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1.
BMC Infect Dis ; 24(1): 899, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39223565

RESUMO

BACKGROUND: The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains resistant to non-beta-lactam antimicrobials poses a significant challenge in treating severe MRSA bloodstream infections. This study explores resistance development and mechanisms in MRSA isolates, especially after the first dalbavancin-resistant MRSA strain in our hospital in 2016. METHODS: This study investigated 55 MRSA bloodstream isolates (02/2015-02/2021) from the University Hospital of the Medical University of Vienna, Austria. The MICs of dalbavancin, linezolid, and daptomycin were assessed. Two isolates (16-33 and 19-362) resistant to dalbavancin were analyzed via whole-genome sequencing, with morphology evaluated using transmission electron microscopy (TEM). RESULTS: S.aureus BSI strain 19-362 had two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene. Isolate 16-33 had a 534 bp deletion in the DHH domain of GdpP and a SNV in pbp2 (p.G146R). Both strains had mutations in the rpoB gene, but at different positions. TEM revealed significantly thicker cell walls in 16-33 (p < 0.05) compared to 19-362 and dalbavancin-susceptible strains. None of the MRSA isolates showed resistance to linezolid or daptomycin. CONCLUSION: In light of increasing vancomycin resistance reports, continuous surveillance is essential to comprehend the molecular mechanisms of resistance in alternative MRSA treatment options. In this work, two novel missense mutations (p.I515M and p.A606D) in the pbp2 gene were newly identified as possible causes of dalbavancin resistance.


Assuntos
Antibacterianos , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Infecções Estafilocócicas , Teicoplanina , Sequenciamento Completo do Genoma , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Áustria/epidemiologia , Antibacterianos/farmacologia , Teicoplanina/farmacologia , Teicoplanina/análogos & derivados , Infecções Estafilocócicas/microbiologia , Daptomicina/farmacologia , Mutação , Linezolida/farmacologia , Masculino , Mutação de Sentido Incorreto , Feminino
2.
Emerg Microbes Infect ; 13(1): 2292077, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38055244

RESUMO

Invasive Staphylococcus aureus infections are associated with a high burden of disease, case fatality rate and healthcare costs. Oxazolidinones such as linezolid and tedizolid are considered potential treatment choices for conditions involving methicillin resistance or penicillin allergies. Additionally, they are being investigated as potential inhibitors of toxins in toxin-mediated diseases. In this study, linezolid and tedizolid were evaluated in an in vitro resistance development model for induction of resistance in S. aureus. Whole genome sequencing was conducted to elucidate resistance mechanisms through the identification of causal mutations. After inducing resistance to both linezolid and tedizolid, several partially novel single nucleotide variants (SNVs) were detected in the rplC gene, which encodes the 50S ribosome protein L3 in S. aureus. These SNVs were found to decrease the binding affinity, potentially serving as the underlying cause for oxazolidinone resistance. Furthermore, in opposite to linezolid we were able to induce phenotypically small colony variants of S. aureus after induction of resistance with tedizolid for the first time in literature. In summary, even if different antibiotic concentrations were required and SNVs were detected, the principal capacity of S. aureus to develop resistance to oxazolidinones seems to differ between linezolid and tedizolid in-vivo but not in vitro. Stepwise induction of resistance seems to be a time and cost-effective tool for assessing resistance evolution. Inducted-resistant strains should be examined and documented for epidemiological reasons, if MICs start to rise or oxazolidinone-resistant S. aureus outbreaks become more frequent.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Oxazolidinonas , Infecções Estafilocócicas , Humanos , Linezolida/farmacologia , Staphylococcus aureus , Oxazolidinonas/farmacologia , Antibacterianos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Testes de Sensibilidade Microbiana
3.
Front Neurol ; 15: 1419134, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39291099

RESUMO

Purpose: The COVID-19 pandemic has led to millions of confirmed cases worldwide, resulting in numerous deaths and hospitalizations. Long-term symptoms after infection or vaccination, known as Post-acute COVID-19 Syndrome (PACS) or Post-acute COVID-19 Vaccination Syndrome (PACVS), present a challenge for the healthcare system. Among the various neurological symptoms, cognitive impairments are frequently observed in PACS/PACVS patients. This study aimed to understand cognitive deficits in PACS/PACVS patients and evaluated potential treatment options, including phosphatidylcholine and computer-assisted cognitive training (CCT). Methods: The Neuro-COVID Outpatient Clinic at Evangelic Hospital Vienna evaluated n = 29 PACS/PACVS patients from May 2023 to October 2023. Enrolled patients were divided into three therapy schemes: Group A received phosphatidylcholine, B received phosphatidylcholine plus access to a computer-assisted cognitive training program, and C (divided into two subgroups) served as a control group. Cognitive impairments were evaluated in multiple assessments (initial and during therapy) using the COGBAT test. Simultaneously, an assessment of the quality of life was conducted using the WHOQOL-BREF. Results: Primary cognitive impairments, especially attentional deficits were notably evident compared to the general population. While all treatment groups showed cognitive improvement (significant or with a positive trend, but without reaching the level of statistical significance) after therapy, no significant interaction was found between assessment time points and treatment schemes for overall cognitive performance, attention, memory, and executive functions, suggesting consistency across the groups. The WHOQOL-BREF primarily demonstrated deficits in the domains of physical health and psychological well-being. Conclusion: This study examined the impact of PACS/PACVS on cognitive performance and evaluated phosphatidylcholine and CCT as potential treatment options. Patients with PACS/PACVS showed notable cognitive deficits, especially in the domain attention. While the effectiveness of phosphatidylcholine and CCT in treating cognitive deficits was inconclusive, the study indicated the possibility of spontaneous remission of cognitive deficits in PACS/PACVS.

4.
Pathogens ; 11(2)2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35215182

RESUMO

Human alveolar echinococcosis (AE), which is caused by the cestode Echinococcus (E.) multilocularis, is an epidemiologically relevant issue in modern medicine and still poses a diagnostic and therapeutic challenge. Since diagnosis mainly relies on imaging procedures and serological testing, we retrospectively and comparatively analyzed the performance of an Echinococcus IgG screening ELISA, whole serum IgE, and two specific confirmatory ELISA platforms using the defined E. multilocularis antigens Em2-Em18 (Em2+) and recombinant Em18 (recEm18). With special emphasis on the clinical usefulness of recEm18, we correlated the laboratory results with clinical characteristics and imaging findings in a large and well-characterized cohort of N = 124 AE patients, who were followed over several years after either surgical plus subsequent pharmacological treatment or pharmacotherapy alone. All patients had routinely received PET-CTI every two years. Our data reveal strong correlations for both Echinococcus IgG and recEm18 with tracer uptake in PET-CTI and parasitic lesion size and number, suggesting additional clinical usefulness of recEm18 for certain constellations only, while IgG and Em2+ still appear reasonable and sensitive screening methods for initial diagnosis of AE. With this study, we aim to contribute to further optimizing medical care of AE patients. For instance, it might be reasonable to consider the replacement of some PET-CTI follow-ups by imaging procedures with less radiation exposure or serological means alone. Further studies that clarify the correlation of serological markers with ultrasound criteria might be particularly useful, and further retrospective as well as prospective investigations are justified in this context.

5.
Pathogens ; 11(2)2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35215203

RESUMO

Echinococcosis is a neglected zoonotic disease and a worldwide public health problem caused by infection with the larval stages of taeniid cestodes of the genus Echinococcus. In vitro studies have demonstrated a protoscolecidal effect of eosinophilic cationic protein (ECP), a granule protein of eosinophilic granulocytes, against E. granulosus. Therefore, the main objective of this study was to evaluate ECP as a biomarker in the treatment of alveolar echinococcosis (AE) and cystic echinococcosis (CE). Data were collected retrospectively from the Vienna Echinococcosis Cohort over 7 years until December 2020. Altogether, 32 patients (16 AE and 16 CE) were included. In the selected patients, serum ECP values were compared before and after the beginning of an operative and/or benzimidazole (BMZ) therapy. Mean ECP serum levels before intervention were significantly (p < 0.05) elevated at 34.0 ± 22.9 µg/L in AE patients and at 38.6 ± 19.9 µg/L in CE patients compared to the control group. After the intervention, mean ECP levels decreased significantly (p < 0.05) to 20.4 ± 14.6 µg/L in AE patients and to 22.4 ± 8.3 µg/L in CE patients. Furthermore, ECP showed a significant (p < 0.05) correlation of k = 0.56 with PET-CTI. Based on the significant decrease after operative and/or BMZ treatment and the correlation with clinical markers such as PET-CTI, it is recommended to investigate ECP more intensively as a marker of AE and CE in prospective studies with larger cohorts.

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