Multifactorial resistance mechanisms associated with resistance to ceftazidime-avibactam in clinical Pseudomonas aeruginosa isolates from Switzerland

BackgroundIncreasing reports of multidrug resistance (MDR) in clinical Pseudomonas aeruginosa have led to a necessity for new antimicrobials. Ceftazidime-avibactam (CZA) is indicated for use against MDR P. aeruginosa across a broad range of infection types and particularly those that are carbapenem resistant. This study sought to determine the molecular mechanisms of CZA and imipenem (IPM)-resistance in clinical P. aeruginosa isolates obtained from Swiss hospitals.MethodsClinical P. aeruginosa isolates were obtained from inpatients in three hospitals in Switzerland. Susceptibility was determined by either antibiotic disc testing or broth microdilution according to EUCAST methodology. AmpC activity was determined using cloxacillin and efflux activity was determined using phenylalanine-arginine β-naphthylamide, in agar plates. Whole Genome Sequencing was performed on 18 clinical isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. Genes of interest were extracted from sequenced isolates and compared to reference strain P. aeruginosa PAO1.ResultsSixteen different STs were identified amongst the 18 isolates in this study indicating a high degree of genomic diversity. No carbapenemases were detected but one isolate did harbor the ESBL blaPER-1. Eight isolates were CZA-resistant with MICs ranging from 16-64 mg/L, and the remaining ten isolates had either low/wildtype MICs (n=6; 1-2 mg/L) or elevated, but still susceptible, MICs (n=4; 4-8 mg/L). Ten isolates were IPM-resistant, seven of which had mutations resulting in truncations of OprD, and the remaining nine IPM-susceptible isolates had intact oprD genes. Within CZA-R isolates, and those with reduced susceptibility, mutations resulting in ampC derepression, OprD loss, mexAB overexpression and ESBL (blaPER-1) carriage were observed in various combinations and one harbored a truncation of the PBP4 dacB gene. Within the six isolates with wildtype-resistance levels, five had no mutations that would affect any antimicrobial resistance (AMR) genes of interest when compared to PAO1.ConclusionThis preliminary study highlights that CZA-resistance in P. aeruginosa is multifactorial and could be caused by the interplay between different resistance mechanisms including ESBL carriage, increased efflux, loss of permeability and derepression of its intrinsic ampC

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview

Late Spinal Implant Infection caused by Cutibacterium acnes.

Cutibacterium spp. have been frequently associated with foreign-body material infections. The vast majority of these infections occur via the exogenous route. Rarely, haematogenous infections occur, possibly seeding from pilosebaceous glands. A late spinal implant-associated infection is presented in this case report, and the possible sources of haematogenous seeding are discussed

Work-in-Progress-Enhancing Training in Virtual Reality with Hand Tracking and a Real Tool

The main goal of Virtual Training Environments(VTEs) is to maximize training success, which can be achievedby increasing the degree of immersion. While prior work mainlyfocused on the visual, auditory, and navigational aspects of im-mersion, proprioceptive aspects may be particularly important.In this work-in-progress paper, we explore this potential byimplementing an industrial VTE, which can be interacted with,using VR gloves and a tracked real tool. Further, we evaluatethe VTE in a pilot study with industry apprentices, providinginitial evidence that participants experienced high presence andlow task load, while being generally satisfied with the training

Work-in-Progress: Effects of Attention Guidance on Virtual Reality Training for an Industrial Assembly Task

One of the main objectives of Virtual Training Environments (VTEs) for industrial training is to train workers for a real world task. Prior work identified a multitude of factors influencing a VTE’s effectiveness. In this work-in-progress paper, we add to this body of research by evaluating the effect of attention guidance (AG) on a VTE’s effectiveness. In a controlled between-subject design pilot study with 42 participants, participants were trained in a VTE either with or without AG. Subsequently, learning transfer was assessed in a Real-World Evaluation (RWE). Our findings indicate that, while not necessary for a VTE’s efficacy, AG appears to be a substantial factor in a VTE’s effectiveness

Virtual Reality Extension for Digital Twins of Machine Tools

ISSN:2196-8705ISSN:2196-871

Designing Virtual Training Environments: Does Immersion increase Task Performance?

One of the main characteristic of virtual reality (VR) is immersion, which leads to the creation of sophisticated illusions of reality. Accordingly, VR is already used for a wide spectrum of applications like entertainment, marketing, and training. Especially in training applications, the effect of immersion on training success is still not entirely clear, since too much immersion may cause side effects such as users experiencing high mental demand whereas too little may disturb users’ well-being. To further investigate the matter, we developed two virtual training environments, wherein users train a typical industrial assembly task either in low or high immersive VR. In a controlled pilot study, we additionally introduced a third condition, the control group, which justifies the necessity of the training. Immediately after the VR Training session, each participant completed the corresponding real assembly task in which their performance was measured. Preliminary results from our pilot study show that participants trained in high immersive VR performed better, while negative side effects could not be detected

Multifactorial resistance mechanisms associated with resistance to ceftazidime-avibactam in clinical Pseudomonas aeruginosa isolates from Switzerland

BACKGROUND: Increasing reports of multidrug resistance (MDR) in clinical Pseudomonas aeruginosa have led to a necessity for new antimicrobials. Ceftazidime-avibactam (CZA) is indicated for use against MDR P. aeruginosa across a broad range of infection types and particularly those that are carbapenem resistant. This study sought to determine the molecular mechanisms of CZA and imipenem (IPM)-resistance in clinical P. aeruginosa isolates obtained from Swiss hospitals. METHODS: Clinical P. aeruginosa isolates were obtained from inpatients in three hospitals in Switzerland. Susceptibility was determined by either antibiotic disc testing or broth microdilution according to EUCAST methodology. AmpC activity was determined using cloxacillin and efflux activity was determined using phenylalanine-arginine β-naphthylamide, in agar plates. Whole Genome Sequencing was performed on 18 clinical isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. Genes of interest were extracted from sequenced isolates and compared to reference strain P. aeruginosa PAO1. RESULTS: Sixteen different STs were identified amongst the 18 isolates in this study indicating a high degree of genomic diversity. No carbapenemases were detected but one isolate did harbor the ESBL bla $_{PER-1}$. Eight isolates were CZA-resistant with MICs ranging from 16-64 mg/L, and the remaining ten isolates had either low/wildtype MICs (n=6; 1-2 mg/L) or elevated, but still susceptible, MICs (n=4; 4-8 mg/L). Ten isolates were IPM-resistant, seven of which had mutations resulting in truncations of OprD, and the remaining nine IPM-susceptible isolates had intact oprD genes. Within CZA-R isolates, and those with reduced susceptibility, mutations resulting in ampC derepression, OprD loss, mexAB overexpression and ESBL (bla $_{PER-1}$) carriage were observed in various combinations and one harbored a truncation of the PBP4 dacB gene. Within the six isolates with wildtype-resistance levels, five had no mutations that would affect any antimicrobial resistance (AMR) genes of interest when compared to PAO1. CONCLUSION: This preliminary study highlights that CZA-resistance in P. aeruginosa is multifactorial and could be caused by the interplay between different resistance mechanisms including ESBL carriage, increased efflux, loss of permeability and derepression of its intrinsic ampC