Inappropriate Antibiotic Prescribing in Managed Care Subjects With Influenza

Retrospective analysis of the US Impact National Benchmark Database indicated that 80% of antibiotics prescribed in subjects with influenza were inappropriate.
Published Online: September 06, 2011
Derek A. Misurski, RPh, PhD; David A. Lipson, MD; and Arun K. Changolkar, PhD

Objectives: To evaluate costs of inappropriate oral antibiotic prescribing in a managed care population with influenza.


Methods: This was a retrospective (January 1, 2005, through December 31, 2009) analysis of the US Impact National Benchmark Database. Patients with an influenza diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 487.xx) and continuous health plan enrollment for >12 months before and 1 month after the index influenza diagnosis date were included. We identified patients with an antibiotic prescription claim within 3 days before or 3 days after the index influenza diagnosis date. Patients were classified as having received appropriate antibiotic treatment if a secondary respiratory infection was observed within the 2-week postindex period or if there was a previous comorbid diagnosis of diabetes, congestive heart failure, chronic obstructive pulmonary disease, asthma, acute myocardial infarction, or sickle cell anemia as identified by ICD-9-CM codes.


Results: We identified 270,057 subjects with influenza (mean age, 31.6 years). Antibiotics were prescribed in 58,477 (21.65%) patients. Among patients receiving antibiotics, 99% did not have a follow-up diagnosis for a respiratory bacterial infection and 79% had neither a secondary infection nor evidence of a comorbidity (ie, received inappropriate antibiotic treatment). Based on a conservative annual seasonal influenza rate of 10%, we estimated that inappropriate antibiotic prescribing for influenza costs the United States approximately $211 million annually.


Conclusions: Empiric antibiotics were inappropriately prescribed in a high percentage of influenza patients. This represents a significant financial burden to the US healthcare system and may contribute to increased antibiotic resistance.


(Am J Manag Care. 2011;17(9):601-608)

Using retrospective analysis of the US Impact National Benchmark Database, we evaluated the costs of inappropriate oral antibiotic prescribing in a managed care population with influenza.


  • Antibiotics were prescribed inappropriately in about 80% of subjects with influenza.


  • The mean cost of an antibiotic prescription in those with influenza was $40.09.


  • Extrapolated to the entire US population, the inappropriate prescribing of antibiotics for subjects with influenza costs more than $200 million.
Influenza is a highly contagious respiratory illness. In the United States, the seasonal influenza epidemic typically occurs in the late fall or early winter months and usually lasts through the spring.1 Annually, approximately 10% to 20% of the US population develops influenza.2 In the United States, influenza A (H3N2) and B viruses are the primary causes of the seasonal influenza epidemic. However, the 2009 influenza pandemic was the result of a new influenza A (H1N1) virus, which resulted in an estimated 12,500 deaths in the United States.3 In the last 30 years the average annual number of influenzarelated deaths with underlying respiratory and circulatory causes has been approximately 23,600, with the majority of deaths (89%) occurring in patients at least 65 years of age.4 The high morbidity and mortality associated with influenza result in substantial productivity losses5 and exert a significant direct and indirect economic burden on the US healthcare system.6 Additionally, a recent study reported that from 2004 to 2008, influenza was the fastest growing disease state in terms of healthcare spending by employers.7

While the mainstay of influenza prevention is immunization, several antiviral medications including oseltamivir, zanamivir, rimantadine, and amantadine are approved for influenza treatment and chemoprophylaxis. In addition to antivirals, empiric antibiotic use (defined as antibiotic use despite a lack of adequate evidence confirming the presence of infection) is a common treatment approach for influenza patients.8-10 Guidelines on clinical management of pandemic influenza patients recommend antibiotic prescribing only among patients who (1) experience worsening of influenza symptoms (eg, increasing breathlessness or recrudescent fever) during the course of illness; (2) have severe preexisting illness or chronic obstructive pulmonary disease (COPD); or (3) have influenza-related pneumonia or are at a high risk of developing influenza-related complications or secondary infections (eg, respiratory disorders, heart disease, renal disease).11 While these recommendations were made in the context of pandemic influenza, antibiotic use is generally not recommended among “seasonal” influenza patients with uncomplicated influenza either.12

Despite current guidelines, unnecessary antibiotic use in influenza continues to be a problem, contributing to the ongoing public health problem of antibiotic drug resistance.8-10 High rates of antibiotic use among patients with respiratory tract infections including influenza have been documented in several previous studies.8-10,13 Unnecessary prescription antibiotics also exert a significant cost burden on healthcare systems.10,13 The use of empiric oral antibiotics among patients with influenza has not been evaluated retrospectively in a US pharmacy and medical claims database. Therefore, the objective of this study was to assess real-world empiric oral antibiotic prescribing and the associated cost of inappropriate prescribing in a large population of influenza patients enrolled in managed care health plans in the United States.


Study Design and Data Source

In this longitudinal retrospective cohort study, we analyzed patient-linked administrative claims data from the United States Impact National Benchmark Database for the years 1997 to 2009. The database consists of administrative insurance claims from a national sample of more than 40 managed care health plans covering approximately 90 million lives and is representative of the US managed care population. Details on adjudicated medical (eg, inpatient, physician office, outpatient) claims, pharmacy claims, and associated costs along with information on health plan enrollment and demographic characteristics are included in the database. The age and sex distribution of health plan enrollees in the Impact National Benchmark Database is representative of national managed care enrollment.14

Patient Selection

We initially selected patients with a diagnosis of influenza (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code 487.xx)10,13 recorded in the medical claims file during the period January 1, 2005, to November 30, 2009. The date of the first influenza diagnosis claim during this period defined the study index date. Patients were required to have continuous health plan enrollment for at least 12 months before and 1 month after the index date. We excluded patients with a diagnosis for conditions requiring antibiotic treatment during the 12-month preindex period (Table 1). To comprehensively identify comorbidities, we looked back as far as data was available for each subject.

Outcome Measures

The primary outcome for this study was to assess the frequency of inappropriate oral antibiotic prescribing among influenza patients. We classified patients based on the presence (antibiotic users) or absence (antibiotic nonusers) of a prescription for an antibiotic medication (see eAppendix at for medication list) within the 3-day preindex to 3-day postindex period. Patients were further classified based on the presence or absence of a secondary bacterial respiratory infection (ICD-9-CM codes available upon request) within a 15-day period following the index date. They were also classified according to the presence or absence of at least 1 related comorbidity. Comorbidities of interest were diabetes, congestive heart failure (CHF), COPD, asthma, acute myocardial infarction (AMI), and sickle cell anemia (ICD-9-CM codes available upon request).

Among patients who received an antibiotic during the 3-day preindex to 3-day postindex period, prescribing of the antibiotic was classified as “appropriate” if these patients also had a diagnosis for a secondary bacterial respiratory infection during the ensuing 15 days or a comorbidity of interest during the preindex period. Accordingly, antibiotic prescribing was considered “inappropriate” in influenza patients who did not have a diagnosis for a secondary infection or evidence of comorbidity. Cost estimates were limited to reimbursements for prescriptions only; thus, costs attributable to other drugs or service categories were not considered. Costs were estimated separately for patients receiving appropriate and inappropriate antibiotic treatment (2009 dollars). Of note, this study also focused only on oral antibiotics in order to illustrate the clinical challenge physicians face in the absence of a definitive influenza diagnosis in the outpatient setting. Thus, the cost associated with inappropriate inpatient prescribing of antibiotics was beyond the scope of the current study.

Background Patient Characteristics

Background patient characteristics considered for this study included patient demographics and baseline (ie, 12-month preindex) comorbidity burden. Patient demographic characteristics included age, sex, geographic region, payer type, and plan type. Baseline comorbidity burden was assessed using the Deyo adaptation of the Charlson Comorbidity Index, which includes 17 categories of conditions identified using ICD-9-CM codes, with corresponding weights that are aggregated into a composite comorbidity score.15 We also assessed whether or not patients received an antiviral medication within 1 day of the preindex or 1 day of the postindex date.

Statistical Analyses

All statistical analyses were conducted using SAS version 9.1.3 (SAS Institute Inc, Cary, North Carolina). All analyses were descriptive. Unadjusted, descriptive statistics were generated for all analysis variables, which included frequency distributions for categorical variables and mean values and standard deviations for continuous variables.


Baseline Patient Characteristics

Figure 1 presents the sample attrition resulting from the study inclusion criteria. The final study cohort consisted of 270,057 influenza patients, with a mean (SD) age

of 31.6 (18.9) years (Table 2). Approximately 52% of the selected patients were male and more than 47% resided in the South. Of the 5 comorbidities of interest, asthma was the most commonly observed (10.4% of patients), followed by diabetes (6.0%), COPD (2.8%), CHF (1.0%), AMI (0.7%), and sickle cell anemia (0.08%). Overall, 112,610 (41.7%) of patients received at least 1 antiviral medication.

Antibiotic Prescribing

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