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Gram-negative Burkholderia cepacia complex (Bcc) isolates were screened for antimicrobial activity against cystic fibrosis microbial pathogens, and the ability of B. ambifaria to inhibit B. multivorans was identified. The activity was mapped to a cluster of cryptic, quorum-sensing-regulated modular polyketide synthase (PKS) genes. Enacyloxin IIa and its stereoisomer designated iso-enacyloxin IIa were identified as metabolic products of the gene cluster, which encoded an unusual hybrid modular PKS consisting of multiple proteins with sequence similarity to cis-acyltransferase (cis-AT) PKSs and a single protein with sequence similarity to trans-AT PKSs. The discovery of the potent activity of enacyloxins against drug-resistant bacteria and the gene cluster that directs their production provides an opportunity for engineered biosynthesis of innovative enacyloxin derivatives and highlights the potential of Bcc bacteria as an underexploited resource for antibiotic discovery.

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The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa is widespread among cystic fibrosis (CF) patients in the United Kingdom and has emerged recently in North America. In this study, we report the analysis of 24 "anomalous" CF isolates of P. aeruginosa that produced inconsistent results with regard to either pulsed-field gel electrophoresis (PFGE) or PCR tests for the LES. We used a new typing method, the ArrayTube genotyping system, to determine that of the 24 anomalous isolates tested, 13 were confirmed as the LES. LES isolates could not be clearly distinguished from non-LES isolates by two other commonly used genetic fingerprinting tests, randomly amplified polymorphic DNA (RAPD) analysis and BOX-PCR, and varied considerably in their carriage of LES genomic islands and prophages. The genomic instability of the LES suggests that identification of this emerging transmissible strain could be a challenging task, and it questions whether discrimination is always a desirable feature of bacterial typing methods in the context of chronic CF infections.

The PleurX peritoneal drainage catheter for drainage of malignant ascites in a community setting has been evaluated by the NICE Medical Technologies Evaluation Programme. This article outlines the evidence included in the Sponsor's submission, the independent critique by the External Assessment Centre (EAC) and the recommendations made by the Medical Technologies Advisory Committee (MTAC). In accordance with the scope issued by NICE, the intervention technology was the indwelling PleurX peritoneal catheter drainage system, the comparator was large-volume paracentesis (LVP; inpatient or outpatient) and the population was patients with treatment-resistant, recurrent malignant ascites. Nine studies (ten papers) were identified with a total of 180 PleurX-treated patients; six were case series with more than four patients that, despite being low in the hierarchy of evidence, provided useful safety information. Technical success of the initial PleurX placement procedure was 100% across five studies which reported this outcome. One study reported equal complication rates between patients treated with indwelling PleurX catheters (40 patients and 40 catheters) and those receiving repeated LVPs (67 patients and 392 procedures), 7.5% (3/40; 95% CI 1.6, 20) and 7.5% (5/67; 95% CI 2.2, 15), respectively. All remaining studies were single-arm and reported complication rates of between 0% and 59%; this wide range was largely due to variation in the definition of complications and adverse events. Using validated tools, one case series reported improvements in several ascites-related symptoms after placement of the PleurX catheter; however, an overall quality-of-life improvement at 12 weeks was not demonstrated. Positive patient opinions relating to improved symptom control and convenience were reported in a qualitative study. Cost analysis demonstrated that PleurX offered savings to the NHS when compared with repeated LVPs performed in an inpatient setting. This saving of £679 per patient was driven primarily by reducing hospital bed days (year 2009-2010 values), but would require 23.5 additional community nurse visits. Advice from clinical experts was that additional home visits were overestimated as many patients would receive such visits regardless of whether a PleurX drain had been fitted. The model demonstrated that PleurX would be more expensive than LVP procedures performed in a setting where one or less hospital bed days were used (e.g. day case or outpatient). There was uncertainty surrounding the number of patients for whom insertion of a PleurX drain would be appropriate as well as the point in the care pathway at which such treatment should be administered. MTAC supported the case for adoption and considered that the available evidence showed PleurX was clinically effective, has low complication rates, can improve quality of life and is less costly than inpatient LVP. In Medical Technology Guidance 9 (MTG9), NICE recommended that PleurX peritoneal catheter drainage system be considered for use in patients with treatm...