Hospital Versus Home Treatment For Acute Infectious Respiratory Exacerbations In Cystic Fibrosis (original) (raw)
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Respiratory Research, 2010
Background: Cystic Fibrosis (CF) is a life-shortening genetic disease in which~80% of deaths result from loss of lung function linked to inflammation due to chronic bacterial infection (principally Pseudomonas aeruginosa). Pulmonary exacerbations (intermittent episodes during which symptoms of lung infection increase and lung function decreases) can cause substantial resource utilization, morbidity, and irreversible loss of lung function. Intravenous antibiotic treatment to reduce exacerbation symptoms is standard management practice. However, no prospective studies have identified an optimal antibiotic treatment duration and this lack of objective data has been identified as an area of concern and interest.
PLoS ONE, 2013
Background: Cystic Fibrosis (CF) patients are vulnerable to airway colonization with Pseudomonas aeruginosa. In case eradication fails after antibiotic treatment, patients become chronically colonized with P. aeruginosa, with recurrent pulmonary exacerbation, for which patients typically are hospitalized for 2 weeks and receive intravenous antibiotic treatment. Normally, improvement of the patients' health is established. Aim: Determination of the correspondence between patient improvement and changes of the P. aeruginosa and total bacterial load in the sputum. Methods: Eighteen CF patients with exacerbation were included for a total of 27 hospitalization episodes. At day 1, 8 and 15, inflammation and lung function parameters were determined, together with the P. aeruginosa load in the sputum using culture, quantitative PCR (qPCR) and propidium monoazide qPCR. Results: Patients improved during hospitalization (decrease in levels of C-reactive protein, white blood cell counts and erythrocyte sedimentation rate, increase of FEV 1), reaching normal values already after one week. Also the P. aeruginosa load and the total bacterial load decreased during the first week of antibiotic treatment (p,0.05), except for patients with a low lung function (FEV 1 #39.4%), for whom no significant decrease of P. aeruginosa was established. Comparison of culturebased and propidium monoazide qPCR-based quantification of P. aeruginosa showed that at the end of the treatment on average 62% of the P. aeruginosa cells are not cultivable, indicating that many cells are alive but dormant, or dead but still structurally intact. Conclusion: Improvement of the clinical status is accompanied with a decrease of the P. aeruginosa load, whereby both occur mainly during the first week of antibiotic treatment. However, for patients with a low lung function, no decrease of the P. aeruginosa load is observed. Comparison of detection techniques shows that a large amount of noncultivable or dead bacteria are present in the samples.
American Journal of Respiratory and Critical Care Medicine, 2021
Rationale: People with cystic fibrosis (CF) experience acute worsening of respiratory symptoms and lung function known as pulmonary exacerbations. Treatment with intravenous antimicrobials is common; however, there is scant evidence to support a standard treatment duration. Objectives: To test differing durations of intravenous antimicrobials for CF exacerbations. Methods: STOP2 (Standardized Treatment of Pulmonary Exacerbations 2) was a multicenter, randomized, controlled clinical trial in exacerbations among adults with CF. After 7-10 days of treatment, participants exhibiting predefined lung function and symptom improvements were randomized to 10 or 14 days' total antimicrobial duration; all others were randomized to 14 or 21 days' duration. Measurements and Main Results: The primary outcome was percent predicted FEV 1 (ppFEV 1) change from treatment initiation to 2 weeks after cessation. Among early responders, noninferiority of 10 days to 14 days was tested; superiority of 21 days compared with 14 days was compared for the others. Symptoms, weight, and adverse events were secondary. Among 982 randomized people, 277 met improvement criteria and were randomized to 10 or 14 days of treatment; the remaining 705 received 21 or 14 days of treatment. Mean ppFEV 1 change was 12.8 and 13.4 for 10 and 14 days, respectively, a-0.65 difference (95% CI [-3.3 to 2.0]), excluding the predefined noninferiority margin. The 21-and 14-day arms experienced 3.3 and 3.4 mean ppFEV 1 changes, a difference of-0.10 (-1.3 to 1.1). Secondary endpoints and sensitivity analyses were supportive. Conclusions: Among adults with CF with early treatment improvement during exacerbation, ppFEV 1 after 10 days of intravenous antimicrobials is not inferior to 14 days. For those with less improvement after one week, 21 days is not superior to 14 days. Clinical trial registered with www.clinicaltrials.gov (NCT02781610).
CHEST Journal, 2009
Pseudomonas aeruginosa airway infection. At study enrollment, patients in the study 1-exacerbation had symptoms indicative of pulmonary exacerbation (n ؍ 84; < 14 years of age, 31 patients; > 14 years of age, 53 patients); patients in study 2-stable had stable respiratory symptoms (n ؍ 140; < 14 years of age, 14 patients; > 14 years, 126 patients). Methods: The anchor-based method utilized a global rating-of-change questionnaire (GRCQ) that assessed patients' perceptions of change in their respiratory symptoms after TIS treatment. The mean change from baseline CFQ-R-Respiratory scores were mapped onto the GRCQ to estimate the MCID. The two distribution-based methods were as follows: (1) 0.5 SD of mean change in CFQ-R-Respiratory scores (baseline to end of TIS treatment); and (2) 1 SEM for baseline CFQ-R-Respiratory scores. Triangulation of these three estimates defined the MCIDs. Results: MCID scores were larger for patients in study 1-exacerbation (8.5 points) than for those in study 2-stable (4.0 points), likely reflecting differences in patient disease status (exacerbation/ stable) between these studies.
American Journal of Respiratory and Critical Care Medicine, 2010
Rationale: Individuals with cystic fibrosis (CF) are subject to recurrent respiratory infections (exacerbations) that often require intravenous antibiotic treatment and may result in permanent loss of lung function. The optimal means of delivering therapy remains unclear. Objectives: To determine whether duration or venue of intravenous antibiotic administration affect lung function. Methods: Data were retrospectively collected on 1,535 subjects recruited by the US CF Twin and Sibling Study from US CF care centers between 2000 and 2007.
Journal of Cystic Fibrosis, 2012
Background: The goal of this study was to determine the association of multiple antibiotic-resistant Pseudomonas aeruginosa (MARPA) acquisition with lung function decline in patients with cystic fibrosis (CF). Methods: Using data from Epidemiologic Study of Cystic Fibrosis (ESCF), we identified patients with spirometry data and MARPA, defined as PA (1) resistant to gentamicin and either tobramycin or amikacin, and (2) resistant to ≥ 1 antipseudomonal beta lactam. MARPA had to be detected in a respiratory culture after ≥ 2 years of PA-positive but MARPA-negative respiratory cultures. Multivariable piecewise linear regression was performed to model the annual rate of decline in forced expiratory volume in 1 second (FEV 1) % predicted 2 calendar years before and after the index year of MARPA detection, adjusting for patient characteristics and CF therapies. Results: In total, 4349 patients with chronic PA and adequate PFT data were identified; 1111 subsequently developed MARPA, while 3238 patients were PA positive but MARPA negative. Compared with patients who did not acquire MARPA, MARPA-positive patients had lower FEV 1 and received more oral (p b 0.013) and inhaled (p b 0.001) antibiotic therapy. Mean FEV 1 decline did not change significantly after MARPA detection (−2.22% predicted/year before detection and −2.43 after, p = 0.45). There was no relationship between persistent infection or FEV 1 quartile and FEV 1 decline. Conclusions: Newly detected MARPA was not associated with a significant change in the rate of FEV 1 decline. These results suggest that MARPA is more likely to be a marker of more severe disease and more intensive therapy, and less likely to be contributing independently to more rapid lung function decline.
Thorax, 2006
Background: This study examined characteristics of adult and adolescent patients with cystic fibrosis (CF) to determine factors associated with an increased risk of pulmonary exacerbations. Methods: 249 patients with CF infected with multidrug resistant bacteria were recruited and prospectively followed for up to 4.5 years until they experienced a pulmonary exacerbation severe enough to require intravenous antibiotics. Multivariable regression analyses were used to compare the characteristics of patients who experienced an exacerbation with those who did not. Results: 124 of the 249 patients (50%) developed a pulmonary exacerbation during the first year and 154 (62%) experienced an exacerbation during the 4.5 year study period. Factors predictive of exacerbations in a multivariable survival model were younger age (OR 0.98, 95% CI 0.96 to 0.99), female sex (OR 1.45, 95% CI 1.07 to 1.95), lower forced expiratory volume in 1 second (FEV 1 ) (OR 0.98, 95% CI 0.97 to 0.99), and a previous history of multiple pulmonary exacerbations (OR 3.16, 95% CI 1.93 to 5.17). Chronic use of inhaled corticosteroids was associated with an increased risk of exacerbation (OR 1.92, 95% CI 1.00 to 3.71) during the first study year. Conclusions: Patients who experience pulmonary exacerbations are more likely to be younger, female, using inhaled steroids, have a lower FEV 1 , and a history of multiple previous exacerbations. It is hoped that knowledge of these risk factors will allow better identification and closer monitoring of patients who are at high risk of exacerbations.
Australian and New Zealand journal of medicine, 1999
Although anti-pseudomonal antibiotics are routinely used in the treatment of acute respiratory exacerbations of adult cystic fibrosis (CF), the specific efficacy of such treatment remains uncertain, the mechanism of action of these agents is not fully understood, and the role of sputum susceptibility testing in clinical decision making is controversial. We investigated the relationship between susceptibility testing and clinical outcome in adult CF patients colonised with Pseudomonas aeruginosa. Sputum samples were collected before, during and after respiratory exacerbations from 31 admissions (17 patients). Sputum colony counts and MIC of P. aeruginosa were performed. Sputum colony counts did not change significantly during or after intravenous (IV) antibiotic therapy. Clinical outcome parameters (lung function, 12-minute walking distance, sputum weight and quality of life) were compared with susceptibility of P. aeruginosa colonies isolated at admission to the antibiotics used, an...