Doi:10.1016/j.juro.2007.10.07

The Incidence of Fluoroquinolone Resistant Infections After
Prostate Biopsy—Are Fluoroquinolones Still Effective Prophylaxis?
Joseph Feliciano,* Ervin Teper, Michael Ferrandino, Richard J. Macchia, William Blank,
Ivan Grunberger† and Ivan Colon
From the State University of New York Downstate Medical School, Brooklyn, New York
Purpose: Fluoroquinolones have been shown to decrease infective complications after prostate biopsy. However, fluoroquin-
olone resistance is emerging. We quantified contemporary rates of infective complications and the incidence of fluoroquino-
lone resistant infections after prostate biopsy under fluoroquinolone prophylaxis.
Materials and Methods: We retrospectively evaluated the records of 1,273 patients who underwent prostate biopsy at
New York Harbor Veterans Affairs Hospital from January 2004 to December 2006. Patients received levofloxacin or
gatifloxacin. Using the Veterans Affairs computerized patient record system we reviewed all patient visits within 1
month after prostate biopsy. Visits were queried for infective symptoms. Positive cultures were evaluated for resistance
patterns. The annual and overall incidence of infective complications and fluoroquinolone resistant infections was
calculated.
Results: Of 1,273 patients 31 (2.4%) presented with infective symptoms after biopsy. The overall incidence of fluoroquinolone
resistant infections was 1.2% (15 cases). When stratified by year, there were statistically significant increases in the incidence
of infective complications and fluoroquinolone resistance from 2004 to 2006. Of the positive cultures those from 89% of
patients yielded Escherichia coli and 90% were fluoroquinolone resistant. Fluoroquinolone resistant E. coli were also resistant
to gentamicin in 22% of cases, trimethoprim/sulfamethoxazole in 44%, piperacillin in 72% and ampicillin in 94%. However,
100% sensitivity was demonstrated for amikacin, ceftazidime and ceftriaxone.
Conclusions: Fluoroquinolones are still effective as antibiotic prophylaxis for prostate biopsies but there is an increase in
infective complications and fluoroquinolone resistance. When patients present with post-prostate biopsy infective symptoms,
almost 50% are associated with fluoroquinolone resistant pathogens. Empirical treatment with ceftriaxone, ceftazidime or
amikacin should be initiated until culture specific therapy can be implemented.
Key Words: prostate, biopsy, infection, fluoroquinolones, drug resistance Many men are now undergoing TRUSBP in the ad- resistant pathogens. Recent reports have shown that flu- vent of prostate specific antigen screening and in- oroquinolone resistant infections after prostate biopsy are creasing awareness of prostate cancer. The risks We identified contemporary rates of infec- and complication rates of TRUSBP have been well docu- tive complications with fluoroquinolone prophylaxis and mented in the They include minor complica- quantified the incidence of fluoroquinolone resistant in- tions such as hematuria and hemospermia as well as clini- Several studies have shown the benefits of fluoroquin- olone prophylaxis for decreasing infective complications after Aron et al observed that infective com- A retrospective evaluation was performed of the records of plications after TRUSBP were significantly decreased all patients who underwent TRUSBP at the Brooklyn and when fluoroquinolones were used compared to placebo in a Manhattan campuses of New York Harbor Veterans Affairs randomized, controlled study (8% vs Numerous Hospital from January 2004 to December 2006. A total of other studies have demonstrated decreases in infective 1,296 patients underwent TRUSBP. Of the 1,296 patients 23 complications with fluoroquinolone use to rates of 1% did not have followup documented after prostate biopsy and were excluded from study. All of these patients were re- Because fluoroquinolones have a broad antimicrobial spec- ferred for biopsy due to abnormal digital rectal examination trum, the use or overuse of these drugs by physicians, in- and/or prostate specific antigen outside the reference range cluding urologists, has led to increasing fluoroquinolone during evaluation by their primary care physician and/orevaluation by a urologist at the VA hospital. Patients re-ceived a minimum of 3 daily doses of 250 mg levofloxacin Submitted for publication July 11, 2007.
orally or 3 doses of 200 mg gatifloxacin orally starting 1 day * Correspondence: (telephone: 917-570-7622; e-mail: Using a computerized patient record system we reviewed † Financial interest and/or other relationship with Sanofi, Pfizer, all patient visits to the VA hospital 1 month after TRUSBP, Copyright 2008 by AMERICAN UROLOGICAL ASSOCIATION DOI:10.1016/j.juro.2007.10.071
FLUOROQUINOLONE RESISTANT INFECTIONS AFTER PROSTATE BIOPSY including visits to the emergency room, primary care physi- year-old patient who underwent TRUSBP in 2005 was a cians, hospitalizations and prostate biopsy followup. We potential outlier, he was included in the study since he fit chose visits within 1 month after TRUSBP as a cutoff to the criterion of abnormal digital rectal examination for the capture only infections that may have been related to pros- tate biopsy. Any events more than 1 month after prostate Of the 1,273 patients 31 (2.4%) presented with infective biopsy were unlikely to have been related to TRUSBP. Pa- symptoms. Of the 31 patients 29 presented to New York tient followup visits were queried for possible infective Harbor VA with symptoms, while during prostate biopsy symptoms, which we defined as fever greater than 100.4F, followup 2 reported a history of febrile UTI 1 day after chills, leukocytosis (greater than 10,000 cells per mm3) or TRUSBP, requiring hospitalization elsewhere. These 2 persistent dysuria requiring medical attention and interven- patients were included in the total number of infective complications but they were considered to have negative All positive blood and urine cultures were evaluated for cultures since their records from elsewhere were not bacteriology and resistance patterns. All cultures were pro- available for review. None of the 31 patients had had prior cessed at the New York Harbor VA microbiology department UTIs on urine culture before prostate biopsy.
using standard protocols and quality measures, as defined Patients presented with symptoms a mean of 5.3 days by the National Committee on Clinical Laboratory Stan- after prostate biopsy. Of these 31 patients 20 (65%) com- dards. There were no changes in laboratory culture prac- plained of subjective fever and 13 (42%) had a measured tices at the microbiology department during our study fever of greater than 100.4F. Patients with fever or chills presented a mean of 3.9 days after TRUSBP. Ten of these 31 The annual and overall incidence of infective complica- patients (35%) presented with dysuria a mean of 9.0 days tions and fluoroquinolone resistant infections was then cal- after prostate biopsy, 15 (48%) had leukocytosis, defined as culated. Chi-square analysis was used to compare variables greater than 10,000 cells per mm3, and 19 (61%) were hos- between various groups in the study.
pitalized with a mean hospital stay of 4.1 days. Nine of the19 patients received a combination of intravenous ampicil- lin/gentamicin, 6 received a fluoroquinolone as the initialtreatment, 3 received penicillin as the initial treatment and There were 1,296 TRUSBPs between January 2004 and 1 received ceftriaxone. There were no cases of septic shock December 2006, of which 23 were excluded because there was no recorded followup on chart review. Thus, 1,273 Of the 31 patients 19 (61%) had positive urine and/or TRUSBPs were evaluated in this study, comprising 98% of blood cultures, including Escherichia coli in 17 (89%), En- all TRUSBPs during this period. lists patient demo- terobacter cloacae in 1 and Staphylococcus epidermidis in 1.
graphics, clinical manifestations of infective complications Of the 19 patients 15 (79%) harbored fluoroquinolone resis- and bacteriology. The mean age of patients undergoing tant pathogens, including E. coli in 14 and S. epidermidis in TRUSBP was 66.7 years (range 25 to 95). Although a 25- 1. Thus, the overall incidence of fluoroquinolone resistancewas 1.2% (15 of 1,273 patients).
A total of 23 positive samples, including 18 urine and TABLE 1. Patient characteristics, clinical manifestations of 5 blood samples, were evaluated for resistance patterns infective complications and bacteriology (tables 2 and 3). Of the 23 positive cultures 21 (91%) yielded E. coli, including 18 (86%) in which E. coli was resistant to fluoroquinolones. Fluoroquinolone resistant E. coli was also resistant to ampicillin in 17 of the 18 cases (94%), tri- methoprim/sulfamethoxazole in 8 (44%), piperacillin in 13 (72%) and gentamicin in 4 (22%). However, 90% or greater susceptibility was demonstrated for the cephalosporins, ti- carcillin/clavulonate, imipenem, aztreonam, tobramycin and As mentioned, the overall incidence of infective complica- tions and fluoroquinolone resistant UTIs was 2.4% (31 of 1,273 cases) and 1.2% (15 of 1,273), respectively. When strat- ified by year, the incidence of infective complications was 3 times higher in 2006 compared to that in 2004 and 2005 The incidence of fluoroquinolone resistant UTIs was also 4.3 and 3.3 times higher in 2006 compared to that in 2004 and 2005, respectively. These 2 increases were sta- tistically significant for infective complications and fluoro- quinolone resistant UTIs (each p ϭ Ͻ0.05).
DISCUSSION
Decreases in infective complication rates after TRUSBP with fluoroquinolone prophylaxis are well documented in the In a randomized, double-blind, controlled study reported in 1998 Kapoor et al noted that using cipro- FLUOROQUINOLONE RESISTANT INFECTIONS AFTER PROSTATE BIOPSY TABLE 2. Susceptibility of bacteria to antibiotics in 22 samples TABLE 4. Incidence of infective complications and fluoroquinolone resistant UTIs by year quinolone resistant pathogens after transrectal prostate bi- The sample with S. epidermidis was resistant to fluoroquinolones and penicillins, only sensitive to vancomycin, linezolid and gentamicin, and it is Should we reassess our practices? Is fluoroquinolone pro- not included (22 samples include urine and blood cultures).
phylaxis still effective? Do rates of infective complicationsafter transrectal prostate biopsy differ in the current settingof emerging fluoroquinolone resistance? floxacin during transrectal prostate biopsy resulted in a 3% To our knowledge this study is the first to address these incidence of UTI compared to 5% in the placebo In questions by quantifying contemporary rates of infective their series 2% of patients were hospitalized due to febrile complications and the true incidence of fluoroquinolone re- UTIs, although none were ciprofloxacin treated patients.
sistant infections after TRUSBP. In our series of 1,273 pa- Aron et al reported that infective complication rates can be tients the overall incidence of infective complications was decreased 3-fold when fluoroquinolones are used compared 2.4% (31 of 1,273) and the overall incidence of fluoroquino- lone resistant infections was 1.2% (15 of 1,273). Our overall Are these values still valid in our dynamic environment of incidence of infective complications is similar to those that antimicrobial resistance? In the 2000 series by Aron et al all have already been However, when stratified by UTIs yielding positive cultures after prostate biopsy were year, the incidence of infective complications was 3 times higher in 2006 (4.8% or 15 of 311 cases) compared to 2004 ported only 2 cases of UTI that were resistant to fluoroquino- (1.7% or 8 of 471) and 2005 (1.6% or 8 of 491). The incidence lones in a series of 4,439 TRUSBPs with fluoroquinolone of specific fluoroquinolone resistant infections in 2006 (2.6% Recent trends have shown that fluoroquinolone or 8 of 311 cases) was also 3.3 to 4.3 times higher compared resistant infections after prostate biopsy are increasingly to 2004 (0.8% or 4 of 491) and 2005 (0.6% or 3 of 471). These noted. In 2003 Tal et al reported on 23 patients who were findings are statistically significant and they suggest that hospitalized with clinical UTIs and in whom bacteria we are encountering increasing fluoroquinolone resistance, showed high resistance to fluoroquinolones after transrectal which may be leading to an increase in infective complica- prostate In 2004 Otrock et al noted that 50% of patients hospitalized with clinical UTIs after transrectal We acknowledge that there were fewer TRUSBPs in prostate biopsy were infected with fluoroquinolone resistant 2006 compared to 2004 and 2005 (311 vs 471 and 491, E. There have also been case reports of septic shock respectively), which may have introduced some bias into and disseminated intravascular coagulation with fluoro- the overall statistical analysis. However, the absolutenumber of cases of infective symptoms and fluoroquino-lone resistance were still higher in 2006 than in 2004 and TABLE 3. Susceptibility of fluoroquinolone resistant E. coli to It is common practice that, when patients present with infective symptoms, urine and blood cultures are ob-tained. In our study 19 of 31 patients (61%) had positive cultures when they presented with infective symptoms, which is similar to rates reported in the literature (61% to Of the 23 positive cultures 21 (92%) yielded E. coli and 19 (83%) were resistant to fluoroquinolones. E. coli is still the chief pathogen in UTIs complicating prostate biopsies but the finding suggests that these pathogens are adapting and developing resistance to fluoroquinolone The overall hospitalization rate in our series was 1.5%, similar to rates already reported in the However, 19 of the 31 patients (61%) presenting with infective complications required hospitalization. Patients Total of 18 samples includes urine and blood cultures.
were hospitalized for various reasons, including fever, FLUOROQUINOLONE RESISTANT INFECTIONS AFTER PROSTATE BIOPSY leukocytosis and hypotension. Upon hospitalization most rectal ultrasound-guided sextant biopsies of the prostate of our patients received combination intravenous ampicil- within a population-based screening program. Urology lin/gentamicin or intravenous fluoroquinolones as the ini- 2002; 60: 826.
tial empirical treatment. However, resistance patterns in Aron M, Rajeev TP and Gupta NP: Antibiotic prophylaxis for our series showed that bacterial isolates from these pa- transrectal needle biopsy of the prostate: a randomized
controlled study. BJU Int 2000; 85: 682.
tients were highly resistant to fluoroquinolones and am- Sieber PR, Rommel FM, Agusta VE, Breslin JA, Huffnagle HW picillin, while only 77% had sensitivity to gentamicin. Our and Harpster LE: Antibiotic prophylaxis in ultrasound series established that despite their resistance to fluoro- guided transrectal prostate biopsy. J Urol 1997; 157: 2199.
quinolones these pathogens were highly susceptible to Kapoor D, Klimberg I, Malek G, Wegenke J, Cox C, Patterson other antibiotics. Fluoroquinolone sensitive and resistant AL et al: Single-dose oral ciprofloxacin versus placebo for E. coli showed greater than 90% sensitivity to ticarcillin/ prophylaxis during transrectal prostate biopsy. Urology clavulonate, aztreonam, imipenem and tobramycin, and 1998; 52: 552.
100% sensitivity to ceftriaxone, ceftazidime, cefotetan, Tal R, Livne P, Lask D and Baniel J: Empirical management of cefotaxime and amikacin. Our data are comparable to an urinary tract infections complicating transrectal ultra- early study describing susceptibility patterns of bacteria sound guided prostate biopsy. J Urol 2003; 169: 1762.
Otrock Z, Oghlakian G, Salamoun M, Haddad M and Bizri AR: isolated from patients with post-prostate biopsy UTIs Incidence of urinary tract infection following transrectal with fluoroquinolone Although combination ultrasound guided prostate biopsy at a tertiary-care medi- ampicillin/gentamicin or intravenous fluoroquinolones cal center in Lebanon. Infect Control Hosp Epidemiol 2004; may be acceptable regimens for the initial management of UTIs, the data clearly demonstrate that they may not be Binsaleh S, Al-Assiri M, Aronson S and Steinber A: Septic the best agents in the setting of UTIs after prostate bi- shock after transrectal ultrasound guided prostate biopsy.
Is ciprofloxacin prophylaxis always protecting? Can J Urol There should be a high index of suspicion for fluoroquino- 2004; 11: 2352.
lone resistant E. coli UTI in patients presenting with infective Hoshi A, Nitta M, Hongoh S, Hanai K, Nishikawa Z, Koba- symptoms after prostate biopsy. Therefore, we recommend yashi Y et al: Sepsis following transrectal prostate biopsy: a that empirical treatment with ceftriaxone, ceftazidime or ami- report of 2 cases and reviewed similar cases in Japan.
Hinyokika Kiyo 2006; 52: 645.
kacin be initiated and continued until culture specific therapycan be implemented.
EDITORIAL COMMENT
CONCLUSIONS
In 2006 an estimated 624,000 TRUSBPs were performed inthe United There are no anecdotal or published To our knowledge this is the first study to quantify the reports that indicate an excessive incidence of infections incidence and possible increase in fluoroquinolone resistant associated with this number of transrectal prostate biopsies.
UTIs after prostate biopsy under fluoroquinolone prophy- The low incidence of post-biopsy morbidity could be attrib- laxis. Fluoroquinolones are still effective for maintaining utable in part to antibiotic prophylaxis.
infective complications to 2% to 5% but they need vigorous Even the use of 12-core biopsy procedures has not had a reassessment in the face of emerging resistance. Empirical significant impact on the post-biopsy infection How- treatment with ceftriaxone, ceftazidime or amikacin should ever, the urologist should not be complacent. In the current be initiated in patients with suspected UTI after prostate study of 1,273 patients after prostate biopsy the authors biopsy because there is a high likelihood of fluoroquinolone noted 2 disturbing trends, including an increase in 2 years of post-biopsy infections (1.7% to 4.8%) and fluoroquinoloneresistance. Their report does not cite comorbidities such asdiabetes or immune suppression that could increase patient Abbreviations and Acronyms
vulnerability. Nevertheless, these observations should serve ϭ transrectal ultrasound guided prostate as a caveat to the urologist. There are changing patterns of infection and an increase in antibiotic resistant bacteria.
Awareness of these epidemiological trends and continued attention to instrument care can minimize the potential forpost-prostate biopsy infection.
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