Prostate Biopsy Antisepsis
Prostate Biopsy Antisepsis
During a prostate biopsy, a needle is guided through the rectum into the prostate. Although
 patients are given antibiotics before the biopsy, there is still a risk of bacteria getting
 from the rectum into the bladder, prostate and bloodstream during the biopsy. For most
 surgical procedures, the surgical field is cleaned with antiseptic solution, but this is not
 common practice for prostate biopsies. In this study patients undergoing prostate biopsy will
 be randomly assigned to either receive an antiseptic preparation of the rectum or no
 preparation prior to biopsy, and the rate of infection after the biopsy will be determined.
1. Purpose This research aims to determine the efficacy and safety of cleaning the rectal
 mucosa with antiseptic solution (Povidone-iodine) prior to transrectal prostate biopsy.

 2. Hypothesis We hypothesize that prophylactic cleaning of the rectal mucosa with
 antiseptic solution prior to transrectal prostate biopsy will decrease the rate of
 infectious complications after biopsy. We believe that this can be achieved without any
 significant complications related to the antiseptic solution.

 3. Justification Prostate cancer is the most common cancer in men. Since the diagnosis of
 prostate cancer requires a transrectal prostate biopsy, this procedure is performed
 frequently. More than 6000 biopsies are performed in British Columbia each year, and
 more than 1000 are performed at Vancouver General and UBC Hospitals (combined numbers).
 In these hospitals, the biopsy is performed by the radiologists using transrectal
 guidance. Subjects receive antibiotic prophylaxis in the form of ciprofloxacin for three
 days starting one day before the biopsy. They also instill an enema into the rectum a
 few hours before the biopsy to empty the rectum. Local anesthetic is injected through
 the rectal mucosa into the periprostatic space prior to the biopsy. Depending on the
 size of the prostate, between 8 and 12 cores of tissue are remove from the prostate by
 repetitive passes of the 18 gauge biopsy needle through the anterior rectal wall.
 Cleaning the rectum with an antiseptic solution prior to biopsy is not routinely
 practiced and is not considered a current standard of care.

 Despite routine antibiotic prophylaxis, prostate biopsies are associated with a
 considerable rate of infectious complications. Sepsis after biopsy is described in the
 literature with an incidence 0.1 to 2.0 %.

 Rate of sepsis has been determined in a retrospective but contemporary study of
 approximately 4500 biopsies at VGH/UBC to occur with a rate of 0.55% (Lange et al.,
 submitted to Journal of Urology). Less severe but more common adverse events include
 urinary tract infection and fever, which both occur in approximately 10% of men
 undergoing biopsy.

 Cleaning the rectum prior to biopsy offers a potential method to decrease the risk of
 these infectious complications, and we propose the use of Povidone-iodine for this
 purpose. Surgical site disinfection is standard in most surgical procedures, and
 Povidone-iodine is a safe antiseptic utilized routinely for the surgical preparation of
 the body surface as well as mucosal surfaces, including the vagina, mouth and bowel.
 Park et al. reported that the mean number of colony-forming units decreased 99.9% after
 Povidone-iodine cleansing of the rectum. Hay et al. reported similar results with
 Povidone-Iodine enema administration when combined with metronidazole. Povidone-iodine
 has been shown to significantly reduce bacterial concentrations in the mucosa of the
 colon and rectum. Brown et al. reported that a Povidone-iodine enema provided a safe and
 effective means for preventing bacteremia and bacteruria after transrectal prostate
 biopsy. Furthermore, severe allergic reaction to Povidone-iodine is rare.

 4. Objectives

 The objectives of this study are:

 1. To determine whether cleaning the lining of the rectum with an antiseptic solution
 before prostate biopsy is effective in decreasing the rate of three outcome variables:

 -  Urinary Tract Infection

 -  Fever

 -  Sepsis

 2. To determine at what rate bacteria are found in the rectum prior to biopsy that are
 resistant to ciprofloxacin.

 3. To determine at what rate bacteria are found in the urine after biopsy, with or without
 rectal cleaning.

 4. To determine any adverse reactions to antiseptic solution in the rectum.

 5. Research Method All subjects undergoing transrectal prostate biopsy as clinically
 indicated and determined by the treating Urologist at Vancouver General Hospital and
 University of British Columbia Hospital will be considered for entry into this trial. If
 the subject consents to participation, he will be randomized to undergo prostate biopsy
 with rectal cleaning with antiseptic solution ("treatment" group) or without rectal
 cleaning ("control" group). A urine sample will be collected before and after biopsy and
 sent for routine culturing. A rectal swab will be taken before the biopsy (and before
 rectal cleaning in treatment group) and will be cultured in ciprofloxacin-enriched
 medium.

 In the treatment group, the radiologist performing the biopsy will wipe the rectal
 lining overlying the prostate with gauze soaked with Povidone-iodine. Otherwise the
 biopsy is performed in standard fashion in both groups. After the procedure, the
 subjects are instructed to measure and record their temperature every 6 hours for 48
 hours. A telephone interview is conducted seven days after biopsy to ascertain any
 adverse events from the biopsy, including whether a temperature ≥38.0˚C was measured.

 6. Statistical Analysis The primary outcome in this study will be the rate of urinary tract
 infection and the rate of fever after biopsy (see definitions below). The rate of sepsis
 will be measured, but the study will not be powered to detect a difference in the rate
 of sepsis.

 The rate of UTI and fever is estimated from the literature data at 10% each. A relative
 reduction of 50% (absolute reduction from 10% to 5%)would be considered clinically
 significant. With type I & II errors set at 0.05 and 0.2, respectively, and a two-sided
 test of significance, the necessary sample size is estimated at 435 in each group.
 Assuming 20% inability to enroll and loss to follow up, the total sample size is 1044.

 Descriptive statistics of baseline parameters will be provided in each group. The mean,
 median, standard deviation or range of the variables will be computed as applicable. The
 association between exposure and the defined outcomes will be assessed in univariate
 analysis. The proportion of each outcome in each group will be compared using the chi
 square test. Multivariate analysis using logistic regression will be performed to assess
 effect of variables such as age, number of biopsy cores, individual performing the
 biopsy and other co-morbidities. A test of interaction will be performed.

 7. Definition of Endpoints

 -  Urinary tract infection: > 100 million colony forming units per liter in the urine
 culture obtained48 hours after biopsy.

 -  Fever: oral temperature ≥38.0˚C within 48 hours after biopsy.

 -  Sepsis(19),(20): positive urine or blood culture plus two or more of the following
 within 1week of biopsy:

 1. temperature ≥38.0˚C or < 36.0˚C,

 2. heart rate >90 beats/minute,

 3. respiratory rate > 20 breaths/min,

 4. WBC count >12.0 or <4.0 x 10 9/L, or > 0.10 immature forms (bands).

 8. Summary of Procedures:

 Eligible subjects will be counseled in the office regarding the prostate biopsy as per each
 physician's routine. This includes instructions for ciprofloxacin prophylaxis (1000 mg of
 extended release ciprofloxacin daily for three days starting the day before the biopsy) and
 the use of a fleet enema at home approximately 2 hours before biopsy. The Urologist will also
 discuss this study with the subject at the same time as he/she orders the biopsy. He/she will
 ensure that the subject meets the eligibility criteria using a pre-biopsy questionnaire. The
 subject will be able to take the consent home for further consideration and discussion. It
 must be signed before the biopsy for the subject to participate in the study.

 Each subject will be assigned a study code. At the time of biopsy, subjects will be
 randomized 1:1 by computer generated random numbers into two groups. The first group
 ("controls") will undergo biopsy according to the current standard of care, which does not
 include antiseptic cleaning. The second group ("treatment") will undergo biopsy in the same
 fashion, but after cleaning the rectal lining with 10% Povidone-iodine.

 Before the biopsy is started, the subject is asked to give a midstream urine sample for
 routine culture. A culture swab is also inserted into the rectum and then cultured in
 ciprofloxacin-enriched media in order to isolate ciprofloxacin-resistant rectal flora prior
 to the biopsy.

 The control group will undergo the routine biopsy while in the treatment group, the
 radiologist performing the biopsy will have a gauze soaked with Povidone-iodine over his/her
 index finger, and will insert this into the rectum. Before this, the Radiologist asks the
 subject again if he has allergy to Povidone-iodine, shellfish or IVP dye. The gauze will be
 wiped back and forth across the prostate with the finger at least five times from one lateral
 margin to the other. The radiologist will allow at least 2 minutes to pass between prep and
 the insertion of the first needle into the prostate in order to allow the Povidone-iodine to
 dry. The radiologist will ask the subject to inform the Radiologist if the subject does
 experience any symptoms of allergic reaction (rash; hives; itching; difficulty breathing;
 tightness in the chest; swelling of the mouth, face, lips, or tongue ). The 2 minutes will be
 spent measuring the prostate size using the rectal ultrasound probe. After those two minutes
 the routine biopsy is done. A second rectal swab for culture will not be taken, as this will
 likely be negative due to the Povidone-iodine contamination of the swab, and due to the added
 cost.

 All subjects will be discharged from the recovery according to standard care. During the
 recovery period, a watchful eye is kept on the subjects in the treatment group for developing
 severe allergic reaction. A crash-cart will be available all the time during the procedure
 and in the recovery room. Should the subject develop an allergic reaction, the radiologist
 will take the necessary measures as per the Radiology Department standard of care protocol.
 The subjects will be asked to provide another midstream urine sample for routine culturing 2
 days after the biopsy. This will be grown in conventional media. Subjects will be asked to
 measure and record their oral temperature once they wake up and just before going to sleep
 and every 6 hours in between, for 2 days after the procedure. A telephone interview using a
 post-biopsy questionnaire will be performed with the subject seven days after the biopsy to
 ascertain any side effects from the biopsy, including whether a temperature ≥38.0˚C was
 measured.
Inclusion Criteria:

 -  All subjects scheduled at Vancouver General & UBC Hospitals for a transrectal
 ultrasound guided prostate biopsy are eligible for this study. The indication for
 biopsy is made according to standard clinical reasoning and judgment, and is not
 affected by this study.

 -  All subjects must be willing and able to sign an informed consent and to take the
 ciprofloxacin prophylaxis before biopsy.