a b s t r a c t

Background: antibiotic stewardship programs have been a major focus in recent years to curtail antibiotic resis- tance. The purpose of this study was to evaluate antibiotic utilization for acute respiratory tract infections (ARTI) in the Emergency Department (ED) setting.

Material and methods: A retrospective analysis of adult ARTI visits to EDs utilizing 2011-2017 National Hospital Ambulatory Medical Care Survey- Emergency Department (NHAMCS-ED) datasets was conducted. Included were all visits of adults (>=18 years) diagnosed with ARTI. Antibiotics were determined based upon NHAMCS- ED use of the Multum Lexicon Drug Database Coding system. All significance tests were two-sided, P-value

<0.05 for significance.

Results: A total of 4632 unweighted ED visits, which represented more than 28 million US ED visits from 2011 to 2017, with 57.2% receiving a prescription for antibiotics. Antibiotic prescriptions for ARTI significantly declined from 65.8% in 2011 to 54.3% in 2017 (P = 0.046). Among all visits, patients were more likely to receive an anti- biotic if they were over age 45 (33.0% vs 27.6%, P = 0.005), male (36.7% vs. 32.3%, P = 0.039), and presenting in a non-MSA ED (21.4% vs. 14.5%, P = 0.002). No association was found between antibiotic prescription and race (P = 0.076) insurance (P = 0.488), CBC (P = 0.148), x-ray (P = 0.278), and blood cultures (P = 0.182).

Conclusion: We found a significant reduction in the utilization of antibiotics among adult ARTI visits to U.S. EDs from 2011 to 2017. This is an improvement from previous studies which showed no change, suggesting that an- timicrobial stewardship efforts may be impacting overall antibiotic use and should continue to be practiced.

(C) 2021

1. Introduction

Antimicrobial resistance has been a growing concern- it is the cause of over 700,000 deaths per year worldwide [1]. In the U.S., it is estimated that more than 2.8 million antibiotic resistant infections occur each year, leading to 35,000 deaths [2]. The ED is an important component of antibiotic stewardship because it serves as an entry point for many patients into the hospital and is a primary location for acute care en- counters. It is estimated that roughly half of all medical encounters occur in the ED with more than 1 in 8 encounters resulting in the utili- zation of antibiotics [3,4]. Assessment and interventions on Prescription use in the ED setting has been a topic of interest as it has not been ade- quately represented as a focus for Antimicrobial stewardship efforts, and in the past it has been slow to change. Recent studies have found that between the years of 2001 and 2010 the use of antibiotics in the

* Corresponding author at: Department of Family & Community Medicine, University of North Dakota School of Medicine, 1301 North Columbia Road, Stop 9037, Grand Forks, ND 58202-9037, USA.

E-mail address: [email protected] (J.R. Beal).

outpatient setting have decreased while antibiotic prescription use in the ED setting has not [1,5,6].

Some conditions such as viral and bacterial acute respiratory tract infections (ARTI), often have a similar presentation that can result in the unnecessary utilization of antibiotics [7]. Between the years of 1995 and 2000, inappropriate Antibiotic prescribing in the Emergency Department (ED) setting for ARTI was found to be comparable to other Primary care settings [8].

We would expect with the increasing pressure to practice antibiotic stewardship, inappropriate antibiotic prescribing has decreased over the past decade. The purpose of this study was to determine recent trends and risk factors for antibiotic utilization for adult acute respira- tory tract infections in United States Emergency Departments.

1. Material and methods

A retrospective analysis of ARTI visits to EDs utilizing National Hos- pital Ambulatory Medical Care Survey-Emergency Departments (NHAMCS-ED) datasets was conducted. The NHAMCS-ED is a national survey whose findings are based on a sample of visits to non-federally

https://doi.org/10.1016/j.ajem.2021.03.018

0735-6757/(C) 2021

employed office-based physicians who are primarily engaged in direct patient care and a separate sample of visits to community health centers. Inclusion criteria were all visits by adults, 18 years of age or older, diag- nosed an ARTIs. Exclusion criteria were visits by children (<18 years) and adults not diagnosed with an ARTIs. Our ARTIs diagnosis classifica- tions were patterned primarily after the study by Donnelly et al. [1] and previous studies [5,8] that used the NHAMCS-ED to examine ARTI’s in both children and adults. Diagnoses that fell under the category of ARTIs included: Otitis media (ICD-9381-382.02/ICD10 H65-H67), tonsil- litis (463/J03), sinusitis (461/J01), pharyngitis (472/J02) non-viral pneu- monia (481-485/J13-J18), nasopharyngitis (460), unspecified URI (465/ J06), bronchitis (466.0/J20), bronchiolitis (466.11/J21), viral pneumonia (480/J12), and influenza (488-488.02/J09-J11). Prescription rates for antibiotic treatment for ARTI were analyzed between 2011 and 2017. The antibiotics prescribed were based upon NHAMCS-ED’s Multum Lexicon Drug Database coding system included: penicillins, cephalo- sporins, macrolides, sulfonamides, lincomycin derivatives, quinolones, other (carbapenems, aminoglycosides, glycylcyclines, glycopeptides, leprostatics, urinary anti-infectives, miscellaneous). Data collected for analysis included: patient age, gender, race, insurance status, diagnosis, patient seen in last 72 h, and metropolitan statistical area (MSA) status- a city of at least 50,000 population and surrounding counties with a high degree of economic integration. Also, if the patient received diagnostic service of complete blood count , blood culture, or X-ray. SPSS Complex Samples 26.0 was used to analyze the data in a man- ner that accounts for the NHAMCS-ED complex sample survey design. Analysis was performed using summary statistics and bivariate compar- isons (Chi-square tests) as well as Likelihood ratio for trend analysis. All significance tests were two-sided, P-value <0.05 for significance. The survey data was analyzed using the sampled visit weight that was the product of the corresponding sampling fractions at each stage in the sample design. Sampling errors were determined using the appro- priate survey procedure following the guidance of the NHAMCS-ED doc- umentation, which takes into account the clustered nature of the sample. This study was approved by the Institutional Review Board

from the University of North Dakota.

1. Results

We analyzed 4632 unweighted ED visits, which represented more than 28 million visits to U.S. emergency departments from 2011 to

2017. For all patient visits, the mean age was 38 years, majority were fe- male (65.2%), white (64%), had government based insurance (50.9%), lived in a metropolitan statistical area (MSA) (81.5%) and not seen in the ED within the last 24 h (97.3%). Overall, 57.2% of visits resulted in the patients receiving a prescription for antibiotics. The rate of antibiotic prescriptions significantly declined from 65.8% in 2011 to 54.3% in 2017 (P = 0.046) (Fig. 1).

There was an association with patients receiving antibiotics and age with those given antibiotics were significantly older than those not given antibiotics, 39.6 vs. 37.2 years (P = 0.003, Table 1). Those re- ceiving antibiotics were more likely to be male compared to those not receiving antibiotics, 36.7% vs. 32.3% (P = 0.039, Table 1). Race (P = 0.076). Receiving an antibiotic was more likely to occur in non- metropolitan statistical area (non-MSA), 21.4% vs. 14.5% (P = 0.002, Table 1). Receiving an antibiotic prescription was not associated with race (P = 0.076), insurance status (P = 0.488), and patient receiving diagnostic services of CBC (P = 0.148), blood cultures (P = 0.182) or X-ray (P = 0.278) (Table 1).

1. Discussion

We found that the utilization rate of antibiotics for ARTI among adult visits to U.S. EDs decreased between 2011 and 2017 from 65.8% to 54.3% (Fig. 1). This is an improvement from a similar study conducted by Donelly, et al. which found that antibiotic prescription use in the ED be- tween 2001 and 2010 had not changed significantly [1]. This decrease may be largely the result of local and national antibiotic stewardship ef- forts such as the CDC’s “Core Elements for Hospital Antibiotic Steward- ship Programs” and choosing wisely‘s antibiotic overuse campaign, among others [9,10].

Whites, females and mean age less than 40 years represented the majority of patient demographics. This was comparable to the study re- sults by Donelly, et al. which listed white females with a younger mean age as representing the majority of the study [1]. Although females more commonly presented to the ED, male gender was found to be a risk factor for being prescribed an antibiotic. Although females were found to be more likely to present to the ED compared to males, males were more likely to be prescribed an antibiotic. This is comparable to previous studies which also found males were more likely to receive an antibiotic [11]. It is important to recognize trends in demographics as antibiotic utilization could be related to a clinician’s unconscious bias.

Percentage

Fig. 1. Antibiotic rates for adult respiratory tract infections visits in United States Emergency Departments, 2011-2017.

70

65

60

55

50

45

40

2011

2012

2013

2014

Year P=0.046

2015

2016

2017

Table 1

Characteristics of adult visits prescribed antibiotics for respiratory tract infections in United States Emergency Department, 2011-2017.

necessary to further elucidate any trends or prescribing biases based on age.

In conclusion, we found prescribing rates of antibiotics for ARTI in

Total Visits Antibiotics

Given

Antibiotics Not Given

P-value

U.S. EDs declined significantly from 2011 to 21,017, suggesting that an- timicrobial stewardship efforts may be impacting overall antibiotic use

Est. =

28,025,319

UWN = 4632

Est. =

16,021,979

UWN = 2651

Est. =

12,003,340

UWN = 1981

and should continue to be practiced. Future studies to consider include observing prescribing rates of specific antibiotic agents and associated hospital antibiograms in addition to assessment of therapy duration.

Age, years +- SE

100% 57.2% 42.8%

38.4 +- 0.4 39.6 +- 0.6 37.2 +- 0.6

0.003

Credit author statement

Gender 0.039

Female	65.2%	63.3%	67.7%	All persons who meet authorship criteria are listed as authors, and
Male	34.8%	36.7%	32.3%	all authors certify that they have participated sufficiently in the work

Race 0.076

to take public responsibility for the content, including participation in the concept, design, analysis, writing, or revision of the manuscript. Fur- thermore, each author certifies that this material or similar material has

I

Black	32.6%	32.4%	32.9%
White	64.0%	64.9%	62.7%
Other	3.5%	2.7%	4.5%
nsurance Status Private Insurance 29.4% 29.1% 29.8%
Government	50.9%	50.3%	51.6%
Self/Charity	19.7%	20.6%	18.6%

Seen in ED within 72 h and discharged

Yes 2.7% 2.2% 3.4%

0.488

0.034

not been and will not be submitted to or published in any other publica- tion before its appearance in the The American Journal of Emergency Medicine.

Authorship contributions

Metropolitan Statistical Area 0.002

MSA	81.5%	78.6%	85.5%	Please indicate the specific contributions made by each author (list
Non-MSA	18.5%	21.4%	14.5%	the authors’ initials followed by their surnames, e.g., J.L. Smith) The

CBC 0.148

Yes 22.9% 23.9% 21.5%

Blood Culture 0.278

Yes 2.9% 3.3% 2.5%

X-Ray 0.182

Yes 34.9% 33.8% 36.3%

Est. = Estimated/Weighted Number of visits. UWN = Unweighted number of visits.

Those receiving an antibiotic were more likely to be from a non- metropolitan statistical area (non-MSA), 21.4% vs. 14.5% (P = 0.002). This could be related to a patient’s Access to healthcare. For patients in a more remote area, clinicians may have a lower threshold for prescribing an antibiotic. Likewise, patients may wait longer to pre- sent to the emergency department, and as a result present more se- verely compared to those in an MSA with access to care more readily available.

Patient assessment with CBC, X-ray, and blood cultures were not as- sociated with antibiotic utilization (P = 0.148, P = 0.278, P = 0.182, re- spectively). This was less surprising, as most ARTI such as otitis media, sinusitis, etc., are regarded as more of a clinical diagnosis which often do not warrant lab evaluation. McKay et al. explains that differentiating between bacterial and viral etiologies based on clinical evidence is sel- dom accurate [11]. Clinicians suspecting bacterial infections should pur- sue confirmatory testing before prescribing antibiotics. However, previous studies have also shown that providers often prescribe antibi- otics as a means to quickly end visits with patients and improve patient satisfaction [11]. This may be a commonly taken route in the ED given the high patient volume and expected quick turnover, and could be an explanation as to why there was no association between these studies and prescribing antibiotics. Further assessment of workflow could re- veal possible modifiable behaviors to reduce inappropriate utilization of antibiotics in the future.

Limitations of this study included we did not separate antibiotics

given at the ED and those prescribed at discharge. An additional limita- tion is we used the rate for total antibiotics received during ED visits. Thus, we did not separate rate of antibiotics for ARTI in which antibiotics are appropriate from rates of antibitoics for ARTI for which antibiotics are inappropriate. A final limitation is that the large estimated sample size may cause small differences in percentages to be considered signif- icant. Future studies with more participants in each subgroup will be

name of each author must appear at least once in each of the three cat- egories below.

Category 1

Conceptualization: A.M. Schroeder, S.S. Lewis, A. E. Sahmoun,

J.R. Beal;

Data curation: J.R. Beal; Formal analysis: J.R. Beal. Category 2

Writing - original draft: A.M. Schroeder, S.S. Lewis;

Writing - review & editing: J.R. Beal, A.E. Sahmoun. Category 3

Approval of the version of the manuscript to be published (the names of all authors must be listed): A.M. Schroeder, S.S. Lewis, A.

E. Sahmoun, J.R. Beal.

Declaration of Competing Interest

The authors report no conflicts of interest.

References

1. Donnelly JP, Baddley JW, Wang HE. Antibiotic utilization for acute respiratory tract infections in U.S. Emergency Departments. Antimicrob Agents Chemother. 2014 March;58(3):1451-7.
2. CDC. antibiotic resistance Threats in the United States. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2019. https://doi.org/10.15620/cdc:82532.
3. Pulia M, Redwood R, May L. Antimicrobial Stewardship in the Emergency Depart- ment. Emerg Med Clin North Am. 2018;36(4):853-72. https://doi.org/10.1016/j. emc.2018.06.012.
4. Denny KJ, Gartside JG, Alcorn K, Cross JW, Maloney S, Keijzers G. Appropriateness of antibiotic prescribing in the Emergency Department. J Antimicrob Chemother. 2019; 74(2):515-20. https://doi.org/10.1093/jac/dky447.
5. Kornblith AE, Fahimi H, Kanzaria HK, Wang RC. Predictors for under-prescribing an- tibiotics in children with Respiratory infections requiring antibiotics. Am J Emerg Med. 2018;36:218-25.
6. Ha DR, Haste NM, Gluckstein DP. The role of antibiotic stewardship in promoting ap- propriate antibiotic use. Am J Lifestyle Med. 2017;13(4):376-83. https://doi.org/10. 1177/1559827617700824.
7. Hersh AL, Jackson MA, Hicks LA. Principles of judicious antibiotic prescribing for upper respiratory tract infections in pediatrics. Pediatrics. 2013;132:1146-54.
8. Thorpe JM, Smith SR, Trygstad TK. Trends in emergency department antibiotic pre- scribing for acute respiratory tract infections. Ann Pharmacother. 2004;38(6): 928-35. https://doi.org/10.1345/aph.1D380.
9. CDC. Core Elements of Hospital Antibiotic Stewardship Programs. Atlanta, GA: U.S. Department of Health and Human Services, CDC; 2021https://www.cdc.gov/ antibiotic-use/core-elements/hospital.html.
10. Choosing Wisely.org. Avoiding Antibiotics Overuse. https://www.choosingwisely. org/resources/updates-from-the-field/avoiding-antibiotics-overuse/; March 6, 2014.
11. McKay R, Mah A, Law MR, McGrail K, Patrick DM. Systematic review of factors asso- ciated with antibiotic prescribing for respiratory tract infections. Antimicrob Agents Chemother. 2016;60(7):4106-18. https://doi.org/10.1128/AAC.00209-16.