Hd Green

The Microbiome and Emerging Pathogens in Cystic Fibrosis and Non–Cystic Fibrosis Bronchiectasis

Chronic pulmonary sepsis is the predominant cause of morbidity for patients with cystic fibrosis (CF) and non-CF bronchiectasis. Previously it was thought that respiratory infection in these patients was mostly limited to a very small number of typical pathogens; however, in recent years there have been increasing reports of infection with other emerging potential pathogens including Burkholderia, Stenotrophomonas, Achromobacter, Ralstonia, Pandoraea, nontuberculous mycobacteria, and fungal species. Furthermore, culture-independent methodologies have established that the lungs of patients with CF and non-CF bronchiectasis comprise mixed microbiological communities of aerobic and anaerobic bacteria, fungal and viral species, collectively referred to as the lung microbiome. This article addresses the clinical relevance of emerging pathogens and the lung microbiome in CF and non-CF bronchiectasis.

The clinical significance of hyperkalaemia-associated repolarization abnormalities in end-stage renal disease

BACKGROUNDnHyperkalaemia is a common potentially fatal complication of chronic kidney disease (CKD). It may manifest as electrocardiogram (ECG) changes, the earliest of which is T-wave tenting. However, this occurs in less than half of episodes of hyperkalaemia. The aim of this study was to determine what other clinical features relate to the probability of T-wave tenting; and if there is a longer-term survival difference between patients who develop tenting and those who do not.nnnMETHODnOne hundred and forty-five patients with end-stage renal disease who had standard 12-lead ECG and concurrent serum potassium measurement were enrolled. The presence of tenting and the ratio of the amplitude of the tallest precordial T-wave and R-wave were determined (T:R).nnnRESULTSnTenting was as common in normal range serum potassium as hyperkalaemia (33 versus 31%) and less common than in left ventricular hypertrophy (44%). T:R was less sensitive (24 versus 33%) but more specific (85 versus 67%) than tenting at correctly identifying hyperkalaemia ≥ 6.0 mmol/L. Tenting became less common with increasing age. Dialysis patients were more likely to show increased T:R that pre-dialysis Stage 5 CKD. Elevated T:R was not associated with worse cardiovascular outcome but was associated with increased risk of sudden death over a mean follow-up of 3.8 years (hazard ratio = 8.3, P = 0.021).nnnCONCLUSIONSnThe reason for the variability in T-wave changes is not clear. The ratio of precordial T-wave to R-wave amplitude is a more specific measure than tenting but both are poorly sensitive at detecting hyperkalaemia. The greater risk for sudden death may represent a susceptibility to cardiac arrhythmia during repolarization.

Central cyanosis on a psychiatric unit treated at the Salford Royal Hospital

We describe a case of acquired methaemoglobinaemia due to frequent use of the ‘legal high’ known as ‘Pink Panthers’. This contains 5,6-Methylenedioxy-2-aminoindane and 2-Aminoindane, both amphetamine analogues with the potential to cause methaemoglobinaemia. Furthermore, the most common ‘cutting agent’ for legal highs in the UK is benzocaine, also known to cause methaemoglobinaemia. Given the increasing prevalence of legal highs, particularly those containing added benzocaine, such presentations may become more common. Furthermore, in one case series, benzocaine gel used for toothache was the second most common reason for hospitalisation due to acquired methaemoglobinaemia after dapsone use. Indeed, the Federal Drug Agency has issued as public warning as to the risk of these products. We therefore think that clinicians and the public should be made more aware of the risk associated with such agents.

43 Gram-negative emerging pathogens: Prevalence and strain typing results from a large UK adult CF centre

Objective In recent years Gram-negative bacterial emerging pathogens (EP) have been noted to infect the airways of patients with CF. Prevalence of EP is increasing but much remains unknown. This study aimed to determine prevalence of EP at a large adult UK centre and whether these organisms may be capable of cross infection. Methods Prevalence of Burkhoderia multivorans; Stenotrophomonas maltophilia and Achromobacter; Ralstonia and Pandoraea species was calculated in October 2013 and 2014. Strain typing was performed on EP isolated from patients from 2008 to present using pulsed field gel electrophoresis. Epidemiology of patients with shared strains was analysed by reviewing patient addresses, outpatient appointments, admissions, paediatric centres and asking patients about their social behaviours. Results Prevalence of most EP increased between 2013 and 2014. EP prevalence in 2014 ranged from 1.9% ( Ralstonia species) to 6.2% ( B. multivorans ). To date, strain typing has been performed on 71 of 106 identified isolates from 90 patients. Shared strains of EP in unrelated patients with epidemiological connections other than place of home residence were found in cases of infection with Achromobacter , Ralstonia and Pandoraea species. Shared strains of B. multivorans were found in a sibling pair, an unrelated pair with no temporal overlap in positive cultures and in 3 patients with no clear links. Conclusion Prevalence of EP is low at our centre but is slowly increasing. Shared strains of Achromobacter , Ralstonia and Pandoraea species have been identified in our centre in small numbers of patients with epidemiological analysis consistent with possible cross infection.

P280 A Single Centre Experience Of Spontaneous Clearance Of Mycobacterium abscessus In Cystic Fibrosis Patients

Introduction The Mycobacterium abscessus complex is an emerging group of pathogens, which pose significant management challenges in CF. Current guidelines specify treatment is indicated in patients with repeated sputum culture positivity alongside radiological or clinical deterioration. However, identifying NTM as the cause of deterioration in the polymicrobial CF lung is challenging. Additionally, M. abscessus complex isolates are usually multi-resistant, requiring lengthy and complex treatment regimens. Whether to treat patients based on culture results alone is contentious and approaches differ between centres. Here we analyse our experience of M. abscessus at a large UK adult CF centre. Methods All patients with 1 or more positive sputum culture for M. abscessus since 2010, and minimum of 1 mycobacterial culture and 1 year of follow-up since first positivity were included. Anti-mycobacterial treatment and culture results following first positivity were recorded. M. abscessus eradication was defined as 4 consecutive negative cultures spanning at least 1 year. Results 21 patients were included. Of these, 6 (29%) have received/are receiving, anti-mycobacterial therapy based on clinician diagnosis of M. abscessus pulmonary disease. All 6 currently remain culture positive. Of the 15 remaining patients, 6 are consistently culture positive (duration 12 months - 5 years), but do not have evidence of NTM pulmonary disease. Spontaneous clearance of M. abscessus from sputum has occurred in 7 patients (Table 1). Of these, 5 (71%) had ≥3 positive cultures including 1 patient with 5 positive samples spread over 2 years and 1 patient with 5 positive samples spread over 9 months. In 2 patients infection status cannot yet be confirmed as these patients have ≤4 mycobacterial culture results following their initial positive result.Abstract P280 Table 1 Mycobacterium abscessus Sputum Culture and Treatment Status of Patients Attending Manchester Adult Cystic Fibrosis Centre Conclusion Patients may spontaneously clear M. abscessus from their sputum, even with a history of multiple positive cultures over many months. If patients are treated on culture results alone there is a risk of initiating potentially unnecessary, lengthy and poorly tolerated treatment. Our results suggest that adhering to clinical guidelines of recognising clinical deterioration secondary to M. abscessus remains paramount before commencing treatment and assessment of treatment success without control data may be very misleading.

P275 Prevalence and Strain Typing Results Of Gram-negative Emerging Bacterial Pathogens in Patients Attending a Large UK Adult CF Centre

Introduction In recent years Gram-negative bacterial emerging pathogens (EP) have been noted to infect the airways of patients with CF. Prevalence of EP is increasing but much remains unknown. This study aimed to determine prevalence of EP at a large adult UK centre and whether these organisms may be capable of cross infection. Methods Prevalence of Burkhoderia multivorans; Stenotrophomonas maltophilia and Achromobacter; Ralstonia and Pandoraea species was calculated in October 2013 and 2014. Strain typing was performed on EP isolated from patients from January 2008 to present using pulsed-field gel electrophoresis following restriction with XbaI. Epidemiology of patients with shared strains was analysed by reviewing patient addresses, outpatient appointments, admissions, paediatric centres and asking patients about their social behaviours. Results In October 2013, 358 patients had at least 1 sputum culture result in the previous 12 months and were included in the prevalence calculation. This increased to 368 patients in October 2014. Prevalence of most EP increased between 2013 and 2014. EP prevalence in 2014 ranged from 1.9% (Ralstonia species) to 6.2% (B. multivorans) (Table 1). 96 patients had ≥ 1 isolation of an EP between January 2008 and July 2015. Of these, 20 (21%) have had >2 strains of EP isolated from their sputum within that timeframe. To date, strain typing has been performed on 97 of 115 identified isolates from 96 patients. Shared strains of EP in unrelated patients with epidemiological connexions other than place of home residence were found in cases of infection with Achromobacter, Ralstonia and Pandoraea species. Shared strains of B. multivorans were found in a sibling pair, an unrelated pair with no temporal overlap in positive cultures and in 4 patients with no clear opportunities for cross infection to have occurred.Abstract P275 Table 1 Prevalence of Gram-negative bacterial emerging pathogens at Manchester Adult Cystic Fibrosis Centre 2013 and 2014 Conclusions Prevalence of EP is low at our centre but is slowly increasing. History of EP infection appears to be a risk factor for infection with other EPs. Shared strains of Achromobacter, Ralstonia and Pandoraea species have been identified in our centre in patients with epidemiological connexions. Numbers are too small to establish whether cross infection or a common environmental source is responsible.

Anabolic agent use in adults with cystic fibrosis

The use of non-prescribed anabolic agents amongst non-athletes is increasing with young, adult males with cystic fibrosis (CF) in the highest risk demographic. There is evidence that anabolic agents increase weight and muscle mass in adults with a variety of catabolic conditions but there is no evidence for their use in hormone sufficient adults with CF. We report a case of anabolic agent use in a male adult with CF and review the clinical features of anabolic agent use with a focus on adults with CF.

321 Changes in lung function and airway microbiology following ivacaftor therapy in an adult G551D homozygote

Objectives Ivacaftor has increased lung function and decreased pulmonary exacerbations and intravenous antibiotic use in patients with CF carrying the G551D mutation. This case study describes the effects of ivacaftor on airway microbiology and lung function in a G551D homozygote with chronic Pseudomonas aeruginosa (PA) infection. Methods All sputum culture reports prior to ivacaftor therapy were reviewed. Following ivacaftor initiation sputum samples were sent for standard culture at each clinic visit. 16S gene rRNA pyrosequencing was performed on paired sputum samples collected immediately prior to and after 6 months of ivacaftor therapy. FEV 1 was measured at baseline and at each follow up visit. Sweat chloride was assessed pre-treatment and at 6 months. Results Mucoid PA infection was acquired in 1983. The pre-ivacaftor baseline sputum sample and all preceding 26 samples taken over 8 years were culture positive for PA. 7 consecutive samples collected over 16 months following ivacaftor were culture negative for PA. A later sample was culture positive for the original infecting strain of PA (using variable number tandem repeat profiling). 16S gene rRNA pyrosequencing showed a drop in relative abundance of PA from 98.2% to 4.8% and an increase in microbial diversity over the 6 month sample period. FEV 1 improved from 68% predicted (baseline) to 90% predicted (20 months post ivacaftor). Sweat chloride reduced from 105 mmol/L (baseline) to 52 mmol/L (6months). Conclusion Bacterial diversity and relative abundance of typical CF pathogens may be significantly altered by modulation of both CFTR alleles. Sputum culture clearance of mucoid PA on should be interpreted with caution.