Novel approaches for the treatment of multidrug-resistant Gram-negative bacterial infections are urgently required. One approach is to potentiate the efficacy of existing antibiotics whose spectrum of activity is limited by the permeability barrier presented by the Gram-negative outer membrane. Cationic peptides derived from polymyxin B have been used to permeabilize the outer membrane, granting antibiotics that would otherwise be excluded access to their targets. We assessed the in vitro efficacies of combinations of SPR741 with conventional antibiotics against Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii. Of 35 antibiotics tested, the MICs of 8 of them were reduced 32-to 8,000-fold against E. coli and K. pneumoniae in the presence of SPR741. The eight antibiotics, azithromycin, clarithromycin, erythromycin, fusidic acid, mupirocin, retapamulin, rifampin, and telithromycin, had diverse targets and mechanisms of action. Against A. baumannii, similar potentiation was achieved with clarithromycin, erythromycin, fusidic acid, retapamulin, and rifampin. Susceptibility testing of the most effective antibiotic-SPR741 combinations was extended to 25 additional multidrug-resistant or clinical isolates of E. coli and K. pneumoniae and 17 additional A. baumannii isolates in order to rank the potentiated antibiotics. SPR741 was also able to potentiate antibiotics that are substrates of the AcrAB-TolC efflux pump in E. coli, effectively circumventing the contribution of this pump to intrinsic antibiotic resistance. These studies support the further development of SPR741 in combination with conventional antibiotics for the treatment of Gram-negative bacterial infections.

objective. To evaluate the microbiologic effectiveness of the World Health Organization's 6-step and the Centers for Disease Control and Prevention's 3-step hand hygiene techniques using alcohol-based handrub.design. A parallel group randomized controlled trial.setting. An acute care inner-city teaching hospital (Glasgow).participants. Doctors (n = 42) and nurses (n = 78) undertaking direct patient care.intervention. Random 1:1 allocation of the 6-step (n = 60) or the 3-step (n = 60) technique.results. The 6-step technique was microbiologically more effective at reducing the median log 10 bacterial count. The 6-step technique reduced the count from 3.28 CFU/mL (95% CI, 3.11-3.38 CFU/mL) to 2.58 CFU/mL (2.08-2.93 CFU/mL), whereas the 3-step reduced it from 3.08 CFU/mL (2.977-3.27 CFU/mL) to 2.88 CFU/mL (−2.58 to 3.15 CFU/mL) (P = .02). However, the 6-step technique did not increase the total hand coverage area (98.8% vs 99.0%, P = .15) and required 15% (95% CI, 6%-24%) more time (42.50 seconds vs 35.0 seconds, P = .002). Total hand coverage was not related to the reduction in bacterial count.conclusions. Two techniques for hand hygiene using alcohol-based handrub are promoted in international guidance, the 6-step by the World Health Organization and 3-step by the Centers for Disease Control and Prevention. The study provides the first evidence in a randomized controlled trial that the 6-step technique is superior, thus these international guidance documents should consider this evidence, as should healthcare organizations using the 3-step technique in practice. 2016;37:661-666 Hand hygiene is argued to be the most important intervention in preventing healthcare-associated infection. Infect Control Hosp Epidemiol1 Despite this, a recent systematic review 2 identified that there is limited evidence to support hand hygiene techniques, and compliance with hand hygiene remains suboptimal. There is little point in getting the opportunity, or the "5 Moments," 1 correct for hand hygiene if a technique effective in reducing the bacterial load on the hand thereafter is not evident.There are 2 main techniques in international guidance on hand hygiene: the first of these is the World Health Organization 6-step technique, 1 which involves applying a palmful of alcohol-based handrub (ABHR) in a cupped hand, covering all surfaces, and rubbing 6 different aspects of the hands. This technique has a limited evidence base for use in clinical practice because it was developed as a standardized technique to test hand hygiene products in a laboratory setting.3 Furthermore, this technique has no evidence of microbiologic effectiveness in clinical settings with ABHR. The second technique is the 3-step technique. This technique involves first, applying ABHR to the palm of one hand and rubbing hands together; second, covering all surfaces; third, continuing to rub until hands are dry. 4 There is some observational evidence base 5 and 1 randomized controlled trial (RCT) to support this technique on the basis of shorter duration, althoug...

POCINR testing can exclude clinically significant coagulopathy in the ED. LABINR is required to confirm non-normal INR results, particularly in the supratherapeutic range.

ReuseUnless indicated otherwise, fulltext items are protected by copyright with all rights reserved. The copyright exception in section 29 of the Copyright, Designs and Patents Act 1988 allows the making of a single copy solely for the purpose of non-commercial research or private study within the limits of fair dealing. The publisher or other rights-holder may allow further reproduction and re-use of this version -refer to the White Rose Research Online record for this item. Where records identify the publisher as the copyright holder, users can verify any specific terms of use on the publisher's website. TakedownIf you consider content in White Rose Research Online to be in breach of UK law, please notify us by emailing eprints@whiterose.ac.uk including the URL of the record and the reason for the withdrawal request. Accepted ManuscriptTitle: Efficacy of rifampicin combination therapy for the treatment of enterococcal infections assessed in vivo using a Galleria mellonella infection model This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Efficacy of rifampicin combination therapy for the treatment of enterococcal infections assessed in vivo using a Galleria mellonella infection model

Isoniazid is a rare overdose that causes seizures and there is limited evidence to guide treatment. We report a 20-year-old female migrant who presented with recurrent seizures after ingesting 25 g of isoniazid. She was treated with activated charcoal, repeated doses of midazolam for the seizures, and given multiple doses of pyridoxine (14 mg), limited by availability. She was admitted to intensive care, and 5.5 hours post-ingestion, she was commenced on continuous veno-venous hemodiafiltration (CVVHDF). She was extubated after 24 hours and CVVHDF was ceased 6 hours later (30 hours post-overdose). Her renal function remained normal and her initial lactate was the highest at 2.3. She made a full recovery. Five plasma samples were collected before, during, and after CVVHDF, and isoniazid was quantified with liquid chromatography-tandem mass spectrometry. A pharmacokinetic analysis of time-isoniazid concentration data was fitted to a two-compartment model with first-order input (with fixed ka ) with the effect of CVVHDF modeled as a time-dependent covariate. This suggested that there was initially good clearance with CVVHDF (4 times endogenous clearance), which rapidly declined within hours.