Bacterial Load: A Useful Marker of Antibiotic Response in Bronchiectasis

In patients with bronchiectasis, bacterial load may be a useful biomarker of disease severity and antibiotic treatment response, according to 3 studies published in the American Journal of Respiratory and Critical Care.

Researchers conducted 2 prospective studies of adults with bronchiectasis and 1 post-hoc analysis of a randomized trial of aztreonam for inhaled solution to help identify the reason for heterogeneous responses to inhaled antibiotics in this patient population. Recognizing that antibiotic treatment in patients with bronchiectasis reduces symptoms, the investigators sought to establish the relationship between bacterial load and clinical outcomes, to evaluate the stability of bacterial load over time, and to test the hypothesis that treatment response to inhaled antibiotics would be predicted by baseline bacterial load.

In study 1, the researchers explored the association among bacterial load, quality of life (QoL), and airway inflammation in 189 patients with bronchiectasis. A priori patients were divided into 3 groups: low bacterial load (<10⁵ colony-forming units [cfu]/g), moderate bacterial load (10⁵-10⁶ cfu/g), and high bacterial load (≥10⁷ cfu/g).

In study 2, the researchers assessed the stability of bacterial load in 2 prospective cohorts of patients, with the first cohort (n=26) receiving systemic antibiotic treatment for bronchiectasis exacerbations and the second cohort (n=10) composed of patients with clinically stable disease in whom day-to-day variability in sputum-derived markers, such as neutrophil biomarkers and airway bacterial load, was evaluated.

Study 3 was a post-hoc analysis of patients who were enrolled in 2 randomized, double-blind trials of aztreonam, both of which were designed to examine the hypothesis that treatment response in patients with bronchiectasis would be predicted by their bacterial load.

Bacterial load was a stable characteristic associated with worse QoL and more airway inflammation in studies 1, 2, and 3. In study 3, patients with a high bacterial load exhibited a significant improvement in the primary study end point (ie, QoL Bronchiectasis Respiratory Symptoms Score at 4 weeks) that favored aztreonam (mean difference, 9.7 points; 95% CI, 3.4-16.0; P =.003). The percentage of patients who attained an increase above the minimum clinically important difference was significantly higher in the aztreonam group vs the placebo group at week 4 (63% vs 37%, respectively; P =.01) and at week 12 (62% vs 38%, respectively; P =.01) only in those patients with a high bacterial load.

The investigators concluded that improved QoL with aztreonam only occurred in patients who had high bacterial load. This is the first study of its kind to identify an inhaled antibiotic response phenotype based on a patient’s baseline bacterial load. The potential for bacterial load to help guide antibiotic therapy in patients with bronchiectasis warrants further exploration in prospective studies.

Disclosures: Gilead Sciences, Inc. funded the analysis of the AIR-BX (Aztreonam for Inhaled Solution in Bronchiectasis) studies.

Reference

Sibila O, Laserna E, Shoemark A, et al. Airway bacterial load and inhaled antibiotic response in bronchiectasis [published online May 21, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201809-1651OC