Abstract
-
Objective
Urinary tract infections are a common consideration when assessing pediatric patients with fever. With rising resistance rates and increased focus on antibiotic stewardship, current management needs to be better understood. This study reports the incidence and antibiotic distribution in a nationwide cohort of pediatric emergency department (ED) patients with cystitis and pyelonephritis during an 8-year period.
-
Methods
We performed a cohort study from January 1, 2016, to December 31, 2023, using Epic Cosmos data. Pediatric ED patients (<18 years) with an ICD-10 code corresponding to cystitis or pyelonephritis were included. The outcomes were the total number of ED presentations, outpatient antibiotic prescriptions, and antibiotics administered in the ED for patients admitted with cystitis or pyelonephritis. Binary logistic regression models were used to measure the relationship between the year and the dependent variables.
-
Results
Among 46,774,814 total pediatric ED visits, 720,863(1.5%) were for cystitis, and 82,717 (0.2%) were for pyelonephritis. Among those admitted, the most common antibiotics were third-generation cephalosporins (cystitis, 55.6%; pyelonephritis, 62.3%), first-generation cephalosporins (cystitis, 13.8%; pyelonephritis, 13.7%), and ampicillin (cystitis, 10.8%; pyelonephritis, 6.6%). First-generation cephalosporin use rose over time, while ampicillin and ciprofloxacin use declined. Among discharged patients, the most common antibiotics were first-generation cephalosporins (cystitis, 43.1%; pyelonephritis, 33.7%), third-generation cephalosporins (cystitis, 20.8%; pyelonephritis, 25.8%), and trimethoprim-sulfamethoxazole (cystitis, 13.5%; pyelonephritis, 11.7%). First-generation cephalosporin use rose over time, while trimethoprim-sulfamethoxazole and ciprofloxacin use declined. Among those with cystitis specifically, the use of third-generation cephalosporins declined over time.
-
Conclusion
Cystitis and pyelonephritis remain common ED presentations, representing nearly 2% of all pediatric ED visits, and antibiotic selection has shifted notably over time. Understanding the current epidemiology can inform public health planning and antibiotic stewardship in the ED.
-
Keywords: Epidemiology; Urinary tract infection; Cystitis; Pyelonephritis; Pediatric
Capsule Summary
What is already known
Pediatric urinary tract infections are a common reason for presentation to the emergency department.
What is new in the current study
From 2016–2023, urinary tract infections accounted for nearly 2% of all pediatric emergency department visits, and the most common antibiotics varied by cystitis versus pyelonephritis and admission versus discharge.
INTRODUCTION
Urinary tract infections (UTIs) are a common consideration in the differential diagnosis of fever because they are among the most common bacterial infections in the pediatric population [
1]. Among infants presenting with fever, UTI can be present in up to 7% of patients [
2]. UTIs remain common throughout childhood, with a pooled prevalence of UTI in the pediatric population of 7.8% [
2].
UTIs vary in severity, ranging from cystitis (an infection localized to the bladder) to pyelonephritis (extension to the kidneys, often requiring different and longer courses of antibiotics). However, most studies have combined these conditions, limiting the ability to delineate the prevalence of cystitis and pyelonephritis [
2,
3]. Moreover, UTIs are a leading cause of antibiotic prescriptions for pediatric patients and a major risk for antibiotic resistance [
3]. Therefore, it is critical to understand the current epidemiology of both cystitis and pyelonephritis and the current antibiotic usage trends to inform healthcare planning and antibiotic stewardship efforts.
Updated research is thus needed to understand the treatments being prescribed for pediatric cystitis and pyelonephritis in emergency departments (EDs). To meet that need, we examined the current incidence and antibiotic prescribing practices for cystitis and pyelonephritis in EDs.
METHODS
Ethics statement
The Institutional Review Board of Rush University Medical Center deemed this study as nonhuman subject research and waived the requirement for informed consent. This study adheres to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guidelines [
4].
We conducted a cohort study of pediatric visits to United States EDs for cystitis and pyelonephritis and the associated treatments and dispositions across an 8-year period using the Cosmos research platform (Epic Systems Corp). Cosmos is a large database that aggregates electronic health record data voluntarily submitted by health systems for the purposes of research. Cosmos data are representative of the United States population and consistent with national census data. At the time of submission, the Cosmos database included more than 289 million patients across 39,000 hospitals and clinics. Patients with records at multiple institutions are deduplicated and anonymized centrally by Epic.
We performed queries of Cosmos using the International Classification of Diseases, 10th Revision (ICD-10) codes corresponding to cystitis (
Suppl. 1) and pyelonephritis (
Suppl. 2) from January 1, 2016, to December 31, 2023. We selected this time period based on the launch of ICD-10 coding requirements in October 2015. The inclusion criteria were pediatric patients (<18 years) with an ED presentation within the United States and an associated ICD-10 code corresponding to cystitis or pyelonephritis.
We analyzed the incidence of cystitis and pyelonephritis presentations, antibiotic treatment, and disposition. Antibiotics were categorized based on their classes and separately analyzed for admitted and discharged patients. Discharge antibiotics were based on prescriptions. Analyses were further subgrouped by age (<2 years vs. ≥2 years) to account for differences in antibiotic prescribing. We used binary logistic regression models to measure the relationship between the year and the dependent variables (i.e., ED encounters due to cystitis, ED encounters due to pyelonephritis, antibiotics). Data are reported as odds ratios (ORs) with 95% confidence intervals (CIs). Analyses were performed with IBM SPSS ver. 26.0 (IBM Corp).
RESULTS
Of 46,774,814 ED encounters with pediatric patients during the 8-year period, 720,863 (1.5%) were due to cystitis, and 82,717 (0.2%) were due to pyelonephritis, with both diseases experiencing a slight rise over time (cystitis: OR, 1.006 [95% CI, 1.005–1.007]; pyelonephritis: OR, 1.019 [95% CI, 1.016–1.022]) (
Suppls. 3–
8). The highest rate was seen in 2020, when cystitis was present in 1.7% of visits and pyelonephritis in 0.2%. The demographics of the study populations with cystitis and pyelonephritis are reported in
Tables 1 and
2.
For patients with cystitis who were admitted, the most common antibiotic class was third-generation cephalosporins (55.6%), followed by first-generation cephalosporins (13.8%) and ampicillin (10.8%). When evaluated over time, there was a notable rise in the use of first-generation cephalosporins (8.3% to 18.5%; OR, 1.157 [95% CI, 1.140–1.175]), fourth-generation cephalosporins (2.7% to 7.8%; OR, 1.146 [95% CI, 1.121–1.171]), meropenem (2.1% to 4.7%; OR, 1.107 [95% CI, 1.077–1.138]), and ertapenem (0.5% to 1.3%; OR, 1.149 [95% CI, 1.085–1.217]) (
Fig. 1A,
Suppl. 9). There was a decline in the use of third-generation cephalosporins (59.2% to 52.6%; OR, 0.962 [95% CI, 0.953–0.972]), ampicillin (13.0% to 9.4%; OR, 0.953 [95% CI, 0.938–0.968]), ciprofloxacin (4.0% to 2.6%; OR, 0.954 [95% CI, 0.929–0.981]), and second-generation cephalosporins (1.1% to 0.5%; OR, 0.864 [95% CI, 0.811–0.920]). When analyzed by age (<2 years vs. ≥2 years), antibiotic selection was similar overall; however, ampicillin (18.0% vs. 3.8%) and gentamicin (9.6% vs. 4.0%) were more commonly prescribed to those <2 years, while fourth-generation cephalosporins (4.4% vs. 8.2%) and piperacillin-tazobactam (1.3% vs. 5.6%) were more commonly prescribed to those ≥2 years (
Suppls. 10,
11).
For patients with pyelonephritis who were admitted, the most common antibiotic class was third-generation cephalosporins (62.3%), followed by first-generation cephalosporins (13.7%) and ampicillin (6.6%). When evaluated over time, there was a notable rise in the use of first-generation cephalosporins (8.4% to 13.7%; OR, 1.155 [95% CI, 1.132–1.178]), fourth-generation cephalosporins (2.1% to 6.1%; OR, 1.186 [95% CI, 1.145–1.228]), and meropenem (2.1% to 3.8%; OR, 1.085 [95% CI, 1.045–1.127]) (
Fig. 1B,
Suppl. 12). There was a decline in the use of third-generation cephalosporins (66.3% to 59.9%; OR, 0.963 [95% CI, 0.950–0.976]), ampicillin (8.4% to 6.0%; OR, 0.947 [95% CI, 0.923–0.971]), and second-generation cephalosporins (1.1% to 0.8%; OR, 0.881 [95% CI, 0.820–0.946]). When analyzed by age (<2 years vs. ≥2 years), antibiotic selection was similar overall; however, ampicillin (14.0% vs. 3.8%) and gentamicin (6.2% vs. 3.7%) were more commonly prescribed to those <2 years, while piperacillin-tazobactam (1.0% vs. 4.6%) was more commonly prescribed to those ≥2 years (
Suppls. 13,
14).
Among discharged patients with cystitis, the most common antibiotic class was first-generation cephalosporins (43.1%), followed by third-generation cephalosporins (20.8%), trimethoprim-sulfamethoxazole (13.5%), and nitrofurantoin (7.8%). When evaluated over time, there was a notable rise in the use of first-generation cephalosporins (29.4% to 50.7%; OR, 1.144 [95% CI, 1.141–1.146]) (
Fig. 2A,
Suppl. 15). The use of most other antibiotics declined, including trimethoprim-sulfamethoxazole (22.4% to 8.4%; OR, 0.841 [95% CI, 0.838–0.843]), nitrofurantoin (8.9% to 6.7%; OR, 0.947 [95% CI, 0.944–0.951]), amoxicillin-clavulanate (4.3% to 2.8%; OR, 0.953 [95% CI, 0.948–0.958]), second-generation cephalosporins (3.0% to 1.7%; OR, 0.869 [95% CI, 0.863–0.876]), and ciprofloxacin (2.9% to 1.4%; OR, 0.841 [95% CI, 0.833–0.848]). When analyzed by age (<2 years vs. ≥2 years), antibiotic selection was similar overall; however, third-generation cephalosporins (33.1% vs. 19.1%) were more commonly prescribed to those <2 years, while trimethoprim-sulfamethoxazole (6.5% vs. 14.5%), and nitrofurantoin (0.8% vs. 8.9%) were more commonly prescribed to those ≥2 years (
Suppls. 16,
17).
Because most children younger than 2 years with pyelonephritis are admitted, we focused the analyses of discharge prescriptions for pyelonephritis on those aged 2 to 17 years. For this population, the most common antibiotic was first-generation cephalosporins (33.7%), followed by third-generation cephalosporins (25.8%), trimethoprim-sulfamethoxazole (11.7%), and ciprofloxacin (6.9%) (
Fig. 2B,
Suppl. 18). When evaluated over time, there was a notable rise in the use of first-generation cephalosporins (24.2% to 36.5%; OR, 1.071 [95% CI, 1.062–1.079]) and third-generation cephalosporins (21.8% to 27.8%; OR, 1.055 [95% CI, 1.046–1.064]) and a decline in the use of trimethoprim-sulfamethoxazole (14.7% to 10.5%; OR, 0.934 [95% CI, 0.923–0.944]), ciprofloxacin (13.5% to 5.3%; OR, 0.852 [95% CI, 0.840–0.865]), and second-generation cephalosporins (3.9% to 2.9%; OR, 0.976 [95% CI, 0.956–0.997]).
DISCUSSION
In a large, nationally representative sample of more than 46 million pediatric visits to the ED, several key findings were identified. Overall, cystitis and pyelonephritis represented nearly 2% of all visits, with a slight rise over time. Interestingly, a spike in the incidence occurred in 2020, which coincided with a decrease in total pediatric ED visits. This might reflect decreased overall ED use during the COVID-19 pandemic, which thus resulted in a higher proportion of visits for UTIs without an absolute increase in the number of diagnoses.
Among those admitted for cystitis or pyelonephritis, the majority received a third-generation cephalosporin. This is consistent with common practice and guidelines from the American Academy of Pediatrics [
5]. Interestingly, the use of third-generation cephalosporins has decreased over time, and the use of first-generation cephalosporins has increased. This might reflect successful efforts to improve antibiotic stewardship because many pediatric UTIs are caused by
Escherichia coli, which is often susceptible to first-generation cephalosporins and might not require broader-spectrum agents [
6]. First-generation cephalosporins are also associated with a reduced risk of adverse events, including the development of
Clostridioides difficile [
7]. Similar declines were seen in trimethoprim-sulfamethoxazole prescriptions for cystitis, which might reflect rising resistance against this agent in pediatric UTIs [
8].
Ciprofloxacin use has also declined. This finding is consistent with other national data showing reductions in fluoroquinolone use [
9]. This shift could reflect recent data demonstrating rising resistance against fluoroquinolones by UTIs [
10]. It might also be influenced by increased recognition of the adverse events associated with fluoroquinolones, including corrected QT interval prolongation and tendinopathy [
11]. Moreover, the American Academy of Pediatrics has advised clinicians to avoid fluoroquinolones except for the treatment of infections for which no safe and effective alternative exists [
12].
Although the use of narrow-spectrum antibiotics (e.g., first-generation cephalosporins) has risen in multiple patient populations, we also found a rise in the use of broader-spectrum antibiotics, such as meropenem, that are often reserved for multidrug resistant organisms [
13]. This might reflect attempts to improve antibiotic stewardship with narrowing antibiotics when appropriate, but it could also reflect a rise in multidrug resistant organisms in general. Further research is needed to determine changes in resistance patterns and determine how antibiotic selection changes based on culture sensitivities.
This study has several important limitations. Although the Cosmos database is representative of the United States population with regards to age, race, and ethnicity, it is limited to organizations that use Epic for their electronic health records and opt to contribute data to Cosmos. Thus, there is the potential for selection bias toward patients that seek care at such institutions, and the data might not fully reflect the entire cohort of pediatric patients with cystitis or pyelonephritis in the United States. Additionally, patients who were transferred to pediatric EDs that did not use Epic or were not part of the Cosmos database do not have available data on the antibiotics administered or prescribed. Moreover, ICD-10 codes were used to identify cases of cystitis and pyelonephritis. Relevant cases that were incorrectly coded might thus have been missed. Cases that were miscoded might also have led to incorrect crossover between cystitis and pyelonephritis. Finally, we were unable to separate out concomitant disease processes or other factors that might have influenced decisions about disposition or antibiotic selection.
Conclusions
Cystitis and pyelonephritis remain common ED presentations, representing nearly 2% of all pediatric ED visits with a slight rise over time. First- and third-generation cephalosporins remain the most commonly prescribed antibiotics, though there have been notable shifts in the prescribing of antibiotics over time. Understanding the current epidemiology can inform public health planning and antibiotic stewardship in the ED.
NOTES
-
Author contributions
Conceptualization: all authors; Investigation: all authors; Project administration: all authors; Supervision: MG; Visualization: all authors; Writing–original draft: all authors; Writing–review & editing: all authors. All authors read and approved the final manuscript.
-
Conflicts of interest
Michael Gottlieb is an editorial board member of this journal, but was not involved in the peer reviewer selection, evaluation, or decision process of this article. The authors have no other conflicts of interest to declare.
-
Funding
The authors received no financial support for this study.
-
Data availability
Data analyzed in this study are available within the article and its supplementary materials.
Supplementary materials
Suppl. 3.
Incidence of cystitis among emergency department all pediatric patients from 2016–2023.
ceem-25-055-Suppl-3.pdf
Suppl. 4.
Incidence of cystitis among emergency department pediatric patients aged <2 years from 2016–2023.
ceem-25-055-Suppl-4.pdf
Suppl. 5.
Incidence of cystitis among emergency department pediatric patients 2–17 years of age from 2016–2023.
ceem-25-055-Suppl-5.pdf
Suppl. 6.
Incidence of pyelonephritis among emergency department all pediatric patients from 2016–2023.
ceem-25-055-Suppl-6.pdf
Suppl. 7.
Incidence of pyelonephritis among emergency department pediatric patients aged <2 years from 2016–2023.
ceem-25-055-Suppl-7.pdf
Suppl. 8.
Incidence of pyelonephritis among emergency department pediatric patients 2–17 years of age from 2016–2023.
ceem-25-055-Suppl-8.pdf
Suppl. 9.
Antibiotic medication classes administered among emergency department pediatric patients 0-18 years admitted with cystitis from 2016–2023.
ceem-25-055-Suppl-9.pdf
Suppl. 10.
Antibiotic medication classes administered among emergency department pediatric patients <2 years admitted with cystitis from 2016–2023.
ceem-25-055-Suppl-10.pdf
Suppl. 11.
Antibiotic medication classes administered among emergency department pediatric patients 2–17 years admitted with cystitis from 2016–2023.
ceem-25-055-Suppl-11.pdf
Suppl. 12.
Antibiotic medication classes administered among emergency department pediatric patients 0–17 years admitted with pyelonephritis from 2016–2023.
ceem-25-055-Suppl-12.pdf
Suppl. 13.
Antibiotic medication classes administered among emergency department pediatric patients <2 years admitted with pyelonephritis from 2016–2023.
ceem-25-055-Suppl-13.pdf
Suppl. 14.
Antibiotic medication classes administered among emergency department pediatric patients 2–17 years admitted with pyelonephritis from 2016–2023.
ceem-25-055-Suppl-14.pdf
Suppl. 15.
Antibiotic prescriptions among discharged emergency department pediatric patients 0–17 years with cystitis from 2016–2023.
ceem-25-055-Suppl-15.pdf
Suppl. 16.
Antibiotic prescriptions among discharged emergency department pediatric patients <2 years with cystitis from 2016–2023.
ceem-25-055-Suppl-16.pdf
Suppl. 17.
Antibiotic prescriptions among discharged emergency department pediatric patients 2–17 years with cystitis from 2016–2023.
ceem-25-055-Suppl-17.pdf
Suppl. 18.
Antibiotic prescriptions among discharged emergency department pediatric patients 2–17 years with pyelonephritis from 2016–2023.
ceem-25-055-Suppl-18.pdf
Fig. 1.Antibiotic medication classes administered to pediatric patients in the emergency department (2016–2023). (A) Admitted with cystitis. (B) Admitted with pyelonephritis.
Fig. 2.Antibiotic prescriptions to pediatric patients in the emergency department (2016–2023). (A) Discharged with cystitis. (B) Discharged with pyelonephritis.
Table 1.Demographics of the pediatric patients (<18 years) with cystitis
Table 1.
|
Demographic |
No. of patients (%)
|
|
Total (n=720,863) |
<2 yr (n=101,120) |
≥2 yr (n=619,743) |
|
Sex |
|
|
|
|
Female |
648,497 (90.0) |
73,350 (72.5) |
575,147 (92.8) |
|
Male |
72,280 (10.0) |
27,764 (27.5) |
44,516 (7.2) |
|
Other/not reported |
86 (0.0) |
6 (0.0) |
80 (0.0) |
|
Racea)
|
|
|
|
|
American Indian/Alaskan Native |
10,367 (1.4) |
1,357 (1.3) |
9,010 (1.5) |
|
Asian |
18,985 (2.6) |
4,826 (4.8) |
14,159 (2.3) |
|
Black/African American |
181,269 (25.1) |
19,142 (18.9) |
162,127 (26.2) |
|
Native Hawaiian/other Pacific Islander |
5,769 (0.8) |
1,198 (1.2) |
4,571 (0.7) |
|
White |
450,131 (62.4) |
62,217 (61.5) |
387,914 (62.6) |
|
Other |
138,336 (19.2) |
22,601 (22.4) |
115,735 (18.7) |
|
Not reported |
18,143 (2.5) |
3,879 (3.8) |
14,264 (2.3) |
|
Ethnicity |
|
|
|
|
Hispanic or Latino |
173,812 (24.1) |
32,546 (32.2) |
141,266 (22.8) |
|
Other |
507,086 (70.3) |
62,314 (61.6) |
444,772 (71.8) |
|
Not reported |
39,965 (5.5) |
6,260 (6.2) |
33,705 (5.4) |
|
Insurancea)
|
|
|
|
|
Private/other |
412,324 (57.2) |
58,736 (58.1) |
353,588 (57.1) |
|
Medicaid |
298,214 (41.4) |
42,077 (41.6) |
25,6137 (41.3) |
|
Medicare |
603 (0.1) |
113 (0.1) |
490 (0.1) |
|
Self-pay |
23,973 (3.3) |
1,698 (1.7) |
22,275 (3.6) |
|
Not reported |
12,722 (1.8) |
1,343 (1.3) |
11,379 (1.8) |
|
US Census Bureau–designated region |
|
|
|
|
South |
375,914 (52.1) |
53,654 (53.1) |
322,260 (52.0) |
|
Midwest |
188,226 (26.1) |
20,366 (20.1) |
167,860 (27.1) |
|
Northeast |
85,035 (11.8) |
13,009 (12.9) |
72,026 (11.6) |
|
West |
70,835 (9.8) |
13,933 (13.8) |
56,902 (9.2) |
|
Not reported |
853 (0.1) |
158 (0.2) |
695 (0.1) |
Table 2.Demographics of pediatric patients (<18 years) with pyelonephritis
Table 2.
|
Demographic |
No. of patients (%)
|
|
Total (n=82,717) |
<2 yr (n=12,130) |
≥2 yr (n=70,587) |
|
Sex |
|
|
|
|
Female |
73,660 (89.1) |
8,537 (70.4) |
65,123 (92.3) |
|
Male |
9,041 (10.9) |
3,593 (29.6) |
5,448 (7.7) |
|
Other/not reported |
16 (0.0) |
0 (0) |
16 (0.0) |
|
Racea)
|
|
|
|
|
American Indian or Alaskan Native |
1,293 (1.6) |
176 (1.5) |
1,117 (1.6) |
|
Asian |
2,458 (3.0) |
781 (6.4) |
1,677 (2.4) |
|
Black or African American |
14,074 (17.0) |
1,888 (15.6) |
12,186 (17.3) |
|
Native Hawaiian or other Pacific Islander |
764 (0.9) |
199 (1.6) |
565 (0.8) |
|
White |
59,107 (71.5) |
7,548 (62.2) |
51,559 (73.0) |
|
Other |
14,518 (17.6) |
2,853 (23.5) |
11,665 (16.5) |
|
Not reported |
1,855 (2.2) |
427 (3.5) |
1,428 (2.0) |
|
Ethnicity |
|
|
|
|
Hispanic or Latino |
17,997 (21.8) |
4,052 (33.4) |
13,945 (19.8) |
|
Other |
60,163 (72.7) |
7,316 (60.3) |
52,847 (74.9) |
|
Not reported |
4,557 (5.5) |
762 (6.3) |
3,795 (5.4) |
|
Insurancea)
|
|
|
|
|
Private or other |
51,770 (62.6) |
7,276 (60.0) |
44,494 (63.0) |
|
Medicaid |
30,640 (37.0) |
4,784 (39.4) |
25,856 (36.6) |
|
Medicare |
85 (0.1) |
16 (0.0) |
69 (0.1) |
|
Self-pay |
2,336 (2.8) |
152 (1.3) |
2,184 (3.1) |
|
Not reported |
1,482 (1.8) |
243 (2.0) |
1,239 (1.8) |
|
US Census Bureau–designated region |
|
|
|
|
South |
37,583 (45.4) |
5,962 (49.2) |
31,621 (44.8) |
|
Midwest |
21,204 (25.6) |
2,053 (16.9) |
19,151 (27.1) |
|
Northeast |
11,563 (14.0) |
1,782 (14.7) |
9,781 (13.9) |
|
West |
12,282 (14.8) |
2,315 (19.1) |
9,967 (14.1) |
|
Not reported |
85 (0.1) |
18 (0.1) |
67 (0.1) |
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