Valerie Waters1, Sanja Stanojevic2, Michelle Klingel3, Jackie Chiang4, Nicole Sonneveld5, Richa Kukkar6, Elizabeth Tullis7, Felix Ratjen8. 1. Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: Valerie.waters@sickkids.ca. 2. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: Sanja.Stanojevic@sickkids.ca. 3. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: Michelle.Klingel@sickkids.ca. 4. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: Jackie.Chiang@sickkids.ca. 5. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: n.sonneveld@erasmusmc.nl. 6. Division of Infectious Diseases, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: 13rk42@queensu.ca. 7. Division of Respirology and Keenan Research Centre of Li Ka Shing Knowledge Institute, Department of Medicine, St. Michael's Hospital, University of Toronto, Toronto, Canada. Electronic address: Tullise@smh.ca. 8. Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. Electronic address: Felix.Ratjen@sickkids.ca.
Abstract
BACKGROUND: Pulmonary exacerbations frequently lead to an irrevocable loss of lung function in cystic fibrosis (CF) patients. Although extended antibiotic duration has not been shown to be associated with improved outcomes in CF overall, it is not known whether there is a subset of patients who may benefit from longer treatment courses. METHODS: This was a retrospective cohort study, using the Toronto CF Database from 1997 to 2012, of CF individuals with pulmonary exacerbations requiring intravenous antibiotic treatment. We investigated factors associated with improvement in forced expiratory volume in 1 second (FEV1) in patients treated with ≤14 days and >14 days of antibiotic treatment. RESULTS: A total of 538 pulmonary exacerbations in 253 patients were used for these analysis; 39% of these exacerbations fully recovered lung function at follow-up. Exacerbations were more frequently treated with >14 days of antibiotics in older patients with lower FEV1 at exacerbation and higher rates of B. cepacia complex infections. Subjects with exacerbations treated for >14 days had a significantly greater increase in FEV1 from day 14 to follow up compared to those with ≤14 days (p<0.001). On multivariable analysis, smaller changes from days 0 to 14 of antibiotics and treatment duration>14 days were associated with greater increases in FEV1 from day 14 to follow-up. In those who received >14 days of antibiotic therapy, smaller improvements in FEV1 change from day 0 to 14 and younger age at exacerbation were significantly associated with a greater FEV1 response from day 14 to end of treatment. Antibiotic treatment >14 days was not associated with longer time to subsequent exacerbation. CONCLUSIONS: This study highlights that in the treatment of pulmonary exacerbations, maximum lung function is not achieved within 14 days in all patients, and that there is continued improvement beyond this period.
BACKGROUND: Pulmonary exacerbations frequently lead to an irrevocable loss of lung function in cystic fibrosis (CF) patients. Although extended antibiotic duration has not been shown to be associated with improved outcomes in CF overall, it is not known whether there is a subset of patients who may benefit from longer treatment courses. METHODS: This was a retrospective cohort study, using the Toronto CF Database from 1997 to 2012, of CF individuals with pulmonary exacerbations requiring intravenous antibiotic treatment. We investigated factors associated with improvement in forced expiratory volume in 1 second (FEV1) in patients treated with ≤14 days and >14 days of antibiotic treatment. RESULTS: A total of 538 pulmonary exacerbations in 253 patients were used for these analysis; 39% of these exacerbations fully recovered lung function at follow-up. Exacerbations were more frequently treated with >14 days of antibiotics in older patients with lower FEV1 at exacerbation and higher rates of B. cepacia complex infections. Subjects with exacerbations treated for >14 days had a significantly greater increase in FEV1 from day 14 to follow up compared to those with ≤14 days (p<0.001). On multivariable analysis, smaller changes from days 0 to 14 of antibiotics and treatment duration>14 days were associated with greater increases in FEV1 from day 14 to follow-up. In those who received >14 days of antibiotic therapy, smaller improvements in FEV1 change from day 0 to 14 and younger age at exacerbation were significantly associated with a greater FEV1 response from day 14 to end of treatment. Antibiotic treatment >14 days was not associated with longer time to subsequent exacerbation. CONCLUSIONS: This study highlights that in the treatment of pulmonary exacerbations, maximum lung function is not achieved within 14 days in all patients, and that there is continued improvement beyond this period.
Authors: Sonya L Heltshe; Natalie E West; Donald R VanDevanter; D B Sanders; Valeria V Beckett; Patrick A Flume; Christopher H Goss Journal: Contemp Clin Trials Date: 2017-11-21 Impact factor: 2.226
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