Clarithromycin For Improved Clinical Outcomes in Community-Acquired Pneumonia: A Subgroup Analysis of the ACCESS Study.

Background: In the ACCESS trial the addition of clarithromycin to standard-of-care (SoC) antibiotics enhanced early clinical response and attenuated the inflammatory burden in adults with community-acquired pneumonia (CAP) requiring hospitalization. A post-hoc analysis was performed to investigate the benefit in specific subgroups.

Methods: The primary endpoint comprised two conditions to be met during the first 72 hours: ≥50% decrease of respiratory symptom severity score; and any of ≥30% decrease of SOFA score and favourable change of kinetics of procalcitonin (defined as ≥80% PCT decrease or PCT <0.25 ng/ml). In this exploratory post-hoc analysis achievement of the study composite primary endpoint was compared between the two treatment groups within subsets differentiated by demographic characteristics, comorbidities, CAP severity, baseline laboratory findings and corticosteroid co-administration. The impact of clarithromycin treatment on the need for mechanical ventilation (MV) in all subgroups was also analysed.

Results: The addition of clarithromycin significantly increased the proportion of patients achieving the primary endpoint across all subgroups and decreased the need for MV in many subgroups. For instance, the primary endpoint was attained by 32.7% of placebo-treated patients and in 67% of clarithromycin-treated patients with CURB-65 score ≥2 (p<0.0001) whereas MV was required in 18.8% and 7.4% respectively (p=0.022). The addition of corticosteroids alone was not as clinically advantageous as the use of clarithromycin alone.

Conclusion: Adding clarithromycin to SoC in the ACCESS study achieved early clinical anti-inflammatory responses and decreased the need for MV in subgroups of hospitalized patients with CAP.

Registration: EudraCT 2020-004452-15; ClinicalTrials.gov NCT04724044.