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Background: Urine cultures are often positive in the absence of a urinary tract infection (UTI). Pyuria is generally considered necessary to diagnose a UTI. Problem: Urine cultures are often positive in the absence of UTI leading to unnecessary antibiotics. Methods: Quasi-experimental pre-post study of all patient urine cultures ordered in a VA acute care hospital, emergency department (ED), and two long-term care (LTC) facilities from August 2016 to August 2018. Urine cultures performed per 100 days were compared pre- (August 2016 to July 2017) versus post-intervention (August 2017 to August 2018) using interrupted time series negative binomial regression. Intervention: We examined whether reflexing to urine culture only if a urinalysis (UA) found greater than 10 WBC/ hpf decreased urine culturing. Results: In acute-care, reflex culturing resulted in a 39% time series regression analysis adjusted decrease in the rate of cultures performed (pre-intervention, 3.6 cultures/100 days vs. Post-intervention, 1.8 cultures/100 days, p < 0.001). Pre-intervention, 29% (4/14) of Catheter-associated UTI (CAUTI) would not have been reported if reflex culturing was employed. In the ED, reflex culturing was associated with a 38% (p = 0.0015) regression analysis adjusted decrease in cultures, from 5.4/100 visits to 3.3/100 visits. In LTC, there was a small absolute, but regression analysis adjusted increase of 89% (p = 0.0018) in rates from (0.4/100 days to 0.5/100 days). Conclusion: In acute care and ED, urine reflex culturing decreased the number of urine cultures performed. A small absolute increase was seen between pre-post time periods in LTC. Reflex testing generally decreases cultures and may lead to more accurate diagnoses of CAUTI. Keywords: Stewardship, Urinary tract infections, Diagnostic microbiology * Correspondence: firstname.lastname@example.org Department of Infection Control, VA Maryland Health Care System, Baltimore, MD, USA Department of Epidemiology and Public Health, University of Maryland, 10 S, Pine St. MSTF 334, Baltimore, MD 21201, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Lynch et al. Antimicrobial Resistance and Infection Control (2020) 9:96 Page 2 of 6 Introduction done as an inpatient. Multiple admissions per patient were Urinary tract infections (UTI) are one of the most common included in analysis. healthcare-associated infections, accounting for more than 12% of infections reported by acute care hospitals and Intervention 20% of infections reported by long-term care (LTC) Urine reflex culturing criterion was a urinalysis with > 10 facilities . white blood cells per high power field (WBC/hpf). This was instituted throughout the system in August 2017. Problem description Urine cultures are frequently ordered as a part of a general- Study of the interventions ized workup for non-specific symptoms (e.g. fevers without Each urine culture result was categorized as negative, traditional UTI symptoms such as dysuria and frequency) positive < 100,000 colony forming units per milliliter . This often results in false-positive urine culture results (CFU/ml), or positive ≥100,000 CFU/ml. No urine cultures . Clinically, this is known as asymptomatic bacteriuria were excluded. (ASB). False-positive urine cultures are associated with CAUTIs for acute care and LTC were reviewed from unnecessary antibiotic treatment of ASB and elevated August 2015 to August 2018 using Centers for Disease catheter-associated UTI (CAUTI) rates . Control and Prevention’sNational Healthcare Safety Network (NHSN) criteria. For acute care, the criteria Available knowledge was a positive urine culture with no more than two species Reflex urine reflex culturing, defined as only performing a of organisms with at least one being a bacterium of ≥100, urine culture if the preceding UA showed pyuria [6–9]. 000 CFU/ml obtained with an indwelling catheter in place may improve unnecessary use of antibiotics for false- for at least two calendar days (or removed within two positive urine cultures. calendar days of indwelling catheter removal) and at least one documented sign or symptom (fever > 38.0 °C; supra- Rationale pubic tenderness; costovertebral angle pain or tenderness; Urine reflex culturing has been shown to decrease the rate urinary urgency; urinary frequency; or dysuria). of urine cultures performed in adult intensive care units For LTC,  the criteria was a positive urine culture but the benefit in other settings is unknown [9, 10]. with no more than two species of organisms with at least one being a bacterium of ≥100,000 CFU/ml obtained Specific aims with an indwelling catheter in place for at least two We evaluated the impact of implementation of urine calendar days (or removed within two calendar days of reflex culturing across a healthcare system including indwelling catheter removal) and at least one documented patient care in acute care, the emergency department sign or symptom (fever > 37.8 °C; rigors; new onset of (ED), and (LTC) facilities. hypotension; new onset of confusion/functional decline and leukocytosis; new or marked increase in suprapubic Methods tenderness; new or marked increase in costovertebral angle Context pain or tenderness; acute pain, swelling, or tenderness of This was a quasi-experimental study at an integrated the testes, epididymis, or prostate; purulent discharge from healthcare system. The VA Maryland Health Care System around catheter insertion site). (VAMHCS) is comprised of three medical centers operat- ing approximately 727 inpatient beds (acute care and Measures LTC) as well as an emergency department with 22 beds Rate of urine culture. and six outpatient clinics throughout Maryland. The study received ethics review and approval from the University of Analysis Maryland Baltimore Institutional Review Board. Comparisons pre- and post-intervention were made An internet-based, data mining surveillance tool (Thera- using time series regression analysis. Negative bino- Doc,DSS inc.) was used to identify all urine cultures mial regression was used to assess immediate changes ordered from August 2016 to August 2018 based on collec- and trends in the number of urine cultures performed. tion location. Acute care included five inpatient units (three A p-value of < 0.05 was considered statistically signifi- intensive care units, one medical unit, and one surgical cant. All analysis was competed using SAS v 9.4 (SAS unit). The ED included all emergency room visits. LTC Institute, Cary, NC). included all eight LTC units in two facilities (including rehabilitation patients and hospice patients). Patients with Ethical considerations urinetesting in theEDwould notbeincludedinthe This description of a patient safety initiative was consid- analysis of acute-care unless they had a separate urine test ered non-human subjects research. Lynch et al. Antimicrobial Resistance and Infection Control (2020) 9:96 Page 3 of 6 Results cancelled), a rate of 3.34 cultures performed per 100 ED Acute care visits. With the institution of urine reflex culturing, there In the pre-intervention period, 908 urine cultures were was an regression analysis adjusted immediate 38% ordered, and 894 urine cultures were performed, a rate of decrease in the rate of cultures performed (p = 0.0015) 3.58 cultures per 100 days. In the post-intervention period, with similar monthly rates of 0.12% through the post- 965 urine cultures were ordered, and 507 urine cultures intervention period (p = 0.9541). Urine reflex culturing were performed, a rate of 1.82 cultures performed per 100 cancelled 51% of urine cultured ordered in the post- days. With the institution of urine reflex culturing, there intervention period (see Fig. 2). was an regression analysis adjusted immediate 39% de- crease in the rate of cultures performed (p < 0.0001) with a Long-term care (LTC) monthly decrease of 6% through the post-intervention In the pre-intervention period, 267 urine cultures were period (p = 0.0003). Urine reflex culturing cancelled 45% of ordered, and 257 urine cultures were performed, a rate urine cultures ordered in the post-intervention period, with of 0.41 cultures performed per 100 days. In the post- 458 cultures cancelled (See Fig. 1). Applying urine reflex intervention period, 432 urine cultures were ordered, culturing during the pre-implementation period would and 354 urine cultures were performed, a rate of 0.52 have resulted in 29% fewer reported CAUTIs. cultures performed per 100 days. With the institution of urine reflex culturing, there was a regression Emergency department (ED) analysis adjusted immediate 89% increase in cultures In the pre-intervention period, 1400 urine cultures were performed (p < 0.0001) and the monthly trend through ordered, and 1393 urine cultures were performed, a rate the post-intervention period stayed the same as in pre- of 5.44 cultures performed per 100 ED visits. In the intervention period (p = 0.83). However, urine reflex post-intervention period, 1959 urine cultures were culturing cancelled 16% of urine cultures ordered in ordered, and 917 urine cultures were performed (1042 the post-intervention period (see Fig. 3). Fig. 1 Acute Care Urine Cultures Ordered vs. Urine Cultures Performed per 100 Days Lynch et al. Antimicrobial Resistance and Infection Control (2020) 9:96 Page 4 of 6 Fig. 2 Emergency Department Urine Cultures Ordered vs. Urine Cultures Performed per 100 ED Visits Catheter-associated urinary tract infections (CAUTI) urine cultures long-term care. Although rates of CAUTI In acute care, from August 2015 to July 2017, there were did not change with reflex culturing, almost 1/3 of CAU- 14 CAUTI with a rate of 1.82 infections per 1000 catheter TIs occurred in patients without pyuria in the pre-period days. Urine reflex culturing would have canceled the in acute care and were likely mis-diagnosed. triggering urine cultures for 4 (29%) of those CAUTI, decreasing the rate to 1.30 infections per 1000 catheter Interpretation days. In the post-intervention period, there were 6 CAUTI Many urine cultures were cancelled due to reflex testing with a rate of 1.64 infections per 1000 catheter days. in acute care and ED with many fewer cancelled in LTC. In LTC, from August 2015 to July 2017, there were 13 This is likely due to the differences in patient popula- CAUTI with a rate of 0.99 infections per 1000 catheter tions with more chronic pyuria among LTC patients. A days. Urine reflex culturing would have canceled the higher urine reflex culturing cutoff for pyuria (e.g. > 25 triggering urine cultures for 1 (8%) of those CAUTI, WBC/hpf or > 50 WBC/hpf) may have resulted in better decreasing the rate to 0.91 infections per 1000 catheter performance among this population but this is unknown. days.Inthe post-interventionperiodthere were 6CAUTI The cutoff of > 10 WBC/hpf was chosen as it is the most with a rate of 1.60 infections per 1000 catheter days. common definition of pyuria, but it is unclear if it is the most effective cutoff for optimal urine culturing. Discussion Urine reflex culturing was well accepted by the Micro- Summary biology Laboratory where it resulted in cost savings due Urine reflex culturing decreased the rate of urine cultures. to the decreased number of urine cultures performed. Urine reflex culturing caused the greatest decrease on Additionally, the intervention was accepted by clinicians urine culturing in acute care and the emergency depart- who interpreted cancelation of urine cultures due to lack ment but was associated with a small absolute increase in of pyuria as negative results. This likely relates to the Lynch et al. Antimicrobial Resistance and Infection Control (2020) 9:96 Page 5 of 6 Fig. 3 Long-Term Care Urine Cultures Ordered vs. Urine Cultures Performed per 100 days extensive education to the clinicians about the interven- Conclusion tion before it was implemented. We found that urine reflex culturing was safe and easy to implement in acute care, ED care, and LTC and led to a nearly 40% decrease in cultures in the hospital. This Limitations intervention likely decreased the number of patients While urine reflex culturing reduced urine cultures treated for ASB, and misidentification of CAUTIs, while performed, it mostly reduced cultures that would have reducing microbiology costs. been negative. It also only partially addressed bacteri- Acknowledgements uria and ASB, as pyuria was often present in patients Not applicable. with ASB. The potential downstream clinical conse- Disclaimer quences of urine reflex testing, in particular, antibiotic The contents do not represent the views of the U.S. Department of Veterans therapy, have not been fully elucidated. It is notable Affairs or the United States Government. that using reflex culturing during the pre-period Authors’ contributions would have resulted in reporting 29% fewer CAUTIs Study design: DJM, CSL, KA, JTB, AAS, RD, MS, DH, AFC. Analysis: KC, MZ, in acute care. Patients could be included more than DJM, CSL. Preparation of manuscript: CSL, JTB, KC, MZ, DJM. All authors read once if they had multiple admissions. We did not and approved the final manuscript evaluate patient characteristics before and after interven- Funding tion, although there were no broad changes to the services This work received no support. provided at our facilities. The appropriate use of urine Availability of data and materials cultures still requires careful clinical judgment to avoid There are legal restrictions on sharing a de-identified data set from Veterans ordering when patients are asymptomatic and interpreted Affairs (VA) because of the inclusion of report data and other details that carefully to avoid unnecessary antibiotics. make it extremely difficult to de-identify. VA has generally not allowed Lynch et al. Antimicrobial Resistance and Infection Control (2020) 9:96 Page 6 of 6 release of de-identified data because they are usually re-identifiable, at least 10. Claeys KC, Blanco N, Morgan DJ, Leekha S, Sullivan KV. Advances and in part. If data are requested, they may apply for data access by submitting challenges in the diagnosis and treatment of urinary tract infections: an approved IRB protocol and VA Research and Development Committee the need for diagnostic stewardship. Curr Infect Dis Rep. 2019 Mar 5; Approval letter to the Veterans Informatics and Computing Infrastructure. 21(4):11. Queries can be directed to VINCI@va.gov. Publisher’sNote Ethics approval and consent to participate Springer Nature remains neutral with regard to jurisdictional claims in Ethical approval was granted by the University of Maryland Baltimore published maps and institutional affiliations. Institutional Review Board. Consent for publication All authors agree to publication of this article. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. Competing interests The authors have no relevant conflicts of interest to disclose. No other relationships or activities have influenced the submitted work. Author details Department of Infection Control, VA Maryland Health Care System, Baltimore, MD, USA. Microbiology Department, VA Maryland Health Care System, Baltimore, MD, USA. Department of Infectious Diseases, VA Maryland Health Care System, Baltimore, MD, USA. Department of Medicine, University of Maryland, Baltimore, MD, USA. Department of Pharmacy, VA Maryland Health Care System, Baltimore, MD, USA. Department of Pharmacy Practice and Science, University of Maryland, Baltimore, MD, USA. Department of Epidemiology and Public Health, University of Maryland, 10 S, Pine St. MSTF 334, Baltimore, MD 21201, USA. Received: 21 January 2020 Accepted: 18 June 2020 References 1. National Healthcare Safety Network (NHSN). 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Published: Jun 29, 2020
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