Clarithromycin in community-acquired pneumonia: a within-trial cost analysis of the ACCESS randomised, double-blind, placebo-controlled study

Community-acquired pneumonia (CAP) remains one of the leading infectious causes of morbidity, mortality, and healthcare expenditure worldwide. Combination therapy with a β-lactam/macrolide antibiotic is widely recommended, but there has been little investigation of the cost consequences of adjunctive macrolide therapy. We evaluated hospital resource utilization and treatment costs associated with adjunctive clarithromycin in the ACCESS trial, a phase 3, prospective, double-blind, randomized controlled trial conducted among 267 adults hospitalized with CAP in Greece. Hospitalization and treatment expenditure were estimated using Greek Diagnosis-Related Groups (DRGs) reimbursement tariffs and prospectively collected trial data. Hospital resource utilization and expenditure were assessed through day 90, and between-group differences in mean cumulative hospitalization costs were estimated using bootstrap analysis with 95% confidence intervals (CIs). Mean cumulative hospitalization costs were lower in patients receiving clarithromycin compared with placebo. By day 90, mean per-capita costs were reduced by approximately 43% in the clarithromycin group (€1158.5 versus €2029.9; mean difference -€871.4; 95% CI -€1661.2 to -€222.5), primarily driven by lower intensive care unit (ICU)-related expenditure (€3556.3 versus €6653.0; mean difference -€3096.8; 95% CI -€6661.2 to -€192.7). Median duration of antibiotic treatment was 9.5 versus 14 days, respectively ( p = 0.049), while median time to hospital discharge alive was 9 versus 14 days. In this prespecified analysis from a controlled trial, adjunctive clarithromycin was associated with lower healthcare costs among adults hospitalized with CAP, with the difference primarily attributable to lower ICU-related costs. These findings indicate that adjunctive clarithromycin in hospitalized patients with CAP in the current Greek reimbursement framework is associated with better clinical outcomes and lower costs of care. A formal cost-effectiveness assessment of adjunct macrolide therapy is needed to develop this line of research. EudraCT 2020-004452-15 (registered 5 November 2020); ClinicalTrials.gov NCT04724044 (registered 20 January 2021; first posted 26 January 2021).