Azithromycin Versus Beta-lactams in Hospitalized Patients with Acute Exacerbations of COPD

Abstract

Background There is a lack of data comparing azithromycin to alternative antibiotic choices in managing COPD exacerbations, making appropriate antibiotic selection controversial. Objective To compare treatment failure in hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) receiving azithromycin or beta-lactams. Design Retrospective, multicenter cohort study using logistic regression for multivariable analysis. Patients were included if they were at least 18 years old, admitted with AECOPD, and received at least two consecutive days of either a beta-lactam or azithromycin. Patients were excluded if they received concomitant azithromycin and beta-lactam antibiotics during the first 2 days, had a history of other severe underlying pulmonary diseases, pregnancy, COVID-19, alpha-1 antitrypsin deficiency, or received a corticosteroid for a diagnosis other than COPD. Participants Five hundred ninety-five patients were included, of which 428 (72%) received azithromycin and 167 patients (28%) received a beta-lactam. Main Measures The primary endpoint was treatment failure rate in patients receiving azithromycin versus beta-lactams, which was a composite endpoint defined as in-hospital mortality, admission to intensive care, initiation of invasive mechanical ventilation, initiation of a new antibiotic, steroid therapy escalation, or readmission due to AECOPD within 30 days. Key Results The composite primary outcome occurred in 84 patients (19.6%) in the azithromycin group and 54 (32.3%) in the beta-lactam group ( p <0.01). The difference in the composite outcome was a result of higher rates of new antibiotics during admission (12.6% vs 4.2%; p <0.01) and higher readmission within 30 days (19.3% vs 12.4%; p =0.032). After controlling for potential confounders, beta-lactams continued to demonstrate a higher risk for treatment failure (OR, 2.30; 95% CI, 1.46–3.63). There was no difference in adverse effects between the groups. Conclusion Azithromycin was associated with less treatment failure in AECOPD which was driven by lower readmission rates and prescription of new antimicrobials.

In-hospital antibiotic use for severe chronic obstructive pulmonary disease exacerbations: a retrospective observational study

“…Subgroup analyses by initial antibiotic indicated that the hazard on discharge was significantly lower for piperacillin-tazobactam and other antibiotics compared to amoxicillin-clavulanic acid. A recent American retrospective, multicenter cohort study observed less treatment failure (initiation of new antibiotic and readmission) and shorter LOS in the azithromycin group compared to the beta-lactam group [35]. However, the most commonly prescribed beta-lactam was ceftriaxone [35], and not amoxicillinclavulanic acid as in our study.…”

“…A recent American retrospective, multicenter cohort study observed less treatment failure (initiation of new antibiotic and readmission) and shorter LOS in the azithromycin group compared to the beta-lactam group [35]. However, the most commonly prescribed beta-lactam was ceftriaxone [35], and not amoxicillinclavulanic acid as in our study. Moreover, azithromycin was probably not used as treatment in our study, but as chronic immunomodulatory treatment [1,34].…”

Azithromycin use prior to ICU admission is associated with a lower short-term mortality for critically ill acute exacerbations of chronic obstructive pulmonary disease patients: A retrospective cohort study

“… 1 , 13 , 44 Numerous controlled trials implied inclusion of azithromycin in the treatment regimen may bring clinical benefits for critically ill patients with AECOPD, including reductions in hospital readmissions, improvements in time to next readmission and decrease of ICU costs. 11 , 45 , 46 In a study involving more than 25,000 patients with AECOPD admitted to the ICU, macrolides initiated within 2 days of admission reduced hospital costs and 30-days ICU readmission rates. 11 Azithromycin is also used in other ICU conditions due to its antibacterial and anti-inflammatory effects.…”