BACKGROUND: Although antimicrobial susceptibility testing (AST) frequently guides cystic fibrosis (CF) pulmonary exacerbation (PEx) management, its clinical utility is unclear. This study examined associations between AST and antimicrobial switching during PEx treatment and time and occurrence of next PEx as treatment outcomes. METHODS: This retrospective cohort study utilized Pediatric Health Information System data. Children and adolescents aged 1-18years admitted for a PEx from 2011 to 2016 were studied. Antimicrobial switching was defined as any intra-admission change in intravenous (IV), oral, and/or inhaled antimicrobials. Time to next PEx was defined as the time between index PEx hospital discharge and subsequent hospital admission requiring IV antimicrobials. Odds of antimicrobial switching >/=5days after treatment initiation were determined by generalized linear mixed models, and associations between AST and time to next PEx were studied using Kaplan-Meier curves and Cox proportional hazards regression. RESULTS: AST occurred in 2518 (39%) of 6451 PEx at 36 hospitals and was associated with increased odds of antimicrobial switching (OR 1.33, 95% CI 1.16-1.52; p=0.001) and increased hazard of future PEx (HR 1.32, 95% CI 1.16-1.50; p<0.001). However, antimicrobial switching was not associated with a longer time to next PEx. CONCLUSIONS: AST was associated with both increased probability of antimicrobial regimen change and increased PEx hazard. There was no evidence that antimicrobial regimen change was associated with clinical benefit as assessed by time to next PEx. However, these results indicate residual indication bias remained after adjustment for available disease covariates. Additional studies of the clinical value of AST are warranted.