Pseudomonas aeruginosa susceptibility patterns and associated clinical outcomes in people with cystic fibrosis following approval of aztreonam lysine for inhalation

Claire L. Keating, Jonathan B. Zuckerman, Pradeep K. Singh, Matthew McKevitt, Oksana Gurtovaya, Mark Bresnik, Bruce C. Marshall, Lisa Saiman

Research output: Contribution to journalArticlepeer-review

Abstract

The approval of aztreonam lysine for inhalation solution (AZLI) raised concerns that additional antibiotic exposure would potentially affect the susceptibility profiles of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients. This 5-year, prospective, observational study tracked susceptibility changes and clinical outcomes in CF patients in the United States with chronic P. aeruginosa infection. Sputum cultures were collected annually (2011 to 2016). The primary study endpoint was the proportion of subjects whose least susceptible P. aeruginosa isolate had an aztreonam MIC that was .8mg/ml (parenteral breakpoint) and increased $4-fold compared with the least susceptible isolate from the previous year. Annualized data for pulmonary exacerbations, hospitalizations, and percent of predicted forced expiratory volume in 1 s (FEV1% predicted) were obtained from the CF Foundation Patient Registry and compared between subjects meeting and those not meeting the primary endpoint. A total of 510 subjects were enrolled; 334 (65%) completed the study. A consistent proportion of evaluable subjects (13 to 22%) met the primary endpoint each year, and AZLI use during the previous 12 months was not associated with meeting the primary endpoint. While the annual declines in lung function were comparable for subjects meeting and those not meeting the primary endpoint, more pulmonary exacerbations and hospitalizations were experienced by those who met it. The aztreonam susceptibility of P. aeruginosa remained consistent during the 5- year study. The relationship between P. aeruginosa isolate susceptibilities and clinical outcomes is complex; reduced susceptibility was not associated with an accelerated decline in lung function but was associated with more exacerbations and hospitalizations, likely reflecting increased overall antibiotic exposure.

Original languageEnglish (US)
Article numbere02327-20
JournalAntimicrobial agents and chemotherapy
Volume65
Issue number3
DOIs
StatePublished - Mar 2021
Externally publishedYes

Keywords

  • Antimicrobial drug resistance
  • Aztreonam
  • Cystic fibrosis
  • Pseudomonas aeruginosa

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Pseudomonas aeruginosa susceptibility patterns and associated clinical outcomes in people with cystic fibrosis following approval of aztreonam lysine for inhalation'. Together they form a unique fingerprint.

Cite this