title: Pseudomonas aeruginosa antibiotic susceptibility during long-term use of aztreonam for inhalation solution (AZLI).
abstract: OBJECTIVE
  Aztreonam for inhalation solution (AZLI) is an inhaled antibiotic for patients with cystic fibrosis (CF) and Pseudomonas aeruginosa airway infection. The risk of selecting for P. aeruginosa isolates with reduced susceptibility to antibiotics is inherent to their use, but is of particular concern following repeated exposure and when complete eradication of lung pathogens is difficult to obtain. We investigated whether repeated treatment courses of AZLI led to decreases in P. aeruginosa susceptibility to aztreonam or other antibiotics.
  
  
  METHODS
  Serial sputum specimens were collected and processed for isolation and quantification of all P. aeruginosa isolates in a Phase 3 open-label, 18 month study (NCT00128492) including 274 CF patients receiving up to nine courses of AZLI twice daily (AZLI2) or thrice daily (AZLI3) (28 days on/28 days off). P. aeruginosa antibiotic susceptibility testing was conducted.
  
  
  RESULTS
  No changes were observed in the aztreonam MIC(50) for all P. aeruginosa isolates collected from AZLI3 patients, while intermittent increases were observed in the aztreonam MIC(90). Approximately 70% of the P. aeruginosa isolates with the highest aztreonam MIC from each patient receiving AZLI3 remained unchanged or decreased relative to that patient's equivalent isolate at baseline; 30% experienced an increase in MIC. Few decreases in P. aeruginosa susceptibility to other antibiotics were observed in AZLI3 patients, while increases in P. aeruginosa susceptibility to tobramycin were observed.
  
  
  CONCLUSIONS
  Few decreases in aztreonam susceptibility were reported in patients receiving AZLI3. Increases in tobramycin susceptibility were observed, suggesting that novel treatment paradigms may be able to prolong antibiotic susceptibility in CF patients.
authors.affiliation: Baylor College of Medicine, Texas Children's Hospital Pediatric Pulmonary Medicine, 6621 Fannin, Suite 1040.12, Houston, TX 77030-2399, USA. coermann@bcm.tmc.edu
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Oermann
authors.forename: Karen S
authors.initials: KS
authors.lastname: McCoy
authors.forename: George Z
authors.initials: GZ
authors.lastname: Retsch-Bogart
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Gibson
authors.forename: Matthew
authors.initials: M
authors.lastname: McKevitt
authors.forename: A Bruce
authors.initials: AB
authors.lastname: Montgomery
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D001398:Aztreonam / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D003550:Cystic Fibrosis / Q000150:complications; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D008168:Lung / Q000382:microbiology; D008297:Male; D008826:Microbial Sensitivity Tests; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D001398:Aztreonam