Antimicrobial Activity of Ceftolozane-Tazobactam, Ceftazidime-Avibactam, and Cefiderocol against Multidrug-Resistant Pseudomonas aeruginosa Recovered at a German University Hospital.

Multidrug-resistant (MDR) Pseudomonas aeruginosa increasingly causes health care-associated infections. In this study, we determined the activity of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against 223 MDR P. aeruginosa clinical isolates recovered from 2013 to 2017 at the University Hospital Frankfurt by using MIC test strips. Furthermore, we evaluated the presence of genes encoding major ß-lactamases, such as VIM, IMP, NDM, GIM, SPM, and KPC; the extended spectrum ß-lactamase (ESBL)-carbapenemase GES; and the virulence-associated traits ExoS and ExoU, as in particular ExoU is thought to be associated with poor clinical outcome. For MDR P. aeruginosa isolates, the MIC50/MIC90 values of ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol were 8/>256 mg/L, 16/>256 mg/L, and 0.25/1 mg/L, respectively. Cefiderocol showed the highest susceptibility rate (97.3%) followed by ceftazidime-avibactam (48.4%) and ceftolozane-tazobactam (46.6%). In 81 (36.3%) isolates, carbapenemase gene blaVIM was detected, and in 5 (2.2%) isolates, blaGES was detected (with a positive association of exoU and blaVIM). More than half of the isolates belong to the so-called international P. aeruginosa "high-risk" clones, with sequence type 235 (ST235) (24.7%) being the most prevalent. This study underlines that ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol are important options for the treatment of infections due to MDR P. aeruginosa, with cefiderocol currently being the most active available antipseudomonal ß-lactam agent. According to our clinical experience, the outcome of cefiderocol therapy (8 patients) was favorable especially in cases of MDR P. aeruginosa-associated complicated urinary tract infections. IMPORTANCE After testing ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol against a collection of 233 multidrug-resistant (MDR) Pseudomonas aeruginosa, we showed that cefiderocol is the most active antipseudomonal ß-lactam agent (susceptibility rates were 46.6%, 48.4%, and 97.4%, respectively). The most prevalent one was sequence type 235 (ST235) (24.7%), followed by ST244, ST175, and ST233, with all belonging to the top 10 P. aeruginosa high-risk clones with worldwide distribution. Our data indicate that during surveillance studies special attention should be paid to the MDR and highly virulent VIM- and ExoU-producing variant of ST235. Furthermore, in the case of infections caused by carbapenemase-producing MDR P. aeruginosa, cefiderocol is the preferred treatment option, while outcomes of complicated urinary tract infections and hospital-acquired pneumonia with cefiderocol were favorable.

Association Between Systemic Inflammation, Carotid Arteriosclerosis, and Autonomic Dysfunction.

Systemic inflammation is associated with arteriosclerotic disease progression and worse stroke outcome in patients with carotid arteriosclerotic disease. We hypothesize that systemic inflammation is mediated by impaired carotid baroreceptor and chemoreceptor function induced by carotid arteriosclerosis rather than by the generalized inflammatory arteriosclerotic process.Heart rate variability (HRV), serum levels of inflammatory markers, demographic and life style factors, and concomitant diseases with potential impact on systemic inflammation were determined in 105 patients with asymptomatic carotid stenosis of varying degree. Multivariate linear regression analyses were performed to ascertain independent determinants of carotid stenosis severity, autonomic function, and inflammation.Systemic inflammation (C-reactive protein, beta = .255; P = .014), age (beta = .232; P < .008), and arterial hypertension (beta = .206; P = .032) were associated with carotid stenosis severity. Only carotid stenosis severity and not generalized arteriosclerotic disease, concomitant diseases (arterial hypertension, diabetes mellitus, dyslipidemia, hypothyroidism), life style factors (smoking, obesity), or age was associated with a reduction in vagal tone (HRV HF band power beta = - .193; P < 0.049). Systemic inflammation was related to a reduction in vagal tone (HRV HF band power, beta = - .214; P = .031), and not to generalized arteriosclerotic disease, concomitant diseases (arterial hypertension, diabetes mellitus, dyslipidemia), life style factors (smoking, obesity), and age.In conclusion, systemic inflammation is associated with carotid rather than with generalized arteriosclerotic disease. The association between systemic inflammation and carotid arteriosclerosis is mediated by a reduction in vagal tone which indicates a major role of carotid arteriosclerosis-mediated autonomic dysfunction in the pathogenesis of systemic inflammation in arteriosclerotic disease.

Dysautonomia in prodromal α-synucleinopathy: peripheral versus central autonomic degeneration.

BACKGROUND AND PURPOSE: There is an urgent need for early predictive markers for the course of disease in prodromal α-synucleinopathies such as idiopathic rapid eye movement (REM) sleep behaviour disorder. Autonomic cardiac/vascular dysfunction is a prominent feature in advanced α-synucleinopathies, but its diagnostic value as an early neurodegenerative marker remains unclear. The latter may be complicated since synuclein-mediated neurodegeneration may involve central and peripheral components of the autonomic nervous system. METHODS: The diagnostic value of autonomic symptoms and central and peripheral autonomic markers of blood pressure and heart rate regulation were prospectively evaluated in 20 subjects with idiopathic REM sleep behaviour disorder and 20 age-matched healthy controls. RESULTS: Although subjects with REM sleep behaviour disorder showed no clinical autonomic symptoms, blood pressure (P ≤ 0.035) and heart rate response (P ≤ 0.065) were slightly diminished during orthostatic challenge. Autonomic dysregulation was distinctively reflected in lower resting heart rate (all components, P ≤ 0.05) and blood pressure variability (low frequency component, P ≤ 0.024) indicating peripheral cardiac/vascular denervation. In contrast, baroreflex sensitivity and central cardiac autonomic outflow (sympathovagal balance) were well preserved indicating intact central autonomic regulation. Heart rate variability [very low frequency component, receiver operating characteristic (ROC) area under the curve (AUC) 0.80, P ≤ 0.001] and blood pressure variability (low frequency component ROC AUC 0.73, P ≤ 0.01) but not baroreflex sensitivity and sympathovagal balance showed an excellent diagnostic accuracy in identifying subjects with REM sleep behaviour disorder and healthy controls. CONCLUSIONS: Cardiac/vascular dysfunction in prodromal α-synucleinopathy arises from peripheral rather than from central autonomic degeneration. Autonomic indices encoded in heart rate and blood pressure variability are precise functional markers of early synuclein-mediated neurodegeneration.

To you I am listening: perceived competence of advisors influences judgment and decision-making via recruitment of the amygdala.

Considering advice from others is a pervasive element of human social life. We used the judge-advisor paradigm to investigate the neural correlates of advice evaluation and advice integration by means of functional magnetic resonance imaging. Our results demonstrate that evaluating advice recruits the "mentalizing network," brain regions activated when people think about others' mental states. Important activation differences exist, however, depending upon the perceived competence of the advisor. Consistently, additional analyses demonstrate that integrating others' advice, i.e., how much participants actually adjust their initial estimate, correlates with neural activity in the centromedial amygdala in the case of a competent and with activity in visual cortex in the case of an incompetent advisor. Taken together, our findings, therefore, demonstrate that advice evaluation and integration rely on dissociable neural mechanisms and that significant differences exist depending upon the advisor's reputation, which suggests different modes of processing advice depending upon the perceived competence of the advisor.

The visual field in advanced glaucoma.

For analysis of the morphology of the visual field in advanced glaucoma, we tested 62 eyes of 54 late stage glaucoma patients using program 10-2 on the Humphrey Field Analyzer. The fields, which were already reduced to a small central isle, had mostly typical, asymmetric borders with their largest extend to the temporal lower quadrant and their smallest extend to the upper nasal quadrant. An upper nasal step was very frequent. The boundaries are equivalent to the retinal nerve fiber lines. Actually, the glaucomatous isle is a 'centro-coecal isle', representing a remnant of intact maculo-papillary nerve fiber bundles. A test with a 2 degrees spacing like the Humphrey program 10-2 proved to be useful for routine perimetry in these cases.

Pharyngeal swallowing in patients with paresis of the recurrent nerve.

Pharyngolaryngeal function during swallowing was investigated cineradiographically in 22 patients with paresis of the recurrent nerve. Nineteen of these patients (86%) had defective closure of the laryngeal vestibule: 10 patients had defective apposition of the corniculate cartilages, (paresis of the oblique cricoarytenoid muscle), 9 patients had defective apposition of the arytenoid cartilages, (paresis of the interarytenoid muscle), 13 patients had defective movement of the epiglottis (paresis of, i.a. the thyrohyoid muscle), 1 patient had defective closure of the subepiglottic portion of the vestibule (paresis of the thyroepiglottic muscle), 2 patients had defective closure of the supraglottic portion of the vestibule (paresis of the superior ventricular segment of the thyroarytenoid muscle). Five patients with immobility of the epiglottis also had paresis of the pharyngeal constrictor musculature indicating paresis of the superior laryngeal nerve. Our investigation has shown that patients with paresis of the recurrent nerve who present with dysphagia with or without aspiration should be examined cineradiographically for pharyngolaryngeal function during swallowing.