Comparative estimated effectiveness of antibiotic classes as initial and secondary treatments of respiratory tract infections: longitudinal analysis of routine data from UK primary care 1991–2012

Abstract

Purpose To compare the estimated effectiveness of seven frequently prescribed antibiotic classes as initial and secondary treatments of upper respiratory tract infections (URTIs) and lower respiratory tract infections (LRTIs) 1991–2012. The main outcome measure was a surrogate for estimated antibiotic effectiveness.

Methods Routine, primary care data from the UK Clinical Practice Research Datalink (CPRD) were used. Having established standardized criteria representing antibiotic treatment failure, estimated treatment effectiveness rates were calculated as one minus the treatment failure rate. For each year from 1991 to 2012, estimated effectiveness rates by treatment line, indication, and sub-indication were calculated. These were presented by antibiotic class, with a sub-analysis for the macrolide clarithromycin.

Findings From approximately 58 million antibiotic prescriptions in CPRD, we analyzed 8,654,734 courses of antibiotic monotherapy: 4,825,422 courses (56%) were associated with URTI; 3,829,312 (44%) were associated with LRTI. Amino-penicillins (4,148,729 [56%]), penicillins (1,304,561 [18%]), and macrolides (944,622 [13%]) predominated as initial treatments; macrolides (375,903 [32%]), aminopenicillins (275,866 [23%]), and cephalosporins (159,954 [14%]) as secondary treatments. Macrolides and aminopenicillins had estimated effectiveness rates ≥80% across the study period as initial treatments of URTI and LRTI. In secondary use, only macrolides maintained these rates: 80.7% vs. 79.8% in LRTI, 85.1% vs. 84.5% in throat infections, 80.7% vs. 82.3% in nasal infections, 83.5% vs. 83.8% in unspecified URTI in 1991 and 2012, respectively.

Implications After more than two decades, macrolides remained amongst the most effective antibiotic classes for both URTI and LRTI in initial and secondary antibiotic treatment when a further antibiotic course was prescribed.

Limitations Antibiotic treatments were classified as intention to treat. It is unknown whether the prescription was redeemed or taken correctly. We do not know the etiology of these infections, therefore evidence of antibiotic non-response may relate to sub-optimal diagnosis and inappropriate treatment rather than antibiotic effectiveness for true bacterial infections.

Keywords:

• Antibiotic non-response
• Clarithromycin
• Macrolides
• Respiratory tract infections

Declaration of funding

The study was funded by Mylan Pharmaceuticals.

Author contributions: C.J.C., H.d.V. and M.O. developed the study protocol. Data extraction and analysis were carried out by E.B. and S.J.-J., supervised by C.J.C. C.C.B. advised on the study question, analysis plan, and interpretation of the study findings and contributed to drafting the final report. C.Ll.M. provided statistical expertise. Because of the conditions of the data license, co-authors from the funding body did not have access to the source data from the Clinical Practice Research Datalink, although they did have access to processed data. All other authors had full access to all of the study data (including statistical reports and tables). All authors contributed to, read, and approved the final manuscript, and all authors take responsibility for the integrity of the data and the accuracy of the data analysis. C.J.C. is guarantor.

Declaration of financial/other relationships

C.Ll.M. has disclosed that he is a contractor of Pharmatelligence, a research consultancy receiving funding from pharmaceutical companies (including Mylan and AstraZeneca). C.J.C. has disclosed that he is a director of Pharmatelligence, reports research grants from various health-related organizations, including Abbott, ALK, Astellas, AstraZeneca, Bristol-Myers Squibb, Diabetes UK, the Engineering and Physical Sciences Research Council, the EASD, Ferring, GSK, Jenson (Internis), Lilly, the Medical Research Council, Medtronic, MSD, the National Health Service, Norgine, Pfizer, Sanofi-Aventis, Shire and Wyeth, and consults for Amylin, Aryx, Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Diabetes UK, Eisel, Ferring, GSK, Ipsen, Lilly, Medtronic, MSD, Pfizer, Sanofi-Aventis, Takeda, and Wyeth. E.B. and S.J-J. have disclosed that they are employees of Pharmatelligence. C.C.B. has disclosed that he has received a research grant in kind from Alere in support of a publically funded study of COPD and has received honoraria from Alere and the Alliance for the Prudent Use of Antibiotics for presentations on point-of-care testing and diagnostics in primary care. H.D.V. has disclosed that she is an employee of Mylan. M.O. has disclosed that he is a former employee of Mylan, currently an employee of AstraZeneca.

CMRO peer reviewer 1 has disclosed that he is a consultant to Teva and Pliva Zagreb; and is on the speakers’ bureau of Astellas. CMRO peer reviewer 2 has no relevant financial or other relationships to disclose.

Acknowledgments

We thank Monica S. Rocha of Mylan EPD for her help with the figures and in critically reviewing the manuscript and Dr. Chris Poole for developing the Read code lists.