Curr Urol Rep (2014) 15:381 DOI 10.1007/s11934-013-0381-2
PROSTATE CANCER (D PAREKH, SECTION EDITOR)
Prevention and Treatment of Biopsy-Related Complications Ramgopal Satyanarayana & Dipen Parekh
Published online: 3 January 2014 # Springer Science+Business Media New York 2014
Abstract Transrectal biopsy of the prostate is necessary in the diagnosis of prostate cancer (PC). Though generally considered safe, patients encounter minor complications such as bleeding and urinary symptoms, and uncommonly, serious infections that may require antibiotic therapy, visits to the emergency room (ER) or hospital admission, causing morbidity and rarely even mortality. It is concerning that infections are on the rise due to resistant bacteria. Urologists will have to be aware of bacterial susceptibility studies to reduce such complications. This review focuses on prostate biopsy and its complications, and measures to reduce these complications in our practice. Keywords Prostate biopsy . Complications . Prevention . Hematuria . Sepsis
Introduction Prostate cancer (PC) is the most common non-skin cancer diagnosed in the United States. An estimated 238,590 new cases will be diagnosed and 29,720 will die because of it in the year 2013 [American Cancer Society Statistics, 2013]. Approximately 1 million biopsies are performed annually, and transrectal guided biopsy of the prostate (TRUS) is the most commonly performed procedure to diagnose PC, and is guided by elevated prostate-specific antigen (PSA) or This article is part of the Topical Collection on Prostate Cancer R. Satyanarayana (*) : D. Parekh Department of Urology, University of Miami Miller school of Medicine, 1400, NW 10th Ave Suite 507, Dominion Towers, Miami, FL 33136, USA e-mail: [email protected] D. Parekh e-mail: [email protected]
abnormal digital rectal examination. Most of the biopsies are well tolerated. However, the most frequently experienced complications are hematuria, hemospermia, rectal bleeding and urinary retention [1–3]. Rarely, infections can result in bacteremia and septicemia. Even more rarely, septic shock and death may result [4•, 5]. There has been a marked increase in the number of prostate biopsies in the last decade and we can expect a commensurate increase in the number of complications. Loeb et al. showed, based on SEER-Medicare data, a higher risk of hospitalization within 30 days after a prostate biopsy, than in a control population. They concluded that risk of infectious complications have increased in recent years, while the rate of serious noninfectious complications are stable [6•]. In another study, Nam et al. showed a four-fold increase in 30-day post biopsy hospital admission, with most of them attributed to infection-related complications [7]. With the new American Urological Association (AUA) guidelines suggesting changed age cut-off for screening for PC, it is likely prostate biopsies will reduce in number [8].
Hematuria Hematuria is relatively common after TRUS biopsy. Severe bleeding is rare, while hematuria might be seen in 5–89 % of biopsies [4•, 9]. The majority of men experience minor hematuria, but a small minority can develop gross hematuria and clot retention, necessitating an emergency room (ER) visit or even surgical intervention [10]. A similar experience was observed by Pinshakov et al. in 0.4 % of their patients, requiring catheterization [4•]. While a large prostate size is associated with higher chances of bleeding [11, 12], a number of biopsy cores obtained did not uniformly relate to this complication [13, 14]. The size of the needle used (18 G versus 16 G) did not alter the incidence of hematuria [15]. As a part of the ProtecT study, Rosario et al. prospectively
381, Page 2 of 8
evaluated short-term outcomes of prostate biopsy, and only 6.2 % rated hematuria after prostate biopsy as a major problem. Thus, for vast the majority of patients, hematuria is not a significant bother after prostate biopsy [16].
Hematochezia In most cases, the rectal bleeding is slight without necessitating further therapeutic intervention. Rectal tissue is supplied by a rich vascular bed that consists of branches of the inferior vesicular artery and the middle and inferior rectal arteries. In patients with hemorrhoids, the venous plexus is also prominent in the sub-mucosal region. The total incidence of rectal bleeding is reported to occur in 1.3–58.6 % of biopsies, and a positive correlation is found with number of cores obtained [11]. Ghani et al. compared the duration and rates of bleeding with the number of cores, and it was shown that higher number of cores of up to 8–10 cores resulted in more rectal bleeding, compared to six cores. The duration of bleeding did not alter between the groups. Rosario et al. recorded hematochazia in 36.8 % of patients, but only 2.5 % found it to be bothersome [16]. Rarely, massive bleeding may result, requiring blood transfusion [17, 18].
Hematospermia Hemospermia is a well-recognized complication of TRUSguided prostatic biopsy. Though it is classified under minor complications, its persistence worries the patient and the partner. The reported incidence varies from 5.1 % to 89 % [19].The varied rates are due to method of collection and reports of data. Rosario reported a high incidence of 92.6 % in their series. However, only 25 % were concerned [16]. In the European Randomized Study of Screening for Prostate Cancer (ERSPC) study, hematospermia was seen in 50.4 % of patients, and the incidence correlated with age, prostate volume and history of previous TURP [11]. The number of cores correlated with incidence of hematospermia. Berger et al. reported incidence of 31.8 % after six core biopsies versus 37.4 % of ten core biopsies and 38.4 % after 15 core biopsies [20]. The mean duration is around 15 days [21], and around 32 % may still experience hematospermia even after 4 weeks [19]. Patients need to be forewarned regarding this possibility.
Treatment of Bleeding Complications Though very rare, the incidence of massive rectal bleeding can be as high as 8.2 % [22]. Brullet et al. [22] reported a 1 % incidence of massive rectal bleeding in 550 cases after TRUS
Curr Urol Rep (2014) 15:381
biopsy, needing hospitalization and transfusions (mean 4, range 2–7). Emergency colonoscopy revealed active bleeding from biopsy sites in the anterior rectal wall. Endoscopic injection of epinephrine and polidocanol achieved control of bleeding and permanent hemostasis in all cases. Rectal pressure after biopsy has been used by others, by application of direct pressure or rectal balloon catheters or even an inflated condom. However, Kilciler et al. observed that although rectal pressure using a balloon catheter reduced the rectal bleeding, it did not affect hematuria or hematospermia [23]. Other measures that have been employed are endoscopic sclerotherapy using adrenaline and ethanol, and using rubber bands that are used for clipping hemorrhoids [24]. Endo clips have been used to arrest bleeding points using colonoscopy in a novel fashion [18]. Massive hematuria needing surgical interventions are extremely rare. This has been reported after a biopsy of a prostate associated with a congenital A-V malformation, diagnosed through magnetic resonance imaging (MRI) and angiography, necessitating angio-embolization and surgical intervention [25]. There are few reports of large pelvic and retroperitoneal hematoma following biopsy; these have been treated by transcatheter embolization [26]. Can we reduce the complications of bleeding, though minor? Perhaps reduction in the number of cores obtained will reduce the chances of moderate or severe bleeding. Recent advances in imaging using combined MRI and magnetic resonance spectroscopic imaging (MRSI) in patients with persistently high PSA levels and negative TRUS-guided biopsy results, have revealed that MRI/MRSI have the potential to guide biopsies to tumor foci in these patients. Multi-parametric-MRI showed good performance at both detection and ruling out clinically significant disease, perhaps obviating biopsies, or at least reducing the number of biopsies in the future [27].
Anticoagulation and Bleeding Complications Anticoagulants are prescribed for prevention of thromboembolic complications in cardiovascular and cerebrovascular disorders in high-risk patients and also postoperatively after percutaneous vascular interventions. The rise in elderly patient population with such comorbid conditions has necessitated the use of antiplatelet agents. The same patient population needs to undergo prostate biopsies because of suspicions of PC. So a physician faces the dilemma of stopping anticoagulants in order to prevent complication of bleeding, versus exposing the patient to the hazards of cardiovascular complications. The relationship between the use of aspirin and bleeding complication after TRUS biopsy was analyzed primarily by Rodriguez et al., who concluded that use of aspirin or
Curr Urol Rep (2014) 15:381
nonsteroidal anti-inflammatory drugs (NSAIDs) is not an absolute contraindication to this procedure [28]. Two recent meta-analyses looked at the issue of whether continuing anti-platelet therapy would result in higher risk of bleeding after prostate biopsy. Carmignani et al. analyzed 3,218 patients, based on articles published between 1990 and 2011. They reported a 1.36-fold increased chances of hematuria, mainly minor bleeding with aspirin use. Hematochezia (OR 1.24, CI 0.80–1.93) and hematospermia (OR 1.52, CI 0.75–3.08) were not statistically increased. They concluded that continued use of aspirin does not increase the risk of overall bleeding after prostate biopsy and suggested not to discontinue this therapy prior to prostate biopsy[29•]. Wang et al. included studies involving transurethral resection of prostate as well as prostate biopsy between the years 1990 and 2012 comparing withholding anti-platelet therapy (control group) with continuing anti-platelet therapy(experimental group). Nine studies having 3,145 cases were identified and included in meta-analysis. Results showed that no differences were found in risk of bleeding after TURP (OR 1.26, CI 0.80– 2.00) and prostate biopsy (OR 0.89, CI 0.45–1.76). Chowdhary et al. studied 902 patients who underwent prostate biopsy and examined if increased sampling numbers were more likely to experience bleeding complications and whether warfarin or low-dose aspirin were independent risk factors. Among 902 patients, 579 (64.2 %) underwent eight core biopsies, 47 (5.2 %) underwent nine, and 276 (30.6 %) underwent ten. Sixty-eight patients were taking warfarin, 216 were taking low-dose aspirin, one was taking both, and 617 were taking neither. 27.9 % of those on warfarin and 33.8 % of those on aspirin experienced hematuria. 37 % of those on no blood thinners experienced hematuria. They concluded that there is an increased risk of bleeding complications following TRUS-guided prostate biopsy with increased sampling numbers, but these are minor. There is also an increased risk with low-dose aspirin use; however, there is no increased risk of bleeding complications with warfarin use [14]. A very recent evidence-based guideline issued by American Academy of Neurology suggested that those stroke patients undergoing TRUS biopsy should not stop aspirin (Level B) [30].
Infection A major problem of TRUS-guided biopsies of the prostate is the risk of infection. They vary from asymptomatic bacteriuria, symptomatic urinary tract infection (UTI), prostatitis, epididymitis, and, rarely, sepsis and septic shock [4•, 7, 10]. Most infectious complications after TRUS biopsy are limited to symptomatic UTI and low-grade febrile illness, which can be readily treated with oral or intravenous antibiotics. However, rare case reports of fatal septicemia after prostate biopsy have been published [31]. Infections can be very
Page 3 of 8, 381
severe, requiring hospital admissions, and the frequency is estimated to be 1-2 % [11]. Before the use of routine antibiotics prior to prostate biopsy, infections rates were as high as 69 % [32]. They have dropped significantly since the introduction of routine antibiotics. Recently, there have been concerns regarding increasing infectious complications, perhaps attributable to antimicrobial and particularly fluoroquinolone resistance. Increasing prevalence of multidrug-resistant microorganisms, mostly extended spectrum beta lactamase (ESBL)-producing and fluoroquinolone-resistant enterobacteriaceae, has increased the post-TRUS biopsy infection rates, including sepsis. Based on Medicare data, Loeb et al. reported that there were 2.26-fold higher hospitalization rates for infections in the period 1991–2007. Nam et al. also reported a rise in urological complications in their study of 75,190 men, from 1 % in 1996 to 4.15 % in 2005 in Canada [6•, 33]. In a study by Pinshakov et al. of 1,000 consecutive biopsies, E. coli was the most common pathogen (92 %) isolated from positive urine cultures. About 73 % were found to be resistant to both Ciprofloxacin and Co-trimoxazole, and the remainder were resistant to either one of them [4•]. In the United States, fluroquinolone resistance has increased from 0 to 12 % in blood stream isolates of E coli in the period 1998–2007 [34]. Similar trends have been reported in Europe, and particularly in Asia and Africa. In one report, 23–37 % of Enterobacteria had reduced antibiotic sensitivity [35]. It may be prudent to think of adding a parenteral antibiotic to the prophylaxis regimen, and this was tried recently. Amikacin prophylaxis has been shown to improve infection rates after prostate biopsy, from 2.5 % to 0.3 % [36].
Measures to Reduce Infection Rates Abughosh et al. prospectively randomized 865 men to rectal cleansing using povidone iodine (421) or no cleansing (444) before transrectal ultrasound-guided prostate biopsy. Patients received ciprofloxacin prophylaxis, and rectal swab cultures were obtained before transrectal ultrasound-guided prostate biopsy. They reported a 42 % reduction in infections in the treated group, but it was not statistically significant [37]. Ghafoori et al. conducted a similar study in Iran with rectal cleansing with povidone iodine prior to biopsy and found a statistically significant reduction in infections between the groups (19.3 % versus 36.4 % P=0.001) [38]. A recent Cochrane review observed effectiveness and adverse effects of prophylactic antibiotic treatment in prostate biopsy, and concluded that 'antibiotic versus antibiotic + enema', risk of bacteremia (RR 0.25; CI 0.08–0.75) was diminished in the latter group'. Long-course treatment was significantly better than short-course treatment only for bacteriuria (RR 2.09; CI
381, Page 4 of 8
1.17–3.73). For 'single versus multiple dose', there was significantly greater risk of bacteriuria for single-dose treatment (RR 1.98;CI 1.18–3.33). Route of administration of antibiotics did not alter infection rates [39]. Although many believe use of a rectal preparation reduces the infection rates, others are of the opinion that this could increase the rate of complications after biopsies as a result of rectal irritation, which might promote bacterial dissemination, and rectal preparations might add to discomfort and cost to the patient [40, 41] Jeon et al. used bisacodyl rectal suppositories in 456 of the total 879 cases prior to prostate biopsy, and found rectal preparation with Bisacodyl significantly reduced the infection, based on their observation of only 1.3 % developing infection in the treated group versus 9.5 % in those who did not have rectal preparation [42]. There have been attempts to expand the antimicrobial regimen. However, this might increase the cost and possible development of antimicrobial resistance in the future. Adibi et al. evaluated the incidence of infectious complications requiring hospitalization after transrectal ultrasound-guided prostate biopsy, comparing an augmented regimen using gentamicin in addition to either Bactrim DS or Ciprofloxacin (standard regimen), and showed that infection rates dropped from 3.8 % to 0.6 %, as well as showing cost-effectiveness because it prevented hospital admissions due to infections [43]. Others have shown similar experience with another aminoglycoside, amikacin [36]. Several centers have reduced infections by adding ciprofloxacin with or without cefoxitin to previous regimen of amoxicillin with clavulanate [44]. Use of Peri-prostate nerve block for anesthetic purposes might be construed to increase the chances of infection because of additional needle punctures. However, this has not been shown, though the study had larger glands and more biopsy cores taken [45]. However, a recent study on mixing of ceftriaxone with local anesthetic has shown reduced incidence of sepsis [46]. Another approach to reducing post-biopsy–related infections is to administer antibiotics based on culture results. Such target-based prophylaxis has gained increasing importance. Taylor et al. identified microbial and antibiotic sensitivity profiles from 849 patients. Ciprofloxacin-resistant Gramnegative organisms were identified in the rectal flora of 19 % of men. Infectious complications were observed in 3.6 % (n=31) of the patient population, and 48 % of these patients grew ciprofloxacin-resistant organisms on the prebiopsy rectal swab (P
PROSTATE CANCER (D PAREKH, SECTION EDITOR)
Prevention and Treatment of Biopsy-Related Complications Ramgopal Satyanarayana & Dipen Parekh
Published online: 3 January 2014 # Springer Science+Business Media New York 2014
Abstract Transrectal biopsy of the prostate is necessary in the diagnosis of prostate cancer (PC). Though generally considered safe, patients encounter minor complications such as bleeding and urinary symptoms, and uncommonly, serious infections that may require antibiotic therapy, visits to the emergency room (ER) or hospital admission, causing morbidity and rarely even mortality. It is concerning that infections are on the rise due to resistant bacteria. Urologists will have to be aware of bacterial susceptibility studies to reduce such complications. This review focuses on prostate biopsy and its complications, and measures to reduce these complications in our practice. Keywords Prostate biopsy . Complications . Prevention . Hematuria . Sepsis
Introduction Prostate cancer (PC) is the most common non-skin cancer diagnosed in the United States. An estimated 238,590 new cases will be diagnosed and 29,720 will die because of it in the year 2013 [American Cancer Society Statistics, 2013]. Approximately 1 million biopsies are performed annually, and transrectal guided biopsy of the prostate (TRUS) is the most commonly performed procedure to diagnose PC, and is guided by elevated prostate-specific antigen (PSA) or This article is part of the Topical Collection on Prostate Cancer R. Satyanarayana (*) : D. Parekh Department of Urology, University of Miami Miller school of Medicine, 1400, NW 10th Ave Suite 507, Dominion Towers, Miami, FL 33136, USA e-mail: [email protected] D. Parekh e-mail: [email protected]
abnormal digital rectal examination. Most of the biopsies are well tolerated. However, the most frequently experienced complications are hematuria, hemospermia, rectal bleeding and urinary retention [1–3]. Rarely, infections can result in bacteremia and septicemia. Even more rarely, septic shock and death may result [4•, 5]. There has been a marked increase in the number of prostate biopsies in the last decade and we can expect a commensurate increase in the number of complications. Loeb et al. showed, based on SEER-Medicare data, a higher risk of hospitalization within 30 days after a prostate biopsy, than in a control population. They concluded that risk of infectious complications have increased in recent years, while the rate of serious noninfectious complications are stable [6•]. In another study, Nam et al. showed a four-fold increase in 30-day post biopsy hospital admission, with most of them attributed to infection-related complications [7]. With the new American Urological Association (AUA) guidelines suggesting changed age cut-off for screening for PC, it is likely prostate biopsies will reduce in number [8].
Hematuria Hematuria is relatively common after TRUS biopsy. Severe bleeding is rare, while hematuria might be seen in 5–89 % of biopsies [4•, 9]. The majority of men experience minor hematuria, but a small minority can develop gross hematuria and clot retention, necessitating an emergency room (ER) visit or even surgical intervention [10]. A similar experience was observed by Pinshakov et al. in 0.4 % of their patients, requiring catheterization [4•]. While a large prostate size is associated with higher chances of bleeding [11, 12], a number of biopsy cores obtained did not uniformly relate to this complication [13, 14]. The size of the needle used (18 G versus 16 G) did not alter the incidence of hematuria [15]. As a part of the ProtecT study, Rosario et al. prospectively
381, Page 2 of 8
evaluated short-term outcomes of prostate biopsy, and only 6.2 % rated hematuria after prostate biopsy as a major problem. Thus, for vast the majority of patients, hematuria is not a significant bother after prostate biopsy [16].
Hematochezia In most cases, the rectal bleeding is slight without necessitating further therapeutic intervention. Rectal tissue is supplied by a rich vascular bed that consists of branches of the inferior vesicular artery and the middle and inferior rectal arteries. In patients with hemorrhoids, the venous plexus is also prominent in the sub-mucosal region. The total incidence of rectal bleeding is reported to occur in 1.3–58.6 % of biopsies, and a positive correlation is found with number of cores obtained [11]. Ghani et al. compared the duration and rates of bleeding with the number of cores, and it was shown that higher number of cores of up to 8–10 cores resulted in more rectal bleeding, compared to six cores. The duration of bleeding did not alter between the groups. Rosario et al. recorded hematochazia in 36.8 % of patients, but only 2.5 % found it to be bothersome [16]. Rarely, massive bleeding may result, requiring blood transfusion [17, 18].
Hematospermia Hemospermia is a well-recognized complication of TRUSguided prostatic biopsy. Though it is classified under minor complications, its persistence worries the patient and the partner. The reported incidence varies from 5.1 % to 89 % [19].The varied rates are due to method of collection and reports of data. Rosario reported a high incidence of 92.6 % in their series. However, only 25 % were concerned [16]. In the European Randomized Study of Screening for Prostate Cancer (ERSPC) study, hematospermia was seen in 50.4 % of patients, and the incidence correlated with age, prostate volume and history of previous TURP [11]. The number of cores correlated with incidence of hematospermia. Berger et al. reported incidence of 31.8 % after six core biopsies versus 37.4 % of ten core biopsies and 38.4 % after 15 core biopsies [20]. The mean duration is around 15 days [21], and around 32 % may still experience hematospermia even after 4 weeks [19]. Patients need to be forewarned regarding this possibility.
Treatment of Bleeding Complications Though very rare, the incidence of massive rectal bleeding can be as high as 8.2 % [22]. Brullet et al. [22] reported a 1 % incidence of massive rectal bleeding in 550 cases after TRUS
Curr Urol Rep (2014) 15:381
biopsy, needing hospitalization and transfusions (mean 4, range 2–7). Emergency colonoscopy revealed active bleeding from biopsy sites in the anterior rectal wall. Endoscopic injection of epinephrine and polidocanol achieved control of bleeding and permanent hemostasis in all cases. Rectal pressure after biopsy has been used by others, by application of direct pressure or rectal balloon catheters or even an inflated condom. However, Kilciler et al. observed that although rectal pressure using a balloon catheter reduced the rectal bleeding, it did not affect hematuria or hematospermia [23]. Other measures that have been employed are endoscopic sclerotherapy using adrenaline and ethanol, and using rubber bands that are used for clipping hemorrhoids [24]. Endo clips have been used to arrest bleeding points using colonoscopy in a novel fashion [18]. Massive hematuria needing surgical interventions are extremely rare. This has been reported after a biopsy of a prostate associated with a congenital A-V malformation, diagnosed through magnetic resonance imaging (MRI) and angiography, necessitating angio-embolization and surgical intervention [25]. There are few reports of large pelvic and retroperitoneal hematoma following biopsy; these have been treated by transcatheter embolization [26]. Can we reduce the complications of bleeding, though minor? Perhaps reduction in the number of cores obtained will reduce the chances of moderate or severe bleeding. Recent advances in imaging using combined MRI and magnetic resonance spectroscopic imaging (MRSI) in patients with persistently high PSA levels and negative TRUS-guided biopsy results, have revealed that MRI/MRSI have the potential to guide biopsies to tumor foci in these patients. Multi-parametric-MRI showed good performance at both detection and ruling out clinically significant disease, perhaps obviating biopsies, or at least reducing the number of biopsies in the future [27].
Anticoagulation and Bleeding Complications Anticoagulants are prescribed for prevention of thromboembolic complications in cardiovascular and cerebrovascular disorders in high-risk patients and also postoperatively after percutaneous vascular interventions. The rise in elderly patient population with such comorbid conditions has necessitated the use of antiplatelet agents. The same patient population needs to undergo prostate biopsies because of suspicions of PC. So a physician faces the dilemma of stopping anticoagulants in order to prevent complication of bleeding, versus exposing the patient to the hazards of cardiovascular complications. The relationship between the use of aspirin and bleeding complication after TRUS biopsy was analyzed primarily by Rodriguez et al., who concluded that use of aspirin or
Curr Urol Rep (2014) 15:381
nonsteroidal anti-inflammatory drugs (NSAIDs) is not an absolute contraindication to this procedure [28]. Two recent meta-analyses looked at the issue of whether continuing anti-platelet therapy would result in higher risk of bleeding after prostate biopsy. Carmignani et al. analyzed 3,218 patients, based on articles published between 1990 and 2011. They reported a 1.36-fold increased chances of hematuria, mainly minor bleeding with aspirin use. Hematochezia (OR 1.24, CI 0.80–1.93) and hematospermia (OR 1.52, CI 0.75–3.08) were not statistically increased. They concluded that continued use of aspirin does not increase the risk of overall bleeding after prostate biopsy and suggested not to discontinue this therapy prior to prostate biopsy[29•]. Wang et al. included studies involving transurethral resection of prostate as well as prostate biopsy between the years 1990 and 2012 comparing withholding anti-platelet therapy (control group) with continuing anti-platelet therapy(experimental group). Nine studies having 3,145 cases were identified and included in meta-analysis. Results showed that no differences were found in risk of bleeding after TURP (OR 1.26, CI 0.80– 2.00) and prostate biopsy (OR 0.89, CI 0.45–1.76). Chowdhary et al. studied 902 patients who underwent prostate biopsy and examined if increased sampling numbers were more likely to experience bleeding complications and whether warfarin or low-dose aspirin were independent risk factors. Among 902 patients, 579 (64.2 %) underwent eight core biopsies, 47 (5.2 %) underwent nine, and 276 (30.6 %) underwent ten. Sixty-eight patients were taking warfarin, 216 were taking low-dose aspirin, one was taking both, and 617 were taking neither. 27.9 % of those on warfarin and 33.8 % of those on aspirin experienced hematuria. 37 % of those on no blood thinners experienced hematuria. They concluded that there is an increased risk of bleeding complications following TRUS-guided prostate biopsy with increased sampling numbers, but these are minor. There is also an increased risk with low-dose aspirin use; however, there is no increased risk of bleeding complications with warfarin use [14]. A very recent evidence-based guideline issued by American Academy of Neurology suggested that those stroke patients undergoing TRUS biopsy should not stop aspirin (Level B) [30].
Infection A major problem of TRUS-guided biopsies of the prostate is the risk of infection. They vary from asymptomatic bacteriuria, symptomatic urinary tract infection (UTI), prostatitis, epididymitis, and, rarely, sepsis and septic shock [4•, 7, 10]. Most infectious complications after TRUS biopsy are limited to symptomatic UTI and low-grade febrile illness, which can be readily treated with oral or intravenous antibiotics. However, rare case reports of fatal septicemia after prostate biopsy have been published [31]. Infections can be very
Page 3 of 8, 381
severe, requiring hospital admissions, and the frequency is estimated to be 1-2 % [11]. Before the use of routine antibiotics prior to prostate biopsy, infections rates were as high as 69 % [32]. They have dropped significantly since the introduction of routine antibiotics. Recently, there have been concerns regarding increasing infectious complications, perhaps attributable to antimicrobial and particularly fluoroquinolone resistance. Increasing prevalence of multidrug-resistant microorganisms, mostly extended spectrum beta lactamase (ESBL)-producing and fluoroquinolone-resistant enterobacteriaceae, has increased the post-TRUS biopsy infection rates, including sepsis. Based on Medicare data, Loeb et al. reported that there were 2.26-fold higher hospitalization rates for infections in the period 1991–2007. Nam et al. also reported a rise in urological complications in their study of 75,190 men, from 1 % in 1996 to 4.15 % in 2005 in Canada [6•, 33]. In a study by Pinshakov et al. of 1,000 consecutive biopsies, E. coli was the most common pathogen (92 %) isolated from positive urine cultures. About 73 % were found to be resistant to both Ciprofloxacin and Co-trimoxazole, and the remainder were resistant to either one of them [4•]. In the United States, fluroquinolone resistance has increased from 0 to 12 % in blood stream isolates of E coli in the period 1998–2007 [34]. Similar trends have been reported in Europe, and particularly in Asia and Africa. In one report, 23–37 % of Enterobacteria had reduced antibiotic sensitivity [35]. It may be prudent to think of adding a parenteral antibiotic to the prophylaxis regimen, and this was tried recently. Amikacin prophylaxis has been shown to improve infection rates after prostate biopsy, from 2.5 % to 0.3 % [36].
Measures to Reduce Infection Rates Abughosh et al. prospectively randomized 865 men to rectal cleansing using povidone iodine (421) or no cleansing (444) before transrectal ultrasound-guided prostate biopsy. Patients received ciprofloxacin prophylaxis, and rectal swab cultures were obtained before transrectal ultrasound-guided prostate biopsy. They reported a 42 % reduction in infections in the treated group, but it was not statistically significant [37]. Ghafoori et al. conducted a similar study in Iran with rectal cleansing with povidone iodine prior to biopsy and found a statistically significant reduction in infections between the groups (19.3 % versus 36.4 % P=0.001) [38]. A recent Cochrane review observed effectiveness and adverse effects of prophylactic antibiotic treatment in prostate biopsy, and concluded that 'antibiotic versus antibiotic + enema', risk of bacteremia (RR 0.25; CI 0.08–0.75) was diminished in the latter group'. Long-course treatment was significantly better than short-course treatment only for bacteriuria (RR 2.09; CI
381, Page 4 of 8
1.17–3.73). For 'single versus multiple dose', there was significantly greater risk of bacteriuria for single-dose treatment (RR 1.98;CI 1.18–3.33). Route of administration of antibiotics did not alter infection rates [39]. Although many believe use of a rectal preparation reduces the infection rates, others are of the opinion that this could increase the rate of complications after biopsies as a result of rectal irritation, which might promote bacterial dissemination, and rectal preparations might add to discomfort and cost to the patient [40, 41] Jeon et al. used bisacodyl rectal suppositories in 456 of the total 879 cases prior to prostate biopsy, and found rectal preparation with Bisacodyl significantly reduced the infection, based on their observation of only 1.3 % developing infection in the treated group versus 9.5 % in those who did not have rectal preparation [42]. There have been attempts to expand the antimicrobial regimen. However, this might increase the cost and possible development of antimicrobial resistance in the future. Adibi et al. evaluated the incidence of infectious complications requiring hospitalization after transrectal ultrasound-guided prostate biopsy, comparing an augmented regimen using gentamicin in addition to either Bactrim DS or Ciprofloxacin (standard regimen), and showed that infection rates dropped from 3.8 % to 0.6 %, as well as showing cost-effectiveness because it prevented hospital admissions due to infections [43]. Others have shown similar experience with another aminoglycoside, amikacin [36]. Several centers have reduced infections by adding ciprofloxacin with or without cefoxitin to previous regimen of amoxicillin with clavulanate [44]. Use of Peri-prostate nerve block for anesthetic purposes might be construed to increase the chances of infection because of additional needle punctures. However, this has not been shown, though the study had larger glands and more biopsy cores taken [45]. However, a recent study on mixing of ceftriaxone with local anesthetic has shown reduced incidence of sepsis [46]. Another approach to reducing post-biopsy–related infections is to administer antibiotics based on culture results. Such target-based prophylaxis has gained increasing importance. Taylor et al. identified microbial and antibiotic sensitivity profiles from 849 patients. Ciprofloxacin-resistant Gramnegative organisms were identified in the rectal flora of 19 % of men. Infectious complications were observed in 3.6 % (n=31) of the patient population, and 48 % of these patients grew ciprofloxacin-resistant organisms on the prebiopsy rectal swab (P
