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  • 1
    Online Resource
    Online Resource
    Frequent Emergence of Resistance Mutations Following Complex Intra-Host Genomic Dynamics in SARS-CoV-2 Patients Receiving Sotrovimab
    American Society for Microbiology ; 2023
    In:  Antimicrobial Agents and Chemotherapy Vol. 67, No. 7 ( 2023-07-18)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 67, No. 7 ( 2023-07-18)
    Abstract: The emergence of the Omicron variant of SARS-CoV-2 represented a challenge to the treatment of COVID-19 using monoclonal antibodies. Only Sotrovimab maintained partial activity, allowing it to be used in high-risk patients infected with the Omicron variant. However, reports of resistance mutations to Sotrovimab demand efforts to better understand the intra-patient emergence of Sotrovimab resistance. A retrospective genomic analysis was conducted on respiratory samples from immunocompromised patients infected with SARS-CoV-2 who received Sotrovimab at our hospital between December 2021 and August 2022. The study involved 95 sequential specimens from 22 patients (1 to 12 samples/patient; 3 to 107 days post-infusion; threshold cycle [ C T ] ≤ 32). Resistance mutations (in P337, E340, K356, and R346) were detected in 68% of cases; the shortest time to detection of a resistance mutation was 5 days after Sotrovimab infusion. The dynamics of resistance acquisition were highly complex, with up to 11 distinct amino acid changes in specimens from the same patient. In two patients, the mutation distribution was compartmentalized in respiratory samples from different sources. This is the first study to examine the acquisition of Sotrovimab resistance in the BA.5 lineage, enabling us to determine the lack of genomic or clinical differences between Sotrovimab resistance in BA.5 relative to that in BA.1/2. Across all Omicron lineages, the acquisition of resistance delayed SARS-CoV-2 clearance (40.67 versus 19.5 days). Close, real-time genomic surveillance of patients receiving Sotrovimab should be mandatory to facilitate early therapeutic interventions.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.00266-23
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Alternative molecular and genomic strategies to provide a rapid response to alerts concerning the introduction of new emerging SARS-CoV-2 variants: the Omicron alert
    American Society for Microbiology ; 2023
    In:  Microbiology Spectrum
    Details
    In: Microbiology Spectrum, American Society for Microbiology
    Abstract: The study presents different experimental alternatives to identify new variants of concern (VOCs) of SARS-CoV-2 entering a certain population. Early detection of a new VOC is crucial for surveillance and control of spread. The objective is to provide laboratories with tools adapted to their resource capabilities that offer a sufficient level of resolution to rule out, confirm, or pre-assign the presence of a suspected VOC. The study describes four different techniques that were applied simultaneously to the first suspected Omicron case in Spain, highlighting the level of resolution and response time achieved in each case. These techniques are based on the detection of mutations in the S-gene of the virus that can easily adapt to potential emerging variants. The results of the study allow any laboratory to prepare for new alerts of SARS-CoV-2 VOCs.
    Type of Medium: Online Resource
    ISSN: 2165-0497
    URL: Article
    DOI: 10.1128/spectrum.01075-23
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2023
    detail.hit.zdb_id: 2807133-5
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  • 3
    Online Resource
    Online Resource
    The ac53 , ac78 , ac101 , and ac103 Genes Are Newly Discovered Core Genes in the Family Baculoviridae
    American Society for Microbiology ; 2012
    In:  Journal of Virology Vol. 86, No. 22 ( 2012-11-15), p. 12069-12079
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 86, No. 22 ( 2012-11-15), p. 12069-12079
    Abstract: The family Baculoviridae is a large group of insect viruses containing circular double-stranded DNA genomes of 80 to 180 kbp, which have broad biotechnological applications. A key feature to understand and manipulate them is the recognition of orthology. However, the differences in gene contents and evolutionary distances among the known members of this family make it difficult to assign sequence orthology. In this study, the genome sequences of 58 baculoviruses were analyzed, with the aim to detect previously undescribed core genes because of their remote homology. A routine based on Multi PSI-Blast/tBlastN and Multi HaMStR allowed us to detect 31 of 33 accepted core genes and 4 orthologous sequences in the Baculoviridae which were not described previously. Our results show that the ac53 , ac78 , ac101 ( p40 ), and ac103 ( p48 ) genes have orthologs in all genomes and should be considered core genes. Accordingly, there are 37 orthologous genes in the family Baculoviridae .
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.01873-12
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2012
    detail.hit.zdb_id: 1495529-5
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  • 4
    Online Resource
    Online Resource
    Feasibility of Flow Cytometry for Measurements of Plasmodium falciparum Parasite Burden in Studies in Areas of Malaria Endemicity by Use of Bidimensional Assessment of YOYO-1 and Autofluorescence
    American Society for Microbiology ; 2011
    In:  Journal of Clinical Microbiology Vol. 49, No. 3 ( 2011-03), p. 968-974
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 49, No. 3 ( 2011-03), p. 968-974
    Abstract: The detection and quantification of Plasmodium falciparum in studies of malaria endemicity primarily relies upon microscopy. High-throughput quantitative methods with less subjectivity and greater reliability are needed for investigational studies. The staining of parasitized erythrocytes with YOYO-1 for flow cytometry bears great potential as a tool for assessing malaria parasite burden. Capillary blood was collected from children presenting to the pediatric ward of the Manhiça District Hospital in Mozambique for parasitemia assessment by thick and thin blood films, flow cytometry (YOYO-1 530/585 ), and quantitative real-time PCR (qRT-PCR). Whole blood was fixed and stained with YOYO-1 for acquisition on a cytometer to assess the frequency of infected erythrocyte events. qRT-PCR was used as the gold standard for the detection of P. falciparum . The YOYO-1 530/585 method was as sensitive and specific as conventional microscopy (area under the receiver operating characteristic, 0.9 for both methods). The interrater mean difference for YOYO-1 530/585 was near zero. Parasite density using flow cytometry and complete blood counts returned density estimates with a mean difference 2.2 times greater than results by microscopy (confidence interval, 1.46 to 3.60) but with limits of agreement between 10 times lower and 50 times higher than those of microscopy. The YOYO-1 530/585 staining pattern was established exactly as demonstrated in animal models, but the assay was limited by the lack of appropriate negative-control samples for establishing background levels and the definition of positives in areas in which malaria is endemic. YOYO-1 530/585 is a high-throughput tool with great potential if the limitations of negative controls and heterogeneous levels of background signal can be overcome.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.01961-10
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    A Retrospective Controlled Cohort Study of the Impact of Glucocorticoid Treatment in SARS-CoV-2 Infection Mortality
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 9 ( 2020-08-20)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 9 ( 2020-08-20)
    Abstract: Evidence to support the use of steroids in coronavirus disease 2019 (COVID-19) pneumonia is lacking. We aim to determine the impact of steroid use for COVID-19 pneumonia on hospital mortality. We performed a single-center retrospective cohort study in a university hospital in Madrid, Spain, during March of 2020. To determine the role of steroids in in-hospital mortality, patients admitted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia and treated with steroids were compared to patients not treated with steroids, and we adjusted with a propensity score for patients on steroid treatment. Survival times were compared using the log rank test. Different steroid regimens were compared and adjusted with a second propensity score. During the study period, 463 out of 848 hospitalized patients with COVID-19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. The median time to steroid treatment from symptom onset was 10 days (interquartile range [IQR], 8 to 13 days). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67]; hazard ratio [HR] , 0.51 [95% confidence interval, 0.27 to 0.96]; P = 0.044). Steroid treatment reduced mortality by 41.8% relative to the mortality with no steroid treatment (relative risk reduction, 0.42 [95% confidence interval, 0.048 to 0.65]). Initial treatment with 1 mg/kg of body weight/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86]; odds ratio [OR] , 0.880 [95% confidence interval, 0.449 to 1.726]; P  = 0.710). Our results show that the survival of patients with SARS-CoV-2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. Rates of in-hospital mortality were not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01168-20
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 6
    Online Resource
    Online Resource
    Proficiency of Clinical Laboratories in Spain in Detecting Vancomycin-Resistant Enterococcus spp
    American Society for Microbiology ; 1999
    In:  Journal of Clinical Microbiology Vol. 37, No. 7 ( 1999-07), p. 2148-2152
    Details
    In: Journal of Clinical Microbiology, American Society for Microbiology, Vol. 37, No. 7 ( 1999-07), p. 2148-2152
    Abstract: Studies in a variety of U.S. clinical laboratories have demonstrated difficulty in detecting intermediate and low-level vancomycin-resistant enterococci (VRE). The misclassification of “at least intermediate resistant isolates” as vancomycin susceptible may have both clinical implications and a negative impact on measures to control the spread of VRE. No published study has assessed the ability of clinical laboratories in Europe to detect VRE. So, the apparent low prevalence of VRE in European hospitals may be, in part, secondary to the inability of these laboratories to detect all VRE. In an effort to assess European laboratories’ proficiency in detecting VRE, we identified 22 laboratories in Spain and asked them to test four VRE strains and one susceptible enterococcal strain from the Centers for Disease Control and Prevention collection. Each organism was tested by the routine antimicrobial susceptibility testing method used by each laboratory. Overall, VRE were correctly identified in 61 of 88 (69.1%) instances. The accuracy of VRE detection varied with the level of resistance and the antimicrobial susceptibility method. The high-level-resistant strain ( Enterococcus faecium ; MIC, 512 μg/ml) was accurately detected in 20 of 22 (91.3%) instances, whereas the intermediate-resistant isolate ( Enterococcus gallinarum ; MIC, 8 μg/ml) was accurately detected in only 11 of 22 (50%) instances. Classification errors occurred in 27 of 88 (30.9%) instances. Misclassification as vancomycin susceptible was the most common error (16 of 27 [59.3%] instances). Our study shows that the participating Spanish laboratories had an overall acceptable proficiency in detecting VRE but that a substantial proportion of VRE isolates with low or intermediate levels of resistance were not detected. We recommend that studies be conducted to validate laboratory proficiency testing as an important step in the prevention and control of the spread of antimicrobial resistance.
    Type of Medium: Online Resource
    ISSN: 0095-1137 , 1098-660X
    URL: Article
    DOI: 10.1128/JCM.37.7.2148-2152.1999
    RVK:
    XA 10000
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1999
    detail.hit.zdb_id: 1498353-9
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Association between Vancomycin Pharmacokinetic Parameters and Clinical and Microbiological Efficacy in a Cohort of Neonatal Patients
    American Society for Microbiology ; 2022
    In:  Antimicrobial Agents and Chemotherapy Vol. 66, No. 11 ( 2022-11-15)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 11 ( 2022-11-15)
    Abstract: Vancomycin pharmacokinetic/pharmacodynamic (PK/PD) targets have not been validated in the neonatal population as no specifically designed studies are available. The main goal of this study was to analyze the therapeutic vancomycin regimen, the 24-h area under the curve (AUC 24 ), and the trough plasma concentration ( C t ) obtained that achieved clinical and microbiological effectiveness in a cohort of neonates. This was an observational, prospective, single-center study covering a period of 2 years. Eligible patients were neonates and young infants who were undergoing treatment with intravenous vancomycin for ≥72 h with ≥1 C t available. The primary outcome was the association of C t and AUC 24 with clinical and microbiological efficacy at the beginning (early clinical evolution [ECE]) and the end (late clinical evolution [LCE] ) of treatment with vancomycin. A total of 43 patients were included, 88.4% of whom were cured. In ECE, the cutoff points of the receiver operating characteristic (ROC) curve were 238 mg · h/L (sensitivity of 61% and specificity of 88%) for AUC 24 and 6.8 μg/mL (sensitivity of 61% and specificity of 92%) for C t . In LCE, the C t value was 11 μg/mL, with a sensitivity of 80% and a specificity of 92%. In this analysis, AUC 24 was not considered a good predictor. Logistic regression showed that a vancomycin C t of ≤6.8 μg/mL was associated with an unfavorable ECE ( P  = 0.001), being 18 times more likely to progress poorly compared to those with higher levels. AUC 24 and C t are good predictors of ECE in this population. Concentrations close to 7 μg/mL and an AUC 24 of around 240 mg · h/L 48 h after antibiotic initiation seem to be sufficient to achieve clinical cure in most cases.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.01109-22
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 8
    Online Resource
    Online Resource
    Early Use of Sarilumab in Patients Hospitalized with COVID-19 Pneumonia and Features of Systemic Inflammation: the SARICOR Randomized Clinical Trial
    American Society for Microbiology ; 2022
    In:  Antimicrobial Agents and Chemotherapy Vol. 66, No. 2 ( 2022-02-15)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 66, No. 2 ( 2022-02-15)
    Abstract: The objective of this study was to investigate the efficacy and safety of early treatment with sarilumab, added to standard of care (SOC), in hospitalized adults with COVID-19. Methods included phase II, open-label, randomized, controlled clinical trial of hospitalized patients with COVID-19 pneumonia and interleukin (IL)-6 levels ≥ 40 pg/mL and/or d-dimer  〉  1,500 ng/mL. Participants were randomized (1:1:1) to receive SOC (control group), SOC plus a single subcutaneous dose of sarilumab 200 mg (sarilumab-200 group), or SOC plus a single subcutaneous dose of sarilumab 400 mg (sarilumab-400 group). The primary outcome variable was the development of acute respiratory distress syndrome (ARDS) requiring high-flow nasal oxygenation (HFNO), non-invasive mechanical ventilation (NIMV) or invasive mechanical ventilation (IMV) at day 28. One-hundred and 15 participants (control group, n  = 39; sarilumab-200, n  = 37; sarilumab-400, n  = 39) were included. At randomization, 104 (90%) patients had supplemental oxygen and 103 (90%) received corticosteroids. Eleven (28%) patients in the control group, 10 (27%) in sarilumab-200, and five (13%) in sarilumab-400 developed the primary outcome (hazard ratio [95% CI] of sarilumab-400 vs control group: 0.41 [0.14, 1.18]; P  = 0.09). Seven (6%) patients died: three in the control group and four in sarilumab-200. There were no deaths in sarilumab-400 ( P  = 0.079, log-rank test for comparisons with the control group). In patients recently hospitalized with COVID-19 pneumonia and features of systemic inflammation, early IL-6 blockade with a single dose of sarilumab 400 mg was safe and associated with a trend for better outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT04357860.)
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/aac.02107-21
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2022
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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