The Pulmonary Microbiome in Cystic Fibrosis

The chronic colonisation of the lower airways by bacterial pathogens is the leading cause of morbidity and mortality in patients with cystic fibrosis (CF). The use of novel culture-independent techniques such as next-generation sequencing (NGS) to analyse the lungs has allowed us to further understand the diversity, the complexity, the effects of acute exacerbations and the use of antibiotics on the bacterial communities. The understanding of the CF microbiome to airway disease remains a fascinating area of research; it presents new opportunities for disease management in CF and has the potential to explore the effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators. It also allows further appreciation regarding the roles played by anaerobic organisms within the CF airways. It is also of interest that a number of studies have demonstrated that the fluctuations of microbiome are not necessarily associated with the patient’s clinical status. Despite the available evidence, there remain many challenges that must be overcome if microbiome profiling is going to influence future clinical practice. The effects of fungus and the emergence of nontuberculous mycobacteria in CF are also briefly discussed in this chapter

Case Report: First report of <i>Elizabethkingia miricola</i> infection in a patient with cystic fibrosis.

Elizabethkingia miricola is a rare non-fermenting Gram-negative rod that has previously been reported to be associated with blood stream and pulmonary abscess infections, but never before in cystic fibrosis (CF). Here we present the first reported case of Elizabethkingia miricola infection in a patient with CF and discuss the management options. We describe a patient with CF in whom we observed clinical and spirometric evidence of pulmonary exacerbation with the associated growth of E. miricola in sputum culture. The period of clinical instability was observed to coincide with the obtainment of four sputum samples from which E. miricola was cultured; improvement was seen following treatment with ciprofloxacin and the subsequent eradication of E. miricola. We conclude that E. miricola is able to survive in the CF lung and in this case was associated with pulmonary exacerbation. Empirical treatment with fluoroquinolones is appropriate, based on our experience

Antibiotic therapy for chronic infection with Burkholderia cepacia complex in people with cystic fibrosis

BACKGROUND:Cystic fibrosis (CF) a life-limiting inherited disease affecting a number of organs, but classically associated with chronic lung infection and progressive loss of lung function. Chronic infection by Burkholderia cepacia complex (BCC) is associated with increased morbidity and mortality and therefore represents a significant challenge to clinicians treating people with CF. This review examines the current evidence for long-term antibiotic therapy in people with CF and chronic BCC infection. OBJECTIVES:The objective of this review is to assess the effects of long-term oral and inhaled antibiotic therapy targeted against chronic BCC lung infections in people with CF. The primary objective is to assess the efficacy of treatments in terms of improvements in lung function and reductions in exacerbation rate. Secondary objectives include quantifying adverse events, mortality and changes in quality of life associated with treatment. SEARCH METHODS:We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched online trial registries and the reference lists of relevant articles and reviews.Date of last search: 29 May 2019. SELECTION CRITERIA:Randomised controlled trials (RCTs) of long-term antibiotic therapy in people with CF and chronic BCC infection. DATA COLLECTION AND ANALYSIS:Two authors independently extracted data, assessed risk of bias and assessed the quality of the evidence using GRADE. MAIN RESULTS:We included one RCT (100 participants) which lasted 52 weeks comparing continuous inhaled aztreonam lysine (AZLI) and placebo in a double-blind RCT for 24 weeks, followed by a 24-week open-label extension and a four-week follow-up period. The average participant age was 26.3 years, 61% were male and average lung function was 56.5% predicted.Treatment with AZLI for 24 weeks was not associated with improvement in forced expiratory volume in one second (FEV1), mean difference 0.91% (95% confidence interval (CI) -3.15 to 4.97) (moderate-quality evidence). The median time to the next exacerbation was 75 days in the AZLI group compared to 51 days in the placebo group, but the difference was not significant (P = 0.27) (moderate-quality evidence). Similarly, the number of participants hospitalised for respiratory exacerbations showed no difference between groups, risk ratio (RR) 0.88 (95% CI 0.53 to 1.45) (moderate-quality evidence). Overall adverse events were similar between groups, RR 1.08 (95% CI 0.98 to 1.19) (moderate-quality evidence). There were no significant differences between treatment groups in relation to mortality (moderate-quality evidence), quality of life or sputum density.In relation to methodological quality, the overall risk of bias in the study was assessed to be unclear to low risk. AUTHORS' CONCLUSIONS:We found insufficient evidence from the literature to determine an effective strategy for antibiotic therapy for treating chronic BCC infection

The renoprotective effect of concomitant fosfomycin in the treatment of pulmonary exacerbations in cystic fibrosis.

Background:Fosfomycin, effective in Cystic Fibrosis (CF), competes with aminoglycosides at renal binding sites and may therefore afford a renoprotective effect when used in combination therapy. We explored this by using markers of acute renal tubular damage [N-acetyl-β-d-glucose-aminidase (NAG), alanine amino-peptidase (AAP) and β2-microglobulin]. Methods:Using a prospective randomized crossover trial design, at an acute pulmonary exacerbation, 18 adult CF patients received either 14 days of intravenous (IV) tobramycin or IV tobramycin and IV fosfomycin, both in combination with a second IV antibiotic (colomycin). Results:Urinary NAG (P = 0.003) and AAP (P = 0.03) following treatment with concomitant fosfomycin were lower than those after treatment with tobramycin and colomycin alone. Fosfomycin attenuated the total 24-h urinary protein leak (P = 0.0001). The 14-day improvements in all surrogate markers of exacerbation resolution (FEV1% predicted, FVC, white cell count and C-reactive protein) were similar for both treatment regimens. Conclusion:The addition of fosfomycin reduces acute renal injury caused by IV aminoglycoside therapy in CF pulmonary exacerbations

Case Report: Haemolytic anaemia with ceftazidime use in a patient with cystic fibrosis.

Drug-induced Immune Haemolytic Anaemia (DIIHA) is a rare but serious complication of cephalosporin use. Ceftazidime is recognized to be a rare cause of DIIHA. We report and discuss a case of DIIHA in a person with cystic fibrosis who developed severe haemolytic anaemia following use of ceftazidime in the management of an acute pseudomonal pulmonary exacerbation

Continuous glucose monitoring systems for monitoring cystic fibrosis-related diabetes

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To establish the impact of insulin therapy guided by continuous glucose monitoring compared to insulin therapy guided by other forms of glucose data collection on the lives of people with cystic fibrosis-related diabetes (pwCFRD)

Characterisation of hemidiaphragm dysfunction using dynamic chest radiography: a pilot study

Dynamic chest radiography (DCR) is a novel real-time digital fluoroscopic imaging system that produces clear, wide field-of-view diagnostic images of the thorax and diaphragm in motion, alongside novel metrics on moving structures within the thoracic cavity. We describe the use of DCR in the measurement of diaphragm motion in a pilot series of cases of suspected diaphragm dysfunction. We studied 21 patients referred for assessment of diaphragm function due to suspicious clinical symptoms or imaging (breathlessness, orthopnoea, reduced exercise tolerance and/or an elevated hemidiaphragm on plain chest radiograph). All underwent DCR with voluntary sniff manoeuvres. Paradoxical motion on sniffing was observed in 14 patients, and confirmed in six who also underwent fluoroscopy or ultrasound. In four patients, DCR showed reduced hemidiaphragm excursion, but no paradoxical motion; in three, normal bilateral diaphragm motion was demonstrated. DCR was quick to perform, and well tolerated in all cases and with no adverse events reported. DCR was achieved in ∼5 min per patient, with images available to view by the clinician immediately within the clinical setting. DCR is a rapid, well-tolerated and straightforward chest radiography technique that warrants further investigation in the assessment of diaphragm dysfunction