Beyond ORBIT: Mapping the Constellation of Pseudomonas Endotypes in Bronchiectasis Clinical Trials

Bronchiectasis antimicrobial trials are marked by paradoxes. Macrolides, lacking in vivo activity against Pseudomonas aeruginosa, show clear benefit, whereas Pseudomonas-active agents often fail, raising concerns of resistance, especially in chronic P. aeruginosa infection associated with worse outc...

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Bibliographic Details
Published inAmerican journal of respiratory and critical care medicine Vol. 211; no. 8; pp. 1321 - 1323
Main Author Mac Aogáin, Micheál
Format Journal Article
LanguageEnglish
Published United States American Thoracic Society 01.08.2025
Subjects
Antibiotics
Bronchitis
Clinical trials
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Summary:Bronchiectasis antimicrobial trials are marked by paradoxes. Macrolides, lacking in vivo activity against Pseudomonas aeruginosa, show clear benefit, whereas Pseudomonas-active agents often fail, raising concerns of resistance, especially in chronic P. aeruginosa infection associated with worse outcomes. Several large multicenter studies of inhaled antimicrobials, including AIR-BX, RESPIRE, and ORBIT, have reported inconsistent results despite rigorous phase 3 designs evaluating inhaled formulations of Pseudomonas-active antibiotic agents. Among these, ORBIT (Once daily Respiratory Bronchiectasis Inhalation Treatment) stands out, encompassing two identically designed trials of inhaled liposomal ciprofloxacin (ORBIT-3 and ORBIT-4) in patients with chronic P. aeruginosa infection. Unlike AIR-BX and RESPIRE, ORBIT targeted a microbiologically defined phenotype: a focused strategy that should, in theory, reduce heterogeneity. This fact makes the failure of ORBIT-3 at once disappointing and all the more intriguing.
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ISSN:1073-449X
1535-4970
1535-4970
DOI:10.1164/rccm.202506-1388ED