Standard care versus protocol based therapy for new onset Pseudomonas aeruginosa in cystic fibrosis

• Published in: Pediatric pulmonology 2013-10, Vol.48 (10), p.943-953
• Main Authors: Mayer-Hamblett, Nicole, Rosenfeld, Margaret, Treggiari, Miriam M., Konstan, Michael W., Retsch-Bogart, George, Morgan, Wayne, Wagener, Jeff, Gibson, Ronald L., Khan, Umer, Emerson, Julia, Thompson, Valeria, Elkin, Eric P., Ramsey, Bonnie W.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - therapeutic use; Child; Child, Preschool; cystic fibrosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis - microbiology; early intervention; Female; historical controls; Hospitalization - statistics & numerical data; Humans; Infant; Male; Prospective Studies; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas Infections - drug therapy; randomized trial; Recurrence; Tobramycin - administration & dosage; Tobramycin - therapeutic use; Treatment Outcome
• ISSN: 8755-6863; 1099-0496
• DOI: 10.1002/ppul.22693

Rationale The Early Pseudomonal Infection Control (EPIC) randomized trial rigorously evaluated the efficacy of different antibiotic regimens for eradication of newly identified Pseudomonas (Pa) in children with cystic fibrosis (CF). Protocol based therapy in the trial was provided based on culture positivity independent of symptoms. It is unclear whether outcomes observed in the clinical trial were different than those that would have been observed with historical standard of care driven more heavily by respiratory symptoms than culture positivity alone. We hypothesized that the incidence of Pa recurrence and hospitalizations would be significantly reduced among trial participants as compared to historical controls whose standard of care preceded the widespread adoption of tobramycin inhalation solution (TIS) as initial eradication therapy at the time of new isolation of Pa. Methods Eligibility criteria from the trial were used to derive historical controls from the Epidemiologic Study of CF (ESCF) who received standard of care treatment from 1995 to 1998, before widespread availability of TIS. Pa recurrence and hospitalization outcomes were assessed over a 15‐month time period. Results As compared to 100% of the 304 trial participants, only 296/608 (49%) historical controls received antibiotics within an average of 20 weeks after new onset Pa. Pa recurrence occurred among 104/298 (35%) of the trial participants as compared to 295/549 (54%) of historical controls (19% difference, 95% CI: 12%, 26%, P