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

<p><b>Purpose</b> 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.</p> <p><b>Methods</b> 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.</p> <p><b>Findings</b> 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.</p> <p><b>Implications</b> 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.</p> <p><b>Limitations</b> 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.</p>