Long term clinical outcome of home and hospital intravenous antibiotic treatment in adults with cystic fibrosis

Methods: A retrospective longitudinal study was performed to compare the clinical outcome over a period of 1 year of all patients attending the Manchester Adult CF Unit who received intravenous antibiotics at home or in hospital. The primary outcome measure was percentage change in forced expiratory volume in 1 second (FEV₁) at the end of the 1 year period. Baseline "best" and "average" FEV₁ values were established for each patient for the year before the study. The secondary outcome measures were percentage changes in forced vital capacity (FVC) and body weight.

Results: A total of 116 patients received 454 courses of intravenous antibiotics. At the end of 1 year there had been a mean percentage decline in FEV₁ compared with the baseline "average" for patients treated mostly at home but an improvement in patients treated mostly in hospital (Tukey's HSD mean difference 10.1%, 95% CI 2.9 to 17.2, p = 0.003). For all patients there was a mean percentage decline in FEV₁ from the baseline "best" value. For each course of treatment the mean percentage improvements in FEV₁ at the end of the course from the start of the course were significantly higher for patients treated in hospital than for those treated at home.

Conclusions: Clinical outcome, as defined by spirometric parameters and body weight, was better after a course of treatment in hospital than after home treatment, and this benefit was maintained over 1 year of treatment. The results suggest that patients treated at home need closer supervision.

     

Pilot safety study of liposomal prostaglandin (PGE1) in respiratory exacerbations in cystic fibrosis.

BACKGROUND: A pilot evaluation to assess the safety and possible benefits of TLC C-53, (prostaglandin E(1) associated with egg phosphatidylcholine liposomes) in acute respiratory exacerbations in children with cystic fibrosis (CF). METHODS: Randomised, double-blind, placebo-controlled study in 20 P. aeruginosa colonised patients. All received intravenous antibiotics. Subjects were given a rising dose of TLC C-53 (0.15-1.8 microg/kg) by 4 x 1-h infusions. Primary outcome measures were sputum IL-6, IL-8 and sputum neutrophil elastase. The rate of decline in lung function was determined at 6 weeks post-therapy as was the interval until the next respiratory exacerbation requiring intravenous antibiotic therapy. RESULTS: Analysis of primary and secondary outcome measures failed to show any significant differences between the two groups, although trends favoured the treated group. Decline in lung function over 6 weeks favoured the TLC C-53 group (FEV(1) mean difference 4.3%, 95% CI=-6.8, 15.4%). Time to next exacerbation also favoured the TLC C-53 group with a mean time to exacerbation for TLC C-53 of 26.0 weeks against 11.9 weeks. CONCLUSIONS: A larger multi-centre trial of TLC C-53 as an adjunct to antibiotic therapy in respiratory exacerbations in CF would appear warranted.     

Effects of hypertonic saline,alternate day and daily rhDNase on healthcare use,costs and outcomes in children with cystic fibrosis

BACKGROUND: Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis (CF). An alternative lower cost therapy is hypertonic saline (HS), which has been shown to improve lung function in short term studies. This study compares the costs and consequences of daily rhDNase with alternate day rhDNase and HS in children with CF. METHODS: In an open, randomised, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once daily 2.5 mg rhDNase, alternate day 2.5 mg rhDNase, and twice daily 5 ml 7% HS. Outcomes assessed included forced expiratory volume in 1 second (FEV(1)) and quality of life. All healthcare resource use was prospectively recorded for each patient. Unit costs were collected and combined with resource use data to give the total health service costs per patient for each treatment strategy. RESULTS: Daily rhDNase resulted in a significantly greater increase in mean FEV(1) than HS (8%, 95% CI 2 to 14) but there was no significant difference in FEV(1) between daily and alternate day rhDNase (2%, 95% CI -4 to 9). Over a 12 week period the mean incremental costs of daily rhDNase compared with HS was pound 1409 (95% CI pound 440 to pound 2318), and the incremental cost of using daily rather than alternate day rhDNase was pound 513 (95% CI - pound 546 to pound 1510). CONCLUSIONS: Daily rhDNase is more effective than 5 ml 7% HS twice daily delivered by jet nebuliser, but significantly increases healthcare costs. Administering rhDNase on an alternate day rather than a daily basis is as effective, with a potential for cost savings.     

Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria

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.     

Wasting as an independent predictor of mortality in patients with cystic fibrosis

BACKGROUND: Cystic fibrosis (CF) is the most common life threatening autosomal recessive disorder in the white population. Wasting has long been recognised as a poor prognostic marker in CF. Whether it predicts survival independently of lung function and arterial blood gas tensions has not previously been reported. METHODS: 584 patients with CF (261 women) of mean (SD) age 21 (7) years were studied between 1985 and 1996, all of whom were being followed up in a tertiary referral centre. Lung function tests, body weight, arterial blood oxygen (PaO(2)) and carbon dioxide (PaCO(2)) tensions were measured. The weight was calculated as a percentage of the ideal body weight for age, height, and sex. RESULTS: Forced expiratory volume in one second (FEV(1)) recorded at the start of the study was 1.8 (1.0) l (52 (26)% predicted FEV(1)), PaO(2) 9.8 (1.9) kPa, PaCO(2) 5.0 (0.9) kPa, and % ideal weight 92 (18)%. During the follow up period (45 (27) months) 137 patients died (5 year survival 72%, 95% CI 67 to 73). FEV(1), % predicted FEV(1), PaO(2), % ideal weight (all p<0.0001), and PaCO(2) (p=0.04) predicted survival. In multivariate analysis, % predicted FEV(1) (p<0.0001), % ideal weight (p=0.004), and PaCO(2) (p=0.02) were independent predictors of outcome. Patients with >85% ideal body weight had a better prognosis at 5 years (cumulative survival 84%, 95% CI 79 to 89) than those with < or =85% ideal weight (survival 53%, 95% CI 45 to 62), p<0.0001. Percentage predicted FEV(1) (area under curve 0.83; 95% CI 0.78 to 0.87) and % ideal weight (area under curve 0.74; 95% CI 0.68 to 0.79) were accurate predictors of survival at 5 years follow up (receiver-operating characteristic analysis). CONCLUSIONS: Body wasting is a significant predictor of survival in patients with CF independent of lung function, arterial blood oxygen and carbon dioxide tensions.     

Comparison of the effects of intravenous and oral montelukast on airway function: a double blind, placebo controlled, three period, crossover study in asthmatic patients

BACKGROUND: Montelukast, a leukotriene receptor antagonist, improves parameters of asthma control including forced expiratory volume in one second (FEV(1)) when given orally to patients aged six years or older. This study was undertaken to compare the effect on FEV(1) of intravenous and oral montelukast and placebo during the 24 hour period following administration. METHODS: Fifty one asthmatic patients (FEV(1) 40-80% predicted and > or =15% improvement after inhaled beta agonist) were enrolled in a double blind, single dose, three period, crossover study to receive intravenous montelukast (7 mg), oral montelukast (10 mg), or placebo in a randomised fashion. The primary end point was area under the curve (AUC)(0-24 h) of the percentage change from baseline in FEV(1). Additional end points were maximum percentage change in FEV(1) and percentage change at different time points. RESULTS: Compared with placebo, intravenous and oral montelukast significantly increased the AUC(0-24 h) (means of 20.70%, 15.72%, and 7.75% for intravenous, oral and placebo, respectively; no statistical difference between intravenous and oral). The difference in least square means from placebo for intravenous montelukast was 13.27% (95% CI 7.07 to 19.46), p<0.001 and for oral montelukast was 7.44% (95% CI 1.20 to 13.68), p = 0.020. The maximum percentage change in FEV(1) was not significantly different for intravenous and oral montelukast (difference in least square means 6.78% (95% CI -0.59 to 14.15), p = 0.071). The mean percentage change in FEV(1) for intravenous montelukast was greater than for oral montelukast within the first hour (15.02% vs 4.67% at 15 min, p< or =0.001; 18.43% vs 12.90% at one hour, p<0.001 for intravenous and oral montelukast, respectively (placebo 3.05% at 15 minutes, 7.33% at one hour). Intravenous and oral montelukast were similar to placebo in the frequency of adverse events. CONCLUSIONS: The onset of action for intravenous montelukast was faster than for oral montelukast and the improvement in airway function lasted over the 24 hour observation period for both treatments. Although not well understood, there was a trend toward a greater improvement in FEV(1) with intravenous than with oral montelukast. These findings suggest that leukotriene receptor antagonists should be investigated as a treatment for acute severe asthma.     

Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis

BACKGROUND: Chest physiotherapy is essential to the management of cystic fibrosis (CF). However, respiratory muscle fatigue and oxygen desaturation during treatment have been reported. The aim of this study was to determine whether non-invasive ventilation (NIV) during chest physiotherapy could prevent these adverse effects in adults with exacerbations of CF. METHODS: Twenty six patients of mean (SD) age 27 (6) years and forced expiratory volume in 1 second (FEV1) 34 (12)% predicted completed a randomised crossover trial comparing standard treatment (active cycle of breathing technique, ACBT) with ACBT + NIV. Respiratory muscle strength (PImax, PEmax), spirometric parameters, and dyspnoea were measured before and after treatment. Pulse oximetry (SpO2) was recorded during treatment. Sputum production during treatment and 4 and 24 hours after treatment was evaluated. RESULTS: There was a significant reduction in PImax following standard treatment that was correlated with baseline PImax (r=0.73, p<0.001). PImax was maintained following NIV (mean difference from standard treatment 9.04 cm H2O, 95% confidence interval (CI) 4.25 to 13.83 cm H2O, p=0.006). A significant increase in PEmax was observed following the NIV session (8.04 cm H2O, 95% CI 0.61 to 15.46 cm H2O, p=0.02). The proportion of treatment time with SpO2 < or =90% was correlated with FEV1 (r=-0.65, p<0.001). NIV improved mean SpO2 (p<0.001) and reduced dyspnoea (p=0.02). There were no differences in FEV1, forced vital capacity (FVC) or sputum weight, but FEF(25-75) increased following NIV (p=0.006). CONCLUSION: Reduced inspiratory muscle strength and oxygen desaturation during chest physiotherapy are associated with inspiratory muscle weakness and severity of lung disease in adults with exacerbations of CF. Addition of NIV improves inspiratory muscle function, oxygen saturation and small airway function and reduces dyspnoea.     

Increase in exhaled carbon monoxide during exacerbations of cystic fibrosis

BACKGROUND: Non-invasive assessment of inflammation is likely to be useful in the management of cystic fibrosis (CF). Exhaled carbon monoxide (CO) concentrations are increased in patients with clinically stable CF. A study was undertaken to determine whether this marker of oxidative damage is further increased during exacerbations of the disease. METHODS: Exhaled CO concentrations were measured in 12 healthy non-smoking control subjects (six men) of mean (SE) age 37 (2) years with forced expiratory volume in one second (FEV(1)) 95 (1)% predicted and in 44 patients with CF (20 men) of mean (SE) age 29 (1) years with FEV(1) 56 (3)% predicted using an on-line CO analyser. RESULTS: Twenty nine patients were in a stable condition while 15 had clinically defined respiratory exacerbations (increased cough and production of sputum, change in the quality of the sputum, shortness of breath, sensation of chest congestion, and deterioration of FEV(1)) and represented the unstable group. Exhaled CO concentrations were 2.0 (0.15) ppm in the control group, were increased in the stable CF group to 2.7 (0.13) ppm (differences between means -0.67 (0.22), 95% confidence interval (CI) 0.22 to 1.12, p<0.01) and further increased in the unstable group to 4.8 (0.3) ppm (differences between means -2.15 (0.32), 95% CI 1.50 to 2.79, p<0.001). A significant correlation was found between the deterioration in FEV(1) and exhaled CO concentrations. CONCLUSIONS: This study shows that the measurement of exhaled CO is of potential value as an indicator of exacerbations in patients with CF and could be used as a simple method to monitor the course of the disease.     

Multiple breath inert gas washout as a measure of ventilation distribution in children with cystic fibrosis

BACKGROUND: Multiple breath inert gas washout (MBW) has been suggested as a tool for detecting early cystic fibrosis (CF) lung disease. A study was undertaken to compare the relative sensitivity of MBW and spirometry for detecting abnormal lung function in school age children with CF and to compare MBW results obtained from healthy children in the UK with those recently reported from Sweden. METHODS: Forced expiratory volume in 1 second (FEV1) and maximal expiratory flow when 25% of forced vital capacity remains to be expired (MEF25) were compared with the lung clearance index (LCI) derived from sulphur hexafluoride MBW in 22 children with CF aged 6-16 years and in 33 healthy controls. RESULTS: LCI was higher in children with CF than in healthy controls (mean difference 5.1 (95% CI of difference 4.1 to 6.1) and FEV1 and MEF25 z-scores were lower (mean difference -2.3 (95% CI -2.9 to -1.7) and -1.8 (95% CI -2.4 to -1.3), respectively; p<0.001 for all). There was a significant negative correlation between LCI and FEV1 (r2 = 0.62) and MEF25 (r2 = 0.46). However, while normal (> or =-1.96 z-scores) FEV1 and MEF25 results were seen in 11 (50%) and 12 (53%) children with CF, respectively, all but one of these children had an abnormally increased LCI. LCI was repeatable in both groups (within subject CV for three measurements 6% for CF and 5% for healthy children). In healthy subjects LCI was independent of age and virtually identical in the British and Swedish children (mean difference 0.1 (95% CI -0.1 to 0.4), p = 0.38) CONCLUSIONS: MBW is reproducible between laboratories, generates normal ranges which are constant over childhood, and is more frequently abnormal than spirometry in children with CF.     

Economic evaluation of Tobramycin nebuliser solution in cystic fibrosis.

Background: The cost effectiveness of inhaled TOBIR tobramycin nebuliser solution (TNS) in CF and chronic pulmonary Pseudomonas aeruginosa infection has been shown in US but not in European studies. Methods: An economic evaluation of TNS was undertaken in children and adults. Lung function and resource utilisation were recorded for 24 months before and during TNS therapy. Interventions were costed. Results: Forty-one patients received TNS; 30 of them matched with a paired control on usual therapy. TNS cases received more inhaled and IV antibiotics in the year before TNS than controls, and were hospitalised more. In the TNS treated group mean days in hospital before and after (change) were 32.0, 24.2 (-7.8); days on IV antibiotics 55.4, 38.9 (-16.4); total cost 22,102 pounds, 28,394 pounds (+ 6292 pounds), composed of cost of TNS 0 pounds, 10,010 pounds (+ 10,010 pounds), cost of hospitalisation 10,897 pounds, 8552 pounds (- 2345 pounds), cost of drugs 11,205 pounds, 9832 pounds (- 1374 pounds). In 19 patients aged < 18 the change in days hospitalised was -10.7 and days on IVs -20.2. Incremental cost was 3830 pounds. Conclusions: TNS was associated with clinically and socially important reductions of hospital attendances and parenteral antibiotics. This would improve patients' quality of life and reduce interference with work and schooling. Its maximal acquisition cost of 10,010 pounds may be reduced by delays in prescribing and dispensing, and was offset by savings of approximately 3500-6200 pounds.     

Association between Stenotrophomonas maltophilia and lung function in cystic fibrosis

BACKGROUND: Stenotrophomonas maltophilia (SM) is a Gram-negative non-fermenting bacteria cultured from the sputum of patients with cystic fibrosis (CF). To date, no information is available regarding the effect of this organism on lung function in CF. METHODS: A cohort study was conducted to assess the effect of SM on lung function among CF patients aged > or =6 years in the CF Foundation National Patient Registry from 1994 to 1999. Repeated measures regression was used to assess the association between SM and lung function. RESULTS: The cohort consisted of 20 755 patients with median age at entry of 13.8 years and median follow up time of 3.8 years; 2739 patients (13%) were positive at least once for SM and 18 016 (87%) were never positive. After adjusting for sex, height and age, patients with SM had a mean forced expiratory volume in 1 second which was 0.09 l less (95% CI 0.05 to 0.14) than those without SM. The mean rate of decline associated with SM positivity was 0.025 l/year (95% CI 0.012 to 0.037) but, after adjusting for confounders (sex, height, weight, intravenous antibiotic courses, hospital admissions, pancreatic insufficiency, and Pseudomonas aeruginosa and Burkholderia cepacia status), the mean rate of decline decreased to 0.008 l/year (-0.008, 95% CI -0.019 to 0.003). CONCLUSIONS: Although CF patients with SM have worse lung function at the time of positivity, no association was found between SM and increased rate of decline after controlling for confounders.     

Modified shuttle test performance in hospitalized children and adolescents with cystic fibrosis.

BACKGROUND: The Modified Shuttle Test (MST) is a valid and sensitive measure of exercise capacity in adult CF patients. Recently, its validity in children has been demonstrated. The aim of this study was to demonstrate the utility of the MST as a measure of responsiveness to hospitalisation for i.v. antibiotic and supportive therapy in children and adolescents with CF. METHODS: 28 children and adolescents (40 admissions) performed a MST and lung function within 48 h of admission and discharge to hospital for administration of intravenous antibiotics. Mean age was 12.7 years and antibiotic therapy length was 14.7 days. RESULTS: Upon admission, the mean (S.D.) FEV(1) was 63 (19)% predicted, FVC was 80 (18)% predicted, FEF(25-75) 43 (29)% predicted and MST distance 718 (232) m. FEV(1) increased by 15% (p相似文献   

Long term follow up of changes in FEV1 and treatment intensity during Pseudomonas aeruginosa colonisation in patients with cystic fibrosis

BACKGROUND: Colonisation with Pseudomonas aeruginosa (PA) is a striking feature of lung involvement in cystic fibrosis. To identify the clinical consequences of the different steps of colonisation with PA under a defined therapeutic regime (no prophylactic antibiotic treatment as long as patients had no severe pulmonary disease), their influence on pulmonary function and on therapeutic intensity was examined. METHODS: Forty patients with cystic fibrosis were followed from first detection of PA (PA1), chronic PA colonisation (PAc), first mucoid PA detection (PAm), to chronic mucoid PA colonisation (PAcm). Percentage predicted forced expiratory volume in one second (FEV1), the number of intravenous antibiotic treatment courses, and the percentage of patients on inhaled antibiotics were followed retrospectively and longitudinally in relation to the different steps of PA colonisation. The annual changes in FEV1 and therapeutic intensity in the two years preceding each step were compared with the two years following each step. Changes in FEV1 were related to therapeutic intensity. RESULTS: The mean (SD) annual changes in FEV1 (% predicted) worsened significantly only with the transition to the mucoid stages (PAm: 4.6 (13.2) versus -4.3 (8.1); PAcm: 7.3 (12.0) versus -4.8 (7.4)) with a mean difference (95% CI) between before and after the transition of 8.9 (2.6 to 15.2) for PAm and 12.1 (6.4 to 17.6) for PAcm. With non-mucoid PA stages the therapeutic intensity increased in the year of transition and with mucoid PA stages it increased in the years following transition. Therapeutic intensity was unrelated to changes in FEV1. CONCLUSION: With the treatment regime used an accelerated decrease in FEV1 was successfully prevented in the non-mucoid stages but not in the mucoid stages of PA colonisation.     

Lung function decline and outcomes in an elderly population

OBJECTIVE: To determine the risk factors for and outcomes associated with the rapid decline in lung function in a cohort of elderly US adults. METHODS: Data from 4923 adult participants aged 65 years and older at baseline in the Cardiovascular Health Study were analysed. Subjects were classified using a modification of the GOLD criteria for chronic obstructive pulmonary disease (COPD) and a "restricted" category (FEV1/FVC>or=70% and FVC<80% predicted) was added. Cox proportional hazard models were used to determine the risk of lung function decline over 4 years on subsequent mortality and COPD hospital admissions after adjusting for age, race, sex, smoking status, and other factors. RESULTS: Of the participants in the initial cohort, 3388 (68.8%) had spirometric tests at the year 4 visit. Participants with GOLD stages 3 or 4 COPD at baseline were less likely than normal subjects to have follow up spirometric tests (52.7% v 77.9%, p<0.01) and were more likely to be in the most rapidly declining quartile of FEV1 (28.2% v 21.3%, p<0.01) with an annual loss of FEV1 of at least 3.5%. Overall, being in the most rapidly declining quartile of FEV1 from baseline to year 4 was associated with an increased risk of admission to hospital for COPD (adjusted hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.3 to 2.0) and all-cause death (adjusted HR 1.5, 95% CI 1.2 to 1.7) over an additional 7 years of follow up. CONCLUSION: More rapid decline in lung function is independently associated with a modest increased risk of hospital admissions and deaths from COPD in an elderly cohort of US participants.     

Towards zero prevalence of chronic Pseudomonas aeruginosa infection in children with cystic fibrosis

BACKGROUND: Data from the Belgian Cystic Fibrosis Registry consistently show that in one of the seven reference centres, the prevalence of Pseudomonas aeruginosa is half that observed at the national level. OBJECTIVES: To report the characteristics of non-transplanted patients in this clinic at the end of 2003, with special focus on paediatric patients. To describe and discuss our policy of inhaled antibiotic therapy. FINDINGS: The prevalence of P. aeruginosa among 116 patients is 20.7%. The chronic colonization rate is 19.8% but only 2.8% in patients aged under 18 (n=72). Serologic data strongly support these results. Most paediatric patients (95%) are prescribed inhaled antibiotics, at least on an intermittent basis but the mean number of days of intravenous antibiotic treatment is four times lower than in other CF children in Belgium. 70% of children have an FEV1> or =90% predicted. DISCUSSION: We have reported a distinctly low rate of chronic colonization by P. aeruginosa in a cohort of CF children and suspect that a strategy of early, often use of inhaled antibiotics, progressively implemented for over 15 years has substantially contributed to these results. Given the major impact of chronic P. aeruginosa colonization on prognosis in CF, it is suggested that a large prospective study of this approach is warranted.     

The clinical and microbiological utility of inhaled aztreonam lysine for the treatment of acute pulmonary exacerbations of cystic fibrosis: An open-label randomised crossover study (AZTEC-CF)

BackgroundThe objective of this study was to explore the clinical and microbiological outcomes associated with substituting inhaled aztreonam lysine for an intravenous antibiotic in the treatment of acute pulmonary exacerbations of CF.MethodsAn open-label randomised crossover pilot trial was conducted at a UK CF centre among 16 adults with CF and P. aeruginosa infection. Median [IQR] age was 29.5 [24.5-32.5], mean ± SD forced expiratory volume in 1 second (FEV1) was 52.4 ± 14.7 % predicted. Over the course of two exacerbations, participants were randomised to sequentially receive 14 days of inhaled aztreonam lysine plus IV colistimethate (AZLI+IV), or dual IV antibiotics (IV+IV). Primary outcome was absolute change in % predicted FEV1. Other outcomes evaluated changes in quality of life, bacterial load and the lung microbiota.ResultsThe difference between mean change in lung function at day 14 between AZLI+IV and IV+IV was +4.6% (95% CI 2.1-7.2, p=0.002). The minimum clinically important difference of the Cystic Fibrosis Revised Questionnaire (CFQ-R) was achieved more frequently with AZLI+IV (10/12, 83.3%) than IV+IV (7/16, 43.8%), p=0.05. No differences were observed for modulation of serum white cell count, C-reactive protein or sputum bacterial load. Microbiome compositional changes were observed with IV+IV (Bray-Curtis r²=0.14, p=0.02), but not AZLI+IV (r²=0.03, p=0.64).ConclusionIn adults with CF and P. aeruginosa infection experiencing an acute pulmonary exacerbation, AZLI+IV improved lung function and quality of life compared to the current standard treatment. These findings support the need for larger definitive trials of inhaled antibiotics in the acute setting.Clinical trial registrationEudraCT 2016-002832-34ClinicalTrials.org NCT02894684     

Improved lung function and body mass index associated with long-term use of Macrolide antibiotics.

BACKGROUND: A number of studies have suggested that the non-antimicrobial actions of macrolide antibiotics may be valuable in treating patients with cystic fibrosis. The use of long-term macrolide antibiotics for the management of CF patients colonised by Pseudomonas aeruginosa and progressive pulmonary disease was introduced into our clinic in 1997. A retrospective study was undertaken to assess of the impact of this therapy. METHODS: Twenty patients with progressive pulmonary disease (>10% fall in FEV(1) over 12 months despite optimising conventional therapy) were commenced on Azithromycin, 250 mg daily during a 21-month period. At the time of assessment they had remained on therapy for a mean of 0.9 years. Changes in lung function, weight, body mass index (BMI) and frequency of pulmonary exacerbations were assessed. A group of 20 patients with stable lung function and matched as far as possible for age and sex was identified for comparison. RESULTS: Pulmonary function increased significantly in the Azithromycin group with FEV1% predicted increasing from a mean of 50.2-59.1% (P=0.001) while FVC% predicted increase from 64.5 to 76.1% (P=0.002). There was small but non-significant fall in lung function in the comparison group. Body mass index increased by a mean of 1.1 in the Azithromycin group but remained unchanged in the comparison group. The number of pulmonary exacerbations requiring intravenous antibiotics declined by 48.3% in macrolide treated subjects compared to the pre-treatment period (P<0.025); frequency of exacerbations in the control group was unchanged. CONCLUSION: Long-term Azithromycin treatment in patients with progressive deterioration in lung function appears to have led to an improvement in pulmonary function, increased body mass index and decreased the frequency of pulmonary exacerbations requiring intravenous antibiotics.     

Association of tumour necrosis factor alpha variants with the CF pulmonary phenotype

BACKGROUND: The pulmonary phenotype in patients with cystic fibrosis (CF), even in those with the same CF transmembrane conductance regulator (CFTR) genotype, is variable and must therefore be influenced by secondary genetic factors as well as environmental factors. Possible candidate genes that modulate the CF lung phenotype may include proinflammatory cytokines. One such protein is tumour necrosis factor alpha (TNFalpha), a member of the immune system. METHODS: Three polymorphic loci in the promoter (-851c/t, -308g/a, -238g/a) and one polymorphic locus in intron 1 (+691g ins/del) of the TNFalpha gene were typed by a single nucleotide primer extension assay in CF patients and healthy controls. Spirometric data and first age of infection with Pseudomonas aeruginosa were collected retrospectively from patients' medical records. RESULTS: An association was found between the TNFalpha +691g ins/del polymorphic locus and severity of CF lung disease. Patients heterozygous for +691g ins and +691g del were more likely to have better pulmonary function (mean (SD) forced expiratory volume in 1 second (FEV1) 79.7 (12.8)% predicted) than patients homozygous for +691g ins (mean (SD) FEV1 67.5 (23.0)% predicted; p = 0.008, mean difference 12.2%, 95% CI 3.5 to 21.0). Also, patients heterozygous for +691g ins and +691g del were more likely to have an older first age of infection with P aeruginosa (mean (SD) 11.4 (6.0) years) than patients homozygous for +691g ins (mean (SD) 8.3 (4.6) years; p = 0.018, mean difference 3.1 years, 95% CI 0.5 to 5.6). An association was also found with the -851c/t polymorphic locus. In the group of patients with more severe FEV1% predicted, a higher proportion of patients were homozygous for the -851c allele than in the other group of patients (p = 0.04, likelihood ratio chi2, odds ratio = 2.4). CONLUSION: TNFalpha polymorphisms are associated with the severity of CF lung disease in Czech and Belgian patients with CF.     

Enteral Antibiotics are Non-inferior to Intravenous Antibiotics After Complicated Appendicitis in Adults: A Retrospective Multicentre Non-inferiority Study

Background

Prolonging post-operative antibiotic treatment beyond 3 days does not seem to reduce the incidence of post-operative abscess formation or wound infection after surgery for complicated appendicitis. The route of administration seems to be based on an empirical basis. Using enteral antibiotics could reduce length of stay and reduce overall costs. We aimed to examine whether treatment with enteral antibiotics during the first three post-operative days is non-inferior to intravenous antibiotics regarding intra-abdominal abscess formation or wound infection after surgery for complicated appendicitis.

Methods

A retrospective study of adult patients having surgery for complicated appendicitis within a period of 32 months in the Capital Region of Denmark. Primary outcome was the incidence of post-operative abscess formation, and secondary outcome was wound infections, both within 30 days of surgery. Route of antibiotic administration for the first three post-operative days was registered for all patients.

Results

A total of 1141 patients were included in the study. The overall risk of developing an intra-abdominal abscess was 6.7% (95% CI 5.2%; 8.1%), and the risk of wound infection was 1.2% (95% CI 0.6%; 1.8%). In a multivariate intention-to-treat analysis, patients treated post-operatively with enteral antibiotics had an odds ratio of 0.78 (95% CI 0.41; 1.45, p = 0.429) for developing an intra-abdominal abscess and an odds ratio of 0.86 (95% CI 0.17; 4.29, p = 0.851) for developing a wound infection compared to patients treated post-operatively with intravenous antibiotics.

Conclusion

Treatment with enteral antibiotics was non-inferior compared to treatment with intravenous antibiotics during the first 3 days after surgery for complicated appendicitis.

     

Effectiveness of a stepwise Pseudomonas aeruginosa eradication protocol in children with cystic fibrosis

Introduction

Antibiotic eradication therapy (AET) for initial Pseudomonas aeruginosa (Pa) infection is standard of care in children with cystic fibrosis (CF), but information is limited on treatment for patients who fail initial AET. The aim of this study was to evaluate the effectiveness of a multi-step protocol for AET for new-onset Pa infections in children with CF.