Emergency Medicine

Factors for return to emergency department and hospitalization in elderly urinary tract infection patients

a b s t r a c t

Background: Appropriate decision of emergency department (ED) disposition is essential for improving the out- come of elderly urinary tract infection patients. However, studies on early return visit (ERV) to the ED in elderly UTI patients are limited. Therefore, we aimed to identify factors for ERV and hospitalization after return visit (HRV) in this population.

Methods: Elderly patients discharged from the ED with International Classification of diseases 10th Revision codes of UTI were selected from the registry for evaluation of ED revisit in 6 urban teaching hospitals. Retrospec- tive data were extracted from the electronic medical records and ERV and hospitalization to scheduled revisit (SRV) were compared.

Result: Among a total of 419 patients found in the study period, 45 were ERV patients and 24 were HRV patients. Absence of UTI-specific symptoms (odds ratio [OR] 2.789; 95% confidence interval [CI] 1.368-5.687; P = 0.005), C-reactive protein levels >30 mg/L (OR 2.436; 95% CI 1.017-3.9; P = 0.024), and body temperature >= 38 ?C (OR 1.992; 95% CI 1.017-3.9; P = 0.044) were independent risk factors for ERV, and absence of UTI-specific symptoms (OR 3.832; 95% CI 1.455-10.088; P = 0.007), CRP levels >30 mg/L (OR 3.224; 95% CI 1.235-8.419;

P = 0.017), and systolic blood pressure <= 100 mmHg (OR 3.795;95% CI 1.156-12.462; P = 0.028) were indepen- dent risk factors for HRV. However, there was no significant difference in empirical antibiotic resistance in ERV and HRV patients, compared to SRV patients.

Conclusion: The independent risk factors of ERV and HRV should be considered for ED disposition in elderly UTI patients; the resistance to Empirical antibiotics was not found to affect ERV or HRV within 3 days.

(C) 2021 Published by Elsevier Inc.

  1. Introduction

Although Urinary tract infections have a relatively good out- come compared to infections of other origins, they are the most com- mon cause of infection in elderly patients who visit the emergency department (ED). UTI mostly occurs in women, but its incidence in- creases with age in men, and men older than 80 years have a similar

* Corresponding author.

E-mail addresses: [email protected] (J.Y. Myoung), [email protected] (J.Y. Hong).

infection rate as women [1,2]. UTI-induced sepsis is more common in el- derly patients than in the general population, and a considerable pro- portion of patients have died from urinary sepsis [3,4]. In elderly patients, UTI is also one of the most frequent causes of return visit to the ED and hospitalization. Return visit, often used as a quality indicator for an ED, is associated with an increased length of stay in the ED, over- crowding, and higher Healthcare costs [5,6]. Therefore, appropriate de- cision of ED disposition is essential for improving the outcome of elderly UTI patients and for Quality management of the ED.

Although recent studies have reported severity prediction models of UTI in the ED, the criteria for hospitalization for UTI remain ambiguous

https://doi.org/10.1016/j.ajem.2021.08.015 0735-6757/(C) 2021 Published by Elsevier Inc.

[7,8]. Moreover, while there have been studies about return visit to the ED and hospitalization for general disease or population, few studies have been conducted on return to the ED in elderly UTI patients.

The aim of this study was to evaluate the risk factors for early return visit to the ED within 3 days (ERV) and hospitalization after return visit (HRV) based on clinical presentation, antibiotic use, and resistance find- ings in elderly patients with UTI.

  1. Method
    1. Patients

We conducted a retrospective analysis of elderly patients with UTI, using the data of six urban teaching hospitals from the “Registry for evaluation of emergency department revisit” in South Korea, between January 2016 and December 2017.

This study was approved by the Institutional Review Board (IRB) of Chung-Ang University Hospital (IRB number: 1910-004-16284). As this study was a retrospective one, the IRB waived the need for written consent from the patients.

UTI was defined as clinically suspected UTI with pyuria (>=5 white blood cells [WBCs] per high power field) on urinalysis or isolated uri- nary pathogens with >105 colony-forming units in confirmed urine culture.

Two investigators reviewed the ED discharge records of elderly pa- tients who were discharged with a diagnosis of UTI with the following International Classification of diseases 10th Revision (ICD-10) codes: N10, N15.1, N30, N34, N39.0 or N41. Among them, patients with 1) con- comitant infections, 2) transfer to other hospital, 3) refusal to be evalu- ated, 4) frequent ED visits (at least 6 times a year), 5) discharge against medical advice, and 6) incomplete medical records were excluded.

A total 354,979 ED visits were recorded; 1502 patients were >= 65 years, with ICD-10 codes of UTI. Of these, 914 patients were hospitalized at the initial ED visit, and 169 patients were excluded on the basis of the exclusion criteria. Finally, 419 elderly UTI patients who were discharged

Fig. 1. Flow diagram of the study cohorts. ED, emergency department; UTI, urinary tract infection; ICD, International Classification of diseases.

from the ED and scheduled for an out-patient department visit were in- cluded in the analysis (Fig. 1).

    1. Data collection

Patients’ demographic characteristics and clinical data were col- lected from electronic medical records. Demographic parameters in- cluded age, sex, use of a urinary catheter, patients’ residence before visiting the ED, and comorbidities. Patients’ clinical symptoms were di- vided into UTI-specific symptoms (dysuria, frequency, urgency, flank pain) and non-specific symptoms (febrile sense, nausea and vomiting, anorexia, altered mental state, lethargy, and dizziness). In addition, lab- oratory data (C-reactive protein [CRP] levels, serum creatinine and lac- tate levels, WBC counts, and platelet count) were collected. Vital signs were collected from the initial ED triage period, and the quick Sequential Organ Failure Assessment score was calculated. To compare the empirical antibiotic use with antibiotic resistance, antibiotics used in the ED were reviewed and patients’ UTI-causing pathogens and antibi- otic resistance data collected from the urine culture analyses were analyzed.

    1. Outcomes

The primary outcomes of this study were the clinical factors asso- ciated with ERV and HRV in elderly UTI patients. In addition, we in- vestigated the antibiotic resistance of elderly UTI patients in the ED and assessed the relationship among empirical antibiotic use, ERV, and HRV.

    1. Statistical analysis

Continuous variables were compared using the student’s t-test and categorical variables were analyzed using the chi-square test or Fisher’s exact test, as appropriate. Continuous and categorical var- iables are presented as mean +- standard deviation and frequency (percentage), respectively. In addition, to determine the indepen- dent factors related to ERV and HRV in elderly patients with UTIs, a multivariate analysis was performed using a binary logistic regres- sion model. Variables with an initial P-value of <0.10 were deemed statistically significant for the univariate analysis and were included in the multivariate analysis. Odds ratios (OR) and 95% confidence in- tervals (CI) were generated from the multivariate analyses. All sta- tistical analyses were conducted using the SPSS statistics version

26.0 (IBM Corp., Armonk, NY) software package. A P-value of <0.05 was considered statistically significant.

  1. Results

Forty-five of 419 patients (10.7%) revisited the ED within 3 days (ERV) and 24 out of 419 patients (5.7%) were hospitalized after their re- turn visit (HRV) (Fig. 1). The analyzed group consisted of 95 men and 324 women, with a median age of 75 years. Table 1 shows the character- istics of ERV and HRV patients. There was no difference in the age, sex, urinary catheterization, state of residence, and comorbidities between ERV patients and scheduled revisit (SRV) patients. HRV patients had a higher incidence of renal diseases (4.8% vs. 16.7%; P = 0.04) than SRV patients. However, there was no difference in the presence of renal dis- eases between the ERV and SRV patients.

The absence of UTI-specific symptoms was significantly more com- mon in ERV and HRV patients than in SRV patients (38.5% vs. 64.4%; P < 0.001; 39.5% vs. 70.8%; P = 0.002, respectively). The absence of non-specific symptoms was significantly more common in ERV and HRV patients than in SRV patients (44.9% vs. 22.2%; P = 0.004; 44.1% vs. 16.7%; P = 0.01, respectively).

Patients with fever >=38 ?C had a higher rate of ERV and HRV than SRV (27.9% vs. 44.4%, p = 0.005 and 25.6% vs. 50.0%; P = 0.009). There was

Table 1

Baseline characteristics of the elderly patients with urinary tract infection

Characteristics

Overall

N = 419

Without ERV

N = 374

ERV

N = 45

P value

Without HRV

N = 395

HRV

N = 24

P value

Age >= 75

225(53.7)

196(52.4)

29(64.4)

0.126

210(53.2)

15(62.5)

0.373

Female gender

324(77.3)

290(77.5)

34(75.6)

0.764

305(77.2)

19(79.2)

0.825

Urinary catheter use

24(5.7)

22(5.9)

2(4.4)

1.000

27(6.1)

0(0)

0.384

Long term care facility

44(10.4)

39(10.4)

5(11.1)

0.888

42(10.6)

2(8.3)

1.000

Diabetes

138(32.9)

121(32.4)

17(37.8)

0.464

128(32.4)

10(41.7)

0.349

Cerebrovascular accident

48(11.5)

42(11.2)

6(13.3)

0.676

46(11.6)

2(8.3)

1.000

Immuno-compromise

9(2.1)

8(2.1)

1(2.2)

1.000

9(2.3)

0(0)

1.000

Renal disease

23(5.5)

19(5.1)

4(8.9)

0.293

19(4.8)

4(16.7)

0.035

Benign prostate hypertrophy

33/95(34.7)

28/84(32.1)

6/11(54.5)

0.142

30(33.3)

3(60.0)

0.338

Urinary stone

5(1.2)

5(1.3)

0(0)

1.000

5(1.3)

0(0)

1.000

Cognitive disorder

52(12.4)

45(12.0)

7(15.6)

0.498

50(12.7)

2(8.3)

0.753

Impaired daily activities

53(12.6)

46(12.3)

7(15.6)

0.535

49(12.4)

4(16.7)

0.526

ERV, early return visit within 3 days; HRV, hospitalization after revisit.

no difference between the rates of ERV and SRV in patients with systolic blood pressure <= 100 mmHg (6.1% vs. 11.1%; P = 0.208); however, HRV

Table 3

multivariate regression analysis for risk factors of ERV and HRV

was more frequent in patients with systolic blood pressure <= 100 mmHg (5% vs. 20.8%; P = 0.004).

HRVs were significantly higher in patients with CRP levels >30 mg/L (17.0% vs. 37.5%; P = 0.013). However, other laboratory findings

Early return visit within 3 days Absence of UTI-specific symptoms C-reactive protein >30 mg/L

OR

2.789

2.436

95% CI

1.368

1.124

5.687

5.281

P value

0.005

0.024

showed no difference in patients with ERVs and HRVs. Two hundred

Body temperature >= 38 ?C

1.992

1.017

3.6

0.044

and one patients had positive urine culture and 70 patients had resis- tance to empirical antibiotics used in the ED. However, there was no dif-

Hospitalization after return visit Absence of UTI-specific symptoms

3.832

1.455

10.088

0.007

ference in terms of bug-drug mismatch in both ERV and HRV groups

C-reactive protein >30 mg/L

3.224

1.235

8.419

0.017

(Table 2).

Systolic blood pressure <= 100 mmHg

3.795

1.156

12.462

0.028

Multivariate logistic regression analysis revealed that the absence of UTI-specific symptoms (OR 2.789; 95% CI 1.368-5.687; P = 0.005), CRP

levels >30 mg/L (OR 2.436; 95% CI 1.017-3.9; P = 0.024), and body temperature >= 38 ?C (OR 1.992; 95% CI 1.017-3.9; P = 0.044) were inde- pendent risk factors for ERV in elderly UTI patients. However, the ab- sence of UTI non-specific symptoms was a nonsignificant risk factor for ERV. In HRV patients, the absence of UTI-specific symptoms (OR

ERV, early return visit within 3 days; HRV, hospitalization after revisit; OR, odds ratio; CI, confidence interval.

3.832; 95% CI 1.455-10.088; P = 0.007), CRP levels >=30 mg/L (OR

3.224; 95% CI 1.235-8.419; P = 0.017), and systolic blood pressure <=

100 mmHg (OR 3.795; 95% CI 1.156-12.462; P = 0.028) were indepen-

dent risk factors (Table 3).

Table 2

Clinical presentation of the elderly patients with urinary tract infection

Overall N = 419

Without ERV N = 374

ERV

N= 45

P value

Without HRV N = 395

HRV

N= 24

P value

UTI-specific symptom Dysuria

171(40.8)

161(43.0)

10(22.2)

0.007

168(42.5)

3(12.5)

0.004

Frequency

130(31.0)

123(32.9)

7(15.6)

0.018

127(32.2)

3(12.5)

0.043

Urgency

54(12.9)

51(13.6)

3(6.7)

0.187

51(12.9)

3(12.5)

1.000

Flank pain

90(21.5)

81(21.7)

9(20.0)

0.798

86(21.8)

4(16.7)

0.798

Absence of UTI-specific symptoms

173(41.3)

144(38.5)

29(64.4)

0.001

156(39.5)

17(70.8)

0.002

Non-specific symptom Febrile sense

201(48.0)

173(46.3)

28(62.2)

0.043

186(47.1)

15(62.5)

0.142

Nausea / vomiting

49(11.7)

40(10.7)

9(20.0)

0.066

43(10.9)

6(25.0)

0.037

Anorexia

18(4.3)

16(4.3)

2(4.4)

1.000

16(4.1)

2(8.3)

0.315

Altered mental state

12(2.9)

11(2.9)

1(2.2)

1.000

11(2.8)

1(4.2)

0.512

Lethargy / dizziness

58(13.8)

50(13.4)

8(17.8)

0.418

53(13.4)

5(20.8)

0.307

Absence of non-specific symptoms

178(42.5)

168(44.9)

10(22.2)

0.004

174(44.1)

4(16.7)

0.010

Vital sign

Body temperature >= 38 ?C

113(27.0)

93(24.9)

20(44.4)

0.005

101(25.6)

12(50.0)

0.009

Systolic blood pressure <= 100 mmHg

28(6.7)

26(6.1)

5(11.1)

0.208

23(5.8)

5(20.8)

0.004

Heart rate >= 100

119(28.4)

105(28.1)

14(31.1)

0.670

112(28.4)

7(29.2)

0.932

Respiratory rate >= 22

58(13.8)

52(13.9)

6(13.3)

0.917

54(13.7)

4(16.7)

0.759

qSOFA >=2

7(1.7)

5(1.3)

2(4.4)

0.167

5(1.3)

2(8.3)

0.055

Laboratory findings Lactate >2 mmol/L

39/79(49.4)

32/68(47.1)

7/11(63.6)

0.348

35/72(48.6)

4/7(57.1)

0.666

Creatinine>1 mg/dL

117/350(33.4)

103/308(33.4)

14/42(33.3

0.989

105/326(32.2)

12/24(50.0)

0.075

C-reactive protein >30 mg/L

63/341(18.5)

51/300(17.0)

12/41(18.5)

0.058

54/317(17.0)

9/24(37.5)

0.013

White blood cell >12,000

79/348(22.7)

68/306(22.2)

11(42(26.2)

0.565

74/324(22.8)

5/24(20.8)

0.821

Platelet <=150

69/347(19.9)

59/305(19.3)

10/42(23.8)

0.497

61/323(18.9)

8/24(33.3)

0.087

ERV, early return visit within 3 days; HRV, hospitalization after revisit; UTI, urinary tract infection; qSOFA, quick sepsis related organ failure assessment.

Fig. 2. Urinary pathogens and empirical antibiotic use in elderly urinary tract infection patients in the emergency department.

Urine culture and antibiotic resistance tests were performed in 327 of 419 patients. Samples of 13 patients were contaminated, whereas 90 patients had negative culture results, and 224 patients had positive culture results. E. coli was the most common urinary or- ganism (77%), followed by Klebsiella spp. (8%) and Enterococcus spp. (6%). The most frequently prescribed empirical antibiotic was fluoroquinolone (58.6%), followed by third-generation cephalospo- rins (35.4%) (Fig. 2.).

We further investigated the influence of empirical antibiotic use and antibiotic resistance on ERV and HRV in the patients with E. coli in urine culture. The group receiving fluoroquinolone as an empirical antibiotic and the group receiving third-generation cephalosporins showed a 38.4% and 24.6% resistance to empirical antibiotics, respectively. How- ever, there was no significant difference in resistance to empirical anti- biotic in ERV and HRV patients compared to SRV patients in both antibiotic groups (Table 4).

  1. Discussion

unscheduled revisit to the ED can be affected by hospital factors such as quality of ED and patient factors such as insurance status, as well as the clinical characteristics of the disease [9-11]. However, most previous studies have investigated unschedulED revisits and hospitali- zation after ED discharge without classifying the disease. This study in- vestigated the predictors of ERVs and HRVs in elderly patients, focusing on UTI, which is one of the most common infections in the elderly in the ED. Our results showed an ERV rate of 10.7% and an HRV rate of 5.7% in

elderly UTI patients, which were higher than the ERV rate of 1.9% to 8.7% and HRV rate of 0.7% to 2% for adult patients from the general disease population [12-16]. Elderly patients and UTI patients were reported as high-risk groups for ERV and HRV; therefore, analyzing the risk factors for the overlap in these groups may be more appropriate to reduce un- scheduled revisits and hospitalization in elderly UTI patients in the ED [12,17].

In this study, lack of UTI-specific symptoms and high CRP levels were independent risk factors for ERV and HRV. Elderly patients visiting the ED often complain of non-specific symptoms, which are associated with lengthened hospitalization and poor prognosis [18-20]. As a result, diagnosing UTI in the ED is difficult. UTIs are overdiagnosed in the ED, and are more common in elderly [21,22]. Although, the gold-standard for the diagnosis of a UTI is based on the specific symptoms, elderly pa- tients often do not complain of UTI-specific symptoms. Therefore, our patient group also included clinically suspected UTI patients without specific UTI symptoms, such as occult infections with asymptomatic bacteriuria, which is common in the elderly. However, all our patients were managed for UTI as the first diagnosis, indicating that elderly UTI patients diagnosed in the ED are more likely to have higher ERV and HRV rates without UTI-specific symptoms. In addition, the patients with ERVs without UTI-specific symptoms were diagnosed with UTI at both index and return visits. Therefore, if a patient without UTI symp- toms was misdiagnosed with UTI, fewer patients with ERVs would have been included in the study than patients with SRVs diagnosed with UTI only at the index visit, which would have reduced the ERV and HRV rates of UTI-specific patients.

Table 4

Univariate analysis of ERV and HRV according to empirical antibiotic resistance in the patients with E. coli in urine culture.

Quinolone group (N = 112)

without ERV (N = 100)

ERV (N = 12)

P value

OR

95% CI

Fluoroquinolone resistance

43 (38.4)

36 (36.0)

without HRV (N = 107) 41 (38.3)

7 (58.3)

HRV (N = 5)

2 (40.0)

0.133

1

2.489

1.073

0.736

0.172

8.414

6.698

3rd cephalosporin resistance

Cephalosporin group (N = 69)

17 (24.6)

without ERV (N = 55)

15 (27.3)

ERV (N = 14)

2 (14.3)

0.491

0.444

0.089

2.224

without HRV (N = 60) 15 (25.0)

HRV (N = 9)

2 (22.2)

1

0.857

0.16

4.583

ERV, early return visit within 3 days; HRV, hospitalization after revisit; OR, odds ratio; CI, confidence interval.

CRP is a well-known biomarker for the diagnosis and severity assess- ment of bacterial infections, including UTI [24,25]. Even a relatively low CRP level influences the frequency of return visit to the ED within 7 days [23]. Similarly, we showed that a CRP level >= 30 mg/L is an independent risk factor for ERV and HRV in elderly UTI patients. CRP can be easily assessed in patients with infections in the ED and is therefore useful as a screening tool to predict ERV and HRV in elderly UTI patients. Thus, emergency physicians should consider CRP when determining the disposition of ED patients.

In our study, patients with an initial low systolic blood pressure were not diagnosed with septic shock and were scheduled to be discharged at the index visit due to suspected transient hypotension. However, sev- eral studies have reported that undifferentiated transient hypotension increases the severity of infectious diseases [26-28]. Additionally, our results showed that a systolic blood pressure below 100 mmHg is an in- dependent risk factor for HRV. Elderly UTI patients with transient hypo- tension need more attention in determining ED disposition.

Fever is one of the most common complaints in the ED, and there are many reports on the association between fever and return visit [12,29]. In our study, fever was found to be a risk factor for ERV, but not for HRV. Contrary to common perceptions, recent studies have reported that the increase in body temperature has a strong inverse association with mor- tality [27,30]. These studies were conducted on patients with severe sepsis, and the association between fever and severity in UTI patients discharged from the ED requires further studies.

Although the use of antimicrobial agents is the most important treatment to eliminate the pathogens causing UTIs, selecting antibi- otics is challenging because the results of antibiotic resistance from urine culture cannot be obtained in the ED and patient information is relatively insufficient [31,32]. Furthermore, elderly patients have higher antibiotic resistance than the general population [33]. There- fore, we hypothesized that ERV and HRV in elderly UTI patients may be affected by antibiotic resistance and selection of empirical antibi- otics. In our results, the most commonly used empirical antibiotics in the ED were fluoroquinolone and third-generation cephalosporins, and the antibiotic resistance of E. coli, which accounts for 76.8% of the pathogens in urine culture, was 44.2% for ciprofloxacin and 25.0% for cefotaxime, both showing more than 20% antibiotic resis- tance. However, ERV and HRV were not significantly associated by empirical antibiotic resistance in either the quinolone group or the third-generation cephalosporin group. This study analyzed the data of patients who revisited the ED within 3 days of the index visit, which is a relatively Short period of time. Moreover, bacteremia is common in elderly patients, and it takes more time for urinary con- centration of antibiotics to reach the appropriate serum concentra- tion. Therefore, return visit to the ED within 3 days may not be enough to analyze the effectiveness of antibiotics. In uncomplicated UTIs, Symptomatic treatment with drugs other than antibiotics, such as NSAIDs, is controversial, but several studies have reported it to be effective [34,35]. Accordingly, the effectiveness of antibiotics is rela- tively low in patients discharged from the ED at the index visit. Therefore, the selection of empirical antibiotics is important in UTI patients; however, it may not be a risk factor for ERV and HRV to the ED within three days.

Our study is subject to several limitations. First, our study had a ret- rospective design and it may have had information bias. However, our data were extracted form electronic medical records, which might limit the errors of classification or variables measurement. Second, ERV was considered in the patients who revisited the same hospital of the index visit and not in those who revisited a different hospital. One study showed that the percentage of patients who returned to a differ- ent hospital for their return visit was 17.4% of all the return visits within 7 days [36]. Although our patients were scheduled for an out-patient

department visit at the same hospital and the period of ERV was 3 days, which was shorter than 7 days, it may have affected the result by classifying patients who revisited a different hospital as SRV. Third, this study was conducted with patients from 6 urban hospital in adja- cent regions. Thus, our results, affected by regional characteristics such as antibiotic resistance, may not be applicable to elderly UTI patients in other regions.

  1. Conclusion

This retrospective study investigated the risk factors for ERV and HRV, which are common among elderly patients with UTI. The absence of UTI-specific symptoms and elevated CRP levels were risk factors for ERV and HRV. High initial body temperature and transient hypotension were risk factors for ERV and HRV, respectively. Therefore, these risk factors should be considered more strongly when deciding to discharge an elderly UTI patient from the ED. In addition, elderly UTI patients who visit the ED have higher antibiotic resistance and bug-drug mismatch; however, the use of resistant empirical antibiotics does not affect ERV or HRV.

Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (No. 2020R1G1A1103080).

Declaration of Competing Interest

None.

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