“Critical access hospital” (CAH) is a Center for Medicare & Medicaid Services (CMS) designation given to rural hospitals with <25 inpatient beds and located >35 miles from another hospital. Reports suggest that antimicrobial stewardship practices should be tailored to the local facility environment; however, published data to guide stewardship interventions are limited in rural and CAHs. Reference Stenehjem, Braun and Chitavi1
Appropriate testing for urinary tract infections (UTIs) and avoiding treatment of asymptomatic bacteriuria (ASB) are important antimicrobial stewardship targets. Reference Nicolle, Gupta and Bradley2 A recent analysis including 84 patients noted both high prevalence and overtreatment of ASB in CAHs. With >1,350 CAHs in the United States, improved awareness of testing and treatment related to ASB on a larger scale would be useful to inform implementation of stewardship initiatives in these settings. We evaluated the prevalence of ASB and proportion of treated ASB in a cohort of CAHs.
Methods
This multisite, quality improvement study included 17 CAHs participating in the University of Washington Center for Stewardship in Medicine (UW CSiM), formerly known as the University of Washington Tele-Antimicrobial Stewardship Program (UW-TASP). UW CSiM is a collaborative between the University of Washington and 87 community hospitals, rural hospitals, and CAHs. In this study, we focused on implementing stewardship in CAHs by targeting the inappropriate diagnosis and treatment of ASB. All sites received prior education about UTIs through their participation in UW-CSiM, and 1 of 17 CAHs implemented an intervention to eliminate automatic urine analyses in long-term care patients, 2 months prior joining the quality improvement cohort. All sites participated in the UW CSiM intensive quality improvement cohort, through which hospitals received didactic education, individual coaching, peer mentorship, and support for data collection and analysis.
Abstractors at each CAH retrospectively identified and collected data between September 1, 2021, and June 10, 2022, using a REDCap electronic data collection tool. Reference Harris, Taylor, Thielke, Payne, Gonzalez and Conde4 Patients aged ≥18 years with a urine culture collected during an ambulatory or inpatient healthcare encounter were included. A positive urine culture was defined as 1 or more species of bacteria growing in the urine at ≥100,000 colony-forming units (CFU)/mL. ASB was defined as a positive urine culture without any documented signs or symptoms of UTI, according to the National Hospital Safety Network (NHSN) definition and Infectious Diseases Society of America (IDSA) guidelines: temperature > 38.0°C, suprapubic tenderness, costovertebral angle pain or tenderness, urinary urgency or frequency, dysuria, hematuria, and altered mental status plus a systemic sign of possible infection (peripheral leukocytosis >10,000 cells/mm Reference Liu, MacDonald and Jain3 , systolic blood pressure <90 mmHg, or ≥2 criteria for systemic inflammatory response syndrome [SIRS]). Reference Nicolle, Gupta and Bradley2,5 Patients who were pregnant, who were receiving antimicrobials for a concomitant bacterial infection, or for whom relevant details were missing during data collection were excluded.
The primary outcomes were the prevalence of ASB and proportion of ASB cases that received treatment, defined as the percentage of individuals with ASB who were prescribed an antibiotic. No statistical testing was performed. The study was reviewed by the University of Washington institutional review board, and approval was not required.
Results
We reviewed the data for 1,087 patients with urine cultures; the median number of cases submitted per CAH was 45 (IQR, 34–90). Among the patients identified, 891 (82%) were included. Exclusions were due to treatment for concomitant bacterial infections (n = 106), missing data (n = 65), age <18 years (n = 17), and pregnancy (n = 8). Overall, 75% were female, and the median age was 69 years. The emergency department (ED) was the most common location for urine culture collection (72%). Also, 75% of urine cultures originated from positive urinalysis results reflexing to culture. Baseline characteristics are summarized in Table 1.
Study Population Baseline and Clinical Characteristics
Note. IQR, interquartile range; ED, emergency department; SIRS, systemic inflammatory response syndrome; WBC, white blood cell count; MDR, multidrug-resistant.
a Units unless otherwise specified.
b Urological comorbidities included chronic indwelling urinary catheter use, chronic intermittent straight catheterization, urologic procedure in last 30 d, urinary retention, neurogenic bladder, abnormal urinary anatomy (eg, nephrostomy, urinary stent, ileal conduit; and did not include horseshoe or solitary kidney).
c Other outpatient includes rehab or long-term care, urgent or quick care facility, or home health.
d Meeting sepsis criteria includes ≥2 criteria for systemic inflammatory response syndrome [SIRS]; temperature >38°C or <36°C, heart rate >90 beats per minute, respiration rate >20 breaths per minute, WBC >10 ×109/L.
e MDR bacteria included the presence of extended-spectrum β-lactamase (ESBL)–producing bacteria, vancomycin-resistant Enterococcus (VRE), or carbapenem-resistant Enterobacterales (CRE).
Among 486 patients with a positive urine culture, 170 (35%) had ASB, and 129 (76%) received antibiotics. We detected a higher proportion of older age, male, urological comorbidities, and acute mental status changes among those treated for ASB. Among the 129 patients with ASB treated with antibiotics, oral agents were prescribed for 105 (81%). Moreover, β-lactams (45%) were most frequently prescribed, followed by nitrofurantoin (19%) and fluoroquinolones (18%) (Table 2). Of the 55 patients who received intravenous therapy, 98% received a β-lactam. The median antibiotic duration was 7 days (IQR, 3–7). Also, 95% of patients treated for ASB had a positive urinalysis that resulted in a reflex to culture.
Antibiotic Prescribing among Patients without Urinary Symptoms
Note. IQR, interquartile range.
a Units unless otherwise specified.
b Received any oral therapy includes during hospitalization, at discharge, or in the outpatient setting.
c Oral β-lactam agents includes amoxicillin, amoxicillin-clavulanate, cefdinir, cefpodoxime, cephalexin.
d Fluoroquinolone agents include levofloxacin and ciprofloxacin.
e Intravenous β-lactam agents includes ampicillin-sulbactam, cefazolin, cefepime, ceftriaxone, ertapenem, meropenem, piperacillin-tazobactam.
Among 405 patients with a urine culture showing <100,000 CFU/mL of bacterial growth (including those with no growth), 160 (40%) had no documented signs or symptoms of UTI. More than half (59%) were treated with antibiotics for a median duration of 7 days (IQR, 3–7).
Discussion
To our knowledge, this study is the largest to evaluate the prevalence and treatment of ASB in CAHs. Importantly, 35% of patients with a positive urine culture had no documented UTI-related symptoms.
Although the prevalence of ASB is notably lower in our study compared to previous reports (45%–71%), 75% of patients were inappropriately prescribed antibiotics for ASB. Reference Liu, MacDonald and Jain3,Reference Grein, Kahn and Eells6,Reference Flokas, Andreatos, Alevizakos, Kalbasi, Onur and Mylonakis7 This finding is consistent with other studies that also reported a high rate of overtreatment. Reference Liu, MacDonald and Jain3,Reference Grein, Kahn and Eells6–Reference Petty, Vaughn and Flanders8 Although a growing body of evidence demonstrates the lack of clinical benefit with treatment of ASB, more concerning are the underrecognized data suggesting potential harm. Reference Nicolle, Gupta and Bradley2 Curren et al Reference Curran, Lo and Leung9 found that each day of antibiotic therapy was associated with 4% increased odds of experiencing an adverse drug event (ADE). Notably, 19% of ADEs have been attributed to antibiotic regimens that were not clinically indicated, most commonly because of treatment of ASB. Reference Curran, Lo and Leung9 In our study, the median duration of therapy was 7 days (IQR, 3–7) among treated ASB patients, which exceeded guideline recommendations for cystitis. Reference Gupta, Hooton and Naber10 Even for those patients with ASB who are inappropriately treated, the potential for antibiotic-associated harm could be reduced through decreased duration of therapy. Reference Liu, MacDonald and Jain3,Reference Curran, Lo and Leung9,Reference Gupta, Hooton and Naber10
In our study, most urine cultures was collected in the EDs of CAHs. Thus, EDs represent a high-yield location for stewardship interventions because urine culture is often ordered before initiating a symptom-driven workup as a triage to optimize ED throughput. Reference Shallcross, Rockenschaub, McNulty, Freemantle, Hayward and Gill11 In our study, almost half of the patients with ASB were discharged directly from the ED, which limits opportunities to re-evaluate appropriateness of therapy as new data become available, including urine culture results. Therefore, ED workflows are a particularly important target for ASB interventions in CAHs.
Interestingly, nearly 60% of asymptomatic patients received treatment despite urine cultures showing <100,000 CFU/mL of bacterial growth or no growth. We postulate that the strict definition of ASB undercaptures the overall inappropriate antibiotic prescribing.
Our study had several limitations. Given the retrospective nature of the study and lack of case selection standardization among sites, there was a potential for bias in the selection of patients across the spectrum of care in both ambulatory and hospital settings. Identification of abnormal urinalyses and criteria to reflex a urinalysis to culture varied from institution to institution. Duration of therapy was based on written prescriptions; therefore, we were not able to confirm whether the antibiotic course was completed or was subsequently discontinued. Lastly, there was an overrepresentation of cases from some sites and insufficient representation from others.
In summary, similar to the well-described overtreatment of ASB in larger, urban, academic hospitals, inappropriate treatment of ASB is common in CAHs, especially in their EDs. Unnecessary antibiotic use in patients with ASB and long duration of therapy in treated patients are important areas for stewardship interventions in the CAH setting.
Acknowledgments
The authors acknowledge the members of the University of Washington Center for Stewardship in Medicine for their participation in this cohort.
Financial support
This work was supported by the University of Washington Center for Stewardship in Medicine.
Competing interests
All authors report no conflicts of interest relevant to this article.
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