Abstract
Objective:
The Veterans Health Administration (VHA), the largest single provider of spinal cord injury and disorder (SCI/D) care in the United States, currently mandates that every patient receives a screening urine culture during the annual evaluation, a yearly comprehensive history and physical examination. This testing has shown in a small subset of patients to overidentify asymptomatic bacteriuria that is then inappropriately treated with antibiotics. The objective of the current analysis was to assess the association of the annual evaluation on urine testing and antibiotic treatment in a national sample of Veterans with SCI/D.
Design/Method:
A retrospective cohort study using national VHA electronic health record data of Veterans with SCI/D seen between October 1, 2017-September 30, 2019 for their annual evaluation.
Results:
There were 9447 Veterans with SCI/D who received an annual evaluation; 5088 (54%) had a urine culture obtained. 2910 cultures (57%) were positive; E. coli was the most common organism obtained (12.9% of total urine cultures). Of the patients with positive urine cultures, 386 were prescribed antibiotics within the 7 days after that encounter (13%); of the patients with negative cultures (n=2178), 121 (6%) were prescribed antibiotics; thus, a positive urine culture was a significant driver of antibiotic use (p <0.001).
Conclusion:
The urine cultures ordered at the annual exam are often followed by antibiotics; this practice may be an important target for antibiotic stewardship programs in SCI.
Keywords: spinal cord injury, urinary tract infection, neurogenic bladder
Introduction
Antibiotic stewardship (interventions promoting appropriate use of antibiotics) is a high-value target to improve healthcare quality and patient safety.(1) Persons with spinal cord injuries and disorders (SCI/D) are vulnerable to inappropriate antibiotic use because of their medical complexity.(2, 3) Specifically, bacteriuria is a common and costly consequence of neurogenic lower urinary tract dysfunction after SCI; asymptomatic bacteriuria (ASB, the presence of bacteria in the urine of a person not otherwise having signs or symptoms of a urinary tract infection, or UTI) has a prevalence of 30–90%, depending on bladder management strategy.(4, 5) For comparison, the prevalence rate in healthy premenopausal women is 5%.(5)
ASB does not require antibiotic treatment in most cases. In fact, evidence-based guidelines published by the Infectious Diseases Society of America (IDSA) recommend against screening urine cultures or treating ASB in persons with SCI.(4) The current Veterans Health Administration (VHA) guideline for persons with SCI, however, recommends a urine culture at the time of the SCI annual examination, regardless of whether signs and symptoms of infection are present; this practice is essentially screening for ASB.(6) The SCI annual examination is recommended yearly for all veterans followed by the spinal cord injuries and disorders system of care. It consists of a history and physical examination by a physician (often a physiatrist with SCI medicine subspecialty training, but not always) or advanced practice provider, a battery of laboratory studies (including a urinalysis and urine culture), a functional evaluation by either an occupational or physical therapist, and psychosocial evaluations by a psychologist and social worker. Urodynamic studies and/or cystoscopy are offered to veteran based on evidence of clinical necessity. While the VHA guideline does not explicitly recommend treatment of ASB, our pilot data examining 2 years of local annual evaluation visits showed that 35% of cases classified as ASB were treated with antibiotics, with no significant difference in clinical outcomes between those who received antibiotics and those who did not.(7) Unfortunately, the rate of multi-drug resistant bacteriuria of VHA patients with SCI is higher than their age and comorbidity-matched cohorts, and infections from these organisms confer high morbidity and mortality, further highlighting the urgency of understanding the clinical consequences of policies surrounding urine testing and treatment in this population. (8, 9)
As our prior investigation on this topic was focused on one medical center, the purpose of this study was to examine the clinical outcomes of urine testing and treatment related to urine tests done at the VHA SCI annual exam using a national sample.
Methods
This was a retrospective cohort study of Veterans with SCI seen in the VA medical centers for an annual evaluation between October 1, 2017-September 30, 2019. Veterans were identified using the SCI/D Registry maintained by the National VHA SCI/D program office. If a Veteran was seen for the annual evaluation in both years, the data from the most recent year only were included. Demographic and clinical characteristics for each participant were extracted from the VA’s electronic health record data repository, corporate data warehouse (CDW). Demographic variables included the participant’s age at the time of the annual evaluation, sex, race, ethnicity, and rurality (urban, rural, highly rural). Pre-existing conditions in the 365 days prior to the annual evaluation were used to calculate the Deyo comorbidity score. Neurologic level of injury (as determined by the ASIA/ISCoS International Standards for Neurological Classification of Spinal Cord Injury, or ISNCSCI examination) and bladder management strategy was also collected. Bladder management strategy was defined as either evidence of catheter use or no evidence of catheter use based on the pharmacy domain in CDW for a predefined list of possible catheter prescriptions or orders to determine this variable for each participant. A Geoscore was calculated for each participant using zip code to describe socioeconomic status.(10) Antibiotic use was identified by querying the pharmacy domain using a predefined list of antibiotics; antibiotic prescription strings indicating a medicine and/or administration route clearly not used to treat UTI (e.g. inhaled tobramycin) were excluded.
We evaluated two primary outcomes in this study- collecting a urine culture during the annual evaluation obtained from microbiology data in the CDW and receiving antibiotics from inpatient or outpatient pharmacy records within seven days of the annual evaluation encounter. A urine culture was considered to have been collected as part of the annual evaluation if it was collected +/− two days from the annual evaluation date. Secondary outcomes included most frequent organisms cultured, most frequent antibiotics prescribed, number of organisms grown on culture and duration of antibiotic use.
Descriptive statistics of demographic and clinical characteristics were calculated by the neurologic level of injury. These were compared between groups using Wald chi squared tests for categorical variables or independent samples t-tests or Mann-Whitney tests for continuous variables. Multivariable logistic regression was used to determine the association of demographic and clinical covariates with the outcomes. Variables were included in the multivariable logistic regression models if they were significant in bivariate logistic regression analyses at the p < 0.1 level. However, some variables such as race, ethnicity, and gender were considered clinically relevant and automatically included in the multivariable models. All analyses were conducted using SAS V9.4.
This study was approved as human subjects research by the institutional review board of Baylor College of Medicine and the research and development committee of the Michael E. DeBakey VA Medical Center. A waiver of informed consent was granted due to the retrospective nature of the study.
Results
Overall, 9,447 Veterans with SCI/D were seen for an annual evaluation during the study period. The majority were male (96%), White 66%), and had an American Spinal Injury Association Impairment Scale (AIS) D grade SCI (43%). The most common etiology of SCI was motor vehicle collision (25%). Those with AIS D grade SCI or unclassified SCI were generally older than those with AIS A-C grade SCI. Additionally, there was a small but significant difference in socioeconomic status between the groups. (Table 1)
Table 1:
Patient demographics by neurologic level of injury, N = 9447
| Tetraplegia AIS A-C | Paraplegia AIS A-C | All AIS D | Not classified | p-value | |
|---|---|---|---|---|---|
| N=9447 | N=1644 | N=2263 | N=4042 | N=1498 | |
| Age, median (range) | 62 (21–91) | 63 (22–97) | 67 (19–100) | 68 (20–101) | <0.01 |
| Male gender (%) | 1593 (96.9) | 2172 (96.0) | 3872 (95.8) | 1432 (95.6) | 0.21 |
| Race/Ethnicity (%) | |||||
| White | 1065 (64.8) | 1602 (70.8) | 2578 (63.8) | 968 (64.6) | <0.01 |
| Non-Latino Black | 401 (24.4) | 392 (17.3) | 1078 (26.7) | 340 (22.7) | |
| Other | 178 (10.8) | 269 (11.9) | 386 (9.6) | 190 (12.7) | |
| Etiology of Injury (%) | |||||
| Motor vehicle collision | 636 (38.7) | 911 (40.3) | 705 (17.5) | 73 (4.9) | <0.01 |
| Fall | 316 (19.2) | 340 (15.0) | 790 (19.5) | 48 (3.2) | |
| Other | 692 (42.1) | 1012 (44.7) | 2547 (63.0) | 1377 (91.9) | |
| Co-morbidity index score, mean (SD) | 2.06 (1.4) | 2.06 (1.4) | 2.37 (1.6) | 2.61 (1.8) | <0.01 |
| Bladder management (%) | |||||
| Evidence of catheter use | 709 (43.1) | 1113 (49.2) | 800 (19.8) | 467 (31.2) | <0.01 |
| No evidence of catheter use | 935 (56.9) | 1150 (50.8) | 3242 (80.2) | 1031 (68.8) | |
| Rurality Score (% rural) | 451 (27.4) | 741 (32.7) | 1098 (27.2) | 417 (27.8) | <0.01 |
| GeoScore, mean (SD) | 99.9 (15.8) | 99.5 (14.8) | 98.7 (15.3) | 99.0 (15.1) | 0.03 |
AIS – American Spinal Injury Association Impairment Scale
SD – Standard Deviation
The classification of patients by urine culture results is shown in Figure 1. Just over half (54%) of the cohort received a urine culture during their annual exam visit, of whom 57% (2910) had a positive culture. Of those with a positive culture, 13% received antibiotics within 7 days of the annual exam encounter, compared to 6% of those with negative cultures and 5% of those that did not receive a culture at all (p<0.001).
Figure 1:
Patient Flowchart describing urine cultures obtained during annual evaluation (AE) in cohort, positive urine culture classification, and antibiotic use.
Figure 2 shows the microbiology of cultures obtained and breakdown of antibiotic use in the cohort. Escherichia coli was the most common isolate on culture (32% of cultures), followed by Klebsiella pneumoniae (19% of cultures) and Enterococcus. faecalis (17% of cultures). (Figure 2, panel A.) Additionally, 44% of cultures grew more than one organism. (Figure 2, panel B.) The most prescribed antibiotic in the cohort was nitrofurantoin, followed by ciprofloxacin and doxycycline. (Figure 2, panel C.) Finally, 19% of participants who received antibiotics were prescribed a course for less than 7 days, while 38% were prescribed a course for 7–10 days, 6% were prescribed a course for 11–14 days, and 37% were prescribed a course of antibiotics for more than 14 days. (Figure 2, panel D.)
Figure 2:
(Panels A-D) Microbiology and Antibiotic Use
The results of multivariable logistic regression analysis demonstrated several demographic and clinical characteristics that were associated with receiving a urine culture during the annual evaluation. (Table 2) Black (vs White) patients were more likely to have a urine culture performed (odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.15–1.43), as well as participants with an AIS-D grade SCI versus those with tetraplegia AIS A-C (OR: 2.04; 95% CI: 1.77–2.35). Conversely, older age, higher comorbidity index score, not having any evidence of catheter use for bladder management, and not receiving antibiotics within 7 days of the annual exam encounter were all significantly associated with a reduced likelihood of receiving a urine culture during the annual exam. (Table 2)
Table 2:
Association of demographic and clinical characteristics with receipt of urine culture during annual evaluation.
| Unadjusted OR (95% CI) |
p-value | Adjusted OR (95% CI) |
p-value | |
|---|---|---|---|---|
| Age | 0.99 (0.991–0.999) | <0.01 | 0.995 (0.991–0.999) | 0.01 |
| Race | ||||
| White | Reference | Reference | ||
| Black | 1.29 (1.04–1.26) | 0.26 | 1.29 (1.15–1.43) | <0.01 |
| Other | 1.15 (1.0–1.32) | 0.31 | 1.1 (0.91–1.29) | 0.35 |
| Ethnicity | ||||
| Non-Hispanic | Reference | Reference | ||
| Hispanic | 0.94 (0.81–1.09) | 0.04 | 1.04 (0.88–1.24) | 0.64 |
| Unknown | 1.28 (1.05–1.55) | 0.01 | 1.26 (0.98–1.61) | 0.07 |
| Gender | ||||
| Male | Reference | Reference | ||
| Female | 1.07(0.87–1.32) | 0.50 | 1.07 (0.84–1.35) | 0.60 |
| Neurologic Level of Injury | ||||
| Tetraplegia AIS A-C | Reference | Reference | ||
| Paraplegia AIS A-C | 1.19 (1.05–1.36) | <0.01 | 1.10 (0.94–1.28) | 0.23 |
| AIS D | 0.93 (0.83–1.05) | 0.71 | 2.04 (1.77–2.35) | <0.01 |
| Not Classified | 0.71 (0.62–0.82) | <0.01 | 1.08 (0.90–1.28) | 0.41 |
| Etiology of Injury | ||||
| Motor Vehicle Collision | Reference | Reference | ||
| Fall | 0.90 (0.79–1.02) | 0.38 | 0.93 (0.80–1.08) | 0.33 |
| Other | 0.72 (0.66–0.80) | <0.01 | 0.89 (0.79–1.01) | 0.07 |
| Comorbidity Index | 0.94 (0.92–0.96) | <0.01 | 0.91 (0.88–0.94) | <0.01 |
| Bladder Management | ||||
| Catheter | Reference | Reference | ||
| No Catheter | 0.11 (0.10–0.12) | <0.01 | 0.11 (0.10–0.12) | <0.01 |
| Antibiotics Prescribed within 7 Days of Annual Exam | ||||
| Yes | Reference | Reference | ||
| No | 0.51 (0.45–0.59) | <0.01 | 0.60 (0.50–0.73) | <0.01 |
Several of the demographic and clinical characteristics analyzed were also associated with antibiotic use within 7 days of the annual examination encounter. (Table 3) A higher comorbidity index score was associated with increased odds of receiving antibiotics within 7 days of the annual exam (OR: 1.06; 95% CI: 1.01–1.11). However, Black participants or those with unknown ethnicity were less likely to receive antibiotics than their White, non-Hispanic peers. Additionally, not having any evidence of catheter use for bladder management, having an organism identified on culture that was not one of the top three organisms identified on culture overall, and not receiving a urine culture during the annual examination encounter were significantly associated with a reduced likelihood of receiving a prescription for antibiotics within 7 days of the annual evaluation.
Table 3:
Association of demographic and clinical characteristics with prescription for antibiotics within 7 days of the annual evaluation.
| Unadjusted OR (95% CI) |
p-value | Adjusted OR (95% CI) |
p-value | |
|---|---|---|---|---|
| Age | 1.00 (0.99–1.0) | 0.71 | 1.00 (0.99–1.01) | 0.40 |
| Race | ||||
| White | Reference | Reference | ||
| Black | 0.71 (0.61–0.84) | 0.01 | 0.70 (0.59–0.83) | <0.01 |
| Other | 0.81 (0.64–1.01) | 0.69 | 0.84 (0.66–1.07) | 0.16 |
| Ethnicity | ||||
| Non-Hispanic | Reference | Reference | ||
| Hispanic | 1.12 (0.89–1.40) | 0.05 | 1.06 (0.80–1.40) | 0.69 |
| Unknown | 0.72 (0.51–1.02) | 0.03 | 0.51 (0.32–0.82) | 0.01 |
| Gender | ||||
| Male | Reference | Reference | ||
| Female | 1.41(1.05–1.88) | 0.02 | 1.22 (0.84–1.76) | 0.29 |
| Neurologic Level of Injury | ||||
| Tetraplegia AIS A-C | Reference | Reference | ||
| Paraplegia AIS A-C | 1.08 (0.90–1.30) | <0.01 | 1.16 (0.92–1.47) | 0.20 |
| AIS D | 0.67 (0.56–0.81) | <0.01 | 1.01 (0.80–1.28) | 0.92 |
| Not Classified | 0.83 (0.67–1.03) | 0.38 | 1.11 (0.83–1.47) | 0.48 |
| Etiology of Injury | ||||
| Motor Vehicle Collision | Reference | Reference | ||
| Fall | 0.82 (0.66–1.00) | 0.16 | 0.97 (0.77–1.25) | 0.83 |
| Other | 0.87 (0.75–1.01) | 0.54 | 1.03 (0.86–1.20) | 0.80 |
| Comorbidity Index | 1.05 (1.01–1.09) | 0.02 | 1.06 (1.01–1.11) | 0.03 |
| Bladder Management | ||||
| Catheter | Reference | Reference | ||
| No Catheter | 0.47 (0.42–0.54) | <0.01 | 0.68 (0.57–0.82) | <0.01 |
| Organism Identified on Culture in Top 3 | ||||
| Yes | Reference | Reference | ||
| No | 0.42 (0.37–0.47) | <0.01 | 0.48 (0.41–0.57) | <0.01 |
| Urine Culture During Annual Evaluation | ||||
| Yes | Reference | Reference | ||
| No | 0.51 (0.45–0.59) | <0.01 | 0.62 (0.51–0.75) | <0.01 |
Discussion
In this study, we examined the demographic and clinical characteristics associated with the collection of a urine culture during the SCI annual evaluation encounter and receipt of antibiotics within 7 days of the annual evaluation in a cohort of veterans who were seen for their annual evaluation during the study period. Just over half of the cohort had a urine culture collected during their annual evaluation, a lower proportion than our previous study at a single SCI center.(7) E. coli was the most common isolate on culture in this group, which is consistent with other studies in this patient population.(9) Most veterans who received antibiotics did so for a 7–10-day duration. Participants with an AIS-D grade SCI were more likely to have a urine culture collected during the annual evaluation. Additionally, Black participants were more likely to have a urine culture collected, however, this group was significantly less likely to receive antibiotics; this warrants further inquiry to promote health equity in this population. Furthermore, higher comorbidity index was significantly associated with and increased likelihood of receiving antibiotics within 7 days of the annual encounter.
The VHA is the largest national integrated health care system for people with SCI in the United States, so while the demographics of this study population are not entirely comparable to the general population(11), important population metrics can still be gleaned. It is not surprising that nitrofurantoin is the most prescribed antibiotic, as there is emerging inquiry and interest in this medication as a UTI prophylactic measure.(12) The duration of antibiotic use is consistent with current IDSA guidelines for complicated UTI/CAUTI (of which most cases in persons with SCI/D would represent);(5) however, recent work has shown that a shorter time course could be just as efficacious.(13) Urine cultures remain a strong positive predictor of antibiotic use in this national cohort, as our previous work at a single site showed.(7)
Study Limitations
As this is a retrospective, relational database study, there is no way to ascertain whether any of the participants had symptoms indicative of an UTI. However, based on our previous work showing a xxx rate of UTI in persons with SCI presenting for an annual evaluation, it is a reasonable assumption that most antibiotics given for a positive urine culture during the annual examination represent treatment of ASB. An appropriate indication for ASB is pre-urologic procedure, which includes urodynamic testing and cystoscopy. These tests are not automatically performed during every annual evaluation encounter, however, rather based on clinical need. Unfortunately, there is not a reliable way to link each annual evaluation encounter with a urodynamic and/or cystoscopy procedure that may or may not have been performed in this relational database, so the exact count is unknown. We are also limited in our ability in ascertain whether an antibiotic was prescribed for a valid non-urinary source of infection. We attempted to mitigate this as much as possible in the antibiotic use data definition described in the methods.
Conclusions
This study shows that performing routine urine cultures resulted in increased unnecessary antibiotic treatment. This study emphasized the importance of patient and health care professional education on judicious stewardship of antibiotics Urine cultures at the annual exam appear to be driving antibiotic use, so minimizing urine testing remains a high-value antibiotic stewardship intervention target.
Footnotes
Conflict of Interest
No authors have any relevant financial conflicts of interest to this work.
Data Availability
The data that supports the findings of this study are available from the Veterans Health Administration but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Veterans Health Administration.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that supports the findings of this study are available from the Veterans Health Administration but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the Veterans Health Administration.