Macrolides reduce in-hospital mortality among patients with Acute Exacerbation of COPD

Thailand: The macrolide treatment at initial admission reduced in-hospital mortality in Acute Exacerbation of Chronic Obstructive Pulmonary Disease (AECOPD) patients compared to the non-macrolide group.

AECOPD may result in worsening lung function. The bacteria and virus are the infectious agents in exacerbation. Macrolides are antibiotics effective against gram-positive, some gram-negative, and atypical bacteria, but there is a lack of evidence mentioning their direct effect on viral infections.

The literature mentions improvements in the clinical course of viral respiratory infections, decreased rate of AECOPD recurrence, and reduced exacerbation attributed to macrolides' anti-inflammatory and immunomodulatory properties. However, the studies mentioning the beneficial effects of macrolides in reducing hospital mortality are controversial.

Against the above framework, Thotsaporn Morasert and a team from the Department of Internal Medicine at Suratthani Hospital and the Department of Clinical Epidemiology from Thammasat University, Thailand, inspected the results of macrolide treatment at initial admission in AECOPD patients on in-hospital mortality.

This original research article is published in the International Journal of Chronic Obstructive Pulmonary Disease, Dovepress.

The study population included AECOPD patients admitted between October 2015 and September 2018. The final cohort had 1882 admissions, of which 55 % (1035 admissions) were treated with macrolides, and 45 % (847 admissions) did not receive macrolides. The multivariate Cox proportional hazard model was performed to eliminate residual confounding after the Propensity Score analysis. Antibiotic co-administration systemic steroids were included in the regression model. The study measured in-hospital mortality as the primary outcome.

The points of focus from the study include:

• 86.2 % of patients were male with a mean ± SD of 75 ± 11.1 years.

• 85 % of the cohort had comorbidities, of which 47.7 % had hypertension.

• Before admission, 72.3 % of patients used inhaled controller medications, 54.7 % had Emergency Department visits, and 43.3 % were hospitalized in the previous year.

• 70 % of patients required intubation due to respiratory failure on initial admission.

• Radiographic consolidation depicted pneumonia in 34 % of patients.

• The most common macrolide given was clarithromycin (80%).

• The patients in the macrolide group were less likely to receive other antibiotics except for ceftriaxone.

• Compared to the non-macrolide group, the macrolide group received more ceftriaxone and systemic steroids. (77 % vs 25 % and 73 % vs 55 %)

• Macrolide treatment significantly reduced in-hospital mortality in AECOPD patients with an adjusted hazard ratio of 0.55, a confidence interval of 95 %, and a P value of 0.034.

• The researchers demonstrated in-hospital mortality outcomes of 11 % in AECOPD patients.

• Macrolides reduced all-cause mortality by 45 %.

Low-dose macrolide therapy is suggested in COPD patients with more than three exacerbations per year requiring steroids and patients with at least one exacerbation requiring hospitalization per year, as per the Latest GOLD Guideline 2022 and British Thoracic Society Guideline, 2020. The minimum duration for which therapy could be considered is six months.

The researchers concluded, "The combined antimicrobial and immunomodulatory effects of macrolide treatment play an essential role in reducing in-hospital mortality in hospitalized AECOPD patients."

References:

Morasert T, Kriengwattanakul O, Kulalert P. Effect of Macrolide Antibiotics on In-Hospital Mortality Among Acute Exacerbation of COPD Patients: A Propensity Score-Matched Analysis. Int J Chron Obstruct Pulmon Dis. 2022;17:2229-2239