Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.
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ABSTRACT:
SUBMITTER: Smith S
PROVIDER: S-EPMC9342853 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Inhaled antibiotics for pulmonary exacerbations in cystic fibrosis.
Smith Sherie S Rowbotham Nicola J NJ Charbek Edward E
The Cochrane database of systematic reviews 20220801
<h4>Background</h4>Cystic fibrosis is a genetic disorder in which abnormal mucus in the lungs is associated with susceptibility to persistent infection. Pulmonary exacerbations are when symptoms of infection become more severe. Antibiotics are an essential part of treatment for exacerbations and inhaled antibiotics may be used alone or in conjunction with oral antibiotics for milder exacerbations or with intravenous antibiotics for more severe infections. Inhaled antibiotics do not cause the sam ...[more]
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Project description:RationalePatients with cystic fibrosis (CF) experience frequent pulmonary exacerbations (PExs). Clinicians manage these episodes of worsening signs and symptoms in a variety of ways.ObjectivesTo characterize the antibiotic management and associated change in lung function following PExs.MethodsWe used 2003-2005 data from the Epidemiologic Study of Cystic Fibrosis to examine antibiotic treatment and the immediate and long-term lung function change associated with clinician reported PExs.ResultsA total of 45,374 PExs were reported in 13,194 unique patients. Most PExs (73%) were treated with oral antibiotics, while 39% were treated IV and 24% were treated with inhaled antibiotics. The likelihood of non-IV versus IV antibiotic treatment was associated with the patient's age, stage of lung disease, and magnitude of lung function drop prior to the PEx. Following treatment, the average improvement in the FEV1 was 3.4 ± 12.2% predicted with a greater (5.1 ± 12.7% predicted) improvement following IV antibiotic treatment than with non-IV treatment (2.0 ± 11.6% predicted). When the best FEV1 from the year before was compared with 180 days following the PEx there was an average fall of 3.8 ± 10.5% predicted with little difference observed between antibiotic treatment routes. Patients with only one exacerbation during the 3-year study had a similar loss of lung function to patients with no reported exacerbations.ConclusionClinicians treat the majority of PExs with oral antibiotics, particularly in younger, healthier patients. Pulmonary function improves with antibiotic therapy, however, PExs are associated with lung function deterioration over time.
| S-EPMC4049300 | biostudies-literature
Project description:BACKGROUND:The Standardized Treatment of Pulmonary Exacerbations (STOP) program has the intent of defining best practices in the treatment of pulmonary exacerbations (PEx) in patients with cystic fibrosis (CF). The objective of this analysis was to describe the clinical presentations of patients admitted for intravenous (IV) antibiotics and enrolled in a prospective observational PEx study as well as to understand physician treatment goals at the start of the intervention. METHODS:We enrolled adolescents and adults admitted to the hospital for a PEx treated with IV antibiotics. We recorded patient and PEx characteristics at the time of enrollment. We surveyed treating physicians on treatment goals as well as their willingness to enroll patients in various study designs. Additional demographic and clinical data were obtained from the CF Foundation Patient Registry. RESULTS:Of 220 patients enrolled, 56% were female, 19% were adolescents, and 71% were infected with P. aeruginosa. The mean (SD) FEV1 at enrollment was 51.1 (21.6)% predicted. Most patients (85%) experienced symptoms for ?7days before admission, 43% had received IV antibiotics within the previous 6months, and 48% received oral and/or inhaled antibiotics prior to IV antibiotic initiation. Forty percent had ?10% FEV1 decrease from their best value recorded in the previous 6months, but for 20% of patients, their enrollment FEV1 was their best FEV1 recorded within the previous 6months. Physicians reported that their primary treatment objectives were lung function recovery (53%) and improvement of symptoms (47%) of PEx. Most physicians stated they would enroll patients in studies involving 10-day (72%) or 14-day (87%), but not 7-day (29%), treatment regimens. CONCLUSIONS:Based on the results of this study, prospective studies are feasible and physician willingness for interventional studies of PEx exists. Results of this observational study will help design future PEx trials.
| S-EPMC5582015 | biostudies-literature
Project description:Although cystic fibrosis (CF) is the most common inherited respiratory disease, the burden of influenza among individuals with CF is not well characterized.We used the CF Foundation Patient Registry to determine the relationship between pulmonary exacerbation incidence rate and influenza virus season from July 2003 through June 2007. The outcome of interest, pulmonary exacerbation, was defined as treatment of a respiratory illness with IV antibiotics. Each influenza season was defined as all months during which >/= 15% of laboratory tests for influenza virus were positive in the US influenza virologic surveillance system. We calculated incidence rates of pulmonary exacerbation during the influenza and summertime seasons as well as relative rates with 95% CIs. A multivariate regression model adjusted for demographic and clinical predictors.In 2003, the patient cohort size was 21,506 patients, and 7,727 patients experienced at least one pulmonary exacerbation. The overall pulmonary exacerbation incidence rate in the influenza season was 595.0 per 10,000 person-months compared with a summertime baseline of 549.6 per 10,000 person-months. The incidence rate ratio was 1.08 (95% CI: 1.06, 1.10). Multivariate analysis did not change our estimate of risk (adjusted odds ratio: 1.07; 95% CI: 1.05, 1.10). An estimated annual excess of 147.6 per 10,000 person-months or an excess 2.1% of total exacerbations occur during the influenza season.Our data demonstrate a substantial contribution of the influenza season to CF morbidity. Further studies to determine any causal link between influenza infection and CF pulmonary exacerbations are necessary.
| S-EPMC2851556 | biostudies-other
Project description:With the improving survival of cystic fibrosis (CF) patients and the advent of highly effective cystic fibrosis transmembrane conductance regulator therapy, the clinical spectrum of this complex multisystem disease continues to evolve. One of the most important clinical events for patients with CF in the course of this disease is an acute pulmonary exacerbation. Clinical and microbial epidemiology studies of CF pulmonary exacerbations continue to provide important insight into the disease course, prognosis, and complications. This work has now led to a number of large scale clinical trials with the goal of improving the treatment paradigm for CF pulmonary exacerbation. The primary goal of this review is to provide a summary of the pathophysiology, the clinical epidemiology, microbial epidemiology, outcome and the treatment of CF pulmonary exacerbation.
| S-EPMC7528649 | biostudies-literature
Project description:BackgroundObligate and facultative anaerobic bacteria are prevalent in cystic fibrosis (CF) airways. Increases in anaerobe relative abundance have been associated with CF pulmonary exacerbations (PEx); however, the impact of antibiotic treatment of anaerobes during PEx is unknown. We hypothesized that PEx treated with antibiotics with activity against anaerobes would improve outcomes compared to antibiotics without anaerobic activity.MethodsThis was a single-center, retrospective study of people with CF, ages 6 years and older, treated with intravenous (IV) antibiotics for PEx. IV antibiotics were classified as either broad or minimal anaerobic activity. PEx treated with broad anaerobe coverage were propensity-score matched to PEx treated with minimal anaerobic coverage. The primary outcome, % of baseline % predicted forced expiratory volume in one second (ppFEV1) recovered, was compared between antibiotic categories with a linear mixed model. The secondary outcome, time to next PEx, was assessed using a Prentice Williams Petersen model.Results514 PEx from 182 patients were included. Broad anaerobe coverage was used in 27% of PEx, and was used more often for older patients (p < 0.001) with worse baseline ppFEV1 (p < 0.001), and with Achromobacter (p < 0.001) or Burkholderia infections (p = 0.002). In the matched PEx, broad anaerobe coverage was not a significant predictor of % of baseline ppFEV1 recovered (∆ppFEV1 = -2.4, p = 0.09). Broad anaerobe coverage was also not a significant predictor of time to next PEx (HR 0.89, 95% CI 0.7-1.13, p = 0.35).ConclusionsIn this single center, retrospective study, antibiotics with broad activity against anaerobes were not associated with improved outcomes of CF PEx.
| S-EPMC8371065 | biostudies-literature
Project description:Pulmonary exacerbations lead to significant morbidity and mortality in patients with cystic fibrosis (CF). National consensus guidelines exist, but few studies report current practice in the treatment and monitoring of pulmonary exacerbations. The goal of this study was to characterize consistency and variability in the inpatient management of CF-related pulmonary exacerbations. We focused on the use of guideline-recommended maintenance therapies, antibiotic selection and treatment regimens, use of systemic corticosteroids, and frequency of lung function testing. We hypothesized that significant variability in these treatment practices exists nationally. This trial was a retrospective cross-sectional study. It included patients with CF aged ≤18 years hospitalized for pulmonary exacerbations between July 1, 2010, and June 30, 2015, at hospitals within the US Pediatric Health Information System database that are also Cystic Fibrosis Foundation-accredited care centers. One exacerbation per patient was randomly selected over the 5-year study period. From 38 hospitals, 4827 individual pulmonary exacerbations were examined. Median length of stay was 10.0 days (interquartile range, 6-14.0 days). Significant variation was seen among centers in the use of hypertonic saline (11%-100%), azithromycin (5%-83%), and systemic corticosteroids (3%-61%) and in the frequency of lung function testing. Four different admission antibiotic regimens were used >10% of the time, and the most commonly used admission antibiotic regimen comprised 2 intravenous antibiotics with no additional oral or inhaled antibiotics (29%). Significant variation exists in the treatment and monitoring of pulmonary exacerbations across Pediatric Health Information System-participating, Cystic Fibrosis Foundation-accredited care centers. Results from this study can inform future research working toward standardized inpatient pulmonary exacerbation management to improve CF care for children and adolescents.
| S-EPMC5472380 | biostudies-literature
Project description:BackgroundPulmonary exacerbations (PEx) in people with cystic fibrosis (PwCF) are associated with significant morbidity. While standard PEx treatment for PwCF with Pseudomonas aeruginosa infection includes two IV antipseudomonal antibiotics, little evidence exists to recommend this approach. This study aimed to compare clinical outcomes of single versus double antipseudomonal antibiotic use for PEx treatment.MethodsRetrospective cohort study using the linked CF Foundation Patient Registry-Pediatric Health Information System dataset. PwCF were included if hospitalized between 2007 and 2018 and 6-21 years of age. Regression modeling accounting for repeated measures was used to compare lung function outcomes between single versus double IV antipseudomonal antibiotic regimens using propensity-score weighting to adjust for relevant confounding factors.ResultsAmong 10,660 PwCF in the dataset, we analyzed 2,578 PEx from 1,080 PwCF, of which 455 and 2,123 PEx were treated with 1 versus 2 IV antipseudomonal antibiotics, respectively. We identified no significant differences between PEx treated with 1 versus 2 IV antipseudomonal antibiotics either in change between pre- and post-PEx percent predicted forced expiratory volume in one second (ppFEV1) (-0.84%, [95% CI -2.25, 0.56]; P = 0.24), odds of returning to ≥90% of baseline ppFEV1 within 3 months following PEx (Odds Ratio 0.83, [95% CI 0.61, 1.13]; P = 0.24) or time to next PEx requiring IV antibiotics (Hazard Ratio 1.04, [95% CI 0.87, 1.24]; P = 0.69).ConclusionsUse of 2 IV antipseudomonal antibiotics for PEx treatment in young PwCF was not associated with greater improvements in measured respiratory and clinical outcomes compared to treatment with 1 IV antipseudomonal antibiotic.
| S-EPMC8563324 | biostudies-literature
Project description:Objective Limited data exist concerning the role of inhaled hypertonic saline (HS) in decreasing pulmonary exacerbations in cystic fibrosis (CF), especially as more advanced stages of CF lung disease were excluded in prior studies. Herein, the authors retrospectively determined the efficacy of inhaled HS in reducing CF pulmonary exacerbations when stratified according to the severity of CF lung disease. Stratification was based on the framework of the Pulmonary Therapeutics Committee's published gradation of obstructive lung physiology in CF, that is, mild (FEV(1) >70%), moderate (FEV(1) 40-70%) and severe (FEV(1) <40%) lung disease, respectively. Design A retrospective review of the Port CF database over a 3-year period performed at an academic CF care centre. Results 340 pulmonary exacerbations were identified; inhaled HS was being used in 99 of these cases. Univariate analysis demonstrated a significant reduction in pulmonary exacerbations only in mild obstruction (OR=0.09, CI 0.01 to 0.81, p=0.012); however, multivariate logistic regression that adjusted for confounding variables showed a reduction in pulmonary exacerbations across the entire spectrum of obstructive lung disease when using inhaled HS, that is, mild obstructive CF lung disease (OR=0.17, CI 0.05 to 0.58, p=0.004), moderate obstructive CF lung disease (OR=0.39, CI 0.16 to 0.93, p=0.034), as well as severe obstructive CF lung disease (OR=0.02, CI 0.001 to 0.45, p=0.015). Moreover, inhaled HS appeared reasonably well tolerated across all stages of lung-disease severity, and was discontinued in only 7% of cases (n=4) with severe lung disease. Conclusion In this study, inhaled HS appeared to reduce pulmonary exacerbations in CF lung disease at all stages of obstruction. This underscores the importance of therapeutic inhaled HS in CF lung disease, regardless of the severity of lung obstruction.
| S-EPMC3191387 | biostudies-literature
Project description:Acute pulmonary exacerbations are associated with progressive lung function decline and increased mortality in cystic fibrosis. The role of pulmonary vascular disease in pulmonary exacerbations is unknown. We aimed to assess the association between pulmonary artery enlargement (defined as pulmonary artery diameter to ascending aorta diameter [PA:A] ratio >1), a marker of pulmonary vascular disease, and exacerbations.In this cohort study, we used clinical, CT imaging, and prospective exacerbation data from a previous prospective clinical trial (derivation cohort) and from The Prince Charles Hospital (TPCH; Brisbane, QLD, Australia) cystic fibrosis registry (validation cohort). In our derivation cohort, we included adults aged 18 years or older with cystic fibrosis and at least one CFTR nonsense mutation, who were enrolled in the trial between Sept 8, 2009, and Nov 30, 2010, randomly assigned to receive placebo, and had baseline CT imaging. Our validation cohort included adult patients with cystic fibrosis who had CT imaging performed between Jan 1, 2002, and Dec 31, 2014. We measured the PA:A ratio at the level of the pulmonary artery bifurcation on CT scans. Patients in each cohort were separated into two groups on the basis of PA:A ratio (>1 or ?1) and were followed up for 1 year in the derivation cohort and 2 years in the validation cohort. The primary endpoint was the development of one or more acute pulmonary exacerbations during follow-up. We used linear and logistic regression models to determine associations between clinical factors, the PA:A ratio, and pulmonary exacerbations. We used Cox regression to determine the time to first exacerbation in the validation cohort.37 (50%) of 74 patients in the derivation cohort and 89 (47%) of 190 patients in the validation cohort had enlarged pulmonary arteries (PA:A>1). 50 (68%) patients in the derivation cohort had one or more exacerbations at 1 year and 133 (70%) patients in the validation cohort had one or more exacerbations at 2 years. At baseline, patients with pulmonary artery enlargement were younger than those without enlargement in both cohorts and had elevated sweat chloride concentrations in the derivation cohort (100·5 mmol/L [SD 10·9] vs 90·4 mmol/L [19·9]; difference 10·1 mmol/L [95% CI 2·5-17·7], p=0·017). Pulmonary artery enlargement was associated with exacerbations in the derivation cohort (odds ratio 3·49 [95% CI 1·18-10·3], p=0·023) when adjusted for sex, body-mass index (BMI), forced expiratory volume in 1 s (FEV1), and PA:A greater than 1, and in the validation cohort (2·41 [1·06-5·52], p=0·037) when adjusted for sex, BMI, chronic Pseudomonas aeruginosa infection, FEV1/FVC (forced vital capacity), PA:A greater than 1, and previous exacerbation. The time to first exacerbation was shorter in patients with enlarged pulmonary arteries than in those with normal-sized pulmonary arteries in the validation cohort (hazard ratio 1·66 [95% CI 1·18-2·34], p=0·0038) in unadjusted analysis, but not when adjusted for sex, BMI, exacerbations within 1 year before index CT scan, FEV1/FVC, and chronic P aeruginosa infection (1·14 [0·80-1·62], p=0·82).Pulmonary artery enlargement is prevalent in adult patients with cystic fibrosis and was associated with acute pulmonary exacerbation risk in two well characterised cohorts. The PA:A ratio could be a predictive marker in cystic fibrosis.US National Heart, Lung, and Blood Institute/National Institutes of Health, Cystic Fibrosis Foundation, the University of Alabama at Birmingham, and the Queensland Health Fellowship.
| S-EPMC5672808 | biostudies-literature
Project description:BackgroundPulmonary exacerbations (PEx), frequently associated with airway infection and inflammation, are the leading cause of morbidity in cystic fibrosis (CF). Molecular microbiologic approaches detect complex microbiota from CF airway samples taken during PEx. The relationship between airway microbiota, inflammation, and lung function during CF PEx is not well understood.ObjectiveTo determine the relationships between airway microbiota, inflammation, and lung function in CF subjects treated for PEx.MethodsExpectorated sputum and blood were collected and lung function testing performed in CF subjects during early (0-3d.) and late treatment (>7d.) for PEx. Sputum was analyzed by culture, pyrosequencing of 16S rRNA amplicons, and quantitative PCR for total and specific bacteria. Sputum IL-8 and neutrophil elastase (NE); and circulating C-reactive protein (CRP) were measured.ResultsThirty-seven sputum samples were collected from 21 CF subjects. At early treatment, lower diversity was associated with high relative abundance (RA) of Pseudomonas (r = -0.67, p<0.001), decreased FEV(1%) predicted (r = 0.49, p = 0.03) and increased CRP (r = -0.58, p = 0.01). In contrast to Pseudomonas, obligate and facultative anaerobic genera were associated with less inflammation and higher FEV₁. With treatment, Pseudomonas RA and P. aeruginosa by qPCR decreased while anaerobic genera showed marked variability in response. Change in RA of Prevotella was associated with more variability in FEV₁ response to treatment than Pseudomonas or Staphylococcus.ConclusionsAnaerobes identified from sputum by sequencing are associated with less inflammation and higher lung function compared to Pseudomonas at early exacerbation. CF PEx treatment results in variable changes of anaerobic genera suggesting the need for larger studies particularly of patients without traditional CF pathogens.
| S-EPMC3639911 | biostudies-literature