Temocillin in the treatment of Burkholderia cepacia infection in cystic fibrosis

AbstractBackgroundInfections due to Burkholderia cepacia complex (Bcc) strains increase morbidity and mortality in cystic fibrosis (CF). Some transplant centres reject Bcc infected patients. We reviewed the results in patients treated with i.v temocillin.MethodsTwenty-three patients who received 38 courses of temocillin (1988–1998) were identified from the CF database at Royal Brompton Hospital. In three patients' data were inadequate; therefore analysis was done in 20. Outcome was measured as improvement, deterioration or no change (compared to admission) in the following categories: clinical (temperature, dyspnoea, sputum volume, chest pain), physiological (FEV1, FVC, oxygen saturation) and inflammatory markers (WBC, ESR, CRP). Patients who improved in two categories were classified as having improved. Antibiotic sensitivities and outcome were recorded.ResultsIn 18 of 32 courses (56.25%) improvement occurred. The organism (Bcc) in eight patients' sputum became resistant (three died). The antibiotics was changed in five patients with Bcc strains sensitive to temocillin because of no improvement and one patient due to allergy (rash). The average time to the next i.v antibiotic was 41 days. Eight patients died (in three the Bcc strain was resistant to temocillin). Fourteen patients with Bcc were transplanted and eight patients survived. Another patient who developed Bcc infection post-operatively, failing to respond to temocillin.ConclusionsThese results suggest the potential benefit of i.v temocillin in CF patients with Bcc for exacerbations and at the time of transplantation

A woman with cystic fibrosis, severe hypoxaemia, an atrial thrombus and a patent foramen ovale: a case report

<p>Abstract</p> <p>Introduction</p> <p>Cystic fibrosis is usually associated with chronic pulmonary sepsis and frequent infective exacerbations. We report a very unusual cause of severe hypoxaemia in a woman with cystic fibrosis caused by thrombus formation in the right atrium.</p> <p>Case presentation</p> <p>A 21-year-old Caucasian woman with cystic fibrosis and a totally implantable venous access device presented with severe hypoxaemia. This was initially treated with antibiotics but her oxygen levels did not improve significantly. Subsequently, a transient ischaemic attack occurred. Further investigations, including a contrast echocardiogram and a cardiac magnetic resonance scan, revealed the presence of a large right atrial thrombus and right-to-left intracardiac shunt through a patent foramen ovale.</p> <p>Conclusion</p> <p>This case highlights the need to consider a right-to-left shunt in chronic respiratory diseases when hypoxaemia is out of proportion to the degree of lung function impairment. Totally implantable venous access devices should always be considered as a source of thrombus formation.</p

Burkholderia cepacia complex and limited cutaneous vasculitis in patients with cystic fibrosis : a case series

There is a high association of reactive skin presentations, mainly limited cutaneous vasculitis in patients with cystic fibrosis and Burkholderia cepcia complex chronic infection. This may be due to raised levels of circulating inflammatory mediators.Publisher PDFPeer reviewe

Airway glucose concentrations and effect on growth of respiratory pathogens in cystic fibrosis

AbstractBackgroundPulmonary decline accelerates in cystic fibrosis-related diabetes (CFRD) proportional to severity of glucose intolerance, but mechanisms are unclear. In people without CF, airway glucose (AG) concentrations are elevated when blood glucose (BG)≥8 mmol L−1 (airway threshold), and are associated with acquisition of respiratory infection.MethodsTo determine the relationship between BG and AG, 40 CF patients underwent paired BG and AG (nasal) measurements. Daily time with BG>airway threshold was compared in 10 CFRD, 10 CF patients with normal glucose tolerance (CF-NGT) and 10 healthy volunteers by continuous BG monitoring. The effect of glucose at airway concentrations on bacterial growth was determined in vitro by optical densitometry.ResultsAG was present more frequently (85%-vs.-19%, p<0.0001) and at higher concentrations (0.5–3 mmol L−1-vs.-0.5–1 mmol L−1, p<0.0001) when BG was ≥8 mmol L−1-vs.-<8 mmol L−1. Daily time with BG≥8 mmol L−1 was CFRD (49±25%), CF-NGT (6±5%), healthy volunteers (1±3%), p<0.0001. Staphylococcus aureus growth increased at ≥0.5 mmol L−1 (p=0.006) and Pseudomonas aeruginosa growth above 1–4 mmol L−1 glucose (p=0.039).ConclusionsBG≥8 mmol L−1 predicted elevated AG concentrations in CF, at least in nasal secretions. CFRD patients spent ∼ 50% day with BG>airway threshold, implying persistently elevated AG concentrations. Further studies are required to determine whether elevated airway glucose concentrations contribute to accelerated pulmonary decline in CFRD

An international/multicentre report on patients with cystic fibrosis (CF) over the age of 40 years

AbstractBackgroundThe lifespan of patients with cystic fibrosis (CF) is increasing significantly. The objective of this international pilot study was to study the characteristics of these long-term survivors.MethodsFour centres with large CF clinics from London (UK), Minneapolis (USA), Toronto (Canada) and Verona (Italy) identified 366 patients who had survived 40years and longer.ResultsAt all centres males survived longer than females. There were more pancreatic sufficient patients in Verona (60%) and Toronto (40%) than in London (16%) and Minneapolis (21%). The percentage of ΔF508 homozygous patients varied between 47% in London and 45% in Minneapolis to only 26% in Toronto and 9% in Verona.Average FEV1 and BMI values of the surviving population appeared to stabilise after 40years of age. FEV1 was on average 12% higher in patients who were pancreatic sufficient (p > 0.0001). There was no difference in survival between the centres. The overall median survival after the age of 40 was 13years. The estimated annual death rate was approximately 3.4% from the age of 40–60years.ConclusionsSignificant numbers of patients are now surviving to 40years or more, and it is hoped that an in-depth study of these patients may identify the factors contributing to longer survival

Does Manual Therapy Provide Additional Benefit To Breathing Retraining In The Management Of Dysfunctional Breathing? A Randomised Controlled Trial

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use. This study sought to investigate whether MT produces additional benefit when compared with breathing retraining alone in patients with DB. Methods: Sixty subjects with primary DB were randomised into either breathing retraining (standard treatment; n¼30) or breathing retraining plus MT (intervention; n¼30) group. Both the groups received standardised respiratory physiotherapy, which included: DB education, breathing retraining, home regimen, and audio disc. Intervention group subjects additionally received MT following further assessment. Data from 57 subjects were analysed. Results: At baseline, standard treatment group subjects were statistically younger (41.7 + 13.5 versus 50.8 + 13.0 years; p¼0.001) with higher Nijmegen scores (38.6 + 9.5 versus 31.5 + 6.9; p¼0.001). However, no significant difference was found between the groups for primary outcome Nijmegen score (95% CI ( 1.1, 6.6) p¼0.162), or any secondary outcomes (Hospital Anxiety & Depression Score, spirometry or exercise tolerance). Conclusion: Breathing retraining is currently the mainstay of treatment for patients with DB. The results of this study suggest MT provides no additional benefit in this patient group.Juliana Burgess, Dr Robert Wilson, Royal Brompton & Harefield NHS Foundation Trust, and Dr Andy Jones fo

Lessons from mouse chimaera experiments with a reiterated transgene marker:revised marker criteria and a review of chimaera markers

Recent reports of a new generation of ubiquitous transgenic chimaera markers prompted us to consider the criteria used to evaluate new chimaera markers and develop more objective assessment methods. To investigate this experimentally we used several series of fetal and adult chimaeras, carrying an older, multi-copy transgenic marker. We used two additional independent markers and objective, quantitative criteria for cell selection and cell mixing to investigate quantitative and spatial aspects of developmental neutrality. We also suggest how the quantitative analysis we used could be simplified for future use with other markers. As a result, we recommend a five-step procedure for investigators to evaluate new chimaera markers based partly on criteria proposed previously but with a greater emphasis on examining the developmental neutrality of prospective new markers. These five steps comprise (1) review of published information, (2) evaluation of marker detection, (3) genetic crosses to check for effects on viability and growth, (4) comparisons of chimaeras with and without the marker and (5) analysis of chimaeras with both cell populations labelled. Finally, we review a number of different chimaera markers and evaluate them using the extended set of criteria. These comparisons indicate that, although the new generation of ubiquitous fluorescent markers are the best of those currently available and fulfil most of the criteria required of a chimaera marker, further work is required to determine whether they are developmentally neutral. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s11248-015-9883-7) contains supplementary material, which is available to authorized users

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data