Unraveling novel mutation patterns and morphological variations in two dalbavancin-resistant MRSA strains in Austria using whole genome sequencing and transmission electron microscopy.

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.

A Multivariant Surrogate Virus Neutralization Test Demonstrates Distinct SARS-CoV-2-Specific Antibody Responses in People Living with HIV after a Fourth Monovalent mRNA Vaccination or an Omicron Breakthrough Infection.

While neutralizing antibodies (nAbs) induced by monovalent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations are primarily directed against the wildtype (WT), subsequent exposure to the Omicron variants may increase the breadth of the antibodies' cross-neutralizing activity. Here, we analyzed the impact of an Omicron breakthrough infection (BTI) or a fourth monovalent mRNA vaccination on nAb profiles in people living with human immunodeficiency virus (PLWH). Using a multivariant surrogate virus neutralization test (sVNT), we quantified nAbs in 36 three-times vaccinated PLWH, of whom 9 acquired a serologically confirmed Omicron BTI, 8 received a fourth vaccine dose, and 19 were neither infected nor additionally vaccinated. While nAbs against WT and Delta increased after the BTI and a fourth vaccination, a significant increase against BA.1, BA.2, and BA.5 was only observed after the BTI. However, there was no significant difference in nAb concentrations between the samples obtained after the BTI and fourth vaccination. In contrast, nAb levels were significantly lower in PLWH, who were neither infected nor additionally vaccinated after three vaccinations. Thus, our study demonstrates the suitability of a multivariant sVNT to assess hybrid humoral immunity after Omicron BTIs in PLWH vaccinated against SARS-CoV-2.

Is there a clinical difference between influenza A and B virus infections in hospitalized patients? : Results after routine polymerase chain reaction point-of-care testing in the emergency room from 2017/2018.

PURPOSE: The clinical presentation, complications and mortality in molecularly confirmed influenza A and B infections were analyzed. METHODS: This retrospective observational single-centre study included all influenza positive patients older than 18 years who were hospitalized and treated at the flu isolation ward during 2017/2018. The diagnosis was based on point-of-care tests with the AlereTM. RESULTS: Of the 396 patients tested positive for influenza, 24.2% had influenza A and 75.8% influenza B. Influenza A patients were younger (median age 67.5 years vs. 77 years, p < 0.001), were more often smokers (27.7% vs. 16.8%, p = 0.021), had chronic pulmonary diseases more frequently (39.6% vs. 26.3%, p = 0.013), presented with a higher body temperature (38.6 °C vs. 38.3 °C, p = 0.004), leucocyte count (8 G/L vs. 6.8 G/L, p = 0.002), C­reactive protein (CRP) level (41 mg/l vs. 23 mg/l, p < 0.001) and had dyspnea more often (41.7% vs. 28%, p = 0.012). Influenza B patients had an underlying chronic kidney disease in 37% vs. 18.8% (p < 0.001) and presented with vomiting on admission more frequently (21.7% vs. 11.5%, p = 0.027). Influenza A patients were admitted for 8 days vs. 7 days (p = 0.023). There were no differences in the rate of complications; however, 22 (5.6%) patients died during the hospital stay. The in-hospital mortality was higher in influenza A patients (8.3% vs 4.7%, p = 0.172). CONCLUSION: Some differences were found between influenza A and B virus infections but symptoms were overlapping, which necessitates polymerase chain reaction point-of-care testing for accurate diagnosis. Influenza A was a more severe disease than influenza B during the period 2017/2018.