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  • American Society for Microbiology  (4)
  • 1
    Online Resource
    Online Resource
    In Vitro Induction of Human Immunodeficiency Virus Type 1 Variants Resistant to Phosphoralaninate Prodrugs of Z -Methylenecyclopropane Nucleoside Analogues
    American Society for Microbiology ; 1999
    In:  Antimicrobial Agents and Chemotherapy Vol. 43, No. 10 ( 1999-10), p. 2479-2483
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 43, No. 10 ( 1999-10), p. 2479-2483
    Abstract: Two methylenecyclopropane nucleoside analogues with a phenylphosphoralaninate moiety, QYL-685 and QYL-609, exert potent and specific activities against human immunodeficiency virus type 1 strain LAI (HIV-1 LAI ) and HIV-2 in vitro. In this study, we induced HIV-1 variants resistant to QYL-685 by exposing HIV-1 LAI to increasing concentrations of QYL-685. After 16 passages, the virus (HIV-1 P16 ) was less sensitive to QYL-685 (104-fold), QYL-609 ( 〉 41-fold), and (−)-β-2′,3′-dideoxy-3′-thiacytidine (3TC) ( 〉 1,100-fold) than was HIV-1 LAI and contained an M184I mutation. Two infectious clones, HIV-1 M184I and HIV-1 M184V , were resistant to QYL-685, QYL-609, and 3TC, confirming that the M184I mutation was responsible for the observed resistance. Viral-fitness analyses (competitive HIV-1 replication assays) revealed that in the absence of drugs, M184I and M184V conferred a replication disadvantage on the virus compared to the replication efficiency of the wild-type infectious clone (HIV-1 wt ). However, in the presence of QYL-685 (4 μM), HIV-1 M184I and HIV-1 M184V showed greater fitness than HIV-1 wt . These data may provide structural and virological relevance with regard to the emergence of M184I and M184V substitutions in HIV-1.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.43.10.2479
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1999
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    A Matched Case-Case-Control Study of the Impact of Clinical Outcomes and Risk Factors of Patients with IMP-Type Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae in Japan
    American Society for Microbiology ; 2021
    In:  Antimicrobial Agents and Chemotherapy Vol. 65, No. 3 ( 2021-02-17)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 65, No. 3 ( 2021-02-17)
    Abstract: IMP-type carbapenemase, found in various Gram-negative bacteria, has been increasingly detected worldwide. We aimed to study the outcomes and risk factors for acquisition of IMP-type carbapenemase-producing carbapenem-resistant Enterobacteriaceae (IMP-CRE), as this has not been evaluated in detail. We conducted a matched case-case-control study of patients from whom IMP-CRE isolates were obtained. All patients who tested positive for IMP-CRE were included; they were matched with patients with carbapenem-susceptible Enterobacteriaceae (CSE) and with controls at a ratio of 1:1:2. The risk factors for acquisition for the CRE and CSE groups and mortality rates, which were calculated using multivariate logistic regression models with weighting according to the inverse probability of propensity scores, were compared. In total, 192 patients (96 patients each in the CRE and CSE groups, with 130 Enterobacter cloacae isolates and 62 Klebsiella sp. isolates) were included. The IMP-11 type was present in 43 patients, IMP-1 in 33, and IMP-60 and IMP-66 in 1 each; 31 patients with CRE (32.3%) and 34 with CSE (35.4%) developed infections. Multivariate analysis identified the following independent risk factors: gastrostomy, history of intravenous therapy or hemodialysis, and previous exposure to broad-spectrum β-lactam antibiotics, including penicillin with β-lactamase inhibitors, cephalosporins, and carbapenems. In propensity score-adjusted analysis, mortality rates for the CRE and CSE groups were similar (15.0% and 19.5%, respectively). We found that IMP-CRE may not contribute to worsened clinical outcomes, compared to CSE, and gastrostomy, previous intravenous therapy, hemodialysis, and broad-spectrum antimicrobial exposure were identified as risk factors for CRE isolation. Fluoroquinolone and aminoglycosides are potentially useful antibiotics for IMP-CRE infections.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01483-20
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
  • 3
    Online Resource
    Online Resource
    In Vitro Anti-Human Immunodeficiency Virus Activities of Z - and E -Methylenecyclopropane Nucleoside Analogues and Their Phosphoro- l -Alaninate Diesters
    American Society for Microbiology ; 1999
    In:  Antimicrobial Agents and Chemotherapy Vol. 43, No. 6 ( 1999-06), p. 1487-1490
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 43, No. 6 ( 1999-06), p. 1487-1490
    Abstract: Nucleoside analogues with a Z - or an E -methylenecyclopropane moiety were synthesized and examined for activity against human immunodeficiency virus type 1 (HIV-1) in vitro. The addition of a methyl phenyl phosphoro- l -alaninate moiety to modestly active analogues resulted in potentiation of their anti-HIV-1 activity. Two such compounds, designated QYL-685 (with 2,6-diaminopurine) and QYL-609 (with adenine), were most potent against HIV-1 in vitro, with 50% inhibitory concentrations of 0.034 and 0.0026 μM, respectively, in MT-2 cell-based assays. Both compounds were active against zidovudine-resistant, didanosine-resistant, and multi-dideoxynucleoside-resistant infectious clones in vitro. Further development of these analogues as potential therapies for HIV-1 infection is warranted.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.43.6.1487
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1999
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
  • 4
    Online Resource
    Online Resource
    A Prospective, Randomized, Open-Label Trial of Early versus Late Favipiravir Therapy in Hospitalized Patients with COVID-19
    American Society for Microbiology ; 2020
    In:  Antimicrobial Agents and Chemotherapy Vol. 64, No. 12 ( 2020-11-17)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 64, No. 12 ( 2020-11-17)
    Abstract: Favipiravir is an oral broad-spectrum inhibitor of viral RNA-dependent RNA polymerase that is approved for treatment of influenza in Japan. We conducted a prospective, randomized, open-label, multicenter trial of favipiravir for the treatment of COVID-19 at 25 hospitals across Japan. Eligible patients were adolescents and adults admitted with COVID-19 who were asymptomatic or mildly ill and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients were randomly assigned at a 1:1 ratio to early or late favipiravir therapy (in the latter case, the same regimen starting on day 6 instead of day 1). The primary endpoint was viral clearance by day 6. The secondary endpoint was change in viral load by day 6. Exploratory endpoints included time to defervescence and resolution of symptoms. Eighty-nine patients were enrolled, of whom 69 were virologically evaluable. Viral clearance occurred within 6 days in 66.7% and 56.1% of the early and late treatment groups (adjusted hazard ratio [aHR], 1.42; 95% confidence interval [95% CI] , 0.76 to 2.62). Of 30 patients who had a fever (≥37.5°C) on day 1, times to defervescence were 2.1 days and 3.2 days in the early and late treatment groups (aHR, 1.88; 95% CI, 0.81 to 4.35). During therapy, 84.1% developed transient hyperuricemia. Favipiravir did not significantly improve viral clearance as measured by reverse transcription-PCR (RT-PCR) by day 6 but was associated with numerical reduction in time to defervescence. Neither disease progression nor death occurred in any of the patients in either treatment group during the 28-day participation. (This study has been registered with the Japan Registry of Clinical Trials under number jRCTs041190120.)
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01897-20
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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