Exploring the Toxin-Mediated Mechanisms in Clostridioides difficile Infection.

Clostridioides difficile infection (CDI) is the leading cause of nosocomial antibiotic-associated diarrhea, and colitis, with increasing incidence and healthcare costs. Its pathogenesis is primarily driven by toxins produced by the bacterium C. difficile, Toxin A (TcdA) and Toxin B (TcdB). Certain strains produce an additional toxin, the C. difficile transferase (CDT), which further enhances the virulence and pathogenicity of C. difficile. These toxins disrupt colonic epithelial barrier integrity, and induce inflammation and cellular damage, leading to CDI symptoms. Significant progress has been made in the past decade in elucidating the molecular mechanisms of TcdA, TcdB, and CDT, which provide insights into the management of CDI and the future development of novel treatment strategies based on anti-toxin therapies. While antibiotics are common treatments, high recurrence rates necessitate alternative therapies. Bezlotoxumab, targeting TcdB, is the only available anti-toxin, yet limitations persist, prompting ongoing research. This review highlights the current knowledge of the structure and mechanism of action of C. difficile toxins and their role in disease. By comprehensively describing the toxin-mediated mechanisms, this review provides insights for the future development of novel treatment strategies and the management of CDI.

Evaluation of the "AMR Direct Flow Chip Kit" DNA microarray for detecting antimicrobial resistance genes directly from rectal and nasopharyngeal clinical samples upon ICU admission.

INTRODUCTION: Prompt detection of antibiotic resistance genes in healthcare institutions is of utmost importance in tackling the spread of multi-drug resistant micro-organisms. We evaluated the Antimicrobial Resistance (AMR) Direct Flow Chip Kit versus phenotypic screening assays for rectal and nasopharyngeal specimens upon ICU admission. METHODS: A total of 184 dual specimens (92 rectal and 92 nasopharyngeal swabs) from 92 patients were collected from 11/2017 to 8/2018. All swabs were subjected to both AMR and phenotypic tests according to their origin. The degree of agreement of the two methods was assessed by the kappa coefficient. RESULTS: The kappa coefficient showed perfect agreement for MRSA, ESBLs, oxacillinases and vancomycin resistance genes (1.000, p<0.01) and very good agreement for mecA-positive CoNS, KPC-carbapenemases and metallo-beta-lactamases (0.870, p<0.01; 0.864, p<0.01; and 0.912, p<0.01, respectively). CONCLUSION: The AMR Direct Flow Chip Kit is a useful alternative to phenotypic testing for rapid detection of resistance markers.

First detection of Rickettsia slovaca in Greece.

Seven hundred and three ticks collected in November and June of 2004-2006 from domestic animals in four localities of Halkidiki prefecture, Northern Greece, were tested for the presence of ricketsial DNA. Rickettsia slovaca was detected in one pool of Rhipicephalus bursa ticks, representing the first report of detection of R. slovaca in Greece.

Aortic elastic properties are related to left ventricular diastolic function in patients with type 1 diabetes mellitus.

OBJECTIVE: The aim of the study was to evaluate left ventricular diastolic function and its relation to aortic wall stiffness in patients with type 1 diabetes mellitus without coronary artery disease or hypertension. PATIENTS: Sixty-six patients with type 1 diabetes mellitus were examined by echocardiography and divided into two groups according to the diastolic filling pattern determined by mitral annulus tissue Doppler velocities. Group A patients (n = 21) presented diastolic dysfunction with a peak early diastolic mitral annular velocity (Em)/peak late diastolic mitral annular velocity (Am) ratio <1 whereas in group B patients (n = 45) the Em/Am ratio was >1. Coronary artery disease was excluded based on normal thallium scintigraphy. Aortic stiffness index was calculated from aortic diameters measured by echocardiography, using accepted criteria. RESULTS: Aortic stiffness index differed significantly among the two groups. Significant correlations were found between parameters of left ventricular diastolic function (Em/Am, isovolumic relaxation time, deceleration time) and aortic stiffness index. Multiple stepwise linear regression analysis revealed aortic stiffness index (beta = -0.39, p = 0.001) and isovolumic relaxation time (beta = -0.46, p < 0.001) as the main predictors of Em/Am ratio. CONCLUSIONS: Aortic stiffness is increased in type 1 diabetic patients with left ventricular diastolic dysfunction. This impairment in aortic elastic properties seems to be related to parameters of diastolic function.

Hospital outbreak due to a Klebsiella pneumoniae ST147 clonal strain co-producing KPC-2 and VIM-1 carbapenemases in a tertiary teaching hospital in Northern Greece.

Here we present the characteristics of a large outbreak caused by a clonal Klebsiella pneumoniae strain producing both KPC-2 and VIM-1 carbapenemases in a tertiary teaching hospital. Between January 2013 and January 2015, 45 carbapenem-resistant K. pneumoniae isolates that gave a positive modified Hodge test and were phenotypically suspected of metallo-ß-lactamase (MBL) and K. pneumoniae carbapenemase (KPC) co-production were recovered from 25 patients hospitalised in AHEPA University Hospital (Thessaloniki, Greece). All of the patients were hospitalised in the three intensive care units of the hospital and 17 (68%) of them developed bloodstream infections; the overall mortality of the patients involved in the outbreak was 48% (12/25). Molecular testing verified that all 45 K. pneumoniae isolates co-harboured blaKPC-2 and blaVIM-1 genes and were associated with OmpK35 deficiency and OmpK36 porin loss. The blaTEM-1 gene was also present in 18 isolates. Pulsed-field gel electrophoresis (PFGE) clustered all of the isolates into a single clonal type, and multilocus sequence typing (MLST) assigned them to the emerging high-risk ST147 clonal lineage. Following recognition of the outbreak, infection control measures were implemented in the affected areas. The outbreak continued for ca. 2 years and since then only sporadic cases of K. pneumoniae harbouring both carbapenemases have been detected.

Evaluation of the “AMR Direct Flow Chip Kit” DNA microarray for detecting antimicrobial resistance genes directly from rectal and nasopharyngeal clinical samples upon ICU admission / Evaluación de la micromatriz de ADN «AMR Direct Flow Chip Kit» para la detección de genes de resistencia antimicrobiana directamente de muestras clínicas rectales y nasofaríngeas en el momento del ingreso en la UCI

Introduction: Prompt detection of antibiotic resistance genes in healthcare institutions is of utmost importance in tackling the spread of multi-drug resistant micro-organisms. We evaluated the Antimicrobial Resistance (AMR) Direct Flow Chip Kit versus phenotypic screening assays for rectal and nasopharyngeal specimens upon ICU admission. Methods: A total of 184 dual specimens (92 rectal and 92 nasopharyngeal swabs) from 92 patients were collected from 11/2017 to 8/2018. All swabs were subjected to both AMR and phenotypic tests according to their origin. The degree of agreement of the two methods was assessed by the kappa coefficient. Results: The kappa coefficient showed perfect agreement for MRSA, ESBLs, oxacillinases and vancomycin resistance genes (1.000, p<0.01) and very good agreement for mecA-positive CoNS, KPC-carbapenemases and metallo-beta-lactamases (0.870, p<0.01; 0.864, p<0.01; and 0.912, p<0.01, respectively). Conclusion: The AMR Direct Flow Chip Kit is a useful alternative to phenotypic testing for rapid detection of resistance markers.(AU)

Introducción: La detección rápida de genes de resistencia a antibióticos en instituciones de salud es de importancia extrema para abordar la propagación de microorganismos multi-resistentes. Evaluamos el Antimicrobial Resistance Direct Flow Chip (AMR) versus los ensayos de detección fenotípica para muestras rectales y nasofaríngeas al ingreso en la UCI. Métodos: Se recogieron 184 muestras duales (92 rectales y 92 nasofaríngeos) de 92 pacientes durante 11/2017-8/2018. Todos los hisopos se sometieron a pruebas de AMR y fenotípicas según su fuente. El grado de acuerdo de los 2 métodos fue evaluado por el coeficiente kappa. Resultados: El coeficiente kappa mostró una concordancia perfecta para MRSA, ESBL, oxacilinasas y para genes de resistencia a vancomicina (1.000, p<0,01) y muy buena concordancia para CoNS mecA positivos, carbapenemasas KPC y metalo-beta-lactamasas (0,870, p<0,01; 0,864, p<0,01 y 0,912, p<0,01, respectivamente). Conclusión: El AMR es una alternativa útil a las pruebas fenotípicas para la detección rápida de marcadores de resistencia.(AU)