Association of Intensity of Antipseudomonal Antibiotic Therapy With Risk of Treatment-Emergent Organisms in Children With Cystic Fibrosis and Newly Acquired Pseudomonas Aeruginosa

Abstract

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 versus never treatment with intravenous antipseudomonal antibiotics during the 18 months of EPIC CT participation. Primary outcomes were risks of acquisition of several respiratory organisms during 5 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 = .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 = .01) and MRSA (HR, 1.57; 95% CI: 1.03-2.40; P = .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 risk of acquisition of drug-resistant organisms.

Keywords: Pseudomonas aeruginosa; antibiotics; cystic fibrosis; pulmonary exacerbations.

Figure 1.

Overview of the study design of the EPIC Clinical Trial and EPIC Observational Study (reproduced with permission). Abbreviations: CF, Cystic Fibrosis; EPIC, Early Pseudomonas Infection Control. (Mayer-Hamblett N, Kloster M, Rosenfeld M, Gibsons RL, Retsch-Bogart GZ, Emerson J, Thompson V, Ramsey BW. Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long-term Outcomes in Cystic Fibrosis. Clinical Infectious Diseases 2015; 61(5): 707-715.)

Figure 2.

Distribution of cumulative weeks of (A) inhaled, (B) oral, and (C) IV antibiotic exposure during EPIC CT. Abbreviations: EPIC CT, Early Pseudomonas Infection Control Clinical Trial; IV, intravenous.