January 8th 2018



PHARMACY RESIDENCY RESEARCH MANUSCRIPTPrevalence of asymptomatic bacteriuria in inpatients at Trillium Health Partners with low urine culture colony counts Elaine MartinPharmacy ResidentTrillium Health Partners 2017-2018Primary investigatorElaine Martin, PharmDPharmacy ResidentTrillium Health Partners (THP)– Mississauga HospitalCo-investigatorsLiliana Yonadam, RPhAntimicrobial Stewardship Pharmacist THP– Mississauga Hospital Christopher Graham, MDInfectious Diseases PhysicianTHP– Mississauga Hospital Project SiteTHP– Mississauga Hospital 100 Queensway Street WestMississauga, ON L5B 1B8THP– Credit Valley Hospital2200 Eglinton Ave WestMississauga, ON L5M 2N1Prevalence of asymptomatic bacteriuria in inpatients at Trillium Health Partners with low urine culture colony countsElaine Martin, PharmD1,2; Liliana Yonadam1, BScPhm, MScEpi, PharmD; Christopher Graham1, MD Trillium Health Partners, Mississauga Hospital (1), Leslie Dan Faculty of Pharmacy, University of Toronto (2)Abstract Rationale & Objectives Most laboratories (including Trillium Health Partners (THP)) report urine cultures with colony counts >10 x 106 cfu/L. This threshold was derived from studies in young non-hospitalized women, which have limited applicability to hospitalized patients. Inpatients have an increased risk of asymptomatic bacteriuria (ASB) compared to outpatients, potentially leading to overtreatment. Our primary objective was to determine the prevalence of ASB in low colony count urine cultures (10-100 x 106 cfu/L). Our secondary objectives assessed characteristics of these cultures. ?Methodology A retrospective chart review of inpatients admitted to THP with urine cultures sent between April 1st 2017 to November 31st 2017 was conducted. Patients were classified as having a urinary tract infection based on modified National Healthcare Safety Network (NHSN) criteria. ?Charts containing no documentation of symptoms or cases where patients had an alternate source of infection were classified as ASB. To demonstrate a prevalence of ASB of >85%, a sample size of 196 inpatients was required. A prevalence of >85% was used by other institutions to implement interventions reducing prescribing for ASB.Results 95/122 (77.9%) of low urine culture colony counts represented ASB at our institution. Of these, 36 (29.5%) patients were on antibiotics for an alternate source of infection and 27 (22.1%) were prescribed antibiotics for ASB. Additionally, 7 patients (5.7%) had bacteremia secondary to a urinary source, of which 2 patients (1.6%) were asymptomatic. Finally, 10% (122/1216) of total urine cultures (any growth) sent from included wards were low growth. Conclusions Based on interim results, the prevalence of ASB for low urine culture colony counts at our institution was <85%. Additional data collection is required to meet sample size (N=196) in order to sufficiently power this outcome. A future intervention altering reporting of low growth urine cultures might reduce prescribing for ASB, and will be considered if our prevalence is >85%.IntroductionAsymptomatic bacteriuria (ASB) is defined as the isolation of a specified quantitative count of bacteria in a urine sample from a patient who experiences no symptoms of a urinary tract infection(UTI) 1,2. The prevalence of ASB varies with age, presence of genitourinary abnormalities, gender; it includes 8% of middle aged women, 30% of elderly institutionalized individuals and up to 100% of catheterized patients 1. The Infectious Diseases Society of America (IDSA) only recommends treating ASB in pregnancy or in patients undergoing urologic procedures that can lead to bleeding1. IDSA recommends against screening and treatment of ASB in premenopausal non-pregnant or diabetic women, older persons living in the community, institutionalized subjects, people with spinal cord injuries or in catheterized patients while the catheter remains in situ1. The rationale against treating ASB in these populations stems from a lack of evidence demonstrating positive clinical outcomes on long-term mortality or morbidity and secondary deleterious consequences associated with antibiotic overuse3. For example, antibiotic overuse can increase healthcare costs, cause adverse drug effects, emergence of multi-drug resistant organisms and increase Clostridium difficile infections3-7. Unfortunately, overprescribing of antibiotics for ASB is common. Studies have shown that 26-68% of cases are treated unnecessarily8; thus, interventions aimed at decreasing antimicrobial therapy for ASB are necessary for improving patient care. Prior studies have attempted to reduce prescribing for ASB in hospital inpatients using various techniques. (Appendix 1) Although interventions trialed in these studies were initially successful, their long-term efficacy is unclear9-12. Additionally, most of these interventions were resource-intensive multi-step processes which questioned their long-term feasibility. Another novel method of discouraging prescribing for ASB, which is currently being studied by Sunnybrook Health Sciences Centre, involves alteration of lab processing and reporting of urine cultures with bacterial growth between 10-100 x 106 cfu/L.The current standard threshold for reporting bacteriuria in a mid-stream urine sample is a urine culture colony count greater than or equal to 100 x 106 cfu/L.8 This was based on a study by Kass et al. 1956 which reported that out of 74 patients with acute or suspected pyelonephritis, 95% had urine cultures colony counts greater than or equal to 100 x 106 cfu/L.13 Currently, most microbiology laboratories (including Trillium Health Partners) will work up urine cultures with colony counts greater than or equal to 10 x 106 cfu/L. This lower threshold was derived from studies in young non-hospitalized women (20-30 years old) that demonstrated this target would better identify bacteriuria in patients with acute dysuria.14,15 However, these studies have limited applicability to hospitalized inpatients who have an increased risk of ASB compared to outpatients. Recent studies have supported a higher threshold for reporting bacteriuria. Kwon et al. 2012 studied 70 inpatients with urine culture colony count of 100 x 106 cfu/L or less. Out of their sample of 70, 67 patients (96%) had ASB. Thus, the study concluded that urine culture colony counts of 100 x 106 cfu/L or less were rarely associated with clinically significant UTIs (p<0.0001) and when reported, they encouraged physicians to prescribe unneeded antibiotics. Coulthard et al. 2010 studied 203 pediatric inpatients <18 years old. They concluded that the minimum urine culture colony count used to diagnose UTIs should be increased to >109 cfu/L from >100 x 106 cfu/L as it would reduce the false positive rate from 7.25% to 4.8% if one urine sample was cultured and from 3.6% to 0.6% if two urine samples were cultured. In this sample, out of 203 pediatrics, 36 were found to have clinically significant UTIs, of which all had urine culture colony growth between 109 to 1011 cfu/L. Researchers at Sunnybrook Health Sciences Centre reviewed more than 400 charts retrospectively and discovered that 85% of urine cultures with growth between 10-100 x 106 cfu/L represented ASB, and only 1.7% represented bacteremic UTI. They also discovered that for all the cases of bacteremic UTIs, taking a urine culture did not influence management as these patients were treated empirically in response to blood cultures or they also had a urine culture in the previous 24h with counts >100 x 106 cfu/L. Additionally, the hospital piloted the intervention of eliminating the processing of urine cultures with bacterial growth between 10-100 x 106 cfu/L and reported that it resulted in a substantial reduction in inappropriate antibiotic use and had an excellent safety profile (personal communications). At our hospital, to decrease prescribing for ASB, the following message appears for every culture reported from the laboratory, “Please correlate this result with clinical symptoms to ensure appropriate use of antibiotics”. This is a passive reminder for clinicians and its effectiveness at decreasing antibiotic prescribing is likely low8. Thus, our hospital may benefit from the novel method of deprescribing antibiotics through the elimination of reporting urine culture results with colony counts between 10-100 x 106 cfu/L. Before implementing this intervention, a prevalence study was conducted to identify whether the intervention had the potential to be successful in our hospital. Rationale for Study The aim of this project was to determine the prevalence of ASB in inpatients at THP with low colony count urine cultures (urine culture growth between 10-100 x 106 cfu/L) based on the Center for Disease Control and Prevention criteria (Table 2). A high prevalence would demonstrate to us that it would be safe to implement a future intervention to reduce antibiotic prescribing of ASB. In this future study, we would examine the impact the elimination of automated reporting of low colony count urine cultures on antibiotic prescribing for ASB in inpatients. A reduction of antibiotic prescribing of ASB is an important antimicrobial stewardship initiative to reduce the consequences of antibiotic overuse, such as the emergence of multidrug resistant organisms, Clostridium difficile infections, increased health care costs and antibiotic adverse effects.4 Study Design The research questions were addressed using a retrospective chart review ofelectronic charts at Trillium Health Partners - Mississauga Hospital/ Credit Hospital from April 1st 2017 to November 31st 2017. Patients were classified as having a symptomatic UTI if they met one or more of the criteria specified in Table 2 from the Center for Disease Control and Prevention. Patients must have had one of the symptoms from Table 2 in the period from 1 calendar day preceding to 1 calendar day following the culture collection to be considered as having a UTI. For charts that did not contain any documentation of symptoms, it was assumed that the patient was asymptomatic. Patients were not be considered to have ASB in the presence of another indication for antimicrobial therapy as indicated in clinical notes. Table 2: Center for Disease Control and Prevention Criteria for diagnosing a UTICenter for Disease Control and Prevention surveillance criteria for diagnosing UTIsFever (>38 degrees Celsius) in a patient 65 years old or younger Suprapubic tenderness Costovertebral angle pain or tenderness Urinary frequency Urinary urgency Dysuria Study PopulationInclusion Criteria: Patients ≥18 years admitted to Trillium Health Partners with a urine culture having up to 2 predominant uropathogens with counts between 10-100 x 106 cfu/L, on non-obstetrical, non-paediatric wards.Exclusion Criteria: Urine cultures collected from emergency room (ER), maternity/neonatal wards, operating room, outpatients, pediatrics, patients admitted for <24 hours Urine samples collected from cystoscopy, percutaneous aspirate, kidney, nephrostomy, suprapubic sources Urine samples with greater than 2 uropathogensOnly the first episode of bacteriuria per patient will be included, subsequent episodes for the same patient will be excluded from the study periodPrimary Objective: The proportion of adult inpatients with urine cultures growing up to 2 pathogenic bacteria in the range of 10-100 x 106 cfu/L who had ASBSecondary Objectives:The proportion of patients who received antibiotic therapy for ASB The number of in-hospital days of antimicrobial therapy starting from days +1 to +5 post urine culture sample for treatment of ASB (per 1000 patient bed days) The annualized cost of antimicrobial therapy for antibiotics started days +1 to +5 after urine culture sample taken for treatment of ASBThe proportion of total urine cultures that are growing up to 2 pathogenic bacteria in the range of 10-100 x 106 cfu/L from the total number of urine cultures collectedThe proportion of patients receiving antibiotic therapy for an infection other than UTIStatistical Analysis Sample Size To demonstrate a prevalence of ASB of >85% in patients with urine culture colony counts of up to 2 pathogenic bacteria between 10-100 x 106 cfu/L, with a precision of 0.05 and a Z-value of 1.96, we determined we required a sample size of 196 inpatients who met that criteria. 85% was chosen as the prevalence based on Sunnybrook Health Science Centre’s prevalence of ASB in low urine culture colony counts (10-100 x 106 cfu/L). Prevalence for the primary objective was determined by the number of inpatients who had ASB with urine culture colony counts between 10-100 x 106 cfu/L divided by the number of inpatients with urine culture colony counts between 10-100 x 106 cfu/L. This value was calculated separately for the Credit Valley and Mississauga hospital sites as well as combined. Results Over the study period, 1216 cultures from both hospital sites were sent from eligible wards. Of these urine cultures, 122 were included in the final analysis; 61 collected from Credit Valley Hospital and 61 collected from Mississauga Hospital. Exclusions are outlined in Figure 1, with the most common reasons for exclusion being urine culture growth >100 x 106 cfu/L, samples with mislabelled specimens, no growth isolated or samples showed mixed organisms with doubtful significance. Given time constraints associated with data collection, the targeted sample size of 196 urine cultures, was unable to be achieved. Figure 1: Patient Selection Of the low growth urine cultures sent from included wards at both hospital sites, 39.3% were from males with a mean age of 74.8 + 16.0 years old. Additionally, the majority of these cultures were sent from medicine floors; 28 (45.9%) from Mississauga Hospital and 44 (72.1%) from Credit Valley Hospital. 77 (63.1%) of low growth urine cultures were collected from a midstream sample for both hospital sites. Primary Outcome 95/122 (77.9%) of low urine culture colony counts represented ASB at our institution. The proportion of ASB was higher at Mississauga Hospital 51/61 (83.6%) than Credit Valley Hospital 44/61 (72.1%), but this difference was not statistically significant (p=0.94)Secondary Outcomes 10% (122/1216) of the total urine cultures sent from included wards from both hospital sites were low growth (10-100 x 106 cfu/L); 61 (8.8%) from Mississauga Hospital and 61 (11.7%) from Credit Valley Hospital. Of the low growth cultures sent from both sites, 36 (29.5%) patients were on antibiotics for an infection other than a UTI; 20 (32%) from Mississauga Hospital and 16 (26.2%) from Credit Valley Hospital. Furthermore, of the low growth cultures that represented ASB sent from both sites 27 (22.1%) were prescribed unnecessary antibiotics for the treatment of ASB; 13 (21.3%) at Mississauga Hospital and 14 (22.9%) from Credit Valley Hospital. Additionally, of the low growth urine cultures, 7 patients (5.7%) had bacteremia secondary to a urinary source, of which 2 patients (1.6%) were asymptomatic. The extrapolated annual cost of antibiotics prescribed unnecessarily for ASB was $110.80. This number was determined by adding the total cost of the antibiotics prescribed unnecessarily for ASB over the 8 month study period and extrapolating to include a 12 month period. The treatment duration was 0.75 days, calculated per 1000 patient bed days. DiscussionThe purpose of this retrospective study was to determine the prevalence of asymptomatic bacteriuria of low growth (10-100 x 106 cfu/L) urine cultures at Trillium Health Partners. This study was undertaken because a reduction of antibiotic prescribing for ASB is an important antimicrobial stewardship initiative to reduce the consequences of antibiotic overuse, such as the emergence of multidrug resistant organisms, Clostridium difficile infections, increased health care costs and antibiotic adverse effects.4 The primary outcome demonstrated that 95/122 (77.9%) of low urine culture colony counts represented ASB at our institution. The proportion of ASB was higher at Mississauga Hospital 51/61 (83.6%) than Credit Valley Hospital 44/61 (72.1%), but this difference was not statistically significant (p=0.94). Although we discovered a large portion of low growth urine cultures represented ASB, we were unable to demonstrate that the prevalence was >85% at our institution. 85% was chosen based on Sunnybrook Health Science Centre’s prevalence of ASB in low urine culture colony counts (10-100 x 106 cfu/L). However, the target sample size (N=196) was unable to be met, thus the primary outcome is not sufficiently powered and further data collection is required to make an accurate conclusion. A future intervention suppressing reporting of low growth urine cultures might reduce prescribing for ASB, and will be considered if our prevalence is determined to be >85%.Our secondary outcome demonstrated that 10% (122/1216) of the total urine cultures sent from included wards from both hospital sites were low growth (10-100 x 106 cfu/L). Of the low growth cultures sent from both sites, 36 (29.5%) patients were on antibiotics for an infection other than a UTI. Additionally, of the low growth cultures that represented ASB sent from both sites 27 (22.1%) were prescribed unnecessary antibiotics for the treatment of ASB. Furthermore, of the low growth urine cultures, 7 patients (5.7%) had bacteremia secondary to a urinary source, of which 2 patients (1.6%) were asymptomatic. Interestingly, neither of the 2 asymptomatic patients had a prior urine culture in the prior 24 hours with growth > 100 x 106 cfu/L. However, if an intervention suppressing automatic reporting of low growth urine cultures were to be implemented, positive blood cultures would prompt antibiotic treatment in these patients. This study was unable to show significant antibiotic costs associated with unnecessary prescribing for ASB given that oral antibiotics are generally inexpensive. It was determined that the extrapolated annual cost of antibiotics prescribed unnecessarily for ASB was $110.80. Limitations This study is not without limitations. This study is not powered for its primary outcome as target sample size was unable to be met. Additionally, data gathered for the study was from paper/electronic charts, thus, there was the risk of bias due to incomplete or illegible documentation of symptoms. Furthermore, due to limitations with access to patient charts, patients on rehabilitation floors were unable to be included in this analysis. Finally, given that this is a prevalence study specific to Trillium Hospital, results are not be generalizable to other institutions. Future DirectionsData Collection for this study will be continued until sample size (N= 196) is met in order to sufficiently power the primary outcome. Further data collection will also include rehabilitation wards in our hospital to capture more of our hospital’s population. Once sample size is met, we will also evaluate the treatment rates of ASB by ward. This will be done to determine if there is an area in the hospital that would benefit most from the potential future intervention of suppressing the reporting of low growth urine cultures.Conclusions Based on interim results, the prevalence of ASB for low urine culture colony counts at our institution was <85%. Additional data collection is required to meet sample size (N=196) in order sufficiently power this outcome. A future intervention suppressing reporting of low growth urine cultures might reduce prescribing for ASB, and will be considered if our prevalence is determined to be >85%.References Nicolle, Lindsay E., et al. "Infectious Diseases Society of America guidelines for the diagnosis and treatment of ASB in adults." Clinical Infectious Diseases (2005): 643-654.Givler, D. N., and A. Givler. "ASB." Statpearls. Treasure Island FL: StatPearls Publishing LLC., 2017. Print.Lee, Myung Jin, et al. "Why is ASB overtreated?: A tertiary care institutional survey of resident physicians." BMC infectious diseases 15.1 (2015): 289.Wagenlehner F, Hoyme U, Kaase M, et al. Clinical practice guideline: uncomplicated UTIs. Dtsch Arztebl Int. 2011;108:415-423.Stewardson A, Huttner B, Harbarth F. At least it won’t hurt: the personal risk of antibiotic exposure. Curr Opin Pharmacol. 2011;11:446-452.Fakih M, Dueweke C, Meisener S, et al. Effect of nurse-led multidisciplinary rounds on reducing the unnecessary use of urinary catheterization in hospitalized patients. Infect Control Hosp Epidemiol. 2008;29:815-819.Gopal Rao G, Patel M. UTI in hospitalized elderly patients in the United Kingdom: the importance of making an accurate diagnosis in the post broad-spectrum antibiotic era. J Antimicrob Chemother. 2009;63:5-6.Dull, Ryan B., et al. "Antimicrobial treatment of ASB in noncatheterized adults: a systematic review." Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 34.9 (2014): 941-960.Leis JA, Palmay L, Elligsen M, Walker SA, Lee C, Daneman N. Lessons from audit and feedback of hospitalized patients with bacteriuria. Am J Infect Control 2014;42:1136-7.Loeb M, Brazil K, Lohfeld L, et al. Effect of a multifaceted intervention on number of antimicrobial prescriptions for suspected UTIs in residents of nursing homes: cluster randomised controlled trial. BMJ 2005;331:669.Linares LA, Thornton DJ, Strymish J, Baker E, Gupta K. Electronic memorandum decreases unnecessary antimicrobial use for ASB and culture-negative pyuria. Infect Control Hosp Epidemiol 2011;32:644-8Trautner, Barbara W., et al. "Effectiveness of an antimicrobial stewardship approach for urinary catheter–associated ASB." JAMA internal medicine 175.7 (2015): 1120-1127.Kass EH. Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 1956;69:56-64.Stamm, Walter E., et al. "Diagnosis of coliform infection in acutely dysuric women."?New England Journal of Medicine?307.8 (1982): 463-468.Arav-Boger R, Leibovici L, Danon YL. UTIs with low and high colony counts in young women. Spontaneous remission and single-dose vs multiple-day treatment. Arch Intern Med 1994;154:300-4.Egger, Martin, et al. "Reduction of urinary catheter use and prescription of antibiotics for ASB in hospitalised patients in internal medicine: before-and-after intervention study." Swiss Med Wkly 143 (2013): w13796.Leis, Jerome A., et al. "Downstream impact of urine cultures ordered without indication at two acute care teaching hospitals." Infection Control & Hospital Epidemiology 34.10 (2013): 1113-1114.Zhang, Xi, et al. "Urine culture guided antibiotic interventions: A pharmacist driven antimicrobial stewardship effort in the ED." The American journal of emergency medicine 35.4 (2017): 594-598.Centre of Disease Control and Prevention. UTI (Catheter-Associated UTI [CAUTI] and Non-Catheter Associated UTI [UTI]) and Other Urinary System Infection [USI]) Events. 1 Jan. 2017, nhsn/PDFs/pscManual/7pscCAUTIcurrent.pdf. Accessed 31 July 2017Coulthard, Malcolm G., et al. "Redefining UTIs by bacterial colony counts."?Pediatrics?125.2 (2010): 335-341.Naik, Aanand D., and Barbara W. Trautner. "Editorial commentary: Doing the right thing for ASB: Knowing less leads to doing less." (2014): 984-985.Kwon JH, Fausone MK, Du H, Robicsek A, Peterson LR. Impact of laboratory-reported urine culture colony counts on the diagnosis and treatment of UTI for hospitalized patients. Am J Clin Pathol 2012;137:778-84.Leis, Jerome A., et al. "Reducing antimicrobial therapy for asymptomatic bacteriuria among noncatheterized inpatients: a proof-of-concept study." Clinical infectious diseases 58.7 (2014): 980-983.Trial Study participants Interventions/MethodsOutcomes Proof-of-concept studyLeis et. al. 2017Non-catheterized inpatients in medical and surgical hospital wards, median age = 73 years old, 59% female Eliminated automatic reporting of all urine culture results to healthcare professionals, irrespective of growth If healthcare professionals wished to review the non-reported culture results, they had to call the microbiology lab, who would immediately release the resultsDecreased the rate of antimicrobial therapy for ASB from 48% to 12% (95% CI, 5%-27%)Healthcare providers called the lab for the cultures not automatically reported only 5 out of 37 cultures withheld, (14%; 95% CI, 6%-28%) Prospective Cohort StudyZhang et. Al. 2017Non-pregnant asymptomatic patients (85%) female, mean age = 50.4?years old (±?23.3)Pharmacists in the emergency department reviewed all finalized urine culture results, patient charts and made recommendations to discontinue/modify antibiotic therapy to healthcare providersPharmacists made recommendations (to discontinue, modify etc.) on 35/54 (65%) of antibiotic therapy. All but one recommendation was accepted by healthcare professionals. Resulted in 122/426 antibiotic days saved (29% of all days). Pre-post study Egger et. al 2013Inpatients at a teaching hospital, 50% female, mean age = 68.0 years old (±?18.4) Lectures and internet-based learning focused on ASBReduction in antibiotic use from 75 to 59 treatment days per 1000 patient days (IRR = 0.79, 95% CI 0.69-0.92) Pre-post study Trautner et al. 2013 Non pregnant catheterized patients on acute medicine wards or in long term care, mean age = 73, >90% male Excluded: planned urologic procedures Distributed a diagnostic algorithm to clinicians to assist in differentiating between UTIs and ASBTaught clinicians in small groups how to use the algorithm through an interactive case-based powerpoint presentationReduction in orders for urine cultures from 41.2 to 23.3 per 1000 bed-days (IRR 0.57; 95% CI, 0.26-0.32 P<0.001) Decreased ASB treatment (1.6 to 0.6 per 1000 bed-days; IRR 0.35; 95% CI, 0.22-0.55)Systematic Review Dull et al. 2017N/AReviewed six clinical trials that used various strategies for reducing prescribing for ASBActive educational activities (e.g formulary restriction, preauthorization, prospective audit with feedback) as effective methods to decrease prescribing in comparison to passive education (guidelines, algorithms) Appendix 1: Literature Review: Summary of Interventions used to reduce prescribing for asymptomatic bacteriuria ................
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