Evolving Landscape of Carbapenem-Resistant

OBJECTIVES: The increased identification of carbapenem-resistant METHODS: A total of 169 CR-PA isolated from clinical specimens at a single centre in Houston, TX, USA were studied. Among them, 61 isolates collected between 1999 and 2005 were defined as historical strains, and 108 collected between 2017 and 2018 were defined as contemporary strains. Antimicrobial susceptibilities against selected β-lactams was determined. WGS data were used for the identification of antimicrobial resistance determinants and phylogenetic analysis. RESULTS: Non-susceptibility to ceftolozane/tazobactam and ceftazidime/avibactam increased from 2% (1/59) to 17% (18/108) and from 7% (4/59) to 17% (18/108) from the historical to the contemporary collection, respectively. Carbapenemase genes, which were not identified in the historical collection, were harboured by 4.6% (5/108) of the contemporary strains, and the prevalence of ESBL genes also increased from 3.3% (2/61) to 16% (17/108). Genes encoding acquired β-lactamases were largely confined to the high-risk clones. Among ceftolozane/tazobactam-resistant isolates, non-susceptibility to ceftazidime/avibactam, imipenem/relebactam and cefiderocol was observed in 94% (15/16), 56% (9/16) and 12.5% (2/16), respectively. Resistance to ceftolozane/tazobactam and imipenem/relebactam was primarily associated with the presence of exogenous β-lactamases. CONCLUSIONS: Acquisition of exogenous carbapenemases and ESBLs may be a worrisome trend i

Effect of comorbidities on survival in patients > 80 years of age at onset of renal replacement therapy: data from the ERA-EDTA Registry

Background. The number of elderly patients on renal replacement therapy (RRT) is increasing. The survival and quality of life of these patients may be lower if they have multiple comorbidities at the onset of RRT. The aim of this study was to explore whether the effect of comorbidities on survival is similar in elderly RRT patients compared with younger ones. Methods. Included were 9333 patients >= 80years of age and 48352 patients 20-79 years of age starting RRT between 2010 and 2015 from 15 national or regional registries submitting data to the European Renal Association-European Dialysis and Transplantation Association Registry. Patients were followed until death or the end of 2016. Survival was assessed by Kaplan-Meier curves and the relative risk of death associated with comorbidities was assessed by Cox regression analysis. Results. Patients >= 80years of age had a greater comorbidity burden than younger patients. However, relative risks of death associated with all studied comorbidities (diabetes, ischaemic heart disease, chronic heart failure, cerebrovascular disease, peripheral vascular disease and malignancy) were significantly lower in elderly patients compared with younger patients. Also, the increase in absolute mortality rates associated with an increasing number of comorbidities was smaller in elderly patients. Conclusions. Comorbidities are common in elderly patients who enter RRT, but the risk of death associated with comorbidities is less than in younger patients. This should be taken into account when assessing the prognosis of elderly RRT patients.Peer reviewe

Guidelines for consideration of bats in lighting projects.

Eighty percent of the world’s population are currently exposed to light-polluted skies, and the Milky Way is no longer visible to more than a third of humanity. The pace the light pollution is increasing is faster than global population growth and economic development. While environmental conditions at night are being dramatically and rapidly altered, circadian rhythms, behaviour and ecology of plants and animals are imminently influenced. In the same time, effects of artificial lighting, various illumination schemes and spectra on biodiversity, including bats, are currently insufficiently understood, whereas only a vague notion of required mitigation and compensation activities exists among decision-makers and other parties involved in lighting projects. Although the bats are almost exclusively nocturnal and extremely sensitive to multiple effects of light pollution, its negative impact on bats alongside essential measures needed to preserve unfragmented nightscapes for these animals are often disregarded during impact assessments, planning and operation. In this volume, we tried to compile available evidence related to the effect of artificial light at night on the European bats. Based on the current state of knowledge, solutions are proposed concerning possible ways to avoid, mitigate and compensate the adverse effects which lighting projects may have on bats and their functional habitats. We also outlined research priorities for future studies, required for in-depth understanding of the problem and assessing efficiency of proposed mitigative measures

Características clínicas, microbiología y resultados de una cohorte de pacientes tratados con ceftolozane/tazobactam en centros de hospitalización de cuidados agudos, Houston, Texas, EE.UU

Antecedentes Ceftolozane/tazobactam es una combinación de β-lactámico/β-inhibidor de lactamasa con actividad contra una variedad de bacterias Gram-negativas, incluyendo Pseudomonas aeruginosa MDR. Este agente está aprobado para la neumonía bacteriana adquirida en el hospital y asociada a la ventilación mecánica. Sin embargo, la mayoría de los datos de resultados en el mundo real proceden de pequeñas cohortes observacionales. Por lo tanto, se trató de evaluar la utilización de ceftolozane/tazobactam en múltiples hospitales terciarios en Houston, TX, EE.UU.. Métodos Realizamos un estudio retrospectivo multicéntrico de pacientes que recibieron al menos 48 h de terapia con ceftolozano/tazobactam desde enero de 2016 hasta septiembre de 2019 en dos sistemas hospitalarios en Houston. Se recopilaron datos demográficos, clínicos y microbiológicos, incluido el aislado bacteriano infectante, cuando estaba disponible. El resultado primario fue el éxito clínico compuesto al alta hospitalaria. Los resultados secundarios incluyeron la mortalidad intrahospitalaria y la disposición clínica a los 14 y 30 días después del inicio de ceftolozane/tazobactam. Se utilizó un análisis de regresión logística multivariable para identificar los factores predictivos del resultado primario y la mortalidad. Los aislados recuperados se sometieron a pruebas de sensibilidad a ceftolozano/tazobactam y a WGS. Resultados Se incluyó a un total de 263 pacientes, y se alcanzó el éxito clínico compuesto en 185 pacientes (70,3%). La gravedad de la enfermedad fue el factor predictivo más consistente del éxito clínico. El tratamiento combinado con ceftolozane/tazobactam y otro agente Gram negativo activo se asoció a una reducción de las probabilidades de éxito clínico (OR 0,32; IC del 95%: 0,16-0,63). Se observó resistencia a ceftolozano/tazobactam en el 15,4% de los aislados disponibles para WGS; las mutaciones en ampC y ftsI fueron frecuentes pero no se agruparon con una ST concreta. Conclusiones La tasa de éxito clínico entre esta cohorte de pacientes tratados con ceftolozane/tazobactam fue similar en comparación con experiencias anteriores. Ceftolozane/tazobactam sigue siendo un agente alternativo para el tratamiento de aislados susceptibles de P. aeruginosaBackground Ceftolozane/tazobactam is a β-lactam/β-lactamase inhibitor combination with activity against a variety of Gram-negative bacteria, including MDR Pseudomonas aeruginosa. This agent is approved for hospital-acquired and ventilator-associated bacterial pneumonia. However, most real-world outcome data come from small observational cohorts. Thus, we sought to evaluate the utilization of ceftolozane/tazobactam at multiple tertiary hospitals in Houston, TX, USA. Methods We conducted a multicentre retrospective study of patients receiving at least 48 h of ceftolozane/tazobactam therapy from January 2016 through to September 2019 at two hospital systems in Houston. Demographic, clinical and microbiological data were collected, including the infecting bacterial isolate, when available. The primary outcome was composite clinical success at hospital discharge. Secondary outcomes included in-hospital mortality and clinical disposition at 14 and 30 days post ceftolozane/tazobactam initiation. Multivariable logistic regression analysis was used to identify predictors of the primary outcome and mortality. Recovered isolates were tested for susceptibility to ceftolozane/tazobactam and underwent WGS. Results A total of 263 patients were enrolled, and composite clinical success was achieved in 185 patients (70.3%). Severity of illness was the most consistent predictor of clinical success. Combination therapy with ceftolozane/tazobactam and another Gram-negative-active agent was associated with reduced odds of clinical success (OR 0.32, 95% CI 0.16–0.63). Resistance to ceftolozane/tazobactam was noted in 15.4% of isolates available for WGS; mutations in ampC and ftsI were common but did not cluster with a particular ST. Conclusions Clinical success rate among this patient cohort treated with ceftolozane/tazobactam was similar compared with previous experiences. Ceftolozane/tazobactam remains an alternative agent for treatment of susceptible isolates of P. aeruginosa

Contemporary Clinical and Molecular Epidemiology of Vancomycin-Resistant Enterococcal Bacteremia: A Prospective Multicenter Cohort Study (VENOUS I)

Background Vancomycin-resistant enterococci (VRE) are major therapeutic challenges. Prospective contemporary data characterizing the clinical and molecular epidemiology of VRE bloodstream infections (BSIs) are lacking. Methods The Vancomycin-Resistant Enterococcal BSI Outcomes Study (VENOUS I) is a prospective observational cohort of adult patients with enterococcal BSI in 11 US hospitals. We included patients with Enterococcus faecalis or Enterococcus faecium BSI with >= 1 follow-up blood culture(s) within 7 days and availability of isolate(s) for further characterization. The primary study outcome was in-hospital mortality. Secondary outcomes were mortality at days 4, 7, 10, 12, and 15 after index blood culture. A desirability of outcome ranking was constructed to assess the association of vancomycin resistance with outcomes. All index isolates were subjected to whole genome sequencing. Results Forty-two of 232 (18%) patients died in hospital and 39 (17%) exhibited microbiological failure (lack of clearance in the first 4 days). Neutropenia (hazard ratio [HR], 3.13), microbiological failure (HR, 2.4), VRE BSI (HR, 2.13), use of urinary catheter (HR, 1.85), and Pitt BSI score >= 2 (HR, 1.83) were significant predictors of in-hospital mortality. Microbiological failure was the strongest predictor of in-hospital mortality in patients with E faecium bacteremia (HR, 5.03). The impact of vancomycin resistance on mortality in our cohort changed throughout the course of hospitalization. Enterococcus faecalis sequence type 6 was a predominant multidrug-resistant lineage, whereas a heterogeneous genomic population of E faecium was identified. Conclusions Failure of early eradication of VRE from the bloodstream is a major factor associated with poor outcomes. Failure to eradicate enterococci from the bloodstream in the first 4 days after the index blood culture was the most consistent factor associated with increased risk of mortality. The association of vancomycin resistance with mortality changed throughout the course of the hospitalization

Neutrophil cannibalism – a back up when the macrophage clearance system is insufficient

BACKGROUND: During a lipopolysaccharide-induced lung inflammation, a massive accumulation of neutrophils occurs, which is normally cleared by macrophage phagocytosis following neutrophil apoptosis. However, in cases of extensive apoptosis the normal clearance system may fail, resulting in extensive neutrophil secondary necrosis. The aim of this study was to explore the hypothesis that neutrophils, in areas of the lung with extensive cellular infiltration, contribute to clearance by phagocytosing apoptotic cells and/or cell debris derived from secondary necrosis. METHODS: Intranasal lipopolysaccharide administration was used to induce lung inflammation in mice. The animals were sacrificed at seven time points following administration, bronchoalveolar lavage was performed and tissue samples obtained. Electron microscopy and histochemistry was used to assess neutrophil phagocytosis. RESULTS: Electron microscopic studies revealed that phagocytosing neutrophils was common, at 24 h after LPS administration almost 50% of the total number of neutrophils contained phagosomes, and the engulfed material was mainly derived from other neutrophils. Histochemistry on bronchoalvolar lavage cells further showed phagocytosing neutrophils to be frequently occurring. CONCLUSION: Neutrophils are previously known to phagocytose invading pathogens and harmful particles. However, this study demonstrates that neutrophils are also able to engulf apoptotic neutrophils or cell debris resulting from secondary necrosis of neutrophils. Neutrophils may thereby contribute to clearance and resolution of inflammation, thus acting as a back up system in situations when the macrophage clearance system is insufficient and/or overwhelmed

Liax Is a Surrogate Marker For Cell Envelope Stress and Daptomycin Non-Susceptibility in Enterococcus Faecium

Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistan

Crystallography of a Lewis-Binding Norovirus, Elucidation of Strain-Specificity to the Polymorphic Human Histo-Blood Group Antigens

Noroviruses, an important cause of acute gastroenteritis in humans, recognize the histo-blood group antigens (HBGAs) as host susceptible factors in a strain-specific manner. The crystal structures of the HBGA-binding interfaces of two A/B/H-binding noroviruses, the prototype Norwalk virus (GI.1) and a predominant GII.4 strain (VA387), have been elucidated. In this study we determined the crystal structures of the P domain protein of the first Lewis-binding norovirus (VA207, GII.9) that has a distinct binding property from those of Norwalk virus and VA387. Co-crystallization of the VA207 P dimer with Ley or sialyl Lex tetrasaccharides showed that VA207 interacts with these antigens through a common site found on the VA387 P protein which is highly conserved among most GII noroviruses. However, the HBGA-binding site of VA207 targeted at the Lewis antigens through the α-1, 3 fucose (the Lewis epitope) as major and the β-N-acetyl glucosamine of the precursor as minor interacting sites. This completely differs from the binding mode of VA387 and Norwalk virus that target at the secretor epitopes. Binding pocket of VA207 is formed by seven amino acids, of which five residues build up the core structure that is essential for the basic binding function, while the other two are involved in strain-specificity. Our results elucidate for the first time the genetic and structural basis of strain-specificity by a direct comparison of two genetically related noroviruses in their interaction with different HBGAs. The results provide insight into the complex interaction between the diverse noroviruses and the polymorphic HBGAs and highlight the role of human HBGA as a critical factor in norovirus evolution

Throat related symptoms and voice: development of an instrument for self assessment of throat-problems

<p>Abstract</p> <p>Background</p> <p>Symptoms from throat (sensation of globus; frequent throat clearing; irritated throat) are common in patients referred to voice clinics and to ENT specialists. The relation to symptoms of voice discomfort is unclear and in some cases patients do not have voice problems at all. Instruments for patients' self-reporting of symptoms, and assessment of handicap, such as the Voice Handicap Index (VHI), are in common use in voice clinics. Symptoms from throat are however only marginally covered. Purpose: To develop and evaluate an instrument that could make the patients' estimation of symptoms from the throat possible. Further to facilitate the consideration of the relation between throat- and voice problems with the Throat subscale together with a Swedish translation of the Voice Handicap Index. Finally to try the VHI with the Throat subscale: the VHI-T, for test-retest reliability and validity.</p> <p>Methods</p> <p>A subscale with 10 throat related items was developed for appliance with the VHI. The VHI was translated to Swedish and retranslated to English. The questionnaire was tried in two phases on a total of 23+144 patients and 12+58 voice healthy controls. The reliability was calculated with Cronbach's alpha, ICC and Pearson's correlation coefficient. The validity was estimated by independent T-test.</p> <p>Results</p> <p>The difference in VHI-T scores between the patients and the voice-healthy controls was significant (<it>p </it>= < 0,01) and there was a good correlation of the test- retest occasions. The reliability testing of the entire questionnaire showed an alpha value of <it>r </it>= 0,90 and that for the Throat subscale separately a value of <it>r </it>= 0,87 which shows a high degree of reliability.</p> <p>Conclusions</p> <p>For the estimation of self-perceived throat and voice problems the scale on throat related problems together with the present Swedish translation of the Voice Handicap Index, (VHI) the VHI-Throat, proves to be a valid and reliable instrument. The throat subscale seems to help revealing a category of symptoms that are common in our patients. These are symptoms that have not earlier been possible to cover with the questionnaires designed for use in the voice clinic.</p