Abstract:
:Viral entry inhibitors represent an emerging mode of therapy for human immunodeficiency virus type 1 (HIV-1) infection. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. PRO 542 binds to the viral surface glycoprotein gp120 and blocks attachment and entry of virus into CD4(+) cells. Previously, PRO 542 demonstrated antiviral activity without significant toxicity when tested at single doses ranging to 10 mg/kg. In this study, 12 HIV-infected individuals were treated with 25-mg/kg single-dose PRO 542 and then monitored for safety, antiviral effects, and PRO 542 pharmacokinetics for 6 weeks. The study examined two treatment cohorts that differed in the extent of HIV-1 disease progression. PRO 542 at 25 mg/kg was well tolerated and demonstrated a serum half-life of 3 days. Statistically significant acute reductions in HIV-1 RNA levels were observed across all study patients, and greater antiviral effects were observed in the cohort of patients with more advanced HIV-1 disease. In advanced disease (HIV-1 RNA > 100,000 copies/ml; CD4 lymphocytes < 200 cells/mm(3)), PRO 542 mediated an 80% response rate and statistically significant approximately 0.5 log(10) mean reductions in viral load for 4 to 6 weeks posttreatment. Similar findings were obtained in an analysis of all (n = 11) advanced disease patients treated to date with single doses of PRO 542 ranging from 1 to 25 mg/kg. In addition, a significant correlation was observed between antiviral effects observed in vivo and viral susceptibility to PRO 542 in vitro. The findings support continued development of PRO 542 for salvage therapy of advanced HIV-1 disease.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Jacobson JM,Israel RJ,Lowy I,Ostrow NA,Vassilatos LS,Barish M,Tran DN,Sullivan BM,Ketas TJ,O'Neill TJ,Nagashima KA,Huang W,Petropoulos CJ,Moore JP,Maddon PJ,Olson WCdoi
10.1128/aac.48.2.423-429.2004subject
Has Abstractpub_date
2004-02-01 00:00:00pages
423-9issue
2eissn
0066-4804issn
1098-6596journal_volume
48pub_type
临床试验,杂志文章abstract::Macrolide-resistant mutants of Campylobacter jejuni and Campylobacter coli were selected in vitro using erythromycin and tylosin. These mutants exhibited modifications in the ribosomal proteins L4 (G74D) and L22 (insertions at position 86 or 98). A synergy between the CmeABC efflux pump and these modifications in conf...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00616-06
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abstract::A set of 20 nucleoside analogs were examined for their inhibitory effects on the cytopathogenicity and growth of influenza virus type A, B, and C strains in Madin-Darby canine kidney (MDCK) cells. Among the compounds evaluated, pyrazofurin, 3-deazaguanine, ribavirin, carbodine, and cyclopentenyl cytosine inhibited vir...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.32.6.906
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abstract::In patients with polytrauma or major surgery, severe bacterial infections leading to septic shock and multiorgan failure are still a major cause of death. Prevention of septic shock in patients at risk would be an alternative to treatment of patients with overt septic shock. We therefore conducted a trial with the mon...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.39.11.2535
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abstract::The inhibition of the lymphadenopathy-associated virus strain of human immunodeficiency virus (HIV) by alternating regimens of two dideoxynucleosides, 3'-azido-3'-deoxythymidine (AZT) (zidovudine) and 2',3'-dideoxycytidine (ddC), was determined in CEM cells. Cultures infected with virus for 2 h were treated with clini...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.6.920
更新日期:1989-06-01 00:00:00
abstract::Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.42.8.1959
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.3.608
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.4.636
更新日期:1978-10-01 00:00:00
abstract::2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA) is an acid-stable purine dideoxynucleoside analog active against a wide spectrum of human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains in vitro. F-ddA is presently undergoing a phase I clinical trial at the National Cancer Institute. We induced HIV-1 variants re...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.41.6.1313
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abstract::In vivo treatment of susceptible Escherichia coli cultures with low concentrations of dihydrostreptomycin leads to a decline in polysomes and a corresponding increase in 70S particles which behave as run-off ribosomes, as well as free 30S and 50S subunits. We have examined the timing and extent of these effects on rib...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.3.341
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.5.876
更新日期:1985-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.4.617
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.958
更新日期:1986-12-01 00:00:00
abstract::A47934, a peptide antibiotic produced by Streptomyces toyocaensis, belongs to the glycopeptide class of compounds which includes ristocetin and vancomycin. Incorporation studies with radioisotope-labeled substrates indicated that tyrosine, p-hydroxyphenylglycine, p-hydroxyphenylglyoxylate, acetate, and sulfate were ef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.10.1497
更新日期:1987-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.2.418
更新日期:1999-02-01 00:00:00
abstract::Acyclovir-resistant clinical isolates of herpes simplex virus type 1 (HSV-1) were analyzed in vitro for their susceptibilities to essential oils of ginger, thyme, hyssop, and sandalwood. All essential oils exhibited high levels of virucidal activity against acyclovir-sensitive strain KOS and acyclovir-resistant HSV-1 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00426-06
更新日期:2007-05-01 00:00:00
abstract::There is increasing interest in the use of lipophilic copper (Cu)-containing complexes to combat bacterial infections. In this work, we showed that Cu complexes with bis(thiosemicarbazone) ligands [Cu(btsc)] exert antibacterial activity against a range of medically significant pathogens. Previous work using Neisseria ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01289-15
更新日期:2015-10-01 00:00:00
abstract::The effects of trifluorothymidine (5-trifluoromethyl-2'-deoxyuridine, F3dThd) on the replication of three mouse cell lines, LM929, Ltk- (and LM929 derivative devoid of cytosolic deoxythymidine [dThd] kinase activity), and Ltk- c139 (a Ltk- derivative which expresses herpes simplex virus type 1-specified dThd kinase su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.5.881
更新日期:1981-05-01 00:00:00
abstract::Invasive aspergillosis is an increasingly frequent opportunistic infection in immunocompromised patients. Only two agents, amphotericin B and itraconazole, are licensed for therapy. Itraconazole acts through inhibition of a P-450 enzyme undertaking sterol 14alpha demethylation. In vitro resistance in Aspergillus fumig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.6.1364
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.37.9.1945
更新日期:1993-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1991-06-01 00:00:00
abstract::Many hospital antimicrobial stewardship programs restrict the availability of selected drugs by requiring prior approval. Carbapenems may be among the restricted drugs, but it is unclear if hospitals that restrict availability actually use fewer carbapenems than hospitals that do not restrict use. Nor is it clear if r...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2009-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1985-08-01 00:00:00
abstract::The interrelationships between the pharmacokinetics of zidovudine alone and of zidovudine plus clarithromycin were evaluated with 18 volunteers with AIDS who had no infection with Mycobacterium avium complex or clinical evidence of gastroenteritis. Patients received 200 mg of zidovudine orally every 8 h on days 1 to 4...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1995-06-01 00:00:00
abstract::Bacterial susceptibility to a new organic acid related to nalidixic acid and oxolinic acid was tested. The in vitro susceptibility pattern of the new compound was found to be very similar to that of nalidixic acid. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1978-03-01 00:00:00
abstract::The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.41.6.1403
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abstract::Clinical isolates of Gardnerella vaginalis, Streptococcus agalactiae, Bacteroides spp., and Mobiluncus spp. were screened for resistance to tetracycline and for the presence of the streptococcal tetM determinant. The S. agalactiae and G. vaginalis strains contained DNA sequences homologous to the tetM determinant, whi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.5.810
更新日期:1986-11-01 00:00:00
abstract::An international interlaboratory quality control program for measurement of antiretroviral drugs was initiated. The first round was confined to protease inhibitors and showed large variability in the performance of participating laboratories. The results demonstrate the need for and utility of an ongoing quality contr...
journal_title:Antimicrobial agents and chemotherapy
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abstract::β-Lactam resistance levels vary among methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates, mediated by chromosomal mutations and exogenous resistance gene mecA However, MRSA resistance mechanisms are incompletely understood. A P440L mutation in the RNA polymerase β' subunit (RpoC) in slow-vancomycin-i...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2019-01-29 00:00:00
abstract::Multidrug-resistant clinical isolate Klebsiella pneumoniae BM4686 was highly resistant to 4,6-disubstituted 2-deoxystreptamines and to fortimicin. Resistance was due to the presence, on the 40-kb non-self-transferable plasmid pIP849, of the rmtF gene which was cotranscribed with the upstream aac(6')-Ib gene. The deduc...
journal_title:Antimicrobial agents and chemotherapy
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