Antimicrobial susceptibility of clinical isolates of Neisseria gonorrhoeae to alternative antimicrobials with therapeutic potential.

Background: The prevalence of MDR Neisseria gonorrhoeae is increasing globally and represents a public health emergency. Development and approval of new anti-gonococcal agents may take years. As a concurrent approach to developing new antimicrobials, the laboratory and clinical evaluation of currently licensed antimicrobials not widely used for the treatment of gonorrhoea may provide new options for the treatment of gonococcal infections. Objectives: To determine the in vitro activity of nine alternative, currently licensed and late-development antimicrobials with the potential to treat gonococcal infections against 112 clinical isolates of N. gonorrhoeae resistant to one or multiple antimicrobials. Methods: The MICs of conventional anti-gonococcal antimicrobials (penicillin, ceftriaxone, cefixime, azithromycin, ciprofloxacin, tetracycline and spectinomycin) and alternative antimicrobials (ertapenem, gentamicin, netilmicin, tigecycline, eravacycline, fosfomycin, linezolid, ceftazidime/avibactam and ceftaroline) were determined by agar dilution. Results: Ertapenem and the novel cephalosporins demonstrated similar MIC values to the third-generation cephalosporins, but increased MICs were observed for isolates with increased cefixime and ceftriaxone MICs. Tigecycline and eravacycline had MIC values below expected serum concentrations for all isolates tested. The aminoglycosides gentamicin and netilmicin were generally more potent than spectinomycin, with netilmicin demonstrating the greatest potency. Fosfomycin MICs were elevated compared with other agents, but remained within the MIC range for susceptible organisms, while linezolid MICs were generally higher than those for organisms considered resistant. Conclusions: Among potentially therapeutically useful alternative agents, the aminoglycosides, eravacycline, tigecycline and fosfomycin had good in vitro activity. The novel cephalosporins and ertapenem had comparable activity to cefixime and ceftriaxone.

Colistin-Nonsusceptible Pseudomonas aeruginosa Sequence Type 654 with blaNDM-1 Arrives in North America.

This study describes 3 different blaNDM-1 genetic platforms in 3 different species obtained from the same patient who was directly transferred to an institution in Calgary, Alberta, Canada, following a prolonged hospital stay in India. The blaNDM-1 in the Escherichia coli isolate was located on a 176-kb IncA/C plasmid contained within an ISCR1 region. The blaNDM-1 in the Providencia rettgeri isolate was located on a 117-kb IncT plasmid contained within Tn3000, while the blaNDM-1 in the Pseudomonas aeruginosa isolate was located on the chromosome within an ISCR3 region. This report highlights the plasticity of the genetic regions and environments associated with blaNDM-1. To the best of our knowledge, this is the first report of P. aeruginosa with blaNDM-1 identified in North America and the first report of blaOXA-181 in P. rettgeri. The P. aeruginosa isolate belonged to the international high-risk sequence type 654 clone and was nonsusceptible to colistin. This case emphasizes the need for the use of appropriate infection prevention and control measures and vigilant screening for carbapenem-resistant Gram-negative bacteria in patients with a history of travel to areas of endemicity, such as the Indian subcontinent.

Decline in Decreased Cephalosporin Susceptibility and Increase in Azithromycin Resistance in Neisseria gonorrhoeae, Canada.

Antimicrobial resistance profiles were determined for Neisseria gonorrhoeae strains isolated in Canada during 2010-2014. The proportion of isolates with decreased susceptibility to cephalosporins declined significantly between 2011 and 2014, whereas azithromycin resistance increased significantly during that period. Continued surveillance of antimicrobial drug susceptibilities is imperative to inform treatment guidelines.

The use of transcutaneous electrical nerve stimulation (TENS) to aid perceptual embodiment of prosthetic limbs.

Integration of prosthetic limb awareness into body schema is likely to aid manual control of the prosthesis. Physiotherapists and prosthetists use techniques to generate mechanical, visual and/or auditory feedback related to stimulation of the stump and proximal residual limb to improve prosthetic limb awareness. Electrical stimulation of afferent nerves using implanted electrodes can generate sensations of touch, joint movement, and position, in the missing, phantom limbs of amputees. We report here a novel hypothesis that non-invasive transcutaneous electrical nerve stimulation (TENS) could be used to facilitate the process of perceptual embodiment of a prosthesis into the body schema of amputees. Using a modified version of the rubber hand illusion (RHI), we have found that TENS paraesthesiae can be made to feel like it is emanating from a prosthetic hand in healthy participants with intact limbs. In addition, participants reported perceptual embodiment of the prosthetic hand into their body schema, i.e. it felt as if it is part of their body. We predict that projecting TENS paraesthesiae into the prosthetic limb(s) of amputees will provide sufficient sensory input to facilitate perceptual embodiment. This could prove to be a simple and inexpensive training aid to improve ambulation and prosthesis success.

Induction of ferritin synthesis in cells infected with Mengo virus.

We have recently identified ferritin as a cellular protein particle whose synthesis is stimulated in mouse or human cells infected by the picornavirus Mengo. Immunoprecipitation of the particle from infected murine L929 cells showed a 4- and 6-fold increase in the intracellular concentrations of H and L apoferritin subunits, respectively. This differential expression altered the H/L subunit ratio from 3.0 in uninfected cells to 2.2 in Mengo virus-infected cells. The induction is not due to an increase in transcription of the apoferritin L and H genes, nor is it due to an increase in stability of the apoferritin mRNAs. At the level of translation, the iron regulatory protein (IRP) remained intact, with similar amounts being detected in uninfected and infected cells. The Mengo virus RNA genome does not compete with the iron regulatory element (IRE) for the binding of IRP, and sequence analysis confirmed that there are no IREs in the virus RNA. The IRE binding activity of IRP in infected cells decreased approximately 30% compared with uninfected cells. The decrease in binding activity could be overcome by the addition of Desferal (deferoxamine mesylate; CIBA) an intracellular iron chelator, which suggests that virus infection causes an increase in intracellular free iron. Electron paramagnetic resonance (EPR) studies have confirmed the increase in free iron in Mengo virus infected cells. The permeability of cells for iron does not change in virus infected cells, suggesting that the induction of ferritin by Mengo virus is due to a change in the form of intracellular iron from a bound to a free state.