Demographicand Geographicinequitiesin Antimicrobialuseandprescribing

D e m o g r a p h i c an d
Geographic Inequities in
A n t i m i c ro b i a l U s e an d P re s c r i b i n g
a, b
Christopher Evans, PharmD *, Zanthia Wiley, MD
KEYWORDS
Antimicrobial prescribing Health disparities Health inequities Race/ethnicity
Antimicrobial stewardship
KEY POINTS
Much of the research on antimicrobial prescribing by race and ethnicity has been per-
formed in the outpatient setting.
White persons report twice as many antimicrobial prescriptions compared with other
races.
Other demographics such as age and gender may be described within antimicrobial pre-
scribing studies, but inequities with respect to these characteristics are rarely their focus.
The South census region remains the geographic region of the United States that pre-
scribes the most antimicrobials in the outpatient setting.
INTRODUCTION
Antimicrobial stewardship research is on the rise, but little is known about how social
determinants of health (SDoH) may impact antimicrobial prescribing among racial and
ethnic minority populations, different age groups and genders, and across geographic
regions.1,2 Antimicrobial resistance is a worldwide threat, and we must seek to under-
stand inequities that exist in antimicrobial stewardship.1 The factors that influence
antimicrobial prescribing are complex but often go beyond prescriber knowledge of
the disease state and the antimicrobials being considered; they may also be influ-
enced by providers’ and patients’ beliefs, emotions, desires, and unfortunately at
times, biases.3 Although the existing data describing racial and ethnic, age, and
gender differences in antimicrobial prescribing are conflicting, demographic and so-
cioeconomic factors (influenced by racism) do influence these reported inequities.4
a
Healthcare-Associated Infections and Antimicrobial Resistance Program, Tennessee Depart-
ment of Health, Andrew Johnson Tower, 3.419C 710 James Robertson Parkway, Nashville, TN
37243, USA; b Emory Division of Infectious Diseases, Emory University Hospital Midtown, 550
Peachtree Street NE, Atlanta, GA 30308, USA
* Corresponding author.
E-mail address: christopher.evans@tn.gov
Infect Dis Clin N Am 37 (2023) 715–728

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716 Evans & Wiley
Actions to address these reported inequities include appreciating that SDoH and pre-
scriber implicit and explicit biases influence antimicrobial prescribing and ensuring
that research is designed to correctly characterize and quantify existing racial and/
or ethnic inequities, which includes race and ethnicity demographic data.4
This review describes the variation in antimicrobial use and prescribing that has
been heretofore published, with a focus on differences observed by race and ethnicity,
age, gender, and geographic region of the United States. Proposed mitigation strate-
gies when feasible will be included throughout. The authors also note that within this
article, race and ethnicity terminology is directly from the cited references.
ANTIMICROBIAL PRESCRIBING INEQUITIES BY RACE AND ETHNICITY

Outpatient Prescribing
Pediatric literature
Data on racial and ethnic differences in antimicrobial prescribing date back nearly
20 years in pediatrics literature with a 2004 publication exploring racial and ethnic dif-
ferences in parents pursuing antimicrobials to treat upper respiratory tract illnesses of
their children, as well as the perceptions of parents’ expectations.5 This study found
most parents believed antimicrobials were definitely necessary (43%) or probably
necessary (27%), and Asian and Latino parents were each 17% more likely (compared
to non-Hispanic [NH] White parents).5 Though physicians recognized Asian parents
expected antimicrobials more often than White parents, they underestimated the
greater expectation for antimicrobials from Latino parents.5 Physicians in this study
were also 21% more likely to prescribe antimicrobials when they believed antimicro-
bials were expected from parents.5
A retrospective study published in 2013 of nearly 1.3 million pediatric encounters by
222 clinicians in 25 practices in Pennsylvania and New Jersey found that Black chil-
dren were less likely to obtain an antimicrobial prescription from the same clinician
per acute visit, even when adjusted for gender, age, comorbidities, health care insur-
ance, and practice site.6 Black children were also less likely to obtain diagnoses that
resulted in justification of antimicrobials (eg, acute otitis media [OM]) and were less
likely to be prescribed broad-spectrum antimicrobials.6
One year later, in 2014, researchers expanded this research objective to determine
whether race was associated with differences in diagnoses of OM and antimicrobial
prescribing on a national level.7 They found that though OM visits (per 1000 popula-
tion) were similar between non-Black and Black children, the percentage of visits
that resulted in an OM diagnosis were 30% less in Black children compared with
others.7 Also, Black children were less likely than non-Black children to receive
broad-spectrum antimicrobials (42% vs 52%; p 5 0.01).7 This study concluded that
treatment choice differences for Black children diagnosed with OM could suggest
race-based variance in practice patterns of physicians, as well as preferences of
parents.7
Another retrospective cohort study of 448,990 outpatient visits (between 2014 and
2016) for upper respiratory tract infections (RTIs) that should not necessitate antimi-
crobial use included family medicine, urgent care, internal medicine, and pediatric
practices from the Carolinas HealthCare System (across nearly 900 providers and
246 practices).8 They found that pediatric African American and Asian patients were
less likely than White patients to receive antimicrobials at a visit.8
In addition to clinic-based pediatric literature evaluating racial and ethnic differ-
ences in prescribing, there is literature from the pediatric emergency department. In
2017, another study of acute RTIs was performed. Of 39,445 pediatric emergency
Inequities in Antimicrobial Use and Prescribing 717
department visits, 2.6% were prescribed antimicrobials, with 4.3% of NH White, 2.6%
of Hispanic children, and 1.9% of NH Black children.9 In multivariable analyses, His-
panic and NH Black children were less likely than NH White children to receive antimi-
crobials in the setting of viral acute RTIs.9
Adult literature
Racial and ethnic disparities in outpatient antimicrobial use have also been docu-
mented in adult literature. One nationwide U.S. survey reported disparities by race/
ethnicity for 2014–2015 antimicrobial drug acquisition.10 Compared with persons of
other race/ethnicities, White people reported twice as many antimicrobial drug pre-
scription fills.10
A predominance of studies in the adult literature focuses on outpatient antimicrobial
prescribing. A study of respiratory urgent care visits in adults 18–65 years reported
that NH and White patients received antimicrobial prescriptions at higher rates than
non-White, Hispanic patients, similar to other studies.11 Another retrospective study
of Medi-Cal (California Medicaid) claims data of beneficiaries enrolled between
2006 and 2011 found that of 10,018,066 systemic antimicrobial claims, Alaskan Na-
tives and Native Americans had the highest rate of use (1086/1000 beneficiaries,
p < 0.001) and that White patients received the highest proportions of broad-
spectrum agents (36.6% [95% CI 36.6–36.7%]).12 The Carolinas HealthCare System
retrospective study (described above in the pediatric section) reported that all other
adult races were less likely to receive an antimicrobial than White patients.8
Disparities in antimicrobial prescribing have been reported in other countries as
well. A national study of outpatient antimicrobial prescribing in New Zealand found
lower antimicrobial use in the Ma ori (indigenous New Zealanders) group compared
with other groups, and that this was out of proportion to their higher burden of infec-
tious diseases.13 Similar findings were noted in another study where the Ma ori were
less likely to receive an antimicrobial prescription (48% of the population) than non-
Ma ori (55%) and also received, on average, smaller quantities.14 Rural Ma ori,
including rural Ma ori children, received fewer prescriptions and lower quantities of an-
timicrobials compared with other population groups.14 Authors hypothesized some
antimicrobial use differences could be due to health care access barriers (eg, cost
of primary care visits and prescriptions), as well as cultural differences in knowledge
and/or understanding of antimicrobials and infectious diseases.13
Although much of the literature evaluating differences in antimicrobial prescribing by
race and ethnicity does note differences, there is at least one study that reports no sig-
nificant difference. In this study of student-run, free, primary care clinics (72.2%
lacked insurance) in Florida, researchers found no statistically significant differences
in the likelihood of receipt of inappropriate prescriptions based on race/ethnicity.15
Inpatient Prescribing
Although there is a relative paucity of literature on inpatient antimicrobial prescribing
health inequities, there is evidence of antimicrobial prescribing disparities in skin
and soft tissue infections (SSTI).16 A cohort study including cross-sectional data
from a multisite sub-analysis of a national survey of acute care hospital groups within
a large health care system found that the recommended first line agent, cefazolin, was
more commonly used in White inpatients than in Black inpatients [13% (n 5 114) vs.
5% (n 5 11)] and clindamycin was more frequently used in Black inpatients than in
White inpatients [12% (n 5 27) vs 7% (n 5 62)].16 Adjusting for multiple factors
including penicillin allergy, presence of methicillin-resistant Staphylococcus aureus,
and infection type, White inpatients were at an increased risk of cefazolin use
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[adjusted odds ratio (aOR) 5 2.82; 95% CI, 1.41–5.63] and decreased risk of clinda-
mycin use (aOR 5 0.54; 95% CI, 0.30–0.96) compared with Black inpatients, despite
the fact that SSTI treatment guidelines consider b-lactams (eg, cefazolin) as first-line
therapy to target S. aureus and Streptococcus spp.16
Overall, these studies suggest that across pediatric and adult literature and in both
inpatient and outpatient settings, Black persons are less likely in the United States at
least to receive antimicrobial therapy and appropriate antimicrobial therapy than White
persons. Though studies are more conflicting, prescribing differences lean toward
fewer antimicrobials being prescribed for Hispanic individuals also. Prescribing dis-
parities in other countries and analyzing other cultures and races are much less well
studied.
ANTIMICROBIAL PRESCRIBING INEQUITIES BY AGE
Many studies that analyze antimicrobial use will report findings by age group, but few
focus primarily on the comparison between adult and pediatric prescribing, and none
focus on inequities in the same. As such, this section seeks to describe several studies
to illustrate contrasts between adult and pediatric prescribing, particularly in the
ambulatory setting.
In an article describing geographic distributions of antimicrobial prescribing in 2011,
Hicks and colleagues,17 evaluated patient population and provider specialty charac-
teristics. Antimicrobial prescribing rates for different age groups ranged from 685 pre-
scriptions per 1,000 persons (20–39 years) to 1,287 prescriptions per 1,000 persons
(infants 0–2 years); persons aged 65 years received 1,048 prescriptions per 1,000
persons (Table 1).17 The largest volume of antimicrobials prescribed were for persons
aged 40–64 years.17 There were also differences observed in types of antimicrobials
received by different age groups; penicillins accounted for the largest number of pe-
diatric prescriptions, whereas macrolides accounted for the largest number of pre-
scriptions for adult patients.17 Similar studies in smaller geographic regions, notably
a high-prescribing region of the United States, have shown similar results, with high
rates of antimicrobial use in infants, declining rates in pediatric and young adults,
and increasing rates once patients reach the age of 65 years.18,19
Further analyses of antimicrobial prescriptions among older adults have shown the
rate remained relatively stable over time following the above analysis.20 From 2011 to
2014, the rate changed from 1,113 prescriptions per 1,000 persons to 1,115 prescrip-
tions per 1,000 persons (p 5 0.89) in this population.20 However, in 2014, persons in
the oldest age group (75 years) had a higher prescribing rate at 1,157 antimicrobials
per 1,000 persons compared with those in the 65–74 years group.20 Of note, fluoroqui-
nolone antimicrobials were the most commonly prescribed antimicrobials in older
Table 1
Antimicrobial prescriptions by age group, 2011
Age Group, y Prescriptions, No. in Millions (%) Prescriptions per 1,000 Persons, Rate
0–2 15.4 (6) 1287
3–9 29.1 (11.3) 1018
10–19 29.3 (11.4) 691
20–39 57.3 (22.3) 685
40–64 82.1 (32) 790
65 43.4 (17) 1048
adults in this study and accounted for 22% of all antimicrobials prescribed despite
their adverse effect profile in this population. In their discussion, the authors speculate
this may be due to increasing incidence of urinary tract infections in older individuals,
including older male patients.20 Given that older individuals in general are at greater
risk of death from resistant antimicrobial infections and developing adverse events
from antimicrobial therapy, such as side effects and Clostridioides difficile infection,
interventions and research in improving antimicrobial use in this population is neces-
sary.21 A recent Morbidity and Mortality Weekly Report showed that using publicly
available Centers for Medicare and Medicaid Services (CMS) Part D Prescriber Public
Use Files (available at https://data.cms.gov/provider-summary-by-type-of-service/
medicare-part-d-prescribers/medicare-part-d-prescribers-by-provider) can help to
identify higher-volume outpatient antimicrobial prescribers for such interventions.21,22
Gouin and colleagues21 found that 41% of all Medicare Part D antimicrobial prescrip-
tions were prescribed by only 10% of prescribers. The Centers for Disease Control
and Prevention (CDC) has encouraged state and local health departments to consider
similar analyses with targeted notification of these prescribers within their respective
jurisdictions. It is helpful that such datasets exist and are publicly available, but a
notable limitation is their applicability to other age groups. The majority of represented
patients are Medicare recipients over the age of 65 years. Similar datasets for younger
adults and pediatric patients are either proprietary or require collaboration with private
payer groups.
Not including influenza and viral pneumonia, acute RTIs account for 44% of all
ambulatory care visits.23 Fleming-Dutra and colleagues23 assessed the prevalence
of inappropriate antimicrobial prescriptions in U.S. ambulatory care visits, with a focus
on acute RTIs. In addition to the large differences in antimicrobial prescribing in pedi-
atric patients described previously, this study found the estimated appropriate annual
rate of antimicrobial prescriptions for all acute respiratory conditions differed among
various age groups. The highest rate of appropriate antimicrobial prescribing occurred
in the pediatric population (aged 0–19 years) at 278 per 1,000 population, whereas
rates for the adult population were significantly lower (45 per 1,000 population for pa-
tients aged 20–64 years and 63 per 1,000 population for patients 65 years).23
Another study performed in urgent cares to assess the appropriateness of antimicro-
bial prescribing found that while overall antimicrobials received was similar between
those aged 18 and 64 years (49.4%) and those aged 65 years and above (50.1%), an-
timicrobials prescribed for tier 3 diagnoses (ie, those diagnoses for which antimicro-
bials are not indicated such as acute bronchitis) differed—30.2% of antimicrobials
used in the 65 years age group were for tier 3 conditions versus 20.8% in the 18–
64 years age group, suggesting a higher rate of inappropriate antimicrobial prescribing
in older patients.11
Differences in measures of quality for outpatient antimicrobial prescribing by age
can also be observed in the Healthcare Effectiveness Data and Information Set
(HEDIS), which is used as a performance measure for 90% of U.S. health plans.24 Pe-
diatric measures for HEDIS were incorporated in 2004 and include appropriate testing
for children for pharyngitis and appropriate treatment of children with upper RTI. Adult
measures for HEDIS were incorporated in 2006 and include avoidance of antimicrobial
treatment of acute bronchitis.24 While these are different measures incorporated at
different time periods, achievement of them is starkly different. For the two pediatric
measures, average national performance across all health plans was 80% and
83%, respectively; for the adult measure of avoidance of antimicrobials in acute bron-
chitis, average national performance across all health plans was 23%.24 The HEDIS
goal for these metrics is 100%.
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Much of the literature assessing antimicrobial prescribing disparities by age comes

from studies that did not assess this demographic as their primary outcome. Nonethe-
less, assessing these together leads to an interesting trend in that antimicrobial pre-
scribing, in the outpatient setting, tends to be high in infants, decreases in older
children in young adults, and increases again for the elderly. Evidence also suggests
that older adults are more likely to receive inappropriate antimicrobials. Given that
appropriate therapy for specific indications can change based on a patient’s age,
future analyses of antimicrobial therapy should overlay specific classes of antimicro-
bials into their consideration.
ANTIMICROBIAL PRESCRIBING INEQUITIES BY GENDER

Gender Differences in Outpatient Antimicrobial Prescribing
In the U.S. cross-sectional, retrospective study using the National Ambulatory Medical
Care Survey (NAMCS) from 2009 to 2016, including 7 billion patient visits (11.3% that
included an antimicrobial prescription), female patients had a higher rate of antimicro-
bial visits compared with male patients (114.1 vs. 112.3 per 1,000 patient visits,
respectively), while male patients had a slightly higher rate of inappropriate antimicro-
bial visits compared with female patients (64.8 vs. 62.4 per 1,000 patient visits,
respectively).25 Another U.S. study found that providers prescribed 262.5 million anti-
microbial courses in 2011 and noted that antimicrobial prescribing was significantly
higher for female over male patients, especially among the age group of 20 years
(female patients, 990 prescriptions per 1,000 persons; male patients, 596 prescrip-
tions per 1000 persons; p < .001).17
Higher prescribing in females has been noted in other countries as well. A large
cross-sectional analysis of medical records of primary care patients in England (be-
tween 2013 and 2015) found that, of 4.57 million antimicrobial prescriptions, females
received 67% more prescriptions than males.26 Female patients received 43% more
antimicrobials than males even when excluding antimicrobials that are used to treat
urinary tract infections.26 These gaps were even more remarkable in adult women,
who received 99% more antimicrobial prescriptions than men.26
A 2016 meta-analysis and systematic review of 11 studies published between 1976
and 2013, including more than 44 million persons from 5 prospective national studies
and 6 regional studies was performed.27 This meta-analysis found that women were
27% (proportional reporting ratio 5 1.27 0.12) more likely than men to receive an
antimicrobial prescription in their lifetime and that the numbers of antimicrobials pre-
scribed to women were 36% [incidence rate ratio (IRR) 5 1.36 0.11] higher than for
men in the 16–34 years age group and 40% (IRR 1.40 0.03) higher in the 35–54 years
age group.27 Cephalosporins and macrolides prescribed for women were 44% (IRR
1.44 0.30) and 32% (IRR 1.32 0.15) higher, respectively, than for men.27
Although most studies report higher antimicrobial prescribing for women patients
compared with men, one cross-sectional study from Argentina, Denmark, Lithuania,
Russia, Sweden, and Spain (HAPPY AUDIT Project) evaluated the possibility of gender
differences in unnecessary antimicrobial prescriptions in those with upper RTI.28 Of
the 15,022 patients who met inclusion criteria (70.8% with upper RTI), antimicrobials
were prescribed in 25.4% of all consultations, and there was no difference between
male and female patients.28 For both genders, 45% of prescriptions were classified
as unnecessary and no gender difference was found in the proportion of unnecessary
antimicrobial prescriptions (OR 5 1.02; 95% CI: 0.90–1.15).28 Of patients who
received unnecessary antimicrobials, 120 (14%) demanded them and, overall, no
differences between male and female demand for antimicrobials were found: rhinitis
(28.5% male versus 19.7% female, p 5 0.56), acute OM (0% male versus 2.7% fe-
male), acute sinusitis (0% male versus 3.3% female), and acute pharyngotonsillitis
(4.5% male versus 6.7% female, p 5 0.16).28 This study reported a high rate of unnec-
essary antimicrobial prescribing for upper RTIs but found no overall gender differ-
ences in receiving unnecessary antimicrobial prescriptions.28
Gender differences in timing of antimicrobial administration

Studies evaluating gender differences in inpatient antimicrobial prescribing are infre-
quent; however, literature does exist on gender differences in timing of antimicrobial
administration in critically ill patients. The DISPARITY I study hypothesized that
women have lower surviving sepsis campaign bundle completion rates.29 This retro-
spective, observational study included adults (>18 years) admitted to the intensive
care unit with severe sepsis or septic shock from October 2005 to February 2012.29
Of 814 enrolled patients, the mean age was 66 years, and women comprised
44.8%.29 Although there was no association between gender and bundle completion
(aOR 5 0.83, 95% CI 0.58–1.16) and in-hospital mortality did not differ by gender,
women were less likely to receive antimicrobials within 3 hours (60.5% vs. 68.8%,
p 5 0.01).29 The DISPARITY II study assessed whether source of infection and/or
gender were associated with delayed antimicrobials in patients with severe sepsis
or septic shock.30 In this study, 771 total patients were included (45.3% women;
mean age of 66 years).30 Mean time to first antimicrobial was 153 minutes (95%
CI 5 143–163 minutes) for men and 184 minutes (95% CI 5 171–197 minutes) for
women (p < 0.001).30 Urinary tract infections were the source of infection for 35.2%
of women (95% CI 5 30.2%–40.3%) compared with 23.7% (95% CI 5 19.6%–
27.8%) of men.30 Pneumonia was the source of infection in 46.9% of men (95%
CI 5 42.1%–51.7%) compared with 35.8% (95% CI 5 30.8%–40.8%) of women.30
The mean time to antimicrobials in women was longer than in men (aOR 5 1.18;
95% CI 5 1.07–1.30), even after adjusting for age, race, ethnicity, presumed source
of infection, SOFA score, and lactate (p 5 0.001).30
Studies mostly suggest that female patients tend to be prescribed antimicrobials in
the outpatient setting more frequently than male patients. While this may be due to
increased usage of health care resources, this finding is consistent over multiple
studies even when controlled for by total numbers of office visits.25 The differences
observed in timing of antimicrobials by gender in DISPARITY I and DISPARITY II
studies do warrant further investigation, as does a broader analysis of antimicrobial
use by gender within the inpatient setting.
Gender differences in antimicrobial stewardship recommendation acceptance

A telehealth-based antimicrobial stewardship program facilitated by local pharmacists
and remote infectious diseases physicians was implemented from 2018 to 2020 in two
community hospitals, and the odds ratios of acceptance of recommendations were
assessed.31 Most (91.2%; 4,863 of 5,333) recommendations were accepted.31 Female
physicians were more likely to accept recommendations compared with males (93.1%
vs 90.3% acceptance; OR 5 1.65; 95% CI, 1.3–2.2).31 In another retrospective evalu-
ation at a single academic medical center conducted in 2019, the association of the
gender of pharmacists with acceptance of antimicrobial stewardship recommenda-
tions by hospitalists was assessed.32 During the 6 month study period, pharmacists
conducted 295 timeouts: 158 (53.6%) were conducted by female pharmacists and
137 (46.4%) by male pharmacists.32 Pharmacists recommended change in antimicro-
bials in 82 timeouts (27.8%) and 51 (62.2%) were accepted.32 In comparison to male
pharmacists, female pharmacists were less likely to recommend an antimicrobial
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change: 30 of 158 (19%) versus 52 of 137 (38.0%) (p < 0.001).32 Female pharmacists
were also less likely to have a recommendation accepted: 41 of 52 (8.8%) versus 10 of
30 (33.3%) (p < 0.001).32 Antimicrobial recommendations directed by female versus
male pharmacists were less likely to result in an antimicrobial change: 10 of 158
(6.3%) versus 41 of 137 (29.9%) (p < 0.001).32 Pharmacist gender remained signifi-
cantly associated with whether recommended changes were accepted (aOR 5 0.10;
95% CI: 0.03–0.36 for female versus male pharmacists), even upon adjustments.32
These two studies suggest that gender bias may be present in antimicrobial steward-
ship recommendation acceptance by both the gender of clinicians accepting recom-
mendations, as well as the gender of pharmacists providing the recommendations—
each of which can affect patient outcomes.31,32
Several reasons have been proposed to explain gender gaps in antimicrobial pre-
scribing. First, infectious diseases, such as urinary tract infections, are more common
in women than men.26 Also women have been shown to present to primary care prac-
titioners more frequently than men and visit rates have been linked to antimicrobial
prescribing.26 Behavioral and social factors may also contribute in that women and
men may communicate differently with health care personnel, and those who pre-
scribe antimicrobials may also have biases that impact their willingness to give antimi-
crobials to women compared with men.26 One study of general practice consultations
found that within female general practitioners, gender concordance with female pa-
tients was associated with decreased prescribing of antimicrobials (OR 5 0.85;
95% CI: 0.72–0.99; p 5 0.034).33 More recently, an analysis of 122,930 adult
(18 years) respiratory encounters from 38 U.S. urgent care clinics between 2018
and 2019 found that female clinicians prescribed antimicrobials for tier 3 respiratory
conditions less often than male clinicians (18.5% vs. 23.6%), and this difference
was preserved irrespective of patient gender.11 Further studies are warranted to deter-
mine the extent to which each of these factors contribute to gender gaps in prescribing
of antimicrobials and acceptance of antimicrobial stewardship recommendations, as
well as delayed antimicrobial administration in female patients.
ANTIMICROBIAL PRESCRIBING INEQUITIES BY GEOGRAPHICAL REGION
Geographic variation in antimicrobial prescribing has been observed in the United

States since the 1990s.34 Multiple studies have shown variation exists in the volume
and appropriateness of antimicrobials prescribed by U.S. Census region—West, Mid-
west, Northeast, and South.17,23,35,36 Many of these studies analyze antimicrobials
prescribed in the outpatient setting at a national or regional level. There is a dearth
of literature on geographic analysis of antimicrobial use in the acute care or long-
term care setting. However, CDC does report on both outpatient antimicrobial use
and the inpatient Standardized Antimicrobial Administration Ratio (SAAR) values on
their Antibiotic Resistance and Patient Safety Portal (ARPSP), both stratified by
state.37 The inpatient SAAR data available here, at the time of writing, is for a single
year (2021), and forming conclusions as to geographic differences based on this
would be inappropriate. Additionally, at this time, within state variations are not avail-
able and individual state data may not reflect regional differences within a state.
Much of the research assessing outpatient antimicrobial prescribing analyses typi-
cally rely on either national survey data, proprietary data sources, or payer-based
databases and are pulled primarily from prescription fill data. Additionally, because
of the propensity to use antimicrobials unnecessarily in these infections, several
studies focus primarily on antimicrobials for RTIs. The ARPSP also reports on outpa-
tient antimicrobial prescribing patterns (captured from one of these proprietary data
sources; Fig. 1).38 Overall, and consistent with the following studies, the South is the
U.S. census region with the highest outpatient antimicrobial prescription rate.38
Further information on these outpatient antimicrobial studies is detailed below.
Possibly the earliest study to report on regional differences in antimicrobials pre-
scribing was a retrospective analysis of primary care office visits for adults with
sore throat reported into the NAMCS from 1989 to 1999.34 Although the South did
have the largest proportion of antimicrobials prescribed for sore throat in this sample,
region of the United States was not a predictor for any antimicrobial use or nonrecom-
mended antimicrobial use.34 Using Medicare Part D data from 2007 to 2009, Zhang
and colleagues36 next analyzed geographic variations in outpatient prescribing among
older adults. Despite controlling for prevalence rates of respiratory infections, the
South again had the highest percentage of patients taking antimicrobials compared
with the West, which had the lowest (21.4% vs. 17.4%, p < 0.001).36 Additionally,
this study went a step further and analyzed state-level data. Similar to their regional
analysis, southern states, including Alabama and Mississippi, had the highest utiliza-
tion and spending compared with states in other regions with the lowest occurring in
Oregon, Washington, Wyoming, Maine, and New Hampshire.36 Finally, Hersh and col-
leagues39 examined prescriptions for acute RTIs using the NAMCS Survey from 2012
to 2013 and split the United States into more granular regions. The Pacific region still
had the lowest rates of respiratory infection visits resulting in an antimicrobial versus
the highest observed in the East South Central and West South Central regions.39
Fig. 2 shows the correlation between visits for RTIs and the rate of visits for which an-
timicrobials were prescribed.39
Much work has been done by the CDC to assess both volume and appropriateness
of antimicrobial prescribing and stratified those analyses by U.S. region. Hicks and
colleagues17 initially reported on antimicrobial prescribing variation based on geogra-
phy, patient population, and provider specialty. This study analyzed outpatient antimi-
crobial prescriptions for calendar year 2011. Antimicrobial prescribing rates were
Fig. 1. Outpatient prescription rate of all antimicrobial classes dispensed in U.S. Pharmacies
by state map, 2021. (Used with permission from Centers for Diseases Control and Prevention.)
724 Evans & Wiley
Fig. 2. Correlation between the acute respiratory tract infection visit rate per 1,000 popula-
tion and the rate with which all respiratory visits are prescribed antimicrobials per 1,000
population. Acute respiratory tract infection (ARTI) 1 are acute respiratory tract infections
for which antimicrobial therapy may be warranted. (Reproduced with permission from
Hersh AL, et al. Infect Dis Ther. 2018 Mar;7(1):171-174. https://doi.org/10.1007/s40121-017-
0181-y.39)
higher in the South census region (931 prescriptions per 1,000 persons) than any other
region and significantly different than the rate in the West census region (647 per 1,000
persons, p < 0.001).17 This trend of higher prescribing in the South continued when
stratified across all age groups.
In their analysis of inappropriate antimicrobials prescribed during ambulatory care
visits, Fleming-Dutra and colleagues23 used 2010–2011 NAMCS and National Hospital
Ambulatory Medical Care Survey to estimate rates of oral antimicrobial prescribing by
age and diagnosis. The rate of visits with antimicrobials prescribed per 1,000 popula-
tion was 553 in the South, 525 in the Northeast, 497 in the Midwest, and 423 in the
West.23 Although overall w30% of antimicrobials prescribed were unnecessary, this
result was not broken down by region.23
Finally, Bizune and colleagues35 analyzed regional variation in outpatient antimicro-
bial prescribing for acute RTIs, incorporated diagnostic codes used from recent pro-
vider visits, and stratified as to whether antimicrobials were always, sometimes, or
rarely indicated. Consistent with results from the previous studies, the South region
had the highest proportion of visits with an antimicrobial prescription (43%), and the
West the lowest (34%).35 Antimicrobial prescribing for indications where antimicro-
bials are rarely indicated was highest in the South (17.9%) and lowest in the West
(13.4). Prescribing for indications where antimicrobials are always indicated was
similar across all regions.35 Overall, patients in the South were 34% more likely to
receive an antimicrobial for an indication where they are rarely indicated than patients
in the West.35
The recurring theme of these studies is that more antimicrobial prescriptions
overall, for respiratory infections, and inappropriate antimicrobials are prescribed
in the South than other regions of the United States This has led many authors to
conclude that a “culture” of prescribing exists in the South, and therefore, antimi-
crobial stewardship efforts need to be tailored by region. This is supported by other
prescribing habits in this region. Opioid prescribing, for example, has also histori-
cally been higher (albeit declining) in the South compared with the rest of the United
States.40
In the commentary to the Bizune study, and because antimicrobial prescribing is
multifactorial, Szymczak and Linder2 have called for both a more nuanced view of
the term “culture” as it relates to geographic prescribing patterns as well as retiring
of the U.S. Census regions as a basis for antimicrobial use research. Their claim is
that regional borders are too broad and not necessarily reflective of a culture of
prescribing. Further research and stewardship interventions should focus on
more granular areas (eg, local and even organizational levels) and that implementa-
tion address other determinants of use (eg, characteristics of specific patient–
provider interaction, larger sociostructural factors).2 Nonetheless, inequities do
exist in prescribing patterns of providers within different geographic areas and
the likelihood of patients receiving antimicrobials, either appropriately or inappro-
priately, is affected by the region in which they live. Further research is needed
to better understand the more granular geographic differences and drivers of anti-
microbial use and the interplay of sociostructural factors that may affect these
regional differences.
SUMMARY
Potential drivers of racial, ethnic, and other demographic inequities in the occurrence
of health care-associated infections may occur at the interpersonal (eg, unconscious
bias of health care professionals), community (eg, inequities in economic and SDoH),
and policy (eg, segregation of health care through chronic underfunding of safety net
facilities, insufficient research into inequities) levels, and a framework to mitigate
them has been proposed.41 This framework can and should also be applied to the
areas of antimicrobial stewardship and antimicrobial prescribing. This would involve,
but is not limited to, raising individual awareness about and mitigating the uncon-
scious biases of health care providers, addressing SDoH inequities, and expanding
literature evaluating differences in prescribing, not only by patient but also by pre-
scriber characteristics. This would include assessing not only the variables of race
and ethnicity, age, gender, and geographical region described herein, but also other
demographic and socioeconomic factors when available that have heretofore not
been studied at all, such as disability status, sexuality, gender identity, preferred lan-
guage, and other aspects of social vulnerability. The work described in this review is
only the beginning to understand where and why these inequities in antimicrobial
prescribing exist. Many studies do not primarily seek to answer questions about anti-
microbial prescribing inequities by a specific characteristic, though prescribing dis-
parities may be observed in their demographic analysis. And the vast majority of
studies that have assessed antimicrobial prescribing by social demographics have
done so in the outpatient setting; there is little information about prescribing ineq-
uities in the acute care or post-acute care setting. Further research is warranted to
identify drivers that promote these inequities in antimicrobial prescribing in the
United States and ultimately to better understand whether these inequities impact
patient outcomes in all settings of the health care continuum. Ultimately, this
research should be used to both mitigate and ultimately eliminate these health
inequities.
726 Evans & Wiley
CLINICS CARE POINTS
Many factors influence the decision to prescribe antimicrobials at the point of care.
Prescribers should assess how their own unconscious biases may influence their antimicrobial
prescribing practices.
These biases may include race and ethnicity, gender, age, but also those social determinants
of health not detailed in this review.
DISCLOSURE
Dr C. Evans has no commercial or financial conflicts to disclose relevant to this work.

Dr Z. Wiley has no commercial or financial conflicts to disclose relevant to this work.
FUNDING
Dr C. Evans work on this project was funded by the Epidemiology and Laboratory
Capacity Cooperative Agreement (federal grant no. NU50CK000528).
REFERENCES
1. Fortin-Leung K, Wiley Z. What about race and ethnicity in antimicrobial steward-

ship? Infect Control Hosp Epidemiol 2022;43(3):400–1.
2. Szymczak J, Linder J. “Cultural variation in antibiotic prescribing: have regional
differences had their day. Open Forum Infect Dis 2023;10(2):e1–2.
3. Szymczak J, Newland J. The social determinants of antibiotic prescribing: implica-
tions for the development and implementation of stewardship interventions. In:
Barlam T, Neuhauser M, Tamma P, et al, editors. Practical implementation of an
antibiotic stewardship program. Cambridge: Cambridge University Press; 2018.
p. 45–62.
4. Abdul-Mutakabbir JC, Simiyu B. Exploring the intersection of racism, antimicrobial
resistance, and vaccine equity. Antimicrob Steward Healthc Epidemiol 2022;2(1):
e134.
5. Mangione-Smith R, Elliott MN, Stivers T, et al. Racial/ethnic variation in parent ex-
pectations for antibiotics: implications for public health campaigns. Pediatrics
2004;113(5):e385–94.
6. Gerber JS, Prasad PA, Localio AR, et al. Racial differences in antibiotic prescrib-
ing by primary care pediatricians. Pediatrics 2013;131(4):677–84.
7. Fleming-Dutra KE, Shapiro DJ, Hicks LA, et al. Race, otitis media, and antibiotic
selection. Pediatrics 2014;134(6):1059–66.
8. Schmidt ML, Spencer MD, Davidson LE. Patient, provider, and practice charac-
teristics associated with inappropriate antimicrobial prescribing in ambulatory
practices. Infect Control Hosp Epidemiol 2018;39(3):307–15.
9. Goyal MK, Johnson TJ, Chamberlain JM, et al. Pediatric care applied research
network (PECARN). Racial and ethnic differences in antibiotic use for viral illness
in emergency departments. Pediatrics 2017;140(4):e20170203.
10. Olesen SW, Grad YH. Racial/ethnic disparities in antimicrobial drug use, United
States, 2014-2015. Emerg Infect Dis 2018;24(11):2126–8.
11. Seibert AM, Hersh AL, Patel PK, et al. Urgent-care antibiotic prescribing: an
exploratory analysis to evaluate health inequities. Antimicrob Steward Healthc
Epidemiol 2022;2(1):e184.
12. Gahbauer AM, Gonzales ML, Guglielmo BJ. Patterns of antibacterial use and
impact of age, race/ethnicity, and geographic region on antibacterial use in an
outpatient medicaid cohort. Pharmacotherapy 2014;34(7):677–85.
13. Williamson DA, Roos R, Verrall A, et al. Trends, demographics and disparities in
outpatient antibiotic consumption in New Zealand: a national study. J Antimicrob
Chemother 2016;71(12):3593–8.
14. Norris P, Horsburgh S, Keown S, et al. Too much and too little? Prevalence and
extent of antibiotic use in a New Zealand region. J Antimicrob Chemother 2011;
66(8):1921–6.
15. Daga A, Nguyen OT, Moothedan E, et al. Antibiotic prescribing patterns for acute
respiratory infections in a free clinic network: a pooled cross-sectional study.
Drugs Ther Perspect 2022;38(1):51–5.
16. Wurcel AG, Essien UR, Ortiz C, et al. Variation by race in antibiotics prescribed
for hospitalized patients with skin and soft tissue infections. JAMA Netw Open
2021;4(12):e2140798.
17. Hicks LA, Bartoces MG, Roberts RM, et al. US outpatient antibiotic prescribing
variation according to geography, patient population, and provider specialty in
2011. Clin Infect Dis 2015;60(9):1308–16.
18. Staub MB, Ouedraogo Y, Evans CD, et al. Analysis of a high-prescribing state’s
2016 outpatient antibiotic prescriptions: Implications for outpatient antimicrobial
stewardship interventions. Infect Control Hosp Epidemiol 2020;41(2):135–42.
19. Katz SE, Staub M, Ouedraogo Y, et al. Population-based assessment of patient
and provider characteristics influencing pediatric outpatient antibiotic use in a
high antibiotic-prescribing state. Infect Control Hosp Epidemiol 2020;41(3):
331–6.
20. Kabbani S, Palms D, Bartoces M, et al. Outpatient antibiotic prescribing among
older adults in the United States, 2011 to 2014. J Am Geriatr Soc 2018;66(10):
1998–2002.
21. Gouin KA, Fleming-Dutra KE, Tsay S, et al. Identifying higher-volume antibiotic
outpatient prescribers using publicly available medicare part D data — United
States, 2019. MMWR Morb Mortal Wkly Rep 2022;71:202–5.
22. Medicare Part D Prescribers - by Provider. Centers for Medicare & Medicaid Ser-
vices Data. (2020). Available at: https://data.cms.gov/provider-summary-by-type-
of-service/medicare-part-d-prescribers/medicare-part-d-prescribers-by-provider.
Accessed May 1, 2023.
23. Fleming-Dutra KE, Hersh AL, Shapiro DJ, et al. Prevalence of inappropriate anti-
biotic prescriptions among US ambulatory care visits, 2010-2011. JAMA 2016;
315(17):1864–73.
24. Roberts RM, Hicks LA, Bartoces M. Variation in U.S. outpatient antibiotic prescrib-
ing quality measures according to health plan and geography, 2008–2012. Am J
Manag Care 2016;22(8):519–23.
25. Young EH, Strey KA, Lee GC, et al. National disparities in antibiotic prescribing
by race, ethnicity, age group, and sex in United States ambulatory care visits,
2009 to 2016. Antibiotics (Basel) 2022;12(1):51.
26. Smith DRM, Dolk FCK, Smieszek T, et al. Understanding the gender gap in anti-
biotic prescribing: a cross-sectional analysis of English primary care. BMJ Open
2018;8(2):e020203.
27. Schröder W, Sommer H, Gladstone BP, et al. Gender differences in antibiotic pre-
scribing in the community: a systematic review and meta-analysis. J Antimicrob
Chemother 2016;71(7):1800–6.
728 Evans & Wiley
28. Bagger K, Nielsen AB, Siersma V, et al. Inappropriate antibiotic prescribing and
demand for antibiotics in patients with upper respiratory tract infections is hardly
different in female versus male patients as seen in primary care. Eur J Gen Pract
2015;21(2):118–23.
29. Madsen TE, Simmons J, Choo EK, et al. The DISPARITY study: do gender differ-
ences exist in surviving sepsis campaign resuscitation bundle completion,
completion of individual bundle elements, or sepsis mortality? J Crit Care 2014;
29(3). 473.e7-11.
30. Madsen TE, Napoli AM. The DISPARITY-II study: delays to antibiotic administra-
tion in women with severe sepsis or septic shock. Acad Emerg Med 2014;21(12):
1499–502.
31. Shively NR, Jacobs MW, Moffa MA, et al. Factors associated with acceptance of
telehealth-based antimicrobial stewardship program recommendations in a com-
munity hospital health system. Open Forum Infect Dis 2022;9(9):ofac458.
32. Vaughn VM, Giesler DL, Mashrah D, et al. Pharmacist gender and physician
acceptance of antibiotic stewardship recommendations: an analysis of the
reducing overuse of antibiotics at discharge home intervention. Infect Control
Hosp Epidemiol 2023;44(4):570–7.
33. Eggermont D, Smit MAM, Kwestroo GA, et al. The influence of gender concor-
dance between general practitioner and patient on antibiotic prescribing for
sore throat symptoms: a retrospective study. BMC Fam Pract 2018;19(1):175.
34. Linder JA, Stafford RS. Antibiotic treatment of adults with sore throat by commu-
nity primary care physicians: a national survey, 1989-1999. JAMA 2001;286(10):
1181–6.
35. Bizune D, Tsay S, Palms D, et al. Regional variation in outpatient antibiotic pre-
scribing for acute respiratory tract infections in a commercially insured popula-
tion, United States, 2017. Open Forum Infect Dis 2023;10(2):ofac584.
36. Zhang Y, Steinman MA, Kaplan CM. Geographic variations in outpatient antibiotic
prescribing in older adults. Arch Intern Med 2012;172(19):1465–71.
37. Centers for Disease Control and Prevention. (2021). Antibiotic Use and Steward-
ship. Antibiotic Resistance and Patient Safety Portal. Available at: https://arpsp.
cdc.gov/profile/antibiotic-use?tab5antibiotic-use. Accessed May 1, 2023.
38. Centers for Disease Control and Prevention. (2021). All Antibiotic Classes. Anti-
biotic Resistance and Patient Safety Portal. Available at: https://arpsp.cdc.gov/
profile/antibiotic-use/all-classes. Accessed May 1, 2023.
39. Hersh AL, Shapiro DJ, Pavia AT, et al. Geographic variability in diagnosis and
antibiotic prescribing for acute respiratory tract infections. Infect Dis Ther 2018;
7(1):171–4.
40. Centers for Disease Control and Prevention. (2021, November 10). U.S. opioid
dispensing rate maps. Centers for Disease Control and Prevention. Available at:
https://www.cdc.gov/drugoverdose/rxrate-maps/index.html. Accessed May 1,
2023.
41. Chen J, Khazanchi R, Bearman G, et al. Racial/ethnic inequities in healthcare-
associated infections under the shadow of structural racism: narrative review
and call to action. Curr Infect Dis Rep 2021;23(10):17. Epub 2021 Aug 27.

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Infect Dis Clin N Am 37 (2023) 715–728

ANTIMICROBIAL PRESCRIBING INEQUITIES BY RACE AND ETHNICITY

ANTIMICROBIAL PRESCRIBING INEQUITIES BY AGE

Much of the literature assessing antimicrobial prescribing disparities by age comes

ANTIMICROBIAL PRESCRIBING INEQUITIES BY GENDER

Gender differences in timing of antimicrobial administration

Gender differences in antimicrobial stewardship recommendation acceptance

ANTIMICROBIAL PRESCRIBING INEQUITIES BY GEOGRAPHICAL REGION

Geographic variation in antimicrobial prescribing has been observed in the United

CLINICS CARE POINTS

Dr C. Evans has no commercial or financial conflicts to disclose relevant to this work.

1. Fortin-Leung K, Wiley Z. What about race and ethnicity in antimicrobial steward-

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