Anti-Infective Drug Utilization Review in Respiratory Tract Infections. Technical Report

Transcription

1 Anti-Infective Drug Utilization Review in Respiratory Tract Infections Technical Report Alberta Drug Utilization Program Alberta Management Committee on Drug Utilization (AMCDU)/ Alberta Drug Utilization Program (ADUP) University of Alberta November 2003

2 Research and Design Catherine V. McCann, B. Sc. Pharm., MBA Drug Utilization Review Proposal Sub-Committees DUR Advisory Panel AMCDU Members Data Processing William Cheung, B.Sc. Pharm., B.Sc., M.Sc.(computing science) Data Analysis Susan Fryters, B. Sc. Pharm. Antimicrobial Utilization/Infectious Diseases Pharmacist Editing Alberta Drug Utilization Program (ADUP) Staff Writing of RTI reports Susan Fryters, B. Sc. Pharm. Antimicrobial Utilization/Infectious Diseases Pharmacist Summary of RTI reports compiled by Diane Blais, B.Pharm., M.Sc. Susan Fryters B. Sc. Pharm. Alberta Drug Utilization Program Antimicrobial Utilization/Infectious Diseases Pharmacist Revision Anita G. Carrie, Ph.D. William Cheung, B.Sc. Pharm., B.Sc., M.Sc.(computing science) DUR Advisory Panel AMCDU Members Art Design This publication can be requested from: Alberta Drug Utilization Program 305 Campus Tower Street Edmonton, AB T6G 1K8 Tel: (780) Fax: (780) Reproduction of this document for non-commercial purposes is permitted provided appropriate credit is given to ADUP. Legal Deposit 2003 National Library of Canada ISBN:

3 LIST OF AMCDU/ADUP MEMBERS Sy Lam, B.Sc.Pharm., MD, CCFP Co-chair Bob Porozni, B.Sc.Pharm. Co-chair David Bougher, BSP, MHSA Robert Burns, B.Sc., MD Lisa DeVos, B.Sc. Greg Eberhart, B.Sc.Pharm., CAE Graham Ferguson FLMI (ex-officio) Sheila Hughes, MD, CCFP Steve Long, B.Sc.Pharm., MBA Harold Lopatka, B.Sc.Pharm, MHSA, Ph.D. Sumit Majumdar, MD, MPH, FRCPC Sharon Mitchell, Pharm.B., M.Pharm. Don Philippon, Ph.D., CHE (ex-officio) Harvey Rabin, MD, FRCPC Marilyn Thornton, B.Sc.Pharm., MSA (alternate) Luxie Trachsel, MD, FRCPC 3

4 ACKNOWLEDGMENTS The AMCDU/ADUP members are grateful to the following persons for providing expertise in the area of information science and/or for their clinical expertise and comments throughout this study. Mr. Carol H. Spooner Mr. A. Simon Pickard Dr. Devidas Menon Dr. Anita G. Carrie Drug Utilization Review Proposal Sub-Committees: Mr. Ayaz Bhanji Dr. Tom Birkness Dr. Edith Blondel-Hill Dr. Irena Buka Ms. Jennifer Carson Dr. Kathy Dauphinais Dr. Derek Drummond Dr. Karen Farris Mr. Graham Ferguson Ms. Susan Fryters Dr. Kevin Hay Dr. Sheila Hughes Dr. Tajdin Jadavji Dr. Harold Lopatka Dr. Patrick Pierce Ms. Laurie Reay Dr. Bharti Rishi Ms. Nancy Rowen Dr. Stephen Shafran Ms. Karen Smilski DUR Advisory Panel: Ms. Diane Blais Dr. Anita Carrie Ms. Susan Fryters Dr. Tajdin Jadavji Ms. Jodi Kluchky Dr. Harold Lopatka Ms. Sharon Mitchell The AMCDU/ADUP members are also grateful to Alberta Health and Wellness (AHW) who provided the data for the present study and to Ms. Linda Holmstrom (AHW) who reviewed the Methodology Section. A special thanks for the assistance of Ms. Lynne Moser, secretary, ADUP and Ms. Doriann Grudzinski, student research assistant, ADUP. 4

5 EXECUTIVE SUMMARY The Alberta Management Committee for Drug Utilization (AMCDU), through the Alberta Drug Utilization Program (ADUP), selected the anti-infective agents used in the treatment of respiratory tract infections as the first topic for the Drug Utilization Review initiative. They were selected because of the significant concerns about emerging patterns of resistance that are frequently due to the excessive or inappropriate use of antibacterial agents for viral respiratory infections. The purpose of this study was to examine anti-infective drug utilization according to the standards set by the Alberta Clinical Practice Guidelines Program for specific respiratory tract infections (acute pharyngitis, acute otitis media, acute and chronic sinusitis, acute bronchitis, acute exacerbation of chronic bronchitis, and community acquired pneumonia) among Alberta Health and Wellness (AHW) Alberta Blue Cross non-group plan beneficiaries. Specific objectives were to quantify the extent that: appropriate oral anti-infective agents (i.e. selection of drug of choice according to Clinical Practice Guidelines [CPGs]) were prescribed for selected respiratory tract infections (RTIs) using selected ICD9 diagnostic codes; this has been defined as adherence to guidelines for anti-infective use; physicians collected a throat swab where the ICD9 diagnosis code was acute pharyngitis; patients received an antibiotic within 7 days of a visit to a physician where the ICD9 diagnosis was for a selected RTI in the elderly population studied; selected variables such as specialty (general practitioner, pediatrician, emergency room physician or other) impact the prescribing of antibiotics for treatment of selected RTIs. This drug utilization review (DUR) was done retrospectively using administrative claims databases as data sources. Two databases came from the Alberta Health Care Insurance Plan (AHCIP), one from Alberta Blue Cross (ABC) who administers the provincial drug plan for non-group plan beneficiaries in Alberta, and one from a private laboratory for microbiological data on acute pharyngitis. The study was limited to the population with drug benefits covered by AHW and who received outpatient antibiotic prescriptions between October 1 st and March 31 st of , and It is important to note that the study period was before the publication and the distribution of most of the CPGs. Adherence to guidelines for anti-infective agent use was analyzed in approximately 54,000 antibiotic treated episodes on the selected RTIs over the overall study period. In most of the RTIs studied, anti-infective agents were prescribed by general practitioners (> 80%). The highest percentages for prescribing of first line anti-infective agents were noted in otitis media with 64%, followed by adult community acquired pneumonia with 55%. Group A Strep acute pharyngitis diagnosis & treatment adherence following a throat swab culture was evaluated only for the study period of and showed a low culture rate of 24.2% of which 44.7% were positive. First line agent use in acute pharyngitis over the study period was only 36%. The highest anti-infective prescription 5

6 rate within 7 days of a physician visit for the ambulatory senior population was found in acute sinusitis (> 60%) and acute bronchitis (> 55%). Other key findings from this study include the following: antibiotic use in RTIs where there is an important viral etiology as in acute bronchitis and acute pharyngitis needs to be reduced; the inappropriate use of broad-spectrum macrolides and quinolones and some cephalosporins needs also to be reduced. Various limitations apply to a retrospective DUR using administrative databases as data sources. This DUR only includes those antibiotics covered by ABC as listed on the AHWDBL during the time periods of the study. Another major limitation of this study was the inability to link the AHCIP practitioner payment data and the ABC drug data due to the absence of a cross-reference number between these two databases. This resulted in an important loss of valuable data. Other limitations included the accuracy of ICD9 coding by physicians or other office personnel as well as inadequate clinical information provided in the databases (e.g. inadequate information on dosage or duration of antibiotic therapy, co-morbidities). An adequate antibiotic-free period before the antibiotic treated episode analysis would also be important to consider in future studies. Despite these limitations, results from this DUR suggest that multifaceted and interdisciplinary interventions to all health care providers as well as to patients and the public in general need to be implemented and repeated in order to improve the appropriate use of antibiotics, to reverse the trend of increasing antibiotic resistance, and to minimize health care costs. 6

7 TABLE OF CONTENTS LIST OF AMCDU/ADUP MEMBERS... 3 EXECUTIVE SUMMARY... 5 TABLE OF CONTENTS... 7 LIST OF TABLES LIST OF FIGURES GLOSSARY OF TERMS & ABBREVIATIONS INTRODUCTION CLINICAL PRACTICE GUIDELINES FOR RESPIRATORY TRACT INFECTIONS Acute Pharyngitis (5) Acute Otitis Media (AOM) (7) Sinusitis (9,15-20) Acute Sinusitis Chronic Sinusitis (9) Bronchitis (10-11,21-26) Acute Bronchitis (AB) (10,21,23,24) Acute Exacerbation of Chronic Bronchitis (AECB) (11,22,25,26) Community Acquired Pneumonia (CAP) (12-13,27-28) Drug Treatment of Respiratory Tract Infections (RTIs) according to Alberta Medical Association (AMA) Clinical Practice Guidelines (CPGs) METHODOLOGY Data Sources Data Sources and Elements Level of Anonymity Data Source Linkages Study Population Acute Pharyngitis Acute Otitis Media Sinusitis (Acute and Chronic) Bronchitis (Acute and Acute Exacerbation of Chronic Bronchitis) Community Acquired Pneumonia Definitions of DUR Terms Relevant Physician Visits Cases DUR Matched Cases Drugs included in the Study Anti-Infectives Adherence to Guidelines for Anti-Infective Agent Use & for Group A Strep Acute Pharyngitis Diagnosis & Treatment Data Analysis Population Descriptive Data Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Matched Cases Descriptive Data

8 3.6.4 Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Other Analyses in Relation to Anti-Infective Agent Use Cost Analysis of All Claims Adherence to Guidelines for Group A Strep Acute Pharyngitis Diagnosis & Treatment (utilizing three linked databases) Complementary Analyses by Regional Health Authority Data Processing RESULTS & DISCUSSION Acute Pharyngitis Population Descriptive Data Matched Cases Descriptive Data Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in Acute Pharyngitis By Patient Age By Physician Specialty Success of First Line Agents Number of Cases that Received Two or More Antibiotic Courses by Age Group in Acute Pharyngitis Cost Analysis of All Claims Cost of Antibiotics for All ICD9 Codes (462, 463, 465) in All ICD9 Codes Cost Avoidance for Antibiotic Therapy in All ICD9 Codes (462, 463, 465) in All Claims Group A Strep Acute Pharyngitis Diagnosis & Treatment Adherence following a throat swab culture in Adherence to Guidelines for Throat Cultures in All Cases of of Selected ICD9 Codes Adherence to Guidelines for Throat Cultures in Matched Cases of Selected ICD9 Codes Discussion Acute Otitis Media (AOM) Population Descriptive Data Matched Cases Descriptive Data Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in AOM By Patient Age By Physician Specialty Success of First Line Agents Number of Cases that Received Two or More Antibiotic Courses and Second Line Agent Use by Age Group in AOM Cost Analysis of All Claims Cost of Antibiotics for AOM in All Claims

9 Cost Avoidance for Antibiotic Therapy in AOM in All Claims Discussion Acute Sinusitis Population Descriptive Data Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Matched Cases Descriptive Data Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in Acute Sinusitis By Patient Age By Physician Specialty Success of First Line Agents Number of Cases that Received Two or More Antibiotic Courses and Second Line Agent Use by Age Group in Acute Sinusitis Cost Analysis of All Claims Cost of Antibiotics for Acute Sinusitis in All Claims Cost Avoidance for Antibiotic Therapy in Acute Sinusitis in in All Claims Discussion Chronic Sinusitis Population Descriptive Data Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Matched Cases Descriptive Data Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in Chronic Sinusitis By Patient Age By Physician Specialty Success of First Line Agents Number of Cases that Received Two or More Antibiotic Courses by Age Group in Chronic Sinusitis Cost Analysis of All Claims Cost of Antibiotics for Chronic Sinusitis in All Claims Added Cost for First Line Antibiotic Therapy in Chronic Sinusitis in All Claims Discussion Acute Bronchitis (AB) Population Descriptive Data Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Matched Cases Descriptive Data

10 4.5.4 Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in Acute Bronchitis By Physician Specialty Number of Matched Cases Receiving Two or More Courses of Antibiotics Cost Analysis of All Claims Cost of Antibiotics for Acute Bronchitis in All Claims Estimated Antibiotic Cost Savings for Seniors with Acute Bronchitis Discussion Acute Exacerbation of Chronic Bronchitis (AECB) Population Descriptive Data Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Matched Cases Descriptive Data Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in CB/AECB By Patient Age By Physician Specialty Success of First Line Agents Number of Cases that Received Two or More Antibiotic Courses and Second Line Agent Use by Age Group in CB/AECB Cost Analysis of All Claims Cost of Antibiotics for CB/AECB in All Claims Cost Avoidance for Antibiotic Therapy in CB/AECB in All Claims Discussion Community Acquired Pneumonia (CAP) Population Descriptive Data Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Matched Cases Descriptive Data Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Antibiotics Used Initially in CAP (all ages) By Patient Age By Physician Specialty Success of First Line Agents Number of Cases that Received Two or More Antibiotic Courses and Second Line Agent Use by Age Group in Adult CAP Cost Analysis of All Claims Cost of Antibiotics for CAP in All Claims

11 Cost Avoidance for Antibiotic Therapy in CAP in All Claims Discussion Summary of Results & Key Findings Percentage of Physician Visits in Seniors where Anti-Infective Prescriptions (Rx) were Received Adherence to Guidelines for Anti-Infective Agent Use in Matched Cases Number of Matched Cases that Received Two or More Antibiotic Courses Cost Analysis Summary Average Drug Cost per Claim Cost Avoidance Summary SUMMARY OF DISCUSSION & STUDY LIMITATIONS Study Limitations Strategies for Improvement CONCLUSION Recommendations BIBLIOGRAPHY APPENDIX 1 Alberta Health & Wellness Drug Benefit List of antibiotics

12 LIST OF TABLES Table 1. Drug treatment of respiratory tract infections (RTIs) according to Alberta Medical Association (AMA) Clinical Practice Guidelines (CPGs) (5,7,9-13) Table 2. Age distribution for patients with ICD9 diagnosis codes selected (462, 463, 465)* per 6 month period (Oct. 1 st March 31 st ) (ACHIP Data) Table 3. Age distribution for acute pharyngitis only (ICD9 code 462) per 6 month Period (Oct. 1 st - March 31 st ) (ACHIP Data) Table 4. Number of patients, matched cases, and antibiotic (Abx) claims for all ICD9 codes selected (462, 463, 465)* per 6 month period (Oct. 1 st March 31 st ) (AHCIP/ABC Data) Table 5. Antibiotics used initially for acute pharyngitis (ICD9 code 462) in matched cases per 6 month period (Oct. 1 st March 31 st ) Table 6. Acute pharyngitis (ICD9 462) first line agent use by age group in matched cases frequency & percent (3 year total; Oct 1 st - March 31 st, ) Table 7. Acute pharyngitis (ICD9 code 462)* first line agent use by physician specialty in matched cases frequency & percent per 6 month period (Oct. 1 st - March 31 st ) Table 8. Acute pharyngitis (ICD9 code 462) first line agent* success by age in matched cases frequency & percent (3 year total; Oct 1 st March 31 st, ).. 49 Table 9. Acute pharyngitis (ICD9 code 462) matched cases receiving > 2 courses of antibiotics (Abx) by age frequency and percent (3 year total; Oct 1 st March 31 st, ) Table 10. Cost of antibiotic therapy per 6 month period for all ICD9 codes (462, 463, 465)* in all claims (ABC Data) Table 11. Throat cultures for Group A Strep by age in all cases of ICD9 codes (462, 463, 465)*- frequency & percent positive in (Oct. 1 st March 31 st ) Table 12. Throat cultures for Group A Strep by ICD9 code in matched cases frequency, percent, & percent positive in (Oct. 1 st March 31 st ) Table 13. Age distribution for patients with AOM diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data) Table 14. Age distribution in patients < 5 years with AOM diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data)

13 Table 15. Number of matched patients, matched cases, and antibiotic (Abx) claims for AOM per 6 month period (Oct. 1 st March 31 st ) (AHCIP/ABC Data) Table 16. Antibiotics used initially for AOM in matched cases per 6 month period (Oct. 1 st March 31 st ) Table 17. AOM first line agent use by age group in matched cases frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 18. AOM first line agent use by physician specialty* in matched cases - frequency & percent per 6 month period (Oct.1 st - March 31 st ) Table 19. AOM first line agents* success by age in matched cases frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 20. AOM matched cases receiving > 2 courses of antibiotics (Abx) and second line agent use by age - frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 21. Cost of antibiotic therapy by 6 month period for AOM in all claims (ABC Data) Table 22. Cost avoidance with use of first line antibiotic therapy in AOM per 6 month period in all claims (ABC Data) Table 23. Age distribution for patients with acute sinusitis diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data) Table 24. Percentage of physician visits for acute sinusitis in seniors where antibiotic prescriptions (Rx) received Table 25. Number of matched patients, matched cases, and antibiotic (Abx) claims for acute sinusitis per 6 month period (Oct. 1 st - March 31 st ) (AHCIP/ABC Data) Table 26. Antibiotics used initially for acute sinusitis in matched cases per 6 month period (Oct. 1 st March 31 st ) Table 27. Acute sinusitis first line agent use by age group in matched cases - frequency & percent (3 year total; Oct. 1 st March 31 st, ) Table 28. Acute sinusitis first line agent use by physician specialty* in matched cases frequency &percent per 6 month period (Oct. 1 st - March 31 st ) Table 29. Acute sinusitis first line agent success* by age in matched cases frequency & percent (3 year total; Oct 1 st - March 31 st, )

14 Table 30. Acute sinusitis matched cases receiving > 2 courses of antibiotics (Abx) and second line agent use by age - frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 31. Cost of antibiotic therapy per 6 month period for acute sinusitis in all claims (ABC Data) Table 32. Cost avoidance with use of first line antibiotic therapy for acute sinusitis per 6 month period in all claims (ABC Data) Table 33. Age distribution for patients with chronic sinusitis diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data) Table 34. Percentage of physician visits for chronic sinusitis in seniors where antibiotic prescriptions (Rx) received Table 35. Number of matched patients, matched cases, and antibiotic (Abx) claims for chronic sinusitis per 6 month period (Oct. 1 st March 31 st ) (AHCIP/ABC Data) Table 36. Antibiotics used initially for chronic sinusitis in matched cases per 6 month period (Oct. 1 st March 31 st ) Table 37. Chronic sinusitis first line agent use by age group frequency & percent (3 year total; Oct. 1 st March 31 st, ) Table 38. Chronic sinusitis first line agent use by physician specialty* - frequency & percent per 6 month period (Oct.1 st - March 31 st ) Table 39. Chronic sinusitis first line agent success* by age in matched cases frequency & percent (3 year total; Oct 1 st - March 31 st, ) Table 40. Chronic sinusitis matched cases receiving > 2 courses of antibiotics (Abx) by age - frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 41. Cost of antibiotic therapy per 6 month period for chronic sinusitis in all claims (ABC Data) Table 42. Added cost for first line antibiotic therapy instead of other agents for chronic sinusitis* per 6 month period in all claims (ABC Data) Table 43. Age distribution for patients with acute bronchitis diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data) Table 44. Percentage of physician visits for acute bronchitis in seniors where antibiotic prescriptions (Rx) received

15 Table 45. Number of matched patients, matched cases, and antibiotic (Abx) claims for acute bronchitis per 6 month period ) (Oct. 1 st March 31 st ) (AHCIP/ABC Data) Table 46. Acute bronchitis* antibiotic use by physician specialty in matched cases frequency & percent per 6 month period (Oct. 1 st - March 31 st ) Table 47. Acute bronchitis matched cases receiving > 2 courses of antibiotics (Abx) by study period frequency and percent (Oct 1 st - March 31 st, ) Table 48. Cost of antibiotic therapy per 6 month period for acute bronchitis in all claims (ABC Data) Table 49. Estimated antibiotic cost savings for seniors (> 65 years old) with AB based on 10% bacterial prevalence Table 50. Age distribution for patients with chronic bronchitis diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data) Table 51. Percentage of physician visits for CB/AECB in seniors where antibiotic prescriptions (Rx) received Table 52. Number of matched patients, matched cases, and antibiotic (Abx) claims for chronic bronchitis/aecb per 6 month period (Oct. 1 st - March 31 st ) (AHCIP/ABC Data) Table 53. Antibiotics used initially for CB/AECB in matched cases per 6 month period (Oct. 1 st March 31 st ) Table 54. CB/AECB first line agent use by age group in matched cases frequency & percent (3 year total; Oct. 1 st March 31 st, ) Table 55. CB/AECB first line agent use by physician specialty* in matched cases frequency & percent per 6 month period (Oct. 1 st - March 31 st ) Table 56. CB/AECB first line agent success* by age in matched cases frequency & percent (3 year total; Oct 1 st - March 31 st, ) Table 57. CB/AECB matched cases receiving > 2 courses of antibiotics (Abx) and second line agent use by age - frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 58. Cost of antibiotic therapy per 6 month period for CB/AECB in all claims (ABC Data) Table 59. Cost avoidance with use of first line antibiotic therapy in CB/AECB per 6 month period in all claims (ABC Data)

16 Table 60. Age distribution for patients with CAP diagnosis per 6 month period (Oct. 1 st March 31 st ) (AHCIP Data) Table 61. Percentage of physician visits for CAP in seniors where antibiotic prescriptions (Rx) received Table 62. Number of matched patients, matched cases, and antibiotic (Abx) claims for CAP per 6 month period (Oct. 1 st March 31 st ) (AHCIP/ABC Data) Table 63. Antibiotics used initially (all ages) for CAP in matched cases per 6 month period (Oct. 1 st March 31 st ) Table 64. CAP first line agent use by age group (adults only) in matched cases frequency & percent (3 year total; Oct. 1 st March 31 st, ) Table 65. Adult CAP first line agent use by physician specialty* in matched cases frequency & percent per 6 month period (Oct. 1 st - March 31 st ) Table 66. Pediatric CAP first line agent use by physician specialty* in matched cases frequency & percent per 6 month period (Oct. 1 st - March 31 st ) Table 67. CAP first line agent success* by age (adults only) in matched cases frequency & percent (3 year total; Oct. 1 st March 31 st, ) Table 68. CAP matched cases receiving > 2 courses of antibiotics (Abx) and second line agent use by age (adults only) - frequency & percent (3 year total; Oct. 1 st - March 31 st, ) Table 69. Cost of antibiotic therapy per 6 month period for CAP (all ages) in all claims (ABC Data) Table 70. Cost avoidance with use of first lineantibiotic therapy in CAP per 6 month period in all claims (ABC Data) Table 71. Adherence to guidelines for anti-infective agent use over the 3 year study period (October 1 st March 31 st, ) Table 72. Comparison of antibiotic use* in this AMCDU DUR with IMS Data for the Prairie Provinces and/or Canada Table 73. Proportion of matched cases that received two or more antibiotic courses (3 year total; Oct. 1 st March 31 st, ) Table 74. Cost avoidance summary if first line antibiotic therapy was used for all RTIs in all claims

17 LIST OF FIGURES Figure 1 Various AHCIP and ABC databases linkages & DUR matched cases for evaluation of adherence to selected CPGs. 37 Figure 2 Number of physician visits in seniors & percent of anti-infective prescriptions (Rx) filled within 7 days by RTI.112 Figure 3 Percent use of first line agents by RTI and each 6 month period (October 1 st March 31 st ).115 Figure 4 Average drug cost per claim for first line, second line and other anti-infective agents by RTI for the 3 year study period (Oct. 1 st March 31 st, )

18 GLOSSARY OF TERMS & ABBREVIATIONS ABC: Alberta Blue Cross ADUP: Alberta Drug Utilization Program AHCIP: Alberta Health Care Insurance Plan AHWDBL: Alberta Health & Wellness Drug Benefit List AHW: Alberta Health and Wellness AMCDU: Alberta Management Committee on Drug Utilization ASN: anonymous stakeholder number which refers to anonymous patient identifier Case: episode of an RTI treated with at least one antibiotic course during the disease length defined for that RTI. See CPGs: Clinical practice guidelines Disease length: a period of time defined for each RTI studied starting with one antibiotic prescription claim and during which time any subsequent antibiotic prescription claims were considered to be for the same episode of infection, i.e. part of the same case. For acute pharyngitis, the disease length was 21 days; for all other RTIs studied, it was 42 days. See DUR: Drug utilization review DUR matched case: an antibiotic treated episode or case where the anti-infective prescription claims from the ABC drug database has been linked or matched to the relevant physician visit associated with a specific ICD9 code from the AHCIP database. See Relevant physician visit: population a visit to a physician by a patient included in the study RTIs: respiratory tract infections Rx: anti-infective prescription Success of a first line agent: defined if there was no anti-infective prescription claim for the same diagnosis (linked with an ICD9 code) within 21 days of the initial prescription claim of a matched case for acute pharyngitis, or 42 days of the initial prescription claim of a matched case for any other RTI 18

19 1. INTRODUCTION The Alberta Management Committee for Drug Utilization (AMCDU), through the Alberta Drug Utilization Program (ADUP), selected the anti-infective agents used in the treatment of respiratory tract infections as the first topic for the Drug Utilization Review initiative. They were selected because of the significant concerns about emerging patterns of resistance that are largely due to the excessive or inappropriate use of antibacterial agents for viral respiratory infections (1,2). The causes of inappropriate or excessive antibacterial agent use are multifaceted and complex (2). Although efforts have been undertaken to address this issue throughout the country, antibacterial agent misuse has been widely recognized and as such, was selected as an important starting point for the AMCDU. As respiratory tract infections (RTIs) account for 75% of all community antibiotic prescriptions (3), RTIs selected for the study were pharyngitis, otitis media, sinusitis, bronchitis, and pneumonia. In 1999, a systematic literature review was conducted of drug utilization review studies in ambulatory settings for three anti-infective classes (cephalosporins, macrolides and quinolones). Only twelve of 587 (2.0%) articles met the selection criteria. Depending on the standards used, appropriateness ratings of anti-infective use in primary care settings vary from 0% to 100% (4). However, only five studies clearly used evidence-based, peerreviewed sources and the same number of studies met standards that would ensure unbiased, validated results, with only two studies that had both characteristics (4). The purpose of this study was to examine anti-infective drug utilization according to the standards set by the Alberta Clinical Practice Guidelines Program for specific respiratory tract infections (acute pharyngitis, acute otitis media, acute and chronic sinusitis, acute bronchitis, acute exacerbation of chronic bronchitis, and community acquired pneumonia) among Alberta Health and Wellness (AHW) Alberta Blue Cross non-group plan beneficiaries. Specific objectives were to quantify the extent that: appropriate oral solid and liquid anti-infective agents (i.e. selection of drug of choice according to Clinical Practice Guidelines) were prescribed for selected respiratory tract infections (RTIs) using selected ICD9 diagnostic codes; physicians collected a throat swab where the ICD9 diagnosis code was acute pharyngitis; patients received an antibiotic within 7 days of a visit to a physician where the ICD9 diagnosis was for a selected RTI in the elderly population studied; selected variables such as specialty (general practitioner, pediatrician, emergency room physician or other) impact the prescribing of antibiotics for treatment of selected RTIs. This drug utilization review (DUR) was done retrospectively using administrative claims databases as data sources. Two databases came from the Alberta Health Care Insurance Plan (AHCIP), one from Alberta Blue Cross (ABC) who administers the provincial drug plan for non-group plan beneficiaries in Alberta, and one from a private laboratory for 19

20 microbiological data on acute pharyngitis. The study was limited to the population with drug benefits covered by AHW and who received outpatient antibiotic prescriptions between October 1st and March 31st of , and Expert user groups assisted in developing research protocols for the study as well as in analyzing data, reviewing reports and formulating recommendations. The report consists of six sections including the Introduction. The second section summarizes the main recommendations from the selected provincial Clinical Practice Guidelines (CPGs) which are relevant to the study. Methodology is described in the third section and includes data sources, study population, definitions of DUR populations, drugs under study, guideline adherence, data analysis and data processing. The fourth section presents the results and a discussion for each RTI studied along with a summary of key findings. A summary of the discussion, study limitations, and strategies for improvement, are presented in the next section. Finally, the conclusion is provided in the sixth section and includes the recommendations from the Alberta Management Committee on Drug Utilization (AMCDU). 2. CLINICAL PRACTICE GUIDELINES FOR RESPIRATORY TRACT INFECTIONS The Alberta Clinical Practice Guidelines Program promotes appropriate, effective and quality medical care in Alberta by supporting the use of clinical practice guidelines (CPGs). The program is administered by the Alberta Medical Association (AMA) under the direction of a multi-stakeholder steering committee. More specifically, the Alberta CPG Working Group for Antibiotics is a multi-disciplinary committee composed of family physicians, infectious diseases specialists, pediatricians, microbiologists, hospital and community pharmacists, an epidemiologist, consumers, and Alberta Blue Cross and Alberta Health and Wellness representatives. CPGs for various RTIs were developed using an evidence-based process (5-14): The Diagnosis and Treatment of Acute Pharyngitis (July 1999) and a Patient Leaflet on Sore Throats (January 2000); The Diagnosis and Treatment of Acute Otitis Media in Children (February 2000, Reviewed November 2001) and a Patient Leaflet on Ear Infections (January 2000); The Diagnosis and Management of Acute Bacterial Sinusitis (December 2000); The Management of Acute Bronchitis (December 2000); The Management of Acute Exacerbation of Chronic Bronchitis (AECB) (December 2000); The Diagnosis and Management of Community Acquired Pneumonia: Pediatric (January 2002); The Diagnosis and Management of Community Acquired Pneumonia: Adult (February 2002); The Diagnosis and Management of Nursing Home Acquired Pneumonia (September 2002). 20

21 These guidelines, which are available on the AMA website ( have been used as the standard for the Anti-Infective DUR of respiratory tract infections. The following provides an overview of each RTI selected for this study along with a brief description of their incidence, diagnosis and optimal treatment according to the Alberta CPGs and complementary literature review information since their publications. 2.1 Acute Pharyngitis (5) Acute pharyngitis is a common infectious disease seen by general practitioners and pediatricians during fall, winter, and spring. The majority (up to 85%) of cases of pharyngitis are of viral etiology and should not be treated with antibiotic therapy. Signs of viral pharyngitis include: rhinorrhea, hoarseness, cough and conjunctivitis. Group A β- hemolytic streptococcus (Group A Strep) is the most commonly encountered bacterial pathogen in pharyngitis. Group A Strep pharyngitis is mainly a disease of youth, with 50% of the patients in the 5 to 15 year old age group. Classic symptoms include: tonsillar exudate, swollen anterior cervical nodes, a history of fever greater than 38 o C, and no cough. Throat cultures do not need to be done in pharyngitis of viral origin. Furthermore, it has been suggested that a throat culture and antibiotics are not indicated if a patient presents with only one of the four classic symptoms of Group A Strep pharyngitis. All other patients should undergo throat cultures and await the results before starting antibiotic therapy. The goal of antibiotics is to prevent acute and long term sequelae (acute rheumatic fever); so, the one to two day delay in initiating antibiotic therapy will still prevent complications. Group A Strep is uniformly susceptible to penicillin. Routine follow-up and post-treatment throat cultures after completion of therapy are not required. 2.2 Acute Otitis Media (AOM) (7) Acute otitis media (AOM) is the most frequently diagnosed bacterial infection in pediatric patients, especially in the fall and winter. AOM is a disease of infancy and childhood, with a peak incidence between 6 and 9 months. Studies indicate that by one year of age, more than 60% of children have had one episode of AOM, and 17% of children have had at least three episodes of AOM. It is critical for physicians to differentiate between AOM, myringitis, and otitis media with effusion (OME), since the latter two conditions do not require antibiotic therapy. The diagnosis of AOM is made by history and direct visualization of the tympanic membrane. Most cases of AOM resolve spontaneously but this is highly dependent on the organism. The most frequent causative agent of AOM is Streptococcus pneumoniae (40%), followed by nontypeable Haemophilus influenzae (25%), Moraxella catarrhalis (10%), Group A Strep (2%) and Staphylococcus aureus (2%). About 20-30% of AOM cases have no bacterial pathogens identified and presumably are viral in etiology. Antibiotic therapy is recommended for AOM in children under 24 months. In children aged 2 years or older, most cases of AOM resolve with symptomatic treatment alone, 21

22 within 72 hours, and do not require antibiotics. Amoxicillin is the antibiotic of choice for AOM. 2.3 Sinusitis (9,15-20) Acute Sinusitis Sinusitis is one of the 10 most common diagnoses in ambulatory practice. According to the 1993 U.S. National Health Interview Survey (NHIS), children less than 15 years old and adults between 25 and 64 years old are most frequently affected by sinusitis. Sinusitis is defined as inflammation of the mucosa of the paranasal sinuses, and since it is almost always accompanied by inflammation of the contiguous nasal mucosa, rhinosinusitis (RS) would be a more accurate term. The diagnosis of sinusitis is primarily clinical and based on a combination of patient s symptoms and signs. Causes of acute sinusitis include infection (viral, bacterial, or rarely fungal), allergy, local irritants, trauma, medications (e.g. overuse of topical decongestants), and anatomic problems. Most cases of acute uncomplicated RS are caused by viral upper respiratory tract infections (URTIs). Making a diagnosis of bacterial sinusitis is challenging but critical as viral rhinosinusitis occurs up to 200 times more commonly. Differentiation of bacterial sinusitis from viral URTI is largely determined by duration and severity of symptoms. A diagnosis of acute bacterial sinusitis may be made in patients with a viral URTI with sinus symptoms without improvement after 10 to 14 days, or worsening after 5 days, but lasting 4 weeks or less in total duration. Recurrent sinusitis is defined as 4 or more episodes of acute sinusitis per year each lasting 10 days or more and absence of symptoms between episodes. S. pneumoniae and H. influenzae (usually nontypeable) are the primary pathogens in over 50% of cases of acute sinusitis. M. catarrhalis is the next most common pathogen. General management of acute sinusitis should include adequate analgesics, antipyretics, saline irrigation/nasal spray, warm or cool humidification, and decongestants. Promoting sinus drainage by relieving nasal obstruction/congestion is essential and may be even more important than antibiotic therapy. Studies indicate that up to 60% of cases of acute sinusitis will resolve without antibiotic treatment. The overuse of antibiotics in ill-defined URTI has led to increasing antibiotic resistance. If used, the first line antibiotic should be amoxicillin, or trimethoprim-sulfamethoxazole (TMP/SMX) in patients who are penicillin allergic Chronic Sinusitis (9) A diagnosis of chronic bacterial sinusitis may be made if sinusitis lasts 12 weeks or more with or without treatment and some or all of the following symptoms are present: purulent nasal discharge, postnasal drip, nasal congestion/obstruction, facial pain/pressure. Symptoms can mimic the pain of dental disease, migraine, or tension headaches. In chronic sinusitis, underlying immunological conditions (e.g. HIV, allergy, diabetes), structural abnormalities (e.g. nasal polyps, septal deviation), or asthma is 22

23 usually present, therefore investigations for these conditions should be included. Although the role of bacterial pathogens in chronic sinusitis is even less clear than in acute sinusitis, the antibiotic chosen must have good activity against the most likely bacterial pathogens in chronic sinusitis, especially anaerobes and Staphylococcus aureus. In chronic sinusitis, the recommended antibiotics are amoxicillin-clavulanate and clindamycin; a prolonged course of 21 days has value although repeated courses of antibiotics are not usually indicated for this condition. In chronic sinusitis, adjunctive therapy is as important as antibiotic therapy. General management of this RTI should include saline irrigation/nasal spray, and warm or cool humidification. Oral or topical (no more than three to 5 days) decongestants may be of limited benefit. Antihistamines may have a role in chronic sinusitis if the patient has predisposing allergies. Topical nasal steroids may be of benefit, especially if allergies are involved. 2.4 Bronchitis (10-11,21-26) It is critical to differentiate between acute bronchitis (AB), and acute exacerbation of chronic bronchitis (AECB), since the former condition is largely viral and does not require antibiotic therapy. Acute bronchitis is defined as an acute cough illness lasting usually less than three weeks although it may persist after that period in 25% of patients. Contrary to common belief, purulent sputum does not signify bacterial infection or the need for antibiotic therapy. It occurs as a result of inflammation secondary to infection, viral or bacterial. In contrast, chronic bronchitis is defined as productive cough lasting at least three months for at least two consecutive years in patients with chronic obstructive pulmonary disease (COPD). In a patient with chronic bronchitis, an acute exacerbation (AECB) is the sudden onset of: increased sputum production, increased sputum purulence and increased dyspnea. An important diagnostic objective is to exclude the presence of pneumonia. In the healthy, non-elderly adult, pneumonia is uncommon in the absence of vital sign abnormalities (heart rate > 100 beats/min, respiratory rate > 24 breaths/min or oral temperature > 38 o C) or asymmetrical lung sounds. Evidence of consolidation (localized crackles, bronchial breath sounds, dullness on percussion) should alert to the possibility and investigation (chest x-ray, sputum cultures) of pneumonia. Interventions that may decrease the incidence of AB and AECB without the risks of antibiotic therapy include smoking cessation, handwashing, influenza & pneumococcal vaccinations, and especially for AECB, rehabilitation and nutritional programs. 23

24 2.4.1 Acute Bronchitis (AB) (10,21,23,24) Acute bronchitis (AB) is one of the most common respiratory tract infections diagnosed by family physicians. It is characterized by acute inflammation of the bronchial tree and affects both adults and children. It is more common in the winter months when viral RTIs are most prevalent. In the absence of diagnostic signs or laboratory tests, the diagnosis of acute bronchitis is purely clinical, resulting in other lower respiratory tract infections, pneumonia and asthma sometimes being diagnosed as acute bronchitis. The vast majority of cases (up to 80-90%) of acute bronchitis are viral. Meta-analyses have shown no benefit of antibiotics in patients with this condition and the excessive or inappropriate use of antibiotics has led to increased antimicrobial resistance. General management of AB should include fluids/increased humidity, analgesics/antipyretics, and antitussives. Bronchodilators may offer modest benefit in patients with prolonged/bothersome cough and/or wheezing. Corticosteroids (inhaled or oral), expectorants, and antihistamines are NOT recommended in the management of AB Acute Exacerbation of Chronic Bronchitis (AECB) (11,22,25,26) Chronic bronchitis (CB) accounts for 85% of chronic obstructive pulmonary disease (COPD). The latter is a disease with significant chronic morbidity, and mortality. Between 1980 and 1995, COPD-related mortality increased 93%, the largest increase in mortality among all major diseases in Canada. Chronic bronchitis is more common in men (although the prevalence in women is increasing), those over 40 years old, and smokers. AECB are often seasonal with the highest incidence in winter, which is related to an increased incidence of viral URTIs during this period. There is evidence to support the benefit of antibiotic therapy in AECB in patients with at least two of the following symptoms: increased sputum production, increased sputum purulence, and increased dyspnea. Therapy should be directed toward Haemophilus spp, M. catarrhalis and Streptococcus pneumoniae. No studies have shown other antibiotics to be superior to amoxicillin, which is the drug of choice in AECB. 2.5 Community Acquired Pneumonia (CAP) (12-13,27-28) The incidence of pneumonia is highest in very young and elderly patients. The annual incidence of pneumonia in children < 5 years is cases per 1000 in Europe and North America, higher than at any other time of life, except perhaps in adults years of age. According to the 1994 U.S. National Health Interview Survey, the rate of pneumonia for those 65 years and older was 28 per 1000 persons per year. The lowest rate was for those aged 25 to 64 years with a rate of 9 cases per 1000 per year. Incidence of CAP is increased in the winter months. Up to 80% of cases of CAP are treated in the outpatient setting. Mortality is less than 1% for outpatients, but rises to an average of 14% for hospitalized patients with CAP. Fifty percent of pneumonia cases and 90% of mortality from pneumonia are found in patients over the age of

25 Pneumonia is defined as acute infection of the pulmonary parenchyma that is associated with at least two of the following symptoms: fever, rigors, new cough +/- sputum, pleuritic chest pain, shortness of breath; and localized crackles or bronchial breath sounds on auscultation; and new opacity on chest x-ray. A chest x-ray is the gold standard for the diagnosis of pneumonia, and to differentiate pneumonia from acute bronchitis or acute exacerbations of chronic bronchitis. Treating patients for community acquired pneumonia (CAP) on the basis of clinical symptoms without x-ray confirmation should be discouraged given the cost of antibiotic therapy and the potential for side effects and antibiotic resistance. A sputum sample for gram stain and culture is recommended if productive cough is present. For those patients with a history of chills and rigor, blood cultures are also recommended. A diagnosis of CAP may be made in patients who have not been in hospital within 14 days prior to onset of symptoms or in hospital less than four days prior to onset of symptoms. In most studies, the specific cause of pneumonia could not be identified in 40 to 60% of cases. In children less than two years old, the majority of cases of pneumonia are of viral etiology. As age increases, the incidence of pneumonia decreases. S. pneumoniae is the most common bacterial pathogen causing CAP. Other pathogens include H. influenzae (mostly nontypeable), M. catarrhalis, Group A Strep, S. aureus and intracellular pathogens such as Mycoplasma pneumoniae and Chlamydia pneumoniae. Klebsiella pneumoniae and other gram-negative bacilli may cause pneumonia in patients with comorbid factors. General management of CAP should include adequate hydration and analgesics/antipyretics. Oxygen therapy is indicated for hypoxemia. Cough suppressants are not routinely recommended. Antibiotics are not indicated for viral pneumonia, bronchiolitis or for prevention of bacterial pneumonia. Choice of empiric therapy is based on severity of illness, patient age, comorbidities, treatment setting (outpatient or hospital), local resistance patterns where available and patient s recent (three months) antibiotic history. The antibiotic chosen must have good activity against the major bacterial pathogens in outpatient CAP: S. pneumoniae, M. pneumoniae, and C. pneumoniae (refer to Table 1). 2.6 Drug Treatment of Respiratory Tract Infections (RTIs) according to the Alberta Clinical Practice Guidelines (CPGs) Table 1 summarizes the main drug treatment recommendations for the RTIs relevant to this DUR according to the Alberta CPGs. It is important to note that the study period ( ) was before the publication and distribution of most of the CPGs. The Acute Pharyngitis CPG was distributed in the fall of 1999, which correlates with the last period of the study (October 1999 March 2000). Although we can look for a trend in the prescription pattern of first line agent use for this condition, it is well documented that guideline distribution alone is not enough to modify behavior (2). The CPGs on Acute Otitis Media in Children, Acute Bacterial Sinusitis, Acute Bronchitis, and Acute Exacerbation of Chronic Bronchitis were distributed to all physicians and pharmacists in 25