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Descriptive epidemiology and outcomes of emergency department visits with complicated urinary tract infections in the United States, 2016–2018

Abstract Objective There are >1 million emergency department visits and 100,000 admissions with urinary tract infection (UTI) annually in the United States. A fraction of total UTI volume, complicated (cUTI) costs the health care system over $3.5 billion per year. We evaluated the contemporary annual burden of emergency department (ED) visits with cUTI. Methods We conducted a cross‐sectional multicenter study within the National Emergency Department database, a 20% stratified sample of all US hospital‐based EDs, 2016–2018, to explore characteristics of visits with a cUTI. We compared cUTI as the principal (PD) versus secondary diagnosis (non‐PD). We applied survey methods to develop national estimates. Results Among 2,379,448 ED cUTI visits (44.8% PD), 40.1% were female (45.1% PD; 36.9% non‐PD) and 62.2% were ≥ 65 years (52.5% PD; 70.2% non‐PD). Mean Charlson score was 2.3 (3.0 PD; 2.1 non‐PD); end‐stage renal disease prevalence was 2.3% (1.4% PD; 3.0% non‐PD). Whereas pyelonephritis occurred in ∼10% of both groups, severe sepsis (7.2% vs 2.0%) and septic shock (7.1% vs 1.8%) were ∼4 times more prevalent among those with cUTI‐non‐PD than cUTI‐PD. Overall, two thirds of all visits ended in hospitalization (44.9% PD; 85.5% non‐PD). Despite similar numbers of visits, the annual national ED bill for cUTI rose from $2.8 billion in 2016 to $3.2 billion in 2018. Conclusion There were over 2 million ED visits with cUTI in 2016–2018. Although <10% met criteria for severe sepsis/septic shock, ∼two thirds were admitted. The aggregate cost for cUTI visits rose by 15% without a substantial increase in volume.


Background
Urinary tract infection (UTI) remains one of the most frequent diagnoses in US hospitals. In the early 2000s there were over 1 million annual emergency department visits related to UTIs along with over 100,000 inpatient admissions for this condition. 1 A decade later, UTI was responsible for ∼400,000 hospitalizations, a 4-fold increase over that time period. 2 Even this staggering number is likely an underestimate of the full burden of UTI, because it fails to account for admissions where the UTI was either incidental to another condition or led to a more serious complication such as sepsis. 2 Despite excluding more severely ill patients with UTI, the annual aggregate hospital costs for these admissions in 2010 were over $2.8 billion. To develop a more comprehensive and up-to-date snapshot of the impact of UTI on health care use, particularly given the growth and aging of the US population, we identified nearly 3 million US hospitalizations involving these infections in 2018, costing in aggregate over $45 billion. 3 Rising rates of antimicrobial resistance (AMR) have complicated the clinical approach to UTI. Because AMR as an etiology distinguishes complicated from uncomplicated infections, the increase in AMR increases the potential for an uncomplicated UTI to transform into a complicated one (cUTI), making clinical approaches to treatment more challenging. 4,5 Indeed, though still a minority of all UTI admissions, cUTIs incur much higher costs than uncomplicated cases. 3 At the same time, some investigators estimate that one fifth of all cUTI-related admissions may be avoidable. 6 They postulate that, if adequate antimicrobial coverage were available orally, these patients could potentially be treated outside the hospital, thus eliminating the need for hospitalizations and the attendant concerns regarding hospital-acquired complications and unnecessary expenditures.

Importance
Because the vast majority of all UTI admissions originate in the ED, the ED is an important locus where admission decisions may be amenable to modification. However, no modification is possible without first understanding the population and practices as they exist today.

Goals of this investigation
To get a better view of cUTI in the ED, we set out to characterize the current volume, characteristics, and outcomes of those ED visits in the United States stratified by whether they were seen specifically for cUTI (ie, principal diagnosis, PD) or whether cUTI was secondary to another reason for the presentation (ie, secondary diagnosis, non-PD).
We specifically examined their demographic, baseline clinical, and hospital characteristics, as well as processes of care in the ED and such outcomes as discharge disposition and charges and costs, both per patient and aggregate annual across ED visits overall.

The Bottom Line
The authors undertake a retrospective analysis of the multicenter cohort National Emergency Department Sample database, looking specifically at the role of complicated urinary tract infection (cUTI) as a primary or secondary diagnosis. The cUTI, whether clothed as a primary or secondary diagnosis, is shown as a major entity to be reckoned with, with respect to the health care of many patients and the economic burden imposed on the health care system. This paper has done a remarkable job in categorizing cUTI as a major player in the emergency department and points to further research for better management and cost management.

Ethics statement
Because this study used publicly available fully deidentified data, we did not seek ethics review, per US 45 CFR 46.101(b)4. 7

Study design and patient population
We conducted a multicenter cross-sectional study of patients with cUTI presenting to EDs in acute care hospitals in the United States.
Because we were interested in the total annual burden of ED visits with cUTI in the United States, we erred on the side of sensitivity and thus did not exclude any visits that our algorithm identified as having this condition. To quantify the prevalence of resistant pathogens, we used their corresponding International Classification of Diseases, Tenth Revision (ICD-10) codes (Table S1).

Definition of complicated UTI
Our case identification approach relied on an ICD-10 algorithm (Table 1). 3,4 Namely, cUTI was defined as co-occurrence of at least 1 ICD-10 code from group B plus at least 1 ICD-10 code from group D or from group E.

Data source
The data for the study derived from the Agency for Healthcare Research stratified sample of all US hospital-based EDs. 8 We applied complex survey methods to develop national and regional estimates for cUTI visits.
The unit of analysis in this database is a discharge and not a patient.
Thus, it is not feasible to distinguish repeat presentations from index ones for any single patient. In the current manuscript, we use the terms "visit," "presentation," and "discharge" interchangeably.

Exposure and outcomes
Primary exposure of interest was whether or not the ED visit was for (cUTI-PD) or with (cUTI-non-PD) a cUTI. The outcomes examined were ED discharge destination and ED costs per visit and as an annual aggregate.

Statistical analyses
We examined demographic, clinical, and hospital characteristics of the individual visits, as well as their ED outcomes. We report con-tinuous variables as means with SD and categorical variables as percentages based on complex survey methods that weight strata provided by NEDS (sample statistical code can be found online at www.hcup-us.ahrq.gov/tech_assist/tutorials.jsp). We further provide medians and interquartile ranges (IQR) for select variables based on observed encounters but without using weighted strata. Consequently, the median and IQR results do not reflect national estimates but do reflect the observed sample. We compared characteristics and outcomes of those with cUTI as PD (cUTI-PD) versus cUTI as non-PD (cUTI-non-PD). Although P < 0.05 represents statistical significance, we note that owing to large numbers, statistical significance may not equate to clinically meaningful differences. All analyses were done using Stata/MP 15.1 for Windows software (StataCorp LLC, College Station, TX).

RESULTS
There were a total of 2,379,448 cUTI ED visits in the United States, divided evenly across the 3 years examined ( The cUTI-PD group was younger (mean ± SD age 62.5 ± 19.8 vs 70.4 ± 16.1 years, P < 0.001) and had a higher proportion of females (45.1% vs 36.9%, P < 0.001) than the group with cUTI-non-PD. Although endstage renal disease was rare, it was more than twice more common in the cUTI-non-PD (3.0%) than cUTI-PD (1.4%) group, P < 0.001. The mean Charlson comorbidity score mirrored this relationship (cUTInon-PD 2.1 ± 2.7; cUTI-PD 1.5 ± 3.0, P < 0.001). In both groups, over 50% of all cUTI visits occurred in metropolitan teaching institutions, with 40% located in the Southern US census region. There was slightly more seasonal variation in visits with cUTI-PD (6.4% in February to 8.1% in July and August) than cUTI-non-PD (6.7% in February to 7.6% in August, Figure 1).
Diagnoses and procedures performed in the ED are listed in Table 3.
Renal ultrasound, though rare overall, was nevertheless 4 times more common in the cUTI-PD than cUTI-non-PD group. Similarly, catheterassociated UTI was twice as likely in cUTI-PD as in cUTI-non-PD. In contrast, diagnoses of severe sepsis (7.2% vs 2.0%, P < 0.001) and sep-tic shock (7.1% vs 1.8%, P < 0.001) were nearly 4 times more prevalent among those with cUTI-non-PD than cUTI-PD (Table 3). Though slightly more common in the setting of cUTI-PD, pyelonephritis was present in ∼1 in 10 visits in both groups. AMR codes were rare in both groups.
ED visits with cUTI-non-PD ended in a hospitalization in 85.5% of the cases, nearly twice the rate for cUTI-PD (44.9%, P < 0.001, Table 4). In contrast, routine discharges home with no further ser-

Limitations
Our study, although large and highly generalizable, has a number of limitations. Because our case definition relied on administrative coding, there may be misclassification. Although our algorithm to identify cUTI has not been clinically validated, our numbers generally comport with other studies, particularly allowing for different times and sample frames. To the best of our knowledge, no study to date has addressed coding practices in the setting of cUTI. Thus, misclassification from this perspective remains a concern. Another possible source of misclassification is that at least some of the cUTI-PD patients may have presented with a secondary complication, such as, for example, a fall, or an altered mental status, but were still coded as cUTI as the principal reason for the visit. Such misclassification would mean we have underestimated the severity of acute illness in the group with cUTI-PD thus overstating the potential for avoidable hospitalizations. Another important limitation is our inability to differentiate between initial and repeat visits.
However, given the aim of the study, this did not preclude us from estimating the full burden of ED presentations with cUTI. Finally, we did not attempt to calculate the attributable burden from cUTI as a secondary diagnosis in the current study. Therefore, though it surely likely contributes to the burden of both ED and admissions, cUTI-non-PD is responsible for only a part of this burden.

DISCUSSION
In this large multicenter study, we have demonstrated that in years 2016-2018 US EDs evaluated nearly 2.5 million visits with cUTI, of which almost half were specifically for cUTI. Although seasonal swings in ED presentations in both groups were narrow, those in cUTI-PD directionally comported with the reported spikes in UTI during warm months. 9,10 Though the cUTI-PD group had a lower burden of both chronic and acute conditions than cUTI-non-PD, nearly half of the former group nevertheless required a hospital admission. Moreover, hospitalization rates in both groups were substantial, despite a low prevalence of such severe conditions as severe sepsis and septic shock, or pyelonephritis. Although the ED charges associated with cUTI-PD were higher than for cUTI-non-PD, neither number reflects the costs incurred for subsequent hospitalizations among those who required admission. Furthermore, the costs for both are 4-5 times higher than the cost of an average ED visit in the United States. 11 Overall, given the nearly identical total numbers of visits in 2016 and 2018, the 15% rise in the annual charges for all cUTI ED visits within the same time period cannot be explained by volume alone. Likewise, if ED costs for cUTI had been on pace with inflationary trends in medical care, the aggregate bill in 2018 would have been $2.9 million instead of the observed $3.2 billion. Although this is consistent with reports of general price increases for ED services, the reasons for such steep rise in the charges for ED visits with cUTI require further investigation. 12 In 2018, total ED visits in the United States exceeded 143 million. 11 Numbering over 3.6 million, UTIs were the seventh most common reason for being seen in the ED. 13 Thus, in the same year, complicated UTIs, which in the NEDS data numbered 787,889, comprised 22% of all UTI in the ED, and accounted for 1 out of every 200 ED visits overall.
Moreover, in that year the average rate of hospital admissions from the ED across all presenting conditions was 14%. 11 This means that cUTI visits were nearly 5 times more likely to result in an acute hospitalization and cUTI-non-PD specifically 6 times more so. given easy availability and already existing pathways for ED evaluation, it may be that the current setup is indeed cost effective. Without further study, however, it is impossible to make an informed policy decision with regard to this matter. Our study is a step in building an evidence platform for understanding how to streamline care for these patients.
In summary, we have estimated the contemporary volume of ED visits associated with cUTIs in the United States, stratified by whether this infection was the principal reason for the visit or incidental to it.
The patient population is large and resource intensive. One important finding is that the aggregate ED charges for cUTI visits skyrocketed between 2016 and 2018, well out of proportion to either increases in the volume of visits or to the background rate of inflation. Another finding with potential policy implications is that only a small proportion of visits where cUTI is either primary or incidental reason for presenting carries a concurrent diagnosis of a serious infection, such as severe sepsis or septic shock or pyelonephritis, and that the relatively high hospital admission rates in both groups are ostensibly much higher than the prevalence of these conditions would imply. This finding requires further exploration in data that contain granular clinical variables. Finally, the near-$1-billion aggregate annual price tag for the ED visits that end in discharge requires further examination of possible less costly alternatives for delivery of care to this population of patients.