publication_date>99201105181200000000222000</publication_date><url> complications after transrectal ultrasound-guided prostate biopsy following a new protocol for antibiotic prophylaxis aimed at reducing hospital-acquired infections</title><number>10</number><subtype>400</subtype><endpage>1602</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Thomas</firstName><lastName>Madden</lastName></author><author><firstName>Andrew</firstName><lastName>Doble</lastName></author><author><firstName>Sani</firstName><middleNames>H</middleNames><lastName>Aliyu</lastName></author><author><firstName>David</firstName><middleNames>E</middleNames><lastName>Neal</lastName></author></authors></publication></publications><cites></cites></citation>(18). Similarly, at Bury St Edmunds 42 miles from Norwich and 28 miles from Cambridge, ciprofloxacin prophylaxis was more effective in comparison to amoxicillin-clavulanate (infection rate 1.68% for ciprofloxacin vs 7.27% amoxicillin-clavulanate) and, again, these findings led to the re-adoption of the fluoroquinolone regimen ADDIN PAPERS2_CITATIONS <citation><uuid>D9FD2F9C-FA75-402B-B74A-466F8CCFA890</uuid><priority>10</priority><publications><publication><uuid>08C1EC7E-ECBA-4BAD-90FE-D4190C4DD89F</uuid><volume>106</volume><doi>10.1111/j.1464-410X.2010.09416.x</doi><subtitle>CHANGING ANTIBIOTIC PROPHYLAXIS FOR TRUSgpb</subtitle><startpage>1298</startpage><publication_date>99201005281200000000222000</publication_date><url> antibiotic prophylaxis for transrectal ultrasound-guided prostate biopsies: are we putting our patients at risk?</title><number>9</number><subtype>400</subtype><endpage>1302</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Satoshi</firstName><lastName>Hori</lastName></author><author><firstName>Anup</firstName><lastName>Sengupta</lastName></author><author><firstName>Alexis</firstName><lastName>Joannides</lastName></author><author><firstName>Ben</firstName><lastName>Balogun-Ojuri</lastName></author><author><firstName>Rebecca</firstName><lastName>Tilley</lastName></author><author><firstName>John</firstName><lastName>McLoughlin</lastName></author></authors></publication></publications><cites></cites></citation>(19). On the other hand, a London hospital that had a post-TRUS biopsy infection rate of 8% despite fluoroquinolone prophylaxis achieved a reduction to 2% after supplementation with a single pre-procedure dose of gentamicin ADDIN PAPERS2_CITATIONS <citation><uuid>1898CD94-9928-4A5C-B142-3B8D2407F013</uuid><priority>11</priority><publications><publication><type>400</type><publication_date>99201300001200000000200000</publication_date><title>BAUS Annual Meeting, 17–20 June 2013, Manchester Central Poster Sessions</title><url>;(20); similar findings were reported in a second London study ADDIN PAPERS2_CITATIONS <citation><uuid>0F098B0F-6797-4E55-8857-82A3533C0744</uuid><priority>12</priority><publications><publication><uuid>2C893B9F-8EF6-4673-A6D4-0FE6CA13822C</uuid><volume>107</volume><doi>10.1111/j.1464-410X.2010.09715.x</doi><subtitle>ANTIMICROBIAL PROPHYLAXIS FOR PROSTATE BIOPSY</subtitle><startpage>760</startpage><publication_date>99201010041200000000222000</publication_date><url> amikacin to fluoroquinolone-based antimicrobial prophylaxis reduces prostate biopsy infection rates</title><number>5</number><subtype>400</subtype><endpage>764</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Deepak</firstName><lastName>Batura</lastName></author><author><firstName>G</firstName><middleNames>Gopal</middleNames><lastName>Rao</lastName></author><author><firstName>Peder</firstName><lastName>Bo Nielsen</lastName></author><author><firstName>André</firstName><lastName>Charlett</lastName></author></authors></publication></publications><cites></cites></citation>(21). These data demonstrate that simple replacement of fluoroquinolones with other broad-spectrum antibiotics has limitations, as these alternative agents may have inferior efficacy, perhaps owing to poor prostatic penetration. Two better alternatives appear to be (i) to adapt prophylaxis to local resistance rates, with supplementation of fluoroquinolone regimens where resistance is prevalent, and (ii) to identify patients carrying ciprofloxacin-resistant organism pre-procedure, by culturing rectal swabs ADDIN PAPERS2_CITATIONS <citation><uuid>25F9C5D5-13B5-4291-80AA-F9A583551B01</uuid><priority>13</priority><publications><publication><uuid>68299EEA-DC33-4DB4-AED3-75CFB25BF984</uuid><volume>79</volume><doi>10.1016/j.urology.2011.09.057</doi><startpage>556</startpage><publication_date>99201203001200000000220000</publication_date><url> Cultures Before Transrectal Ultrasound-guided Prostate Biopsy Reduce Post-prostatic Biopsy Infection Rates</title><publisher>Elsevier</publisher><number>3</number><subtype>400</subtype><endpage>563</endpage><bundle><publication><publisher>Elsevier</publisher><title>Urology</title><type>-100</type><subtype>-100</subtype><uuid>8B269E15-9CA2-48F8-A419-8CAD8C4839C6</uuid></publication></bundle><authors><author><firstName>Christopher</firstName><middleNames>A</middleNames><lastName>Duplessis</lastName></author><author><firstName>Mary</firstName><lastName>Bavaro</lastName></author><author><firstName>Mark</firstName><middleNames>P</middleNames><lastName>Simons</lastName></author><author><firstName>Charles</firstName><lastName>Marguet</lastName></author><author><firstName>Michael</firstName><lastName>Santomauro</lastName></author><author><firstName>Brian</firstName><lastName>Auge</lastName></author><author><firstName>Daniel</firstName><middleNames>A</middleNames><lastName>Collard</lastName></author><author><firstName>Joshua</firstName><lastName>Fierer</lastName></author><author><firstName>James</firstName><lastName>Lesperance</lastName></author></authors></publication></publications><cites></cites></citation>(22), and to adapt prophylaxis individually.. Local variation is well illustrated by comparing the studies for East Anglia versus those for London. In East Anglia, post-TRUS infection rates with fluoroquinolone prophylaxis ranged from 0.3% (Norwich, this study) to 1.6% (Bury St Edmunds) to 2.4% (Cambridge) and, at Norwich in 2012, just 3.7% of patients carried ciprofloxacin-resistant E. coli, with none of these individuals suffering from post-TRUS infective complications warranting hospital admission. In London, by contrast, 1.5-8% of patients developed infections and up to 10% carried ciprofloxacin-resistant Enterobacteriaceae ADDIN PAPERS2_CITATIONS <citation><uuid>077FB96A-5BCC-4959-9342-8C3AFD1E0C5D</uuid><priority>14</priority><publications><publication><uuid>B295B543-8618-4F82-B9C1-2D1C2872ADA8</uuid><volume>106</volume><doi>10.1111/j.1464-410X.2010.09294.x</doi><subtitle>ANTIMICROBIAL RESISTANCE IN INTESTINAL FLORA OF PATIENTS UNDERGOING PROSTATIC BIOPSY</subtitle><startpage>1017</startpage><publication_date>99201009141200000000222000</publication_date><url> of antimicrobial resistance in intestinal flora of patients undergoing prostatic biopsy: implications for prophylaxis and treatment of infections after biopsy</title><number>7</number><subtype>400</subtype><endpage>1020</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Deepak</firstName><lastName>Batura</lastName></author><author><firstName>G</firstName><middleNames>Gopal</middleNames><lastName>Rao</lastName></author><author><firstName>Peder</firstName><middleNames>Bo</middleNames><lastName>Nielsen</lastName></author></authors></publication></publications><cites></cites></citation>(16). Even between Norwich and Cambridge there was a 0 vs 2.4% range in post-procedure infections. A possible explanation is that Norwich is a more isolated city than Cambridge, which has a more fluid population, with greater ethnic diversity and a higher rate of intercontinental travel, possibly with a higher carriage rate of resistant Enterobacteriaceae. In Birmingham, Wickramasinghe et al. found that carriage rates for resistant Enterobacteriaceae varied among ethnic groups, perhaps reflecting the frequency of travel to and from South Asia, where these organisms are extremely prevalent ADDIN PAPERS2_CITATIONS <citation><uuid>42CAE526-1E14-4964-B86C-2257C8AFE80F</uuid><priority>15</priority><publications><publication><uuid>1862D10E-9C00-4BAE-8706-8418CF69D695</uuid><volume>67</volume><doi>10.1093/jac/dks018</doi><startpage>1108</startpage><publication_date>99201205001200000000220000</publication_date><url> community faecal carriage rates of CTX-M ESBL-producing Escherichia coli in a specific population group in Birmingham, UK.</title><institution>Department of Microbiology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.</institution><number>5</number><subtype>400</subtype><endpage>1113</endpage><bundle><publication><title>Journal of Antimicrobial Chemotherapy</title><type>-100</type><subtype>-100</subtype><uuid>101E02B3-9D38-4FA7-9756-0565F655EB57</uuid></publication></bundle><authors><author><firstName>Nimal</firstName><middleNames>H</middleNames><lastName>Wickramasinghe</lastName></author><author><firstName>Li</firstName><lastName>Xu</lastName></author><author><firstName>Andrew</firstName><lastName>Eustace</lastName></author><author><firstName>Sahida</firstName><lastName>Shabir</lastName></author><author><firstName>Tranprit</firstName><lastName>Saluja</lastName></author><author><firstName>Peter</firstName><middleNames>M</middleNames><lastName>Hawkey</lastName></author></authors></publication></publications><cites></cites></citation>(23); this view is supported by a study done by Patel et al. in London ADDIN PAPERS2_CITATIONS <citation><uuid>3D35757E-09A3-426C-98AB-BD678430CAF8</uuid><priority>16</priority><publications><publication><uuid>8349C9E2-55A4-4082-AFEE-9A97537BDADA</uuid><volume>109</volume><doi>10.1111/j.1464-410X.2011.10561.x</doi><subtitle>RISK FACTORS FOR INFECTION AFTER PROSTATE BIOPSY</subtitle><startpage>1781</startpage><publication_date>99201110311200000000222000</publication_date><url> after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use</title><number>12</number><subtype>400</subtype><endpage>1785</endpage><bundle><publication><title>BJU International</title><type>-100</type><subtype>-100</subtype><uuid>992E82CA-2A44-4C5E-954D-3DFBFE8CCFAE</uuid></publication></bundle><authors><author><firstName>Uday</firstName><lastName>Patel</lastName></author><author><firstName>Prokar</firstName><lastName>Dasgupta</lastName></author><author><firstName>Peter</firstName><lastName>Amoroso</lastName></author><author><firstName>Ben</firstName><lastName>Challacombe</lastName></author><author><firstName>James</firstName><lastName>Pilcher</lastName></author><author><firstName>Roger</firstName><lastName>Kirby</lastName></author></authors></publication></publications><cites></cites></citation>(24).Based on these findings we conclude that ciprofloxacin remains an appropriate prophylactic antibiotic for TRUS in our local setting. Whether or not it should be supplemented or changed elsewhere must depend on the local population. We suggest that periodic rectal swab cultures should be taken to ascertain the prevalence of ciprofloxacin resistance and to confirm its continued appropriateness. In regions with high fluoroquinolone resistance, pre-procedure screening could also be used to identify individual patients carrying resistant organisms, who might benefit from supplementary antibiotics. According to The Department of Health ADDIN PAPERS2_CITATIONS <citation><uuid>49901CB5-06C1-46DD-AF26-3D88E81041E2</uuid><priority>17</priority><publications><publication><publication_date>99201211061200000000222000</publication_date><startpage>1</startpage><title>To:</title><uuid>E260F777-A60B-42FB-BD50-0469136AEB6F</uuid><subtype>400</subtype><endpage>64</endpage><type>400</type><url>;(25) an A&E admission costs, on average, ?108, plus ?400 per 24 hours of hospital stay. On this basis, screening becomes cost-effective even if only one patient in a hundred would otherwise experience an infection necessitating hospitalisation, even before individual suffering and economic costs are considered.ConclusionCiprofloxacin resistance remains rare in the intestinal Enterobacteriaceae flora in our local TRUS population. Due to the geographical location of Norwich and the limited access of our patients to other hospitals, we are confident with this result genuinely reflects the local situation. Prophylaxis may need review in settings of higher resistance or for individual high-risk patients.Works Cited ADDIN PAPERS2_CITATIONS <papers2_bibliography/>1.Batura D, Gopal Rao G. The national burden of infections after prostate biopsy in England and Wales: a wake-up call for better prevention. Journal of Antimicrobial Chemotherapy. 2013 ;68:247–9. 2.Deliveliotis C, John V, Louras G, Andreas S, Alargof E, Sofras F, et al. Multiple transrectal ultrasound guided prostatic biopsies: morbidity and tolerance. Int Urol Nephrol. 1999;31:681–6. 3.Collins GN, Lloyd SN, Hehir M, McKELVIE GB. Multiple Transrectal Ultrasound-Guided Prostatic Biopsies-True Morbidity and Patient Acceptance. Br J Urol. 1993 ;71:460–3. 4.Aron M, Rajeev TP, Gupta NP. Antibiotic prophylaxis for transrectal needle biopsy of the prostate: a randomized controlled study. Br J Urol. 2001 24;85:682–5. 5.Rommel FM, Agusta VE, Breslin JA, Huffnagle HW. Antibiotic prophylaxis in ultrasound guided transrectal prostate biopsy. The Journal of Urology 1997. 6.Malek GH, Wegenke JD, Cox CE, Patterson AL. Single-dose oral ciprofloxacin versus placebo for prophylaxis during transrectal prostate biopsy. Urology. 1998. 7.Carignan A, Roussy JF, Lapointe V, Valiquette L. Increasing Risk of Infectious Complications After Transrectal Ultrasound–Guided Prostate Biopsies: Time to Reassess Antimicrobial Prophylaxis? European Urology. 2012. 8.Bjerklund-Johansen TE, Botto H, Cek M. Management of urinary and male genital tract infections. UPDATE. 2008. 9.Batura D, Rao GG, Nielsen PB. Prevalence of antimicrobial resistance in intestinal flora of patients undergoing prostatic biopsy: implications for prophylaxis and treatment of infections after biopsy. BJU Int. 2010 14;106:1017–20. 10.Nam RK, Saskin R, Lee Y, Liu Y, Law C, Klotz LH, et al. Increasing Hospital Admission Rates for Urological Complications After Transrectal Ultrasound Guided Prostate Biopsy. The Journal of Urology. Elsevier; 2010 ;183:963–9. 11.Carlson WH, Bell DG, Lawen JG. Multi-drug resistant E.coli urosepsis in physicia... [Can J Urol. 2010] - PubMed - NCBI. The Canadian journal of Urology 2010. 12.Young JL, Liss MA, Szabo RJ. Sepsis Due to Fluoroquinolone-resistant Escherichia coli After Transrectal Ultrasound-guided Prostate Needle Biopsy. Urology. Elsevier; 2009 ;74:332–8. 13.Loeb S, van den Heuvel S, Zhu X, Bangma CH, Schr?der FH, Roobol MJ. Infectious Complications and Hospital Admissions After Prostate Biopsy in a European Randomized Trial. European Urology. 2012 ;61:1110–4. 14.Patel U, Kirby R. Infections after prostate biopsy and antibiotic resistance. BJU Int. 2008 ;101:1201–2. 15.Nys S. Antibiotic resistance of faecal Escherichia coli from healthy volunteers from eight developing countries. Journal of Antimicrobial Chemotherapy. 2004 29;54:952–5. 16.Batura D, Rao GG, Nielsen PB. Prevalence of antimicrobial resistance in intestinal flora of patients undergoing prostatic biopsy: implications for prophylaxis and treatment of infections after biopsy. BJU Int. 2010 14;106:1017–20. 17.Carlene A Muto MM, Marian Pokrywka MBC, Kathleen Shutt MS, Aaron B Mendelsohn P, Kathy Nouri MRBC, Kathy Posey MBC, et al. A Large Outbreak of Clostridium difficile‐Associated Disease With an Unexpected Proportion of Deaths and Colectomies at a Teaching Hospital Following Increased Fluoroquinolone Use. . The University of Chicago Press; 2005. 18.Madden T, Doble A, Aliyu SH, Neal DE. Infective complications after transrectal ultrasound-guided prostate biopsy following a new protocol for antibiotic prophylaxis aimed at reducing hospital-acquired infections. BJU Int. 2011 18;108:1597–602. 19.Hori S, Sengupta A, Joannides A, Balogun-Ojuri B, Tilley R, McLoughlin J. Changing antibiotic prophylaxis for transrectal ultrasound-guided prostate biopsies: are we putting our patients at risk? BJU Int. 2010 28;106:1298–302. 20.MALIGNANCY UT. BAUS Annual Meeting, 17–20 2013, Manchester Central Poster Sessions. 2013. 21.Batura D, Rao GG, Bo Nielsen P, Charlett A. Adding amikacin to fluoroquinolone-based antimicrobial prophylaxis reduces prostate biopsy infection rates. 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Department of Health To:. 2012 Nov 6;:1–64.()Table 1 Risk factors in patients with ciprofloxacin-resistance isolatesPatientsTravel History (Past 12 months)Hospitalisation for over 48 h (Past 12 months)Antibiotic treatments (Past 3 months)P1NoYesNoP2NoNoNoP3NoNoNoP4USANoNoP5FranceNoNoP6NoNoNoP7NoNoNoP8NoNoUnknownP9NoNoNP10GreeceNoAmoxicillin +FlucloxacillinTable 2: Antimicrobial susceptibility of ciprofloxacin-resistant isolates recovered from 10 patients in 2012.Nbr PatientsAmpAugPipPtzCltCxmFoxCtxCazCpmAztErtMemAmkGenTobCipTigTmpSusceptible48224678878910797097Intermediate0001202011000200000Resistant62503402111000121000Not Tested0037101001110101013Abbreviations: Amp. ampicillin; Aug, co-amoxiclav; Pip, piperacillin; Ptz, piperacillin-tazobactam; Cltn, cephalothin; Cxm, cefuroxime; F Fox, cefoxitin; Ctx, cefotaxime; Caz, ceftazidime; Cpm, cefepime; Azt, aztreonam; Ert, ertapenem; Mem, meropenem; Amk, amikacin; Gen, gentamicin; Cip, ciprofloxacin; Tig, tigecycline and Tmp, trimethoprim. Susceptibility testing methods: 9 isolates tested by Vitek. 1 patient tested by BSAC disc diffusion ................
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