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Recent Antibiotic Treatment Increases the Risk of Urinary Tract Infection after Outpatient Cystoscopy
urologypracticejournal.com
Recent Antibiotic Treatment Increases the Risk of Urinary Tract Infection after Outpatient Cystoscopy Justin R. Gregg,*,y Caroline Lai,y Roger Dmochowski,z Thomas R. Talboty and Daniel A. Barocasy From the Department of Urologic Surgery (JRG, CL, RD, DAB), and Departments of Medicine and Health Policy (TRT), Vanderbilt University Medical Center, Nashville, Tennessee
Abstract
Abbreviations and Acronyms
Introduction: Symptomatic urinary tract infection is a complication of office based cystoscopy. AUA guidelines recommend prophylactic antibiotics for patients with an increased risk of urinary tract infection. However, study results are mixed regarding the efficacy of prophylaxis for urinary tract infection prevention. We evaluate predictors of infection to identify groups at increased risk for urinary tract infection after cystoscopy. Methods: We identified all office cystoscopies performed at a single institution from April 2012 through May 2014. Patients with a positive urine culture within 30 days of the procedure were reviewed for symptomatic urinary tract infection. Those with a urinary tract infection were matched to 4 controls. Patient characteristics were extracted and examined for association with urinary tract infection. A multivariable logistic regression model was fit to identify associations between composite clinical variables and urinary tract infection.
AUA = American Urological Association EMR = electronic medical record UTI = urinary tract infection
Results: During the study period 5,488 patients underwent cystoscopy, of whom 29 (0.53%) had a urinary tract infection. Cultures showed quinolone resistant organisms in 13 of 29 (45%) urinary tract infections. The use of an external catheter or intermittent catheterization (p¼0.04), hospitalization within 4 weeks (p¼0.04) and the use of antibiotics within 6 months of cystoscopy (p¼0.01) were associated with urinary tract infection. Recent antibiotic exposure, recent nongenitourinary infection or recent hospitalization was associated with urinary tract infection on multivariable analysis (OR 5.26, 95% CI 1.87e14.8, p <0.01). Conclusions: Recent antibiotic exposure, infection or hospitalization is associated with an increased risk of urinary tract infection after cystoscopy. Most symptomatic urinary tract infections are due to quinolone resistant organisms in this population. The optimal prophylactic regimen should be tailored to regional antibiotic susceptibility patterns and individual patient risk factors. Submitted for publication April 14, 2015. Supported by National Center for Advancing Translational Sciences/ National Institutes of Health Grant UL1 TR000445. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; 2352-0779/16/32-90/0 UROLOGY PRACTICE Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Correspondence: Vanderbilt University Medical Center, Nashville, Tennessee (e-mail address: [email protected]). y No direct or indirect commercial incentive associated with publishing this article. z Financial interest and/or other relationship with Medtronic and Allergan.
RESEARCH, INC.
http://dx.doi.org/10.1016/j.urpr.2015.06.010 Vol. 3, 90-96, March 2016 Published by Elsevier
Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
91
Key Words: cystoscopy, urinary tract infections, antibiotic prophylaxis
Flexible cystoscopy is a common procedure performed in the outpatient setting by urologists and other practitioners for a variety of indications. Symptomatic urinary tract infection is a known complication of cystoscopy. Rates of UTI after cystoscopy performed without antibiotic prophylaxis range from less than 1% to 10% using varying definitions of infection.1e4 The AUA recommends onetime pre-procedural antibiotic prophylaxis for patients considered at high risk for infection before cystoscopy (see Appendix).5 Multi-specialty surgical prophylaxis guidelines also endorse single dose prophylaxis in patients with risk factors who undergo cystoscopy.6 Randomized controlled trials report mixed results regarding the efficacy of antibiotic prophylaxis before cystoscopy in preventing post-procedural bacteriuria and UTI.1e4,7 Furthermore, it is unknown if clinical benefit is derived from the prevention of post-procedural bacteriuria,8 the primary outcome investigated in most randomized trials. Recent studies challenge the notion that even high risk individuals need prophylaxis before cystoscopy, considering the rarity and often mild nature of UTI.9,10 This is especially relevant given the increasing importance of antibiotic stewardship during a time of increased antibiotic resistance rates.11 To better identify patients at increased risk for symptomatic UTI after cystoscopy we performed a matched casecontrol study of patients diagnosed with symptomatic UTI within 30 days of outpatient cystoscopy at our institution. This study design enabled us to evaluate risk factors and antimicrobial resistance patterns in patients with symptomatic, culture proven UTI, further elucidating patient groups that could potentially benefit from prophylaxis. Methods Clinic Protocol
Between April 2012 and May 2014, 5,488 outpatient cystoscopies were performed in the 2 outpatient urology clinics at our institution. Flexible cystoscopy was performed after the genitalia were prepped with povidone-iodine solution and 2% lidocaine jelly was instilled into the urethra. After each procedure the cystoscopes were cleaned using an enzymatic cleanser (V. MuellerÒ), sterile water wash and chemical sterilization with peracetic acid (Steris S40Ò). After the procedure the patients were given an informational handout and instructed to notify the clinic if they
experienced a temperature of 101F or greater. Neither clinic had a formalized protocol regarding the use of preprocedural prophylactic antibiotics and the administration of antibiotic prophylaxis was left to clinician preference (approximately 75% of patients received prophylactic fluoroquinolone pre-procedural antibiotic).
Study Design
After obtaining institutional review board approval, urine culture results within 30 days of cystoscopy were extracted from the EMR for all patients who underwent cystoscopy during the study period. Recognizing that this methodology would systematically miss infections treated outside of our health system and those treated empirically based on symptoms without obtaining a urine culture (thereby underestimating our infection rate), determining the incidence of infection was not a goal of this study. Positive cultures with pathogenic organisms were selected for review. Using prior literature and Centers for Disease Control and Prevention surveillance definitions as a guide,6,12 and working with the hospital epidemiologist (TRT), we developed several criteria to define patients with symptomatic UTI. The criteria included one of several signs or symptoms with no other recognized cause (fever, urgency, frequency, dysuria, prostate tenderness or suprapubic tenderness) AND a positive urine culture (105 colonies per ml or greater microorganisms) with no more than 2 species present, OR 2 of the previously mentioned signs and symptoms with no other recognized cause AND at least 1 of 7 signs including 1) positive dipstick for leukocyte esterase and/or nitrate, 2) pyuria (urine specimen with greater than 10 white blood cells per mm3), 3) organisms seen on Gram stain of unspun urine, 4) at least 2 urine cultures with repeated isolation of the same uropathogen (gram-negative bacteria or Staphylococcus saprophyticus) with 102 or greater colonies per ml in nonvoided specimens, 5) less than 105 colonies per ml of a single uropathogen in a patient being treated with an effective antimicrobial agent for UTI, 6) physician diagnosis of UTI or prostatitis and 7) physician initiation of appropriate therapy for UTI or prostatitis. Patients who met these criteria were defined as cases. Matching was then performed using STATAÒ (release 11) based on surgeon, clinic location, ICD-9 and CPT codes.
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Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
Four matched controls were selected at random for each case. Patient characteristics of interest including demographics and infection risk factors5,6 were then extracted from the EMR using Research Electronic Data Capture (REDCap) software.13 Risk factors for infection were grouped into composite variables to maximize statistical efficiency and power, including 1) standard antibiotic dosed fluoroquinolone (or other appropriate antibiotic) administration before procedure;5 2) host factorsduse of immunosuppressive medication, diagnosis of diabetes mellitus or current smoker; 3) recent health care or antibiotic exposuredhospitalization within 1 month, nongenitourinary infection within 1 month or antibiotic use within 6 months before cystoscopy; and 4) urinary colonizationdcurrent use of indwelling catheter or intermittent catheterization or underwent instrumentation of the genitourinary tract within 1 month. The chi-square test and Student’s t-test were used to evaluate patient characteristics for association with symptomatic UTI. Chi-square tests were 2-sided and all tests with p <0.05 were considered significant. A multivariate logistic regression was fit to identify risk factors associated with the development of symptomatic UTI. The previously mentioned composite variables as well as patient age and gender were included in the analysis. All statistics were completed using STATA.
Results
Overall 29 patients were identified as having met the criteria for infection and were considered cases. Automatic matching was successful in all but 2 cases (for which matching was completed manually), yielding 29 cases and 116 controls. Patient characteristics and associations with symptomatic UTI are shown in table 1. Standard antibiotic prophylaxis based on AUA guidelines was administered in 110 patients (76%), including 21 (72%) of those with UTI (p¼0.63 compared to those patients in whom a postprocedural UTI did not develop). A full dose fluoroquinolone was administered to 103 of the 110 patients who received antibiotics. Overall 70 patients (48%) were female and 128 (88%) were Caucasian. There were no statistically significant differences in demographic characteristics between cases and controls. In terms of etiologic factors 13 patients (45%) with a UTI had quinolone resistant organisms as the cause of their infection. Among these 13 patients 9 (69%) had received preoperative fluoroquinolone prophylaxis. Given the high rates of fluoroquinolone prophylaxis and pathogen resistance, it is likely that many of the infections seen in this
group were breakthrough UTIs. The etiologic organisms were Escherichia coli in 28%, Pseudomonas in 21%, Klebsiella in 17% and various other organisms in 34%. Infections were generally not severe. Four patients required brief hospital admission for complicated cystitis and 1 required intensive care unit admission for sepsis of a urinary or pulmonary source. Factors associated with UTI on univariate analyses were use of an external catheter or intermittent catheterization (p¼0.04), patient hospitalization within 1 month (p¼0.04) and the use of antibiotics within 6 months of cystoscopy (p¼0.01). Among the composite variables only recent health care or antibiotic exposure was significantly associated with UTI (p <0.01, table 1). In the multivariate model only recent health care or antibiotic exposure was associated with UTI, while age, gender, host factors, use of standard regimen and urinary tract colonization were not significant (table 2).
Discussion
Outpatient cystoscopy is a common procedure, and is generally considered safe and well tolerated. Symptomatic UTI is a known complication of the procedure, and the AUA and other organizations recommend prophylactic antibiotic use for patients at increased risk for infection (see Appendix). Using a matched case-control cohort we identified novel risk factors for symptomatic UTI after cystoscopy, namely, patients who have recently been diagnosed with an infection, admitted to a hospital within the last month or who have received antibiotics within the last 6 months. While AUA guidelines do not categorize recent antibiotic exposure as a risk factor,5 it has been shown that antibiotic use within 4 weeks of transrectal ultrasound guided prostate biopsy is associated with severe infection.14 In addition, prospective studies investigating symptomatic UTI often exclude patients with recent antibiotic exposure.7 Many of the risk factors found in the AUA guidelines are derived from studies of diverse populations and procedures,5,6,15 and have not specifically been evaluated in patients undergoing cystoscopy. The consideration of recent antibiotic use by urologists can aid in risk stratification, clinical decision making and counseling. However, the question remains whether prophylactic antibiotics can effectively prevent infections in at risk groups. Randomized trials evaluating the effect of antibiotic prophylaxis on UTI risk report mixed results. Johnson et al randomized 2,481 patients to receive placebo, ciprofloxacin or trimethoprim-sulfamethoxazole and observed
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Table 1. Patient characteristics associated with UTI after cystoscopy Overall Mean age (SD) No. gender (%): M F No. race (%): Caucasian African American Other No. diabetes mellitus (%): No Yes No. current smoker (%): No Yes No. immune suppression (%): No Yes No. external catheter (%): No Yes No. nongenitourinary infection within 1 mo (%): No Yes No. genitourinary tract instrumentation within 1 mo (%): No Yes No. hospitalized within 1 mo (%): No Yes No. received antibiotics within 6 mos (%): No Yes No. received standard pre-cystoscopy antibiotic dose (%): No Yes No. host factors (%):z No Yes No. recent health care or antibiotic exposure (%):z No Yes No. urinary colonization (%):z No Yes
No UTI
UTI
59.6 (14.7)
62.1 (12.4)
(52) (48)
59 57
(51) (49)
16 13
(55) (45)
128 (88.3) 15 (10.3) 1 (0.7)
101 13 1
(88) (11) (1)
27 2 0
(93) (7) (0)
60.1 75 70
p Value 0.4* 0.68y
0.69
0.27 120 25
(83) (17)
94 22
(81) (19)
26 3
(76) (24)
120 25
(83) (17)
96 20
(83) (17)
24 5
(83) (17)
122 23
(84) (16)
98 18
(84) (16)
24 5
(83) (17)
130 12
(90) (10)
107 9
(92) (8)
23 6
(79) (21)
143 2
(99) (1)
115 1
(99) (1)
28 1
(96) (4)
107 38
(74) (26)
88 28
(76) (24)
19 10
(66) (34)
119 26
(82) (18)
99 17
(85) (15)
20 9
(69) (31)
86 59
(59) (41)
75 41
(65) (35)
11 18
(38) (62)
35 110
(24) (76)
27 89
(23) (77)
8 21
(28) (72)
86 59
(59) (41)
67 49
(58) (42)
19 10
(66) (34)
83 62
(57) (43)
74 42
(64) (34)
9 20
(31) (69)
100 45
(69) (31)
84 32
(72) (28)
16 13
(55) (45)
1
0.82
0.04
0.29
0.26
0.04
0.01
0.63
0.45
0.001
0.07
*Student’s t-test. y Pearson chi-square test. Other results use chi-square tests unless otherwise noted. z Composite variables.
no significant difference in symptomatic UTI between the groups, although the study was not adequately powered for this end point.4 Several smaller placebo controlled trials of fluoroquinolones also did not identify decreased rates of UTI with prophylaxis.1,2,16 In contrast, Jiménez Cruz et al randomized 2,284 patients undergoing cystoscopy to ceftriaxone or placebo and found a decreased rate of post-procedural UTI (10.2% vs 2.5%) in the treatment arm.7 Many of these studies were likely underpowered to detect the benefit of prophylactic antibiotics on
symptomatic UTI prevention. However, the sample size needed to demonstrate significant differences highlights the large number of patients who must be exposed to the potential harms of antibiotics to prevent UTIs. The use of a case-control design in the current study enabled us to identify risk factors for uncommon UTIs with a limited number of cases. While individual patients may experience side effects of antibiotics ranging from self-limited gastrointestinal distress to Clostridium difficile infection, allergic reaction or
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Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
Table 2. Multivariable logistic regression examining associations between patient factors and UTI after cystoscopy Age Gender (female as reference) Host factors* Recent health care or antibiotic exposure* Urinary colonization* Standard pre-cystoscopy antibiotic dose*
OR
95% CI
1.03 1.45 0.39 5.26 1.73 0.96
0.99e1.06 0.55e3.80 0.14e1.10 1.87e14.80 0.61e4.91 0.32e2.87
p Value 0.14 0.76 0.08 <0.01 0.3 0.94
*Reference is absence of listed characteristic or composite variable.
fluoroquinolone related tendinopathy,15 increasing rates of antibiotic resistance and antibiotic stewardship concern communities and populations.17 A recent study of E. coli isolates from U.S. outpatients showed an increase in ciprofloxacin resistance from 3% to 17% from 2000 to 2010.11 Furthermore, rates of trimethoprim-sulfamethoxazole resistance in E. coli are often more than 20% in outpatient settings, a threshold above which empiric therapy is not indicated.11,18 In our cohort 45% of UTIs were due to fluoroquinolone resistant organisms, which is comparable to the resistance pattern in all urology clinic cultures during the same period according to our institutional antibiogram (unpublished data). Increased antimicrobial resistance is concerning, particularly given that fluoroquinolone use and urinary tract abnormalities are associated with resistant UTIs in urological patients.19 Given the risks associated with prophylaxis and the unclear benefits, the question remains whether average risk or even high risk patients can safely forego preprocedural antibiotics. A recent study evaluated the incidence of symptomatic UTI (as defined by fever and dysuria) in a cohort of 1,110 predominantly high risk patients who underwent 3,108 cystoscopies and were not given prophylactic antibiotics. UTI developed in 1.9% of these patients, none of whom required hospitalization.20 These data suggest it may be safe to limit antibiotics even in high risk populations. However, this study had a narrow definition of post-procedural UTI, excluded patients with recent antibiotic use and is not generalizable to the many conditions for which cystoscopy is performed. Our study had a few notable limitations. As stated previously the case-control methodology and the use of a single-institution EMR to ascertain UTI status do not allow us to compute the incidence of UTI after cystoscopy in this population, although this was not the goal of our study. Furthermore, while our study was likely limited by power based on the number of identified symptomatic UTIs, we
did not demonstrate an association between many high risk features identified by the AUA, including age, smoking, corticosteroid use, anatomical abnormalities and immune deficiency (although we did confirm that externalized catheter, recent hospitalization and recent nongenitourinary infection were associated with infection at least on univariate analyses). In addition, the use of prophylactic antibiotics was not associated with a decreased risk of symptomatic UTI. If our findings hold true, then it may be possible to withhold antibiotics in a diverse population of patients undergoing outpatient cystoscopy without significantly increasing the risk of infection. However, we would emphasize that an evolving list of risk factors should be taken into account when determining the use of prophylactic antibiotics for individual patients and clinic protocols. Ultimately clinicians and their associated practices and support staff are responsible for all aspects of antibiotic use, including type, duration, patient selection and stewardship. Expert guidelines offer an excellent starting point in terms of selection. However, local resistance rates are of prime importance when considering antibiotic choice. While some practice variation is to be expected based on this fact alone, the amount of variability in antibiotic use in community practice urology is disconcerting. We encourage providers to establish local protocols that take into account guidelines, patient risk factors and local resistance rates. As an example, the high rates of fluoroquinolone resistance present at our institution coupled with a relatively rare risk of UTI prompted our group to establish a new protocol for outpatient cystoscopy prophylaxis. Patients with risk factors identified in this study or who have 2 or more risk factors present on a list derived from the previously mentioned guidelines will receive a onetime pre-procedural dose of ceftriaxone. Patients who do not meet these criteria will not receive prophylaxis. Admittedly, future prospective studies of UTIs and resistance rates are necessary to confirm the effectiveness of this new clinic protocol in our population. In summary, analysis of patients with symptomatic UTI after outpatient cystoscopy compared to matched controls showed that antibiotic use within the last 6 months, hospitalization within the last month or nongenitourinary infection within the last month were significantly associated with UTI, often in the setting of fluoroquinolone prophylaxis. Further prospective studies are needed to determine which, if any, groups of patients benefit from pre-procedural antibiotic prophylaxis, especially among subgroups of patients who have recently been hospitalized or who have received antibiotics.
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Appendix. Published risk factors for infection after cystoscopy AUA Guidelines
American Society of Health-System Pharmacists Guidelines*
Advanced age Poor nutritional status Smoking Distant coexistent infection Immunodeficiency Chronic corticosteroid use Prolonged hospitalization Colonized endogenous or exogenous material Anatomical anomalies of the urinary tract
Extremes of age Nutritional status Tobacco use Coexistent remote body site infection Altered immune response Corticosteroid therapy Length of preoperative hospitalization Colonization with microorganisms Anatomical anomalies of the urinary tract Obesity Diabetes mellitus Recent surgical procedure Urinary obstruction Urinary stone Indwelling or externalized catheter
*Developed jointly by the Infectious Diseases Society of America, the Surgical Infection Society and the Society for Healthcare Epidemiology of America.
References 1. Wilson L, Ryan J, Thelning C et al: Is antibiotic prophylaxis required for flexible cystoscopy? A truncated randomized doubleblind controlled trial. J Endourol 2005; 19: 1006. 2. García-Perdomo HA, López H, Carbonell J et al: Efficacy of antibiotic prophylaxis in patients undergoing cystoscopy: a randomized clinical trial. World J Urol 2013; 31: 1433. 3. Alsaywid BS and Smith GH: Antibiotic prophylaxis for transurethral urological surgeries: systematic review. Urol Ann 2013; 5: 61. 4. Johnson MI, Merrilees D, Robson WA et al: Oral ciprofloxacin or trimethoprim reduces bacteriuria after flexible cystoscopy. BJU Int 2007; 100: 826. 5. Wolf JS Jr, Bennett CJ, Dmochowski RR et al: Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol 2008; 179: 1379. 6. Bratzler DW, Dellinger EP, Olsen KM et al: Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70: 195. 7. Jiménez Cruz JF, Sanz Chinesta S, Otero G et al: Antimicrobial prophylaxis in urethrocystoscopy. Comparative study. Actas Urol Esp 1993; 17: 172. 8. Bootsma AM, Laguna Pes MP, Geerlings SE et al: Antibiotic prophylaxis in urologic procedures: a systematic review. Eur Urol 2008; 54: 1270. 9. Herr HW: The risk of urinary tract infection after flexible cystoscopy in patients with bladder tumor who did not receive prophylactic antibiotics. J Urol 2015; 193: 548. 10. Herr HW: Should antibiotics be given prior to outpatient cystoscopy? A plea to urologists to practice antibiotic stewardship. Eur Urol 2014; 65: 839.
11. Sanchez GV, Master RN, Karlowsky JA et al: In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob Agents Chemother 2012; 56: 2181. 12. Centers for Disease Control and Prevention: Urinary Tract Infection and Non-Catheter-Associated Urinary Tract Infection and Other Urinary System Events (2015). Available at www.cdc.gov/nhsn/ pdfs/pscManual/7pscCAUTIcurrent.pdf. Accessed March 4, 2015. 13. Harris PA, Taylor R, Thielke R et al: Research electronic data capture (REDCap)ea metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377. 14. Patel U, Dasgupta P, Amoroso P et al: Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. BJU Int 2012; 109: 1781. 15. Schaeffer A and Schaeffer E: Infections of the urinary tract. In: Campbell-Walsh Urology, 10th ed. Edited by AJ Wein, LR Kavoussi, AC Novick et al. Philadelphia: Elsevier Saunders 2012, pp 2335e2354. 16. Tsugawa M, Monden K, Nasu Y et al: Prospective randomized comparative study of antibiotic prophylaxis in urethrocystoscopy and urethrocystography. Int J Urol 1998; 5: 441. 17. Pollack LA and Srinivasan A: Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis 2014; 59: S97. 18. Grigoryan L, Trautner BW and Gupta K: Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA 2014; 312: 1677. 19. Ena J, Amador C, Martinez C et al: Risk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant Escherichia coli. J Urol 1995; 153: 117. 20. Herr HW, Sheinfeld J, Puc HS et al: Surgery for a postchemotherapy residual mass in seminoma. J Urol 1997; 157: 860.
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Editorial Commentaries
We practice in an era in which 50% of antibiotic use may be unwarranted and carries risks for C. difficile or drug resistance.1 Opportunities exist to reduce antibiotic use before cystoscopy to only those who would benefit most, using the best antibiotic for a given population. Using a study design that mimicked real-world practice, Gregg et al identified 3 simple predictors of infection after cystoscopy, including antibiotic use within 6 months, hospitalization within 1 month and nonurological infection within 1 month. They also noted that 75% of their patients received antibiotics, almost exclusively quinolones, despite a locally predicted 45% quinolone resistance rate. If supported by further research, these predictors may prove easier to use than the currently recommended 9 to 15 risk factors or clinician preference (reference 5 in article).2 Can we reduce the number of patients receiving antibiotics? Can we choose
The AUA guidelines recommend onetime antibiotic prophylaxis for patients considered at high risk for infection before cystoscopy (reference 5 in article). In this study the determination for antimicrobial prophylaxis was left to the clinician’s preference. It is unlikely in an outpatient setting that 75% of the patients were at high risk for infection before cystoscopy and, therefore, it is possible that antimicrobial prophylaxis was overused. The rate of post-procedural UTI was less than 1%. This study clearly shows that the use of antimicrobial prophylaxis does not affect the rate of symptomatic post-procedural urinary tract infections.
better antibiotics than quinolones for all? This study suggests we can. Christopher S. Baliga Section of Infectious Diseases Virginia Mason Medical Center Seattle, Washington References 1. Dellit TH, Owens RC, McGowan JE Jr et al: Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007; 44: 159. 2. Bratzler DW, Dellinger EP, Olsen KM et al: Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70: 195.
If one’s goal is to prevent symptomatic urinary tract infections, the conclusion to draw from this article is that antimicrobial prophylaxis should not be used. However, if the goal is to prevent UTIs from developing in patients with significant risk factors, prophylaxis should be used as per AUA guidelines.
Anthony J. Schaeffer Northwestern University Feinberg School of Medicine Chicago, Illinois
Reply by Authors
We appreciate the insightful comments. Certainly there is the potential that antibiotics are overused in clinical practice, particularly when local antibiograms indicate high pathogen resistance rates to antibiotics used locally for prophylaxis. However, we would caution that our study does not determine a true rate of symptomatic urinary tract infection after cystoscopy. Rather, based on the design it served to examine risk factors for UTI that were detected via review of a nested
group of patients who had positive urine cultures collected at our institution and symptoms of UTI within 30 days of cystoscopy. Large cohort series are necessary to determine true rates of UTI. Nonetheless, judicious antibiotic stewardship may entail withholding antibiotic prophylaxis in selected groups of patients while administering them to patients at higher risk for infection, such as those identified in this study.
Recent Antibiotic Treatment Increases the Risk of Urinary Tract Infection after Outpatient Cystoscopy Justin R. Gregg,*,y Caroline Lai,y Roger Dmochowski,z Thomas R. Talboty and Daniel A. Barocasy From the Department of Urologic Surgery (JRG, CL, RD, DAB), and Departments of Medicine and Health Policy (TRT), Vanderbilt University Medical Center, Nashville, Tennessee
Abstract
Abbreviations and Acronyms
Introduction: Symptomatic urinary tract infection is a complication of office based cystoscopy. AUA guidelines recommend prophylactic antibiotics for patients with an increased risk of urinary tract infection. However, study results are mixed regarding the efficacy of prophylaxis for urinary tract infection prevention. We evaluate predictors of infection to identify groups at increased risk for urinary tract infection after cystoscopy. Methods: We identified all office cystoscopies performed at a single institution from April 2012 through May 2014. Patients with a positive urine culture within 30 days of the procedure were reviewed for symptomatic urinary tract infection. Those with a urinary tract infection were matched to 4 controls. Patient characteristics were extracted and examined for association with urinary tract infection. A multivariable logistic regression model was fit to identify associations between composite clinical variables and urinary tract infection.
AUA = American Urological Association EMR = electronic medical record UTI = urinary tract infection
Results: During the study period 5,488 patients underwent cystoscopy, of whom 29 (0.53%) had a urinary tract infection. Cultures showed quinolone resistant organisms in 13 of 29 (45%) urinary tract infections. The use of an external catheter or intermittent catheterization (p¼0.04), hospitalization within 4 weeks (p¼0.04) and the use of antibiotics within 6 months of cystoscopy (p¼0.01) were associated with urinary tract infection. Recent antibiotic exposure, recent nongenitourinary infection or recent hospitalization was associated with urinary tract infection on multivariable analysis (OR 5.26, 95% CI 1.87e14.8, p <0.01). Conclusions: Recent antibiotic exposure, infection or hospitalization is associated with an increased risk of urinary tract infection after cystoscopy. Most symptomatic urinary tract infections are due to quinolone resistant organisms in this population. The optimal prophylactic regimen should be tailored to regional antibiotic susceptibility patterns and individual patient risk factors. Submitted for publication April 14, 2015. Supported by National Center for Advancing Translational Sciences/ National Institutes of Health Grant UL1 TR000445. The corresponding author certifies that, when applicable, a statement(s) has been included in the manuscript documenting institutional review board, ethics committee or ethical review board study approval; principles of Helsinki Declaration were followed in lieu of formal ethics committee approval; institutional animal care and use committee approval; 2352-0779/16/32-90/0 UROLOGY PRACTICE Ó 2016 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
all human subjects provided written informed consent with guarantees of confidentiality; IRB approved protocol number; animal approved project number. * Correspondence: Vanderbilt University Medical Center, Nashville, Tennessee (e-mail address: [email protected]). y No direct or indirect commercial incentive associated with publishing this article. z Financial interest and/or other relationship with Medtronic and Allergan.
RESEARCH, INC.
http://dx.doi.org/10.1016/j.urpr.2015.06.010 Vol. 3, 90-96, March 2016 Published by Elsevier
Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
91
Key Words: cystoscopy, urinary tract infections, antibiotic prophylaxis
Flexible cystoscopy is a common procedure performed in the outpatient setting by urologists and other practitioners for a variety of indications. Symptomatic urinary tract infection is a known complication of cystoscopy. Rates of UTI after cystoscopy performed without antibiotic prophylaxis range from less than 1% to 10% using varying definitions of infection.1e4 The AUA recommends onetime pre-procedural antibiotic prophylaxis for patients considered at high risk for infection before cystoscopy (see Appendix).5 Multi-specialty surgical prophylaxis guidelines also endorse single dose prophylaxis in patients with risk factors who undergo cystoscopy.6 Randomized controlled trials report mixed results regarding the efficacy of antibiotic prophylaxis before cystoscopy in preventing post-procedural bacteriuria and UTI.1e4,7 Furthermore, it is unknown if clinical benefit is derived from the prevention of post-procedural bacteriuria,8 the primary outcome investigated in most randomized trials. Recent studies challenge the notion that even high risk individuals need prophylaxis before cystoscopy, considering the rarity and often mild nature of UTI.9,10 This is especially relevant given the increasing importance of antibiotic stewardship during a time of increased antibiotic resistance rates.11 To better identify patients at increased risk for symptomatic UTI after cystoscopy we performed a matched casecontrol study of patients diagnosed with symptomatic UTI within 30 days of outpatient cystoscopy at our institution. This study design enabled us to evaluate risk factors and antimicrobial resistance patterns in patients with symptomatic, culture proven UTI, further elucidating patient groups that could potentially benefit from prophylaxis. Methods Clinic Protocol
Between April 2012 and May 2014, 5,488 outpatient cystoscopies were performed in the 2 outpatient urology clinics at our institution. Flexible cystoscopy was performed after the genitalia were prepped with povidone-iodine solution and 2% lidocaine jelly was instilled into the urethra. After each procedure the cystoscopes were cleaned using an enzymatic cleanser (V. MuellerÒ), sterile water wash and chemical sterilization with peracetic acid (Steris S40Ò). After the procedure the patients were given an informational handout and instructed to notify the clinic if they
experienced a temperature of 101F or greater. Neither clinic had a formalized protocol regarding the use of preprocedural prophylactic antibiotics and the administration of antibiotic prophylaxis was left to clinician preference (approximately 75% of patients received prophylactic fluoroquinolone pre-procedural antibiotic).
Study Design
After obtaining institutional review board approval, urine culture results within 30 days of cystoscopy were extracted from the EMR for all patients who underwent cystoscopy during the study period. Recognizing that this methodology would systematically miss infections treated outside of our health system and those treated empirically based on symptoms without obtaining a urine culture (thereby underestimating our infection rate), determining the incidence of infection was not a goal of this study. Positive cultures with pathogenic organisms were selected for review. Using prior literature and Centers for Disease Control and Prevention surveillance definitions as a guide,6,12 and working with the hospital epidemiologist (TRT), we developed several criteria to define patients with symptomatic UTI. The criteria included one of several signs or symptoms with no other recognized cause (fever, urgency, frequency, dysuria, prostate tenderness or suprapubic tenderness) AND a positive urine culture (105 colonies per ml or greater microorganisms) with no more than 2 species present, OR 2 of the previously mentioned signs and symptoms with no other recognized cause AND at least 1 of 7 signs including 1) positive dipstick for leukocyte esterase and/or nitrate, 2) pyuria (urine specimen with greater than 10 white blood cells per mm3), 3) organisms seen on Gram stain of unspun urine, 4) at least 2 urine cultures with repeated isolation of the same uropathogen (gram-negative bacteria or Staphylococcus saprophyticus) with 102 or greater colonies per ml in nonvoided specimens, 5) less than 105 colonies per ml of a single uropathogen in a patient being treated with an effective antimicrobial agent for UTI, 6) physician diagnosis of UTI or prostatitis and 7) physician initiation of appropriate therapy for UTI or prostatitis. Patients who met these criteria were defined as cases. Matching was then performed using STATAÒ (release 11) based on surgeon, clinic location, ICD-9 and CPT codes.
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Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
Four matched controls were selected at random for each case. Patient characteristics of interest including demographics and infection risk factors5,6 were then extracted from the EMR using Research Electronic Data Capture (REDCap) software.13 Risk factors for infection were grouped into composite variables to maximize statistical efficiency and power, including 1) standard antibiotic dosed fluoroquinolone (or other appropriate antibiotic) administration before procedure;5 2) host factorsduse of immunosuppressive medication, diagnosis of diabetes mellitus or current smoker; 3) recent health care or antibiotic exposuredhospitalization within 1 month, nongenitourinary infection within 1 month or antibiotic use within 6 months before cystoscopy; and 4) urinary colonizationdcurrent use of indwelling catheter or intermittent catheterization or underwent instrumentation of the genitourinary tract within 1 month. The chi-square test and Student’s t-test were used to evaluate patient characteristics for association with symptomatic UTI. Chi-square tests were 2-sided and all tests with p <0.05 were considered significant. A multivariate logistic regression was fit to identify risk factors associated with the development of symptomatic UTI. The previously mentioned composite variables as well as patient age and gender were included in the analysis. All statistics were completed using STATA.
Results
Overall 29 patients were identified as having met the criteria for infection and were considered cases. Automatic matching was successful in all but 2 cases (for which matching was completed manually), yielding 29 cases and 116 controls. Patient characteristics and associations with symptomatic UTI are shown in table 1. Standard antibiotic prophylaxis based on AUA guidelines was administered in 110 patients (76%), including 21 (72%) of those with UTI (p¼0.63 compared to those patients in whom a postprocedural UTI did not develop). A full dose fluoroquinolone was administered to 103 of the 110 patients who received antibiotics. Overall 70 patients (48%) were female and 128 (88%) were Caucasian. There were no statistically significant differences in demographic characteristics between cases and controls. In terms of etiologic factors 13 patients (45%) with a UTI had quinolone resistant organisms as the cause of their infection. Among these 13 patients 9 (69%) had received preoperative fluoroquinolone prophylaxis. Given the high rates of fluoroquinolone prophylaxis and pathogen resistance, it is likely that many of the infections seen in this
group were breakthrough UTIs. The etiologic organisms were Escherichia coli in 28%, Pseudomonas in 21%, Klebsiella in 17% and various other organisms in 34%. Infections were generally not severe. Four patients required brief hospital admission for complicated cystitis and 1 required intensive care unit admission for sepsis of a urinary or pulmonary source. Factors associated with UTI on univariate analyses were use of an external catheter or intermittent catheterization (p¼0.04), patient hospitalization within 1 month (p¼0.04) and the use of antibiotics within 6 months of cystoscopy (p¼0.01). Among the composite variables only recent health care or antibiotic exposure was significantly associated with UTI (p <0.01, table 1). In the multivariate model only recent health care or antibiotic exposure was associated with UTI, while age, gender, host factors, use of standard regimen and urinary tract colonization were not significant (table 2).
Discussion
Outpatient cystoscopy is a common procedure, and is generally considered safe and well tolerated. Symptomatic UTI is a known complication of the procedure, and the AUA and other organizations recommend prophylactic antibiotic use for patients at increased risk for infection (see Appendix). Using a matched case-control cohort we identified novel risk factors for symptomatic UTI after cystoscopy, namely, patients who have recently been diagnosed with an infection, admitted to a hospital within the last month or who have received antibiotics within the last 6 months. While AUA guidelines do not categorize recent antibiotic exposure as a risk factor,5 it has been shown that antibiotic use within 4 weeks of transrectal ultrasound guided prostate biopsy is associated with severe infection.14 In addition, prospective studies investigating symptomatic UTI often exclude patients with recent antibiotic exposure.7 Many of the risk factors found in the AUA guidelines are derived from studies of diverse populations and procedures,5,6,15 and have not specifically been evaluated in patients undergoing cystoscopy. The consideration of recent antibiotic use by urologists can aid in risk stratification, clinical decision making and counseling. However, the question remains whether prophylactic antibiotics can effectively prevent infections in at risk groups. Randomized trials evaluating the effect of antibiotic prophylaxis on UTI risk report mixed results. Johnson et al randomized 2,481 patients to receive placebo, ciprofloxacin or trimethoprim-sulfamethoxazole and observed
Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
93
Table 1. Patient characteristics associated with UTI after cystoscopy Overall Mean age (SD) No. gender (%): M F No. race (%): Caucasian African American Other No. diabetes mellitus (%): No Yes No. current smoker (%): No Yes No. immune suppression (%): No Yes No. external catheter (%): No Yes No. nongenitourinary infection within 1 mo (%): No Yes No. genitourinary tract instrumentation within 1 mo (%): No Yes No. hospitalized within 1 mo (%): No Yes No. received antibiotics within 6 mos (%): No Yes No. received standard pre-cystoscopy antibiotic dose (%): No Yes No. host factors (%):z No Yes No. recent health care or antibiotic exposure (%):z No Yes No. urinary colonization (%):z No Yes
No UTI
UTI
59.6 (14.7)
62.1 (12.4)
(52) (48)
59 57
(51) (49)
16 13
(55) (45)
128 (88.3) 15 (10.3) 1 (0.7)
101 13 1
(88) (11) (1)
27 2 0
(93) (7) (0)
60.1 75 70
p Value 0.4* 0.68y
0.69
0.27 120 25
(83) (17)
94 22
(81) (19)
26 3
(76) (24)
120 25
(83) (17)
96 20
(83) (17)
24 5
(83) (17)
122 23
(84) (16)
98 18
(84) (16)
24 5
(83) (17)
130 12
(90) (10)
107 9
(92) (8)
23 6
(79) (21)
143 2
(99) (1)
115 1
(99) (1)
28 1
(96) (4)
107 38
(74) (26)
88 28
(76) (24)
19 10
(66) (34)
119 26
(82) (18)
99 17
(85) (15)
20 9
(69) (31)
86 59
(59) (41)
75 41
(65) (35)
11 18
(38) (62)
35 110
(24) (76)
27 89
(23) (77)
8 21
(28) (72)
86 59
(59) (41)
67 49
(58) (42)
19 10
(66) (34)
83 62
(57) (43)
74 42
(64) (34)
9 20
(31) (69)
100 45
(69) (31)
84 32
(72) (28)
16 13
(55) (45)
1
0.82
0.04
0.29
0.26
0.04
0.01
0.63
0.45
0.001
0.07
*Student’s t-test. y Pearson chi-square test. Other results use chi-square tests unless otherwise noted. z Composite variables.
no significant difference in symptomatic UTI between the groups, although the study was not adequately powered for this end point.4 Several smaller placebo controlled trials of fluoroquinolones also did not identify decreased rates of UTI with prophylaxis.1,2,16 In contrast, Jiménez Cruz et al randomized 2,284 patients undergoing cystoscopy to ceftriaxone or placebo and found a decreased rate of post-procedural UTI (10.2% vs 2.5%) in the treatment arm.7 Many of these studies were likely underpowered to detect the benefit of prophylactic antibiotics on
symptomatic UTI prevention. However, the sample size needed to demonstrate significant differences highlights the large number of patients who must be exposed to the potential harms of antibiotics to prevent UTIs. The use of a case-control design in the current study enabled us to identify risk factors for uncommon UTIs with a limited number of cases. While individual patients may experience side effects of antibiotics ranging from self-limited gastrointestinal distress to Clostridium difficile infection, allergic reaction or
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Antibiotic Use and Risk of Urinary Tract Infection after Cystoscopy
Table 2. Multivariable logistic regression examining associations between patient factors and UTI after cystoscopy Age Gender (female as reference) Host factors* Recent health care or antibiotic exposure* Urinary colonization* Standard pre-cystoscopy antibiotic dose*
OR
95% CI
1.03 1.45 0.39 5.26 1.73 0.96
0.99e1.06 0.55e3.80 0.14e1.10 1.87e14.80 0.61e4.91 0.32e2.87
p Value 0.14 0.76 0.08 <0.01 0.3 0.94
*Reference is absence of listed characteristic or composite variable.
fluoroquinolone related tendinopathy,15 increasing rates of antibiotic resistance and antibiotic stewardship concern communities and populations.17 A recent study of E. coli isolates from U.S. outpatients showed an increase in ciprofloxacin resistance from 3% to 17% from 2000 to 2010.11 Furthermore, rates of trimethoprim-sulfamethoxazole resistance in E. coli are often more than 20% in outpatient settings, a threshold above which empiric therapy is not indicated.11,18 In our cohort 45% of UTIs were due to fluoroquinolone resistant organisms, which is comparable to the resistance pattern in all urology clinic cultures during the same period according to our institutional antibiogram (unpublished data). Increased antimicrobial resistance is concerning, particularly given that fluoroquinolone use and urinary tract abnormalities are associated with resistant UTIs in urological patients.19 Given the risks associated with prophylaxis and the unclear benefits, the question remains whether average risk or even high risk patients can safely forego preprocedural antibiotics. A recent study evaluated the incidence of symptomatic UTI (as defined by fever and dysuria) in a cohort of 1,110 predominantly high risk patients who underwent 3,108 cystoscopies and were not given prophylactic antibiotics. UTI developed in 1.9% of these patients, none of whom required hospitalization.20 These data suggest it may be safe to limit antibiotics even in high risk populations. However, this study had a narrow definition of post-procedural UTI, excluded patients with recent antibiotic use and is not generalizable to the many conditions for which cystoscopy is performed. Our study had a few notable limitations. As stated previously the case-control methodology and the use of a single-institution EMR to ascertain UTI status do not allow us to compute the incidence of UTI after cystoscopy in this population, although this was not the goal of our study. Furthermore, while our study was likely limited by power based on the number of identified symptomatic UTIs, we
did not demonstrate an association between many high risk features identified by the AUA, including age, smoking, corticosteroid use, anatomical abnormalities and immune deficiency (although we did confirm that externalized catheter, recent hospitalization and recent nongenitourinary infection were associated with infection at least on univariate analyses). In addition, the use of prophylactic antibiotics was not associated with a decreased risk of symptomatic UTI. If our findings hold true, then it may be possible to withhold antibiotics in a diverse population of patients undergoing outpatient cystoscopy without significantly increasing the risk of infection. However, we would emphasize that an evolving list of risk factors should be taken into account when determining the use of prophylactic antibiotics for individual patients and clinic protocols. Ultimately clinicians and their associated practices and support staff are responsible for all aspects of antibiotic use, including type, duration, patient selection and stewardship. Expert guidelines offer an excellent starting point in terms of selection. However, local resistance rates are of prime importance when considering antibiotic choice. While some practice variation is to be expected based on this fact alone, the amount of variability in antibiotic use in community practice urology is disconcerting. We encourage providers to establish local protocols that take into account guidelines, patient risk factors and local resistance rates. As an example, the high rates of fluoroquinolone resistance present at our institution coupled with a relatively rare risk of UTI prompted our group to establish a new protocol for outpatient cystoscopy prophylaxis. Patients with risk factors identified in this study or who have 2 or more risk factors present on a list derived from the previously mentioned guidelines will receive a onetime pre-procedural dose of ceftriaxone. Patients who do not meet these criteria will not receive prophylaxis. Admittedly, future prospective studies of UTIs and resistance rates are necessary to confirm the effectiveness of this new clinic protocol in our population. In summary, analysis of patients with symptomatic UTI after outpatient cystoscopy compared to matched controls showed that antibiotic use within the last 6 months, hospitalization within the last month or nongenitourinary infection within the last month were significantly associated with UTI, often in the setting of fluoroquinolone prophylaxis. Further prospective studies are needed to determine which, if any, groups of patients benefit from pre-procedural antibiotic prophylaxis, especially among subgroups of patients who have recently been hospitalized or who have received antibiotics.
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Appendix. Published risk factors for infection after cystoscopy AUA Guidelines
American Society of Health-System Pharmacists Guidelines*
Advanced age Poor nutritional status Smoking Distant coexistent infection Immunodeficiency Chronic corticosteroid use Prolonged hospitalization Colonized endogenous or exogenous material Anatomical anomalies of the urinary tract
Extremes of age Nutritional status Tobacco use Coexistent remote body site infection Altered immune response Corticosteroid therapy Length of preoperative hospitalization Colonization with microorganisms Anatomical anomalies of the urinary tract Obesity Diabetes mellitus Recent surgical procedure Urinary obstruction Urinary stone Indwelling or externalized catheter
*Developed jointly by the Infectious Diseases Society of America, the Surgical Infection Society and the Society for Healthcare Epidemiology of America.
References 1. Wilson L, Ryan J, Thelning C et al: Is antibiotic prophylaxis required for flexible cystoscopy? A truncated randomized doubleblind controlled trial. J Endourol 2005; 19: 1006. 2. García-Perdomo HA, López H, Carbonell J et al: Efficacy of antibiotic prophylaxis in patients undergoing cystoscopy: a randomized clinical trial. World J Urol 2013; 31: 1433. 3. Alsaywid BS and Smith GH: Antibiotic prophylaxis for transurethral urological surgeries: systematic review. Urol Ann 2013; 5: 61. 4. Johnson MI, Merrilees D, Robson WA et al: Oral ciprofloxacin or trimethoprim reduces bacteriuria after flexible cystoscopy. BJU Int 2007; 100: 826. 5. Wolf JS Jr, Bennett CJ, Dmochowski RR et al: Best practice policy statement on urologic surgery antimicrobial prophylaxis. J Urol 2008; 179: 1379. 6. Bratzler DW, Dellinger EP, Olsen KM et al: Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70: 195. 7. Jiménez Cruz JF, Sanz Chinesta S, Otero G et al: Antimicrobial prophylaxis in urethrocystoscopy. Comparative study. Actas Urol Esp 1993; 17: 172. 8. Bootsma AM, Laguna Pes MP, Geerlings SE et al: Antibiotic prophylaxis in urologic procedures: a systematic review. Eur Urol 2008; 54: 1270. 9. Herr HW: The risk of urinary tract infection after flexible cystoscopy in patients with bladder tumor who did not receive prophylactic antibiotics. J Urol 2015; 193: 548. 10. Herr HW: Should antibiotics be given prior to outpatient cystoscopy? A plea to urologists to practice antibiotic stewardship. Eur Urol 2014; 65: 839.
11. Sanchez GV, Master RN, Karlowsky JA et al: In vitro antimicrobial resistance of urinary Escherichia coli isolates among U.S. outpatients from 2000 to 2010. Antimicrob Agents Chemother 2012; 56: 2181. 12. Centers for Disease Control and Prevention: Urinary Tract Infection and Non-Catheter-Associated Urinary Tract Infection and Other Urinary System Events (2015). Available at www.cdc.gov/nhsn/ pdfs/pscManual/7pscCAUTIcurrent.pdf. Accessed March 4, 2015. 13. Harris PA, Taylor R, Thielke R et al: Research electronic data capture (REDCap)ea metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009; 42: 377. 14. Patel U, Dasgupta P, Amoroso P et al: Infection after transrectal ultrasonography-guided prostate biopsy: increased relative risks after recent international travel or antibiotic use. BJU Int 2012; 109: 1781. 15. Schaeffer A and Schaeffer E: Infections of the urinary tract. In: Campbell-Walsh Urology, 10th ed. Edited by AJ Wein, LR Kavoussi, AC Novick et al. Philadelphia: Elsevier Saunders 2012, pp 2335e2354. 16. Tsugawa M, Monden K, Nasu Y et al: Prospective randomized comparative study of antibiotic prophylaxis in urethrocystoscopy and urethrocystography. Int J Urol 1998; 5: 441. 17. Pollack LA and Srinivasan A: Core elements of hospital antibiotic stewardship programs from the Centers for Disease Control and Prevention. Clin Infect Dis 2014; 59: S97. 18. Grigoryan L, Trautner BW and Gupta K: Diagnosis and management of urinary tract infections in the outpatient setting: a review. JAMA 2014; 312: 1677. 19. Ena J, Amador C, Martinez C et al: Risk factors for acquisition of urinary tract infections caused by ciprofloxacin resistant Escherichia coli. J Urol 1995; 153: 117. 20. Herr HW, Sheinfeld J, Puc HS et al: Surgery for a postchemotherapy residual mass in seminoma. J Urol 1997; 157: 860.
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Editorial Commentaries
We practice in an era in which 50% of antibiotic use may be unwarranted and carries risks for C. difficile or drug resistance.1 Opportunities exist to reduce antibiotic use before cystoscopy to only those who would benefit most, using the best antibiotic for a given population. Using a study design that mimicked real-world practice, Gregg et al identified 3 simple predictors of infection after cystoscopy, including antibiotic use within 6 months, hospitalization within 1 month and nonurological infection within 1 month. They also noted that 75% of their patients received antibiotics, almost exclusively quinolones, despite a locally predicted 45% quinolone resistance rate. If supported by further research, these predictors may prove easier to use than the currently recommended 9 to 15 risk factors or clinician preference (reference 5 in article).2 Can we reduce the number of patients receiving antibiotics? Can we choose
The AUA guidelines recommend onetime antibiotic prophylaxis for patients considered at high risk for infection before cystoscopy (reference 5 in article). In this study the determination for antimicrobial prophylaxis was left to the clinician’s preference. It is unlikely in an outpatient setting that 75% of the patients were at high risk for infection before cystoscopy and, therefore, it is possible that antimicrobial prophylaxis was overused. The rate of post-procedural UTI was less than 1%. This study clearly shows that the use of antimicrobial prophylaxis does not affect the rate of symptomatic post-procedural urinary tract infections.
better antibiotics than quinolones for all? This study suggests we can. Christopher S. Baliga Section of Infectious Diseases Virginia Mason Medical Center Seattle, Washington References 1. Dellit TH, Owens RC, McGowan JE Jr et al: Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship. Clin Infect Dis 2007; 44: 159. 2. Bratzler DW, Dellinger EP, Olsen KM et al: Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm 2013; 70: 195.
If one’s goal is to prevent symptomatic urinary tract infections, the conclusion to draw from this article is that antimicrobial prophylaxis should not be used. However, if the goal is to prevent UTIs from developing in patients with significant risk factors, prophylaxis should be used as per AUA guidelines.
Anthony J. Schaeffer Northwestern University Feinberg School of Medicine Chicago, Illinois
Reply by Authors
We appreciate the insightful comments. Certainly there is the potential that antibiotics are overused in clinical practice, particularly when local antibiograms indicate high pathogen resistance rates to antibiotics used locally for prophylaxis. However, we would caution that our study does not determine a true rate of symptomatic urinary tract infection after cystoscopy. Rather, based on the design it served to examine risk factors for UTI that were detected via review of a nested
group of patients who had positive urine cultures collected at our institution and symptoms of UTI within 30 days of cystoscopy. Large cohort series are necessary to determine true rates of UTI. Nonetheless, judicious antibiotic stewardship may entail withholding antibiotic prophylaxis in selected groups of patients while administering them to patients at higher risk for infection, such as those identified in this study.