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 Development's 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 visit's 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
[1]
R. Hamm,et al.
Antibiotics and respiratory infections: are patients more satisfied when expectations are met?
,
1996,
The Journal of family practice.
[2]
P. Shekelle,et al.
Evidence assessment of management of acute otitis media: I. The role of antibiotics in treatment of uncomplicated acute otitis media.
,
2001,
Pediatrics.
[3]
J. Blair,et al.
The cephalosporins.
,
1999,
Mayo Clinic proceedings.
[4]
D. Scholes,et al.
Increasing prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in women.
,
1999,
JAMA.
[5]
K. O'Brien,et al.
Acute Sinusitis—Principles of Judicious Use of Antimicrobial Agents
,
1998,
Pediatrics.
[6]
J. Lau,et al.
Meta-analysis of randomized controlled trials on the comparative efficacy and safety of azithromycin against other antibiotics for upper respiratory tract infections.
,
2001,
The Journal of antimicrobial chemotherapy.
[7]
M. Loeb,et al.
Why are antibiotics prescribed for asymptomatic bacteriuria in institutionalized elderly people? A qualitative study of physicians' and nurses' perceptions.
,
2000,
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.
[8]
R. Gonzales,et al.
Principles of Appropriate Antibiotic Use for Treatment of Nonspecific Upper Respiratory Tract Infections in Adults: Background
,
2001,
Annals of Internal Medicine.
[9]
R A Weinstein,et al.
Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in Hospitals. A challenge to hospital leadership.
,
1996,
JAMA.
[10]
R. Stafford,et al.
Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999.
,
2001,
JAMA.
[11]
A. van der Kuy,et al.
[The penicillins].
,
1974,
Tijdschrift voor ziekenverpleging.
[12]
Resistance of Streptococcus pneumoniae to fluoroquinolones--United States, 1995-1999.
,
2001,
MMWR. Morbidity and mortality weekly report.
[13]
Ralph Gonzales,et al.
Changing Use of Antibiotics in Community-Based Outpatient Practice, 19911999
,
2003,
Annals of Internal Medicine.
[14]
G. Doern.
Antimicrobial use and the emergence of antimicrobial resistance with Streptococcus pneumoniae in the United States.
,
2001,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
[15]
R. Gonzales,et al.
Principles of Appropriate Antibiotic Use for Treatment of Acute Bronchitis in Adults
,
2001,
Annals of Internal Medicine.
[16]
R. Gonzales,et al.
What will it take to stop physicians from prescribing antibiotics in acute bronchitis?
,
1995,
The Lancet.
[17]
M. Cetron,et al.
Minimizing the impact of drug-resistant Streptococcus pneumoniae (DRSP). A strategy from the DRSP Working Group.
,
1996,
JAMA.
[18]
A. Wazana,et al.
Physicians and the pharmaceutical industry: is a gift ever just a gift?
,
2000,
JAMA.
[19]
M. Chren,et al.
Physicians' behavior and their interactions with drug companies. A controlled study of physicians who requested additions to a hospital drug formulary.
,
1994,
JAMA.
[20]
P Huovinen,et al.
The effect of changes in the consumption of macrolide antibiotics on erythromycin resistance in group A streptococci in Finland. Finnish Study Group for Antimicrobial Resistance.
,
1997,
The New England journal of medicine.
[21]
W. Stamm,et al.
Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis.
,
2001,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
[22]
T. Bodenheimer,et al.
Uneasy alliance--clinical investigators and the pharmaceutical industry.
,
2000,
The New England journal of medicine.
[23]
S. Dowell,et al.
Acute otitis media: management and surveillance in an era of pneumococcal resistance--a report from the Drug-resistant Streptococcus pneumoniae Therapeutic Working Group.
,
1999,
The Pediatric infectious disease journal.
[24]
H. Neu,et al.
The Crisis in Antibiotic Resistance
,
1992,
Science.
[25]
R. Gonzales,et al.
Principles of Appropriate Antibiotic Use for Treatment of Nonspecific Upper Respiratory Tract Infections in Adults
,
2001,
Annals of Internal Medicine.
[26]
J. Enders,et al.
Infectious Diseases Society of America.
,
1969,
Antimicrobial agents and chemotherapy.
[27]
E. Hemminki,et al.
Review of literature on the factors affecting drug prescribing.
,
1975,
Social science & medicine.
[28]
J. Hickner,et al.
Principles of Appropriate Antibiotic Use for Acute Sinusitis in Adults
,
2001,
Annals of Internal Medicine.
[29]
R Hartley,et al.
Scientific versus commercial sources of influence on the prescribing behavior of physicians.
,
1982,
The American journal of medicine.
[30]
S. Dowell,et al.
Pharyngitis—Principles of Judicious Use of Antimicrobial Agents
,
1998,
Pediatrics.
[31]
Michael J Fine,et al.
Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults
,
2000,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
[32]
M. Cetron,et al.
Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United States.
,
2000,
The New England journal of medicine.
[33]
Susan R. Johnson,et al.
Macrolide Resistance among Invasive Streptococcus Pneumoniae Isolates
,
2022
.
[34]
Jerry Avorn,et al.
Cultural and Economic Factors That (Mis)Shape Antibiotic Use: The Nonpharmacologic Basis of Therapeutics
,
2000,
Annals of Internal Medicine.
[35]
J. Hughes,et al.
Trends in antimicrobial drug prescribing among office-based physicians in the United States.
,
1995,
JAMA.
[36]
J. Avorn,et al.
Improving drug prescribing in primary care: a critical analysis of the experimental literature.
,
1989,
The Milbank quarterly.
[37]
T. Hooton,et al.
Increasing Antimicrobial Resistance and the Management of Uncomplicated Community-Acquired Urinary Tract Infections
,
2001,
Annals of Internal Medicine.
[38]
D E Low,et al.
Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. Canadian Bacterial Surveillance Network.
,
1999,
The New England journal of medicine.
[39]
Anthony E. McDavid.
Acute Otitis Media: Management and Surveillance in an Era of Pneumococcal Resistance-A Report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group
,
2000
.
[40]
D. Low,et al.
Antimicrobial drug use and resistance among respiratory pathogens in the community.
,
2001,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
[41]
J. Piccirillo,et al.
Impact of first-line vs second-line antibiotics for the treatment of acute uncomplicated sinusitis.
,
2001,
JAMA.
[42]
L. G. Smith,et al.
Beta-lactamase inhibitor combinations.
,
1995,
The Medical clinics of North America.
[43]
R. Stafford,et al.
National patterns in the treatment of urinary tract infections in women by ambulatory care physicians.
,
2002,
Archives of internal medicine.
[44]
A. Sauaia,et al.
Office Evaluation and Treatment of Elderly Patients with Acute Bronchitis
,
2004,
Journal of the American Geriatrics Society.
[45]
J. Avorn,et al.
Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based "detailing".
,
1983,
The New England journal of medicine.
[46]
S. Mcphee,et al.
Of principles and pens: attitudes and practices of medicine housestaff toward pharmaceutical industry promotions.
,
2001,
The American journal of medicine.
[47]
L. Rice,et al.
Effect of antibiotic therapy on the density of vancomycin-resistant enterococci in the stool of colonized patients.
,
2000,
The New England journal of medicine.
[48]
Vincenza Snow,et al.
Principles of Appropriate Antibiotic Use for Acute Pharyngitis in Adults
,
2001,
Annals of Internal Medicine.
[49]
P. Appelbaum.
Microbiological and pharmacodynamic considerations in the treatment of infection due to antimicrobial-resistant Streptococcus pneumoniae.
,
2000,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
[50]
J. Córdoba-Doña,et al.
Multivariate analysis of risk factors for infection due to penicillin-resistant and multidrug-resistant Streptococcus pneumoniae: a multicenter study.
,
1997,
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.
[51]
J Ogden,et al.
General practitioners' experiences of patients' complaints: qualitative study
,
1999,
BMJ.
[52]
W. Scheld,et al.
Fluoroquinolones: how to use (but not overuse) these antibiotics.
,
1993,
Geriatrics.
[53]
Ralph Gonzales,et al.
Predictors of broad-spectrum antibiotic prescribing for acute respiratory tract infections in adult primary care.
,
2003,
JAMA.
[54]
Stephen B. Soumerai,et al.
Improving Drug-Therapy Decisions through Educational Outreach
,
1983
.
[55]
S. Dowell,et al.
The Common Cold—Principles of Judicious Use of Antimicrobial Agents
,
1998,
Pediatrics.
[56]
R. Anderson,et al.
The relationship between the volume of antimicrobial consumption in human communities and the frequency of resistance.
,
1999,
Proceedings of the National Academy of Sciences of the United States of America.
[57]
K. O'Brien,et al.
Cough Illness/Bronchitis—Principles of Judicious Use of Antimicrobial Agents
,
1998,
Pediatrics.
[58]
B. Bloom,et al.
Daily regimen and compliance with treatment
,
2001,
BMJ : British Medical Journal.