Association of Intensity of Anti-Pseudomonal Antibiotic Therapy With Risk of Treatment-Emergent Organisms in Cystic Fibrosis Children with Newly Acquired Pseudomonas Aeruginosa

Clin Infect Dis. 2021 Mar 6:ciab208. doi: 10.1093/cid/ciab208. Online ahead of print.


BACKGROUND: While Pseudomonas aeruginosa (Pa) eradication regimens have contributed to a decline in Pa prevalence in people with cystic fibrosis (CF), this antibiotic exposure might increase the risk of acquisition of drug-resistant organisms. This study evaluated the association between antipseudomonal antibiotic exposure intensity and acquisition risk of drug-resistant organisms among children with CF and new Pa infection.

METHODS: We utilized data from the Early Pseudomonas Infection Control Clinical Trial (EPIC CT), a randomized controlled trial comparing Pa eradication strategies in children with CF and new Pa. The exposure was the number of weeks of oral or inhaled antipseudomonal antibiotics, or ever vs. never treatment with intravenous antipseudomonal antibiotics, during the 18 months of EPIC CT participation. The primary outcomes were risks of acquisition of several respiratory organisms during five years of follow up after EPIC CT estimated using Cox proportional hazards models separately for each specific organism.

RESULTS: Among 249 participants, there was no increased acquisition risk of any organism associated with greater inhaled antibiotic exposure. With each additional week of oral antibiotics, there was an increased hazard of Achromobacter xylosoxidans acquisition (HR=1.24, 95% CI: 1.02-1.50; p=0.03). Treatment with intravenous antibiotics was associated with an increased hazard of acquisition of multidrug-resistant Pa (HR=2.47; 95% CI 1.28-4.78; p=0.01) and MRSA (HR=1.57; 95% CI 1.03-2.40); p=0.04).

CONCLUSIONS: Results from this study illustrate the importance of making careful antibiotic choices to balance the benefits of antibiotics in people with CF while minimizing the risk of acquisition of drug-resistant organisms.

PMID:33693586 | DOI:10.1093/cid/ciab208