Antimicrobial prophylaxis for the prostate biopsy
Author
Seung-Ju Lee (Department of Urology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of Korea) Sang Rak Bae (Department of Urology, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Republic of Korea)
Executive summary
Epidemiology and pathogenesis
1. Incidence of infectious complications after TRUS-Bx is reported to be 0.1-7%, those requiring admission is 0.6-4.1%.
2. Overall, reported prevalence of fluoroquinolone resistance in infectious complications after TRUS-Bx is 24-100% and considering the recent trend of increasing antimicrobial resistance, fluoroquinolone resistance is expected to rise rapidly.
Diagnosis
1. The purpose of monitoring for fluoroquinolone resistant E. coli before TRUS-Bx would be to select appropriate prophylactic antibiotics that can specifically target antimicrobial-resistant organisms.
Treatment
1. Solutions for fluoroquinolone resistance are Identifying high risk patients with history taking, pre-biopsy rectal swab culture, and changing prophylactic antimicrobials for TRUS-Bx. If prebiopsy rectal swab culture was done, susceptible antimicrobial agent targeting the suspected causative bacteria should be used. If not, 3rd generation cephalosporins and aminoglycoside may be the optimal choice, at least in Korea.
Introduction
Transrectal ultrasound–guided prostate biopsy (TRUS-Bx) is one of the most commonly performed urologic procedure in USA and Europe, with approximately one million biopsies performed annually in each continent. TRUS-Bx is a relatively safe procedure and chances of severe complication is low, but incidence of infectious complications is recently rising, along with the potential for more severe complications such as sepsis.[1][2] Escherichia coli is the most common pathogen found in infections after TRUS-Bx.[3][4][5][6] Randomized, controlled trials showed that antibiotic prophylaxis was effective in preventing infectious complications following TRUS-Bx.[7] Fluoroquinolone is the most commonly used antimicrobial agent for prophylaxis.[7][8] However, worldwide antimicrobial resistance is rising,[9][10][11] and as such, infectious complications after TRUS-Bx by fluoroquinolone resistant E. coli is rising as well.[9][12][13][14]
Incidence of infectious complications after TRUS-Bx
Incidence of infectious complications after TRUS-Bx is reported to be 0.1-7%, those requiring admission is 0.6-4.1%.[15] In Korea, reported incidence of infectious complications after TRUS-Bx was 0.65-3.1% [16][17][18] and in another Asia-Europe multicenter study that included Korea, the reported incidence of febrile urinary tract infection (UTI) was 3.5% and those requiring admission was 3.1%.[19] In Japan, the reported incidence of febrile UTI was 0.5%-0.76%,[20][21] and in Taiwan, the incidence was 5.4% before fluoroquinolone prophylaxis and 0.9% after fluoroquinolone prophylaxis.[22] Turkish study reported an incidence of 2% that required admission.[23] Incidence of infectious complications after TRUS-Bx has been rising in recent years.
In a study that analyzed complications after prostate biopsy from SEER-Medicare data from 1991 to 2007, infectious complications after prostate biopsy have increased in recent years,[1]and in a Canadian report, incidence of infectious complications that required admission was 1.0% in 1996 but the incidence increased to 4.1% in 2005, 72% of which was sepsis.[2][13] Another recent Canadian report also stated that incidence of infectious complications was 0.52% from 2002 to 2009, but the incidence increased to 2.15% from 2010 to 2011.[24] The main reason for this increase in infectious complications is the rise of fluoroquinolone resistance.[9]
Prevalence of fluoroquinolone resistance in infectious complications
In one Korean study, acute bacterial prostatitis after TRUS-Bx occurred in 1.36% of the patients and prevalence of fluoroquinolone-resistant strain was 23.8%.[25] In a Japanese study, acute bacterial prostatitis developed in 1.3% of the patients and all urine and blood cultures yielded levofloxacin-resistant E. coli.[26] In another Japanese study, rate of genitourinary tract infection was 0.76% and E. coli was the most frequently isolated, of which 77.8% showed levofloxacin resistance.[21] In a North American cohort, 2.77% developed infection after biopsy, of which 55% had fluoroquinolone-resistant infection,[6] In a French prospective study, 0.67% had an acute bacterial prostatitis, of which 95% showed fluoroquinolone resistance.[27] In an Australian study that analyzed E. coli bacteremia that occurred after TRUS-Bx, 62% were fluoroquinolone resistant.[28] Overall, reported prevalence of fluoroquinolone resistance in infectious complications after TRUS-Bx is 24-100% and considering the recent trend of increasing antimicrobial resistance, fluoroquinolone resistance is expected to rise rapidly. Along with the problem of fluoroquinolone resistance, one should also be wary of the emergence of extended-spectrum beta-lactamase(ESBL) producing bacteria, which in one study reported an incidence of 43% of acute prostatitis occurred after TRUS-Bx.[29]
Rectal swab culture before TRUS Bx
Investigators from US[12] and Japan[30] monitored the rates of fluoroquinolone resistant E. coli before TRUS-Bx, with results of 23% and 13% respectively. The purpose of monitoring for fluoroquinolone resistant E. coli before TRUS-Bx would be to select appropriate prophylactic antibiotics that can specifically target antimicrobial-resistant organisms. Targeted prophylaxis may not only prevent infectious complications and sepsis after TRUS-Bx, but also suppress the rise of antimicrobial resistant bacteria. In a study conducted to evaluate targeted antimicrobial prophylaxis in men undergoing TRUS-Bx in US, there were no infectious complications in the 112 men who received targeted antimicrobial prophylaxis, while there were 9 cases (including 1 of sepsis) among the 345 on empirical therapy.[31] This study also evaluated the cost-effectiveness of targeted prophylaxis, which revealed that targeted prophylaxis yielded a cost savings of $4,499 per TRUS-Bx infectious complication averted. However, debate still exists whether rectal swab culture should be routinely performed before TRUS-Bx. In a Canadian study, despite a significant correlation between those patients who developed infections and the detection of ciprofloxacinresistant organisms, only 9.0% of the total group with ciprofloxacin resistance developed an infectious complication.[32] Future studies will need to evaluate the cost effectiveness and clinical utility of a pre-biopsy rectal culture in targeted antibiotic prophylaxis.[32]
Solutions for fluoroquinolone resistance
Identifying high risk patients with history taking
Fluoroquinolone use in the previous 3-6 months prior to TRUS-Bx was the common risk factor for fluoroquinolone resistance found in several studies.[5][33][34][35] The longer the period of fluoroquinolone use, the higher the incidence of fluoroquinolone resistance.[35] Therefore, thorough history taking is of paramount importance in order to identify recent fluoroquinolone usage for other conditions such as urinary tract infection, chronic prostatitis, heart valve surgery, artificial instrument insertion surgery etc.
Pre-biopsy rectal swab culture
Evidence for routine rectal swab culture before all TRUS-Bx is still indeterminate. However, in cases of high risk of fluoroquinolone resistance, performing pre-biopsy rectal swab culture to identify rectal bacterial flora would be of great assistance in preventing or treating infectious complications. Pre-biopsy rectal swab culture should be done 1-2 weeks before TRUS-Bx and if the patient has history of recent antimicrobial use, pre-biopsy rectal swab culture should be postponed or its results should be interpreted cautiously.
Changing prophylactic antimicrobials for TRUS-Bx
Currently, fluoroquinolone is the recommended antimicrobial for TRUS-Bx in US and European guidelines. It is also the most widely used antimicrobial agent for antimicrobial prophylaxis for TRUS-Bx in practice. However, in regions such as Korea where rates of fluoroquinolone resistance is high, following the US and European guidelines may be less effective for antimicrobial prophylaxis. If pre-biopsy rectal swab culture is done, susceptible antimicrobial agent should be used, and if it is not done, prophylactic antimicrobial agent should be changed in patients suspected of fluoroquinolone resistance. For this, there are attempts of adding aminoglycoside such as amikacin to fluoroquinolone, or using 3rd generation cephalosporins for prophylaxis.
However, this may cause another problem in addition to fluoroquinolone resistance; emergence of ESBL producing bacteria. In a Korean report, 20% of patients with infectious complications were found to have ESBL producing bacteria,[25] and in a Canadian report, the incidence of ESBL producing bacteria was 4.6%.[32] ESBL producing bacteria are usually resistant to most antimicrobials with the exception of carbapenems (imipenem, meropenem). However, it is not recommended to use potent antimicrobials such as imipenem or piperacillin/tazobactam for general prophylaxis because this may eventually cause emergence of carbapenem-resistant enterobacteriaceae that could potentially make us vulnerable to fatal infections.
Treating Fluoroquinolone resistant E. coli
Because infectious complications after TRUS-Bx could be fatal, immediate admission and implementation of antimicrobials is warranted in cases suspected of sepsis. If pre-biopsy rectal swab culture was done, susceptible antimicrobial agent targeting the suspected causative bacteria should be used. If not, 3rd generation cephalosporins and aminoglycoside may be the optimal choice, at least in Korea. Because resistance of gentamicin and tobramycin is already high in Korea, amikacin is the recommended aminoglycoside. If ESBL producing bacteria is suspected or cephalosporins are ineffective, use of carbapenems such as imipenem or meropenem should not be delayed. Once the results of antimicrobial susceptibility test is confirmed, de-escalation therapy is recommended, which consists of switching from a broad-spectrum empiric antimicrobial therapy to a narrower spectrum. After patient is discharged, continued treatment for a sufficient period of time is necessary to cure prostatitis.
Figure 1. Flow chart to choose antibiotic prophylaxis for transrectal prostate biopsy. *Alternative antibiotics may be recommended in regions where the rate of fluorequinolone resistance is high, but levels of evidence from clinical studies are not high.
Abbreviation
TRUS-Bx: transrectal ultrasound–guided prostate biopsy, UTI: urinary tract infection, ESBL:extended-spectrum beta-lactamase
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