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Pseudomonas aeruginosa antimicrobial susceptibility test (AST) results and pulmonary exacerbation treatment responses in cystic fibrosis
Authors:Donald R. VanDevanter  Sonya L. Heltshe  Jay B. Hilliard  Michael W. Konstan
Affiliation:1. Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland OH, USA;2. CFF Therapeutics Development Network Coordinating Center, Seattle Children''s Research Institute, Seattle, WA and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA;3. Department of Pediatrics, Rainbow Babies and Children''s Hospital, Cleveland OH, USA
Abstract:Background Antimicrobial susceptibility testing (AST) of bacterial isolates is a time- and resource-intensive procedure recommended by cystic fibrosis (CF) treatment guidelines for antimicrobial selection for pulmonary exacerbation (PEx) treatment.Methods We studied relationships between Pseudomonas aeruginosa (Pa) isolate AST results, antipseudomonal PEx treatments, and treatment responses as change in weight and percent predicted forced expiratory volume in 1 s (ppFEV1) as well as future antimicrobial treatment hazard for PEx occurring at a CF care center from 1999 through 2018. Treatments were categorized by “Pa coverage” as complete (all Pa isolates susceptible by AST to at least one administered agent), none (no isolates susceptible), incomplete (some, but not all isolates susceptible), and indeterminant (administered antipseudomonals not evaluated by AST). Weight and ppFEV1 responses were compared across Pa coverage categories using unadjusted and adjusted general estimating equations; hazard of future treatment was assessed by Cox and logistic regression.Results Among 3820 antimicrobial PEx treatment events in 413 patients with Pa, 62.6% (2390) had complete Pa coverage; 8.9% (340), 2.4% (99), and 26.2% (1000), had no, incomplete, and indeterminant Pa coverage, respectively. Mean baseline to follow-up weight change was +0.74 kg [95% CI 0.63, 0.86]; ppFEV1 change was +1.60 [1.29, 1.90]. Pa coverage category was not associated with significant differences in weight or ppFEV1 change or with future antimicrobial treatment hazard.Conclusions We did not observe superior responses for AST-defined complete Pa coverage treatments versus lesser coverage treatments, suggesting that AST may be of little utility in choosing antimicrobials for CF PEx treatment.
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