Each year in the United States, approximately two million persons become infected
with antibiotic-resistant bacteria, at least 23,000 persons die as a direct result
of these infections, and many more die from conditions complicated by a resistant
infection (1). Antibiotic-resistant infections contribute to poor health outcomes,
higher health care costs, and use of more toxic treatments (2). Although emerging
resistance mechanisms are being identified and resistant infections are on the rise,
new antibiotic development has slowed considerably (2).
Inappropriate antibiotic prescribing is an important and modifiable contributor to
antibiotic resistance and is a problem in all health care settings (1). Inappropriate
antibiotic use contributes to excess health care costs, promotes antibiotic resistance,
and contributes to preventable adverse drug reactions. Antibiotics cause approximately
142,000 adult emergency department visits annually for adverse drug reactions; almost
four out of five of these visits are for allergic reactions (3). Antibiotics also
contribute to both health care- and community-associated Clostridium difficile infections,
which are associated with considerable costs to patients and the health care system
(1,4). In 2009, approximately $10.7 billion was spent on antibiotic therapy in the
United States, including $6.5 billion, $3.6 billion, and $526.7 million in the outpatient,
inpatient acute, and long-term care settings, respectively (5). The cost of antibiotic
resistance to the U.S. economy is an estimated $20 billion annually in excess direct
health care costs, with an additional $35 billion in lost productivity (1).
Antibiotic prescribing must be tracked to understand and improve antibiotic use. Several
data sources and surveillance systems have been employed to examine antibiotic prescribing
in hospitals and the community. These include the National Ambulatory Medical Care
Survey, the National Hospital Ambulatory Medical Care Survey, the National Healthcare
Safety Network, claims data from health plans and insurance companies, and data from
private vendors (6). An accurate assessment of antibiotic prescribing, regardless
of clinical setting, is important to identify opportunities to improve prescribing
and maintain provider accountability.
An estimated half of antibiotic prescriptions given during pediatric ambulatory care
visits are inappropriate, and over one quarter of adult prescriptions are for conditions
for which antibiotics are rarely indicated (6,7). Health care providers prescribed
262.5 million courses of antibiotics in 2011 (842 prescriptions per 1000 persons),
and prescriptions per 1,000 persons vary markedly according to geography (8). The
highest prescribing states in 2011, Kentucky and West Virginia, had a rate more than
twice that of the lowest prescribing state (Alaska). Why such variability exists is
unclear, but this variability is unlikely to be explained by differences in population
distribution and extent of infectious diseases.
Inappropriate antibiotic use is not limited to the outpatient setting. A recent evaluation
of prescribing for inpatients in two specific scenarios (urinary tract infections
in patients without indwelling catheters and treatment with intravenous vancomycin)
identified that antibiotic use could have been improved in 37% of cases (9). Frequency
of antibiotic prescribing among inpatients varies considerably among hospitals. A
recent study of 19 hospitals that had completed data validation and submitted antibiotic
use data from one or more patient care settings, found threefold differences in usage
rates among 26 medical/surgical wards (9).
Visits for acute respiratory tract infections lead to more inappropriate antibiotic
prescribing than visits for any other group of diagnoses. For example, antibiotic
treatment for acute uncomplicated bronchitis is not recommended, and despite decades-long,
widespread efforts to curb antibiotic prescribing, in 2010, 71% of all outpatient
visits for this condition resulted in an antibiotic prescription (10). Similarly,
overprescribing for pharyngitis is common. Only 5%–10% of pharyngitis cases among
adults are caused by group A Streptococcus, for which antibiotic treatment is recommended,
yet antibiotics are prescribed for approximately 60% of ambulatory care visits for
adult pharyngitis (7). Outpatient antibiotic prescribing for children with acute respiratory
tract infections has been decreasing since the mid- to late-1990s, but the rate of
decline has slowed and might have reached a plateau (11). Several factors have been
hypothesized to have contributed to this decrease, including the increased use of
pneumococcal conjugate and influenza vaccines, national education campaigns to promote
appropriate antibiotic use, and increasing concern among both the general public and
health care professionals about antibiotic resistance.
In addition to the problem of overuse, antibiotic selection is often inappropriate.
Prescribers often choose second- or third-line antibiotics, which are typically broad-spectrum
drugs, despite established clinical practice guidelines recommending more targeted
agents. Overuse of broad-spectrum antibiotics (e.g., second- or third-generation cephalosporins,
fluoroquinolones) is especially problematic because of their potential for increased
selection of resistant bacterial populations and their role in treating serious infections.
Among U.S. ambulatory care visits during 2007–2009, broad-spectrum antibiotics accounted
for 74% of antibiotics prescribed to patients during visits for respiratory conditions
(7). Among hospitalized patients, 56% received an antibiotic during their stay and
30% received at least 1 dose of a broad-spectrum antibiotic (9).
Improving Prescribing and Antibiotic Stewardship
The goal of antibiotic stewardship is to maximize the benefit of antibiotic therapy
while minimizing harms to both the individual person and the community. Modest reductions
in antibiotic prescribing can make a substantial impact. One study predicted that
a 10% decrease in outpatient antibiotic prescribing rates would lead to a 16% decrease
in C. difficile infection incidence in the community (12). Likewise, reducing exposure
of hospitalized patients to broad-spectrum antibiotics by 30% can result in an estimated
26% reduction in inpatient C. difficile infections (9).
To reduce inappropriate prescribing, recent guidelines for common outpatient infections
emphasize stringent case definitions and clinical observation for mild cases. For
example, children aged ≥24 months with unilateral acute otitis media and mild symptoms
are less likely to benefit from antibiotics, and are good candidates for close observation
with shared decision-making that involves clinicians and caregivers. A mechanism for
follow-up in 48–72 hours in such cases is recommended (8).
Several interventions have been shown to improve antibiotic prescribing. Audit and
feedback involves tracking individual provider prescribing behaviors and giving feedback
on their performance relative to peers or established benchmarks. Academic detailing
is a method that adapts some strategies developed by pharmaceutical companies to influence
prescribing behaviors that involves active, tailored, and personalized education to
promote desired behaviors. Clinical decision support can be integrated with electronic
health records to promote appropriate prescribing practices for common infections.
Effective ambulatory care interventions have been summarized previously (13) and may
be adapted to different settings. Although no single intervention can improve all
prescribing behaviors in a given outpatient setting, multifaceted interventions involving
active provider education appear to have the greatest benefit. Evidence increasingly
supports the reduction of unnecessary antibiotic use through delayed prescribing strategies,
where patients are given an antibiotic prescription to be filled within a specified
timeframe if symptoms do not improve (8).
Measures promoting appropriate antibiotic prescribing in inpatient settings are primarily
implemented through antimicrobial stewardship programs, which CDC recommends for all
hospitals in the United States (http://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html)
(9). In a recent review of hospital interventions to improve antibiotic prescribing
(14), both restrictive interventions (e.g., required approval from an infectious disease
specialist to order certain antibiotics) and persuasive interventions (e.g., audit
and feedback on prescribing behaviors or provider education) appeared to be equally
effective after approximately 6 months. Interventions intended to reduce excess antibiotic
prescribing have also been associated with reductions in C. difficile infection, and
a meta-analysis of clinical outcomes found no significant increases in mortality caused
by reductions in antibiotic prescribing when intervention groups were compared with
controls (risk for mortality 0.92; 95% confidence interval = 0.81–1.06).
Educational campaigns aim to decrease inappropriate antibiotic prescribing by promoting
judicious prescribing among providers and by increasing general public and provider
knowledge about antibiotic resistance. Strategies to further employ appropriate antibiotic
use messages include distribution of public health messages via pharmacies, child
daycare centers, and workplaces. The CDC “Get Smart: Know When Antibiotics Work” and
“Get Smart for Healthcare” campaigns (http://www.cdc.gov/getsmart) inform consumers
and providers about antibiotic use and resistance, promote adherence to clinical practice
guidelines, and support state- and local-level appropriate antibiotic use programs.
Challenges, Success Factors, and Directions for the Future
Although guidelines exist for diagnosis and treatment of common infections, diagnostic
uncertainty remains a challenge. Health care providers are frequently influenced by
psychosocial factors which drive prescribing decisions, including concerns for both
patient satisfaction with a clinical visit and potential negative consequences because
of missed diagnoses (15). Providers are also concerned about losing dissatisfied patients
to other providers who might be more likely to prescribe antibiotics. Patients who
are aware of the potential risks for antibiotic overuse might still express a preference
for antibiotic treatment because of perceived benefits. Antibiotic stewardship interventions
and educational efforts aimed at addressing both diagnostic uncertainty and patient
expectations will remain important.
Interventions to improve antibiotic prescribing have proven effective in the short-term
and within specific settings. It remains less clear which interventions are sustainable
and scalable. For this reason, strong stakeholder partnerships and buy-in at the personal,
clinic, and health care system levels are fundamental to improving antibiotic prescribing.
CDC is working with federal partners, including the Centers for Medicare and Medicaid
Services, the U.S. Food and Drug Administration, and the Veterans Health Administration
to improve prescribing. CDC partnerships with nonfederal stakeholders, such as vendors
of antibiotic prescribing data, state health departments, and professional medical
societies are also important.
In March 2015, The National Action Plan for Combating Antibiotic-Resistant Bacteria
was released, outlining key actions to combat antibiotic resistance in the United
States (https://www.whitehouse.gov). These actions include preventing the development
and spread of resistant infections, increasing surveillance efforts, developing new
drugs and diagnostic tests, and promoting international collaboration to prevent and
control antibiotic resistance. In the United States, changes in health care delivery
and increased implementation of quality measures provide opportunities to integrate
antibiotic stewardship practices. Tracking antibiotic prescribing, regardless of clinical
setting, is important in identifying opportunities to improve prescribing and maintain
provider accountability. Priority should be placed on reducing prescribing for diagnoses
for which inappropriate antibiotic prescribing is common (e.g., acute bronchitis)
and on U.S. regions with higher antibiotic prescription rates. Reducing inappropriate
antibiotic use and addressing the threat of antibiotic resistance is critical to improve
health care quality and to safeguard patient safety across all health care settings.