Jeffrey A. Linder

Changing Use of Antibiotics in Community-Based Outpatient Practice, 1991-1999

Context Indiscriminate use of antibiotics promotes the development of antibiotic-resistant strains of bacteria. Contribution This survey of patient visits to community-based clinics shows that antibiotic use for ambulatory infections, especially upper respiratory tract infections, decreased from 19911992 to 19981999. However, the use of broad-spectrum antibiotics rose over this period. Implications Efforts to encourage rational use of antibiotics should focus on which antibiotic to use as well as whether or not to use antibiotics. The Editors Over the past decade, antibiotic resistance has increased substantially in the United States (1-3). In response, many experts have advocated a judicious approach to antibiotic use in both inpatient and outpatient settings (4-6). Such an approach may decrease community rates of antibiotic resistance, even to older drugs with long-standing histories of resistance (7, 8). Similarly, judicious use of potent newer agents may preserve their utility in the treatment of severe or complicated infections, forestalling the emergence of widespread resistance (9, 10). In a landmark study, McCaig and Hughes (11) documented increasing outpatient use of amoxicillin and the cephalosporins between 1980 and 1992 in the United States. Over the past decade, several studies and interventions have focused on the excess use of antibiotics. However, only recently has increasing attention been paid to the type of agents being prescribed (12-14). As a result, relatively little is known about the impact of antibiotic prescribing choices on quality of care, health care costs, and antibiotic resistance. In this study, we used a large, nationally representative sample of community-based physicians to evaluate outpatient antibiotic prescribing during the 1990s. First, we examined the ways in which patterns of antibiotic use have changed over the past decade, particularly among broad-spectrum agents such as azithromycin and clarithromycin, quinolones, amoxicillinclavulanate, and second- and third-generation cephalosporins. Next, we determined the association between these patterns of use and clinical factors related to the need for broad-spectrum therapy. Methods National Ambulatory Medical Care Survey We used the National Ambulatory Medical Care Survey (NAMCS) to collect data on outpatient antibiotic use. We collapsed 6 survey years into three study periods (19911992, 19941995, and 19981999), combining data from consecutive years to add power to our analyses. The NAMCS is an annual sample of outpatient visits to office-based community physicians who are principally engaged in patient care. Patient care encounters in emergency departments or hospital-based clinics and visits outside the office (for example, house calls or nursing home visits) were not recorded. Visits were sampled by using a multistage clustered probability sample design based on geographic location, provider specialty, and visits within individual physician practices. When patient weights are used, these data can be extrapolated to the approximately 650 million community-based outpatient visits that occur in the United States each year (15). Participation in the survey ranged from 63% to 73% of invited practices, with different physicians and patients being surveyed each year (15, 16). The NAMCS collected information on up to five (19911994) or six (19951999) medications prescribed for each patient at the conclusion of his or her visit, including both new and ongoing prescriptions. The NAMCS also collected data on up to three physician diagnoses related to the visit, including new diagnoses and ongoing medical conditions. All data, including demographic char acteristics, were recorded by the physician or by office staff completing the visit encounter form. Design and Classification We were interested in the use of oral and intramuscular antibiotics, but the NAMCS does not provide information on the route of drug administration. We therefore excluded patient visits to dermatologists and ophthalmologists because these specialists frequently prescribe topical antibiotics, which we could not distinguish from systemic forms of the same drugs. Visits to these specialists made up approximately 10% of patient encounters in each study period. Among the remaining sample, 60 252 visits were recorded in 19911992, 62 169 visits were recorded in 19941995, and 37 467 visits were recorded in 19981999. The smaller sample size in the last study period reflects a smaller number of visits surveyed by the NAMCS in those years. We divided the remaining sample into patient visits that did and did not involve an antibiotic. Antimicrobial medications used by outpatients almost exclusively in topical or intravenous form, such as polymyxins and aminoglycosides, were not counted as antibiotics. We also did not count antimycobacterial medications as antibiotics because they are infrequently used for typical bacterial infections. Antibiotic use, according to these criteria, was recorded in 8208 sampled visits in 19911992, 7944 visits in 19941995, and 4200 visits in 19981999. In each study period, 3% to 4% of these visits involved the use of more than one antibiotic. In total, there were 8514 antibiotic prescriptions in 19911992, 8308 antibiotic prescriptions in 19941995, and 4406 antibiotic prescriptions in 19981999. For the purposes of this study, we defined broad-spectrum agents as azithromycin and clarithromycin, quinolones, amoxicillinclavulanate, and second- and third-generation cephalosporins (17). Many of the broad-spectrum agents we studied were introduced more recently than narrow-spectrum ones. All nine narrow-spectrum agents that made up at least 2% of total antibiotic prescriptions in any study period received U.S. Food and Drug Administration approval before 1979. Among broad-spectrum agents that made up at least 2% of total antibiotic prescriptions, Food and Drug Administration approval was granted between 1979 and 1984 for amoxicillinclavulanate, cefaclor, and cefuroxime; in 1987 for ciprofloxacin; in 1991 for azithromycin, cefprozil, and clarithromycin; and in 1996 for levofloxacin (Bergman E. Personal communication. Publically available data from the Tufts Center for the Study of Drug Developments approved products database). Patients were considered to have a common infectious condition if the corresponding International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code appeared as the first, second, or third diagnosis for that visit (18). Diagnoses included nasopharyngitis (the common cold) or upper respiratory tract infection not otherwise specified (ICD-9-CM codes 460, 465); acute or chronic sinusitis (ICD-9-CM codes 461, 473); pharyngitis and streptococcal sore throat (ICD-9-CM codes 462, 34.0); suppurative or nonsuppurative otitis media (ICD-9-CM codes 381.0381.4, 382); acute or acute-on-chronic bronchitis and bronchiolitis (ICD-9-CM codes 466, 490, 491.21); acute tonsillitis, laryngitis, and tracheitis (ICD-9-CM codes 463464); bacterial or unspecified pneumonia (ICD-9-CM codes 481483, 485486); urinary tract infection or acute or unspecified cystitis (ICD-9-CM codes 599.0, 595.0, 595.9); cellulitis, carbuncle, or furuncle (ICD-9-CM codes 680682); prostatitis or pelvic inflammatory disease (ICD-9-CM codes 601, 614); and sexually transmitted diseases, including syphilis, gonococcal infections, and other venereal infections (ICD-9-CM codes 9099, 647.0647.2). In each study period, 11% to 13% of patients who were prescribed antibiotics received a diagnosis of more than one of these infectious conditions. To prevent confusion over which disease was treated by the listed antibiotics, we excluded these patients from the diagnosis-specific analyses. Among adults with a single diagnosis of an infectious disease, there were 1657 visits for the common cold and unspecified upper respiratory tract infections, 2652 visits for sinusitis, 963 visits for pharyngitis, 908 visits for otitis media, 1674 visits for acute bronchitis, and 1636 visits for urinary tract infection over the entire study period. Among children, there were 1976 visits for the common cold and unspecified upper respiratory tract infections, 651 visits for sinusitis, 1120 visits for pharyngitis, 3107 visits for otitis media, and 625 visits for acute bronchitis. Statistical Analysis We analyzed overall antibiotic use for a given patient at the level of the patient visit. Individual prescriptions were analyzed at the level of the antibiotic prescription. For example, a patient visit involving amoxicillin and ciprofloxacin would be counted twice, once for each medication. We did not account for clustering of more than one antibiotic in a single visit because only 3% to 4% of visits at which an antibiotic was prescribed in each period involved more than one antibiotic. To make our point estimates nationally representative, we used patient weights, which weight each visits contribution in inverse proportion to the likelihood of that visit being sampled from all community-based visits (15, 19). Patient weight can be interpreted as the number of visits in the population that the sampled visit represents. To adjust for the effects of survey design on standard errors, we clustered our analyses at the level of the physician. This accounts for correlation among outcomes sampled from the same physician and increases the standard errors to account for weighting and clustering within physicians. Identifiers of the true primary sampling unit (county or county equivalent) were not available to the public at the time this study was performed and therefore could not be used in our analyses. As a result, the calculated variances and point estimates in our analyses may differ slightly from those in analyses that incorporate both the primary and secondary sampling units. We conducted all analyses using the design-based F test, comparing the first study period (19911992) with the

Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011

IMPORTANCE The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. OBJECTIVE To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. DESIGN, SETTING, AND PARTICIPANTS Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. EXPOSURES Ambulatory care visits. MAIN OUTCOMES AND MEASURES Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. RESULTS Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. CONCLUSIONS AND RELEVANCE In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Healthcare utilization and cost of pneumococcal disease in the United States

BACKGROUND Streptococcus pneumoniae continues to cause a variety of common clinical syndromes, despite vaccination programs for both adults and children. The total U.S. burden of pneumococcal disease is unknown. METHODS We constructed a decision tree-based model to estimate U.S. healthcare utilization and costs of pneumococcal disease in 2004. Data were obtained from the 2004-2005 National (Hospital) Ambulatory Medical Care Surveys (outpatient visits, antibiotics) and the National Hospital Discharge Survey (hospitalization rates), and CDC surveillance data. Other assumptions regarding the incidence of each syndrome due to pneumococcus, expected health outcomes, and healthcare utilization were derived from literature and expert opinion. Healthcare and time costs used 2007 dollars. RESULTS We estimate that, in 2004, pneumococcal disease caused 4.0 million illness episodes, 22,000 deaths, 445,000 hospitalizations, 774,000 emergency department visits, 5.0 million outpatient visits, and 4.1 million outpatient antibiotic prescriptions. Direct medical costs totaled

Antibiotic Prescribing to Adults With Sore Throat in the United States, 1997-2010

3.5 billion. Pneumonia (866,000 cases) accounted for 22% of all cases and 72% of pneumococcal costs. In contrast, acute otitis media and sinusitis (1.5 million cases each) comprised 75% of cases but only 16% of direct medical costs. Patients ≥ 65 years old, accounted for most serious cases and the majority of direct medical costs (

Antibiotic prescribing for adults with acute bronchitis in the United States, 1996-2010.

1.8 billion in healthcare costs annually). In this age group, pneumonia caused 242,000 hospitalizations, 1.4 million hospital days, 194,000 emergency department visits, 374,000 outpatient visits, and 16,000 deaths. However, if work loss and productivity are considered, the cost of pneumococcal disease among younger working adults (18-<50) nearly equaled those ≥ 65. CONCLUSIONS Pneumococcal disease remains a substantial cause of morbidity and mortality even in the era of routine pediatric and adult vaccination. Continued efforts are warranted to reduce serious pneumococcal disease, especially adult pneumonia.

Complementary methods of system usability evaluation: Surveys and observations during software design and development cycles

Antibiotic Prescribing to Adults With Sore Throat in the United States, 1997-2010 Among adults seeking care with sore throat, the prevalence of group A Streptococcus (GAS) infection—the only common cause of sore throat requiring antibiotics—is about 10%.1 Penicillin remains the antibiotic of choice. Penicillin is narrowspectrum, well-tolerated, and inexpensive, and GAS is universally susceptible to penicillin. We previously found that the antibiotic prescribing rate for adults making a visit with sore throat dropped from about 80% to 70% around 1993.2 Since then, the Centers for Disease Control and Prevention and others have continued efforts to reduce inappropriate antibiotic prescribing.3-5 To measure changes in antibiotic prescribing for adults with sore throat, we conducted a cross-sectional analysis of ambulatory visits in the United States.

An electronic health record-based intervention to improve tobacco treatment in primary care: a cluster-randomized controlled trial.

Acute bronchitis is a cough-predominant acute respiratory illness of less than 3 weeks’ duration. For over 40 years, trials have shown that antibiotics are not effective for acute bronchitis.1 Despite this, between 1980 and 1999, the acute bronchitis antibiotic prescribing rate in the United States was between 60% and 80%.2 Over the past 15 years, the Centers for Disease Control and Prevention (CDC) has spearheaded efforts to decrease antibiotic prescribing for acute bronchitis.3,4 Since 2005, a Healthcare Effectiveness Data and Information Set (HEDIS) measure has stated that the antibiotic prescribing rate for acute bronchitis should be zero.5 To assess the effectiveness of ongoing CDC efforts and the implementation of the HEDIS measure, we estimated the antibiotic prescribing rate for acute bronchitis in the United States between 1996 and 2010.

Association between antibiotic prescribing and visit duration in adults with upper respiratory tract infections

Poor usability of clinical information systems delays their adoption by clinicians and limits potential improvements to the efficiency and safety of care. Recurring usability evaluations are therefore, integral to the system design process. We compared four methods employed during the development of outpatient clinical documentation software: clinician email response, online survey, observations and interviews. Results suggest that no single method identifies all or most problems. Rather, each approach is optimal for evaluations at a different stage of design and characterizes different usability aspect. Email responses elicited from clinicians and surveys report mostly technical, biomedical, terminology and control problems and are most effective when a working prototype has been completed. Observations of clinical work and interviews inform conceptual and workflow-related problems and are best performed early in the cycle. Appropriate use of these methods consistently during development may significantly improve system usability and contribute to higher adoption rates among clinicians and to improved quality of care.

Time of Day and the Decision to Prescribe Antibiotics

BACKGROUND To improve the documentation and treatment of tobacco use in primary care, we developed and implemented a 3-part electronic health record enhancement: (1)smoking status icons, (2) tobacco treatment reminders, and (3) a Tobacco Smart Form that facilitated the ordering of medication and fax and e-mail counseling referrals. METHODS We performed a cluster-randomized controlled trial of the enhancement in 26 primary care practices between December 19, 2006, and September 30, 2007. The primary outcome was the proportion of documented smokers who made contact with a smoking cessation counselor. Secondary outcomes included coded smoking status documentation and medication prescribing. RESULTS During the 9-month study period, 132 630 patients made 315 962 visits to study practices. Coded documentation of smoking status increased from 37% of patients to 54% (+17%) in intervention practices and from 35% of patients to 46% (+11%) in control practices (P < .001 for the difference in differences). Among the 9589 patients who were documented smokers at the start of the study, more patients in the intervention practices were recorded as nonsmokers by the end of the study (5.3% vs 1.9% in control practices; P < .001). Among 12 207 documented smokers, more patients in the intervention practices made contact with a cessation counselor (3.9% vs 0.3% in control practices; P < .001). Smokers in the intervention practices were no more likely to be prescribed smoking cessation medication (2% vs 2% in control practices; P = .40). CONCLUSION This electronic health record-based intervention improved smoking status documentation and increased counseling assistance to smokers but not the prescription of cessation medication.

Desire for antibiotics and antibiotic prescribing for adults with upper respiratory tract infections.

BACKGROUND Upper respiratory tract infections (URTIs) are the most common reason for individuals to seek health care in the United States. Inappropriate antibiotic use exposes patients unnecessarily to potential adverse events and increases the prevalence of antibiotic-resistant bacteria. One of the reasons physicians may prescribe an antibiotic inappropriately is to save time. OBJECTIVE The aim of this study was to determine whether there is an association between antibiotic use and a shorter visit duration in adults with URTIs. METHODS Visits to office-based primary care physicians made by adults aged 18 to 60 years from 1995 through 2000 were extracted from the National Ambulatory Medical Care Survey. Visits that resulted in a primary diagnosis of acute URTI; acute nasopharyngitis; acute bronchitis; sinusitis; streptococcal sore throat, acute pharyngitis, or acute tonsillitis; or otitis media were included in the study. Visits associated with >1 diagnosis were included in a separate category Visit duration was defined as the face-to-face time between the patient and physician. RESULTS There were 3764 visits that met the criteria for inclusion in this study, representing an estimated 27 million annual visits to office-based primary care physicians by adults with URTIs. Antibiotics were prescribed in 67% of visits. The mean visit duration associated with prescription of an antibiotic was 14.2 minutes, compared with 15.2 minutes without prescription of an antibiotic (P = 0.007). In multivariable modeling, independent predictors of visit duration were calendar year (additional 0.3 minute per year; 95% CI, 0.1 to 0.6), internal medicine specialty (additional 2.2 minutes vs family practice; 95% CI, 1.3 to 3.1), covisit with a nurse-practitioner or physician assistant (6.6 minutes shorter; 95% CI, -2.7 to -10.6), and Midwestern location of practice (1.1 minutes shorter vs Northeast; 95% CI, -0.1 to -2.2). Antibiotic use was marginally associated with a shorter visit duration (0.7 minute shorter; 95% CI, 0.0 to -1.3; P = NS). CONCLUSIONS In the present study, antibiotic use was marginally associated with a shorter visit duration for adults with URTIs. Any potential efficiencies gained by physicians through prescribing antibiotics for adults with URTIs are likely to be outweighed by increases in antimicrobial resistance and exposure of patients to unneeded medication.