Abstract:
:A comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV) genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay. The data indicated that genotype 1b (GT-1b) has the highest relative resistance barrier and genotype 2a (GT-2a M31) has the lowest. The rank order of resistance barriers to DCV was 1b>4a≥5a>6a≅1a>2a JFH>3a>2a M31. Importantly, DCV in combination with a protease inhibitor (PI) eliminated GT-2a M31 replicon RNA at a clinically relevant concentration. Previously, we reported the antiviral activity and resistance profiles of DCV on HCV genotypes 1 to 4 evaluated in the replicon system. Here, we report the antiviral activity and resistance profiles of DCV against hybrid replicons with NS5A sequences derived from HCV GT-5a and GT-6a clinical isolates. DCV was effective against both GT-5a and -6a hybrid replicon cell lines (50% effective concentrations [EC50s] ranging from 3 to 7 pM for GT-5a, and 74 pM for GT-6a). Resistance selection identified amino acid substitutions in the N-terminal domain of NS5A. For GT-5a, L31F and L31V, alone or in combination with K56R, were the major resistance variants (EC50s ranging from 2 to 40 nM). In GT-6a, Q24H, L31M, P32L/S, and T58A/S were identified as resistance variants (EC50s ranging from 2 to 250 nM). The in vitro data suggest that DCV has the potential to be an effective agent for HCV genotypes 1 to 6 when used in combination therapy.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Wang C,Jia L,O'Boyle DR 2nd,Sun JH,Rigat K,Valera L,Nower P,Huang X,Kienzle B,Roberts S,Gao M,Fridell RAdoi
10.1128/AAC.02788-14subject
Has Abstractpub_date
2014-09-01 00:00:00pages
5155-63issue
9eissn
0066-4804issn
1098-6596pii
AAC.02788-14journal_volume
58pub_type
杂志文章abstract::The binding of antibiotics to plasma (serum) proteins through hydrogen bonding can significantly influence the biological characteristics of these drugs. A rapid spectrophotometric assay has been developed that measures the level of free (unbound) penem antibiotic in serum ultrafiltrates. Whole human serum was adjuste...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.2.159
更新日期:1988-02-01 00:00:00
abstract::Seven clinical isolates of Shigella sonnei with reduced susceptibilities to fluoroquinolones (sparfloxacin, ciprofloxacin, and ofloxacin) were obtained. The MICs of fluoroquinolones against these S. sonnei strains were 16 to 32 times higher than those obtained against typical strains that are highly susceptible to the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.11.2486
更新日期:1993-11-01 00:00:00
abstract::The etiological treatment of Chagas disease remains neglected. The compounds available show several limitations, mainly during the chronic phase. Lychnopholide encapsulated in polymeric nanocapsules (LYC-NC) was efficacious in mice infected with Trypanosoma cruzi and treated by intravenous administration during the ac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00178-16
更新日期:2016-08-22 00:00:00
abstract::Durlobactam (DUR; also known as ETX2514) is a novel β-lactamase inhibitor with broad activity against Ambler class A, C, and D β-lactamases. Addition of DUR to sulbactam (SUL) in vitro restores SUL activity against clinical isolates of Acinetobacter baumannii The safety and pharmacokinetics (PK) of DUR alone and with ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00071-20
更新日期:2020-06-23 00:00:00
abstract::The survival of three bacterial species and Candida albicans was studied on SPI-ARGENT II. The immediate recovery from silver-impregnated polymer and control polymer (1 cm2) was approximately 10(6) to 10(7) microorganisms. After incubation (37 degreesC) and neutralization of silver with horse serum (5%), surviving org...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.9.2440
更新日期:1998-09-01 00:00:00
abstract::The effects of amphotericin B and fluconazole on the extracellular and intracellular growth of Candida albicans were studied. With respect to the extracellular growth of C. albicans, antifungal activity was measured in terms of MICs and minimal fungicidal concentrations as well as by determination of the concentration...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.11.2275
更新日期:1991-11-01 00:00:00
abstract::Methylene blue (MB) represents a promising antimalarial drug candidate for combination therapies against drug-resistant parasite strains. To support and facilitate the application of MB in future field trials, we studied its antiparasitic effects in vitro. MB is active against all blood stages of both chloroquine (CQ)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.11.4592-4597.2005
更新日期:2005-11-01 00:00:00
abstract::This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rate...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02505-15
更新日期:2016-04-22 00:00:00
abstract::Eighty-five patients with cystic fibrosis who were experiencing an acute infectious exacerbation of their disease were randomized in double-blind fashion to receive either 50 or 75 mg of ceftazidime per kg (body weight) per dose administered intravenously every 8 h for 14 days. Three patients were dropped from the stu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.31.5.698
更新日期:1987-05-01 00:00:00
abstract::Three percent 5-ethyl-2'-deoxyuridine (EdU) in an aqueous cream base was compared with 5% acyclovir (ACV) in polyethylene glycol ointment and 3% EdU in 95% dimethyl sulfoxide (DMSO) for efficacy in the topical treatment of an experimental dorsal cutaneous herpes simplex virus type 1 infection in guinea pigs. Topical A...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.1.103
更新日期:1985-07-01 00:00:00
abstract::A total of 113 patients were randomly allocated to receive either ticarcillin plus clavulanic acid (total dose, 20.8 g) or clindamycin (total dose, 2.4 g) plus amikacin (total dose, 1 g) as perioperative antimicrobial prophylaxis for major head and neck surgery. The two groups were similar in age, prior antineoplastic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.32.10.1557
更新日期:1988-10-01 00:00:00
abstract::We have studied the aminoglycoside resistance gene, which confers high levels of resistance to both amikacin and gentamicin, that is carried by plasmid pSTI1 in the PER-1 beta-lactamase-producing strain of Salmonella enterica serovar Typhimurium previously isolated in Turkey. This gene, called aac(6')-Ib(11), was foun...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.2.697-703.2003
更新日期:2003-02-01 00:00:00
abstract::Purified recombinant protein encoded by the BXLF-I open reading frame of the Epstein-Barr virus genome has thymidine kinase activity. The substrate behaviors of various nucleosides toward this enzyme were tested. Halogenated deoxyuridines, zidovudine, and bromovinyldeoxyuridine are efficient substrates, while acyclovi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2175
更新日期:1994-09-01 00:00:00
abstract::The efficacy of clarithromycin in a murine model of acute toxoplasmosis was studied. Clarithromycin was administered alone and concurrently with minocycline, and efficacy was assessed by survival rates and sequential determination of parasite burden in blood, brains, and lungs. Limited protection resulted from adminis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2852
更新日期:1992-12-01 00:00:00
abstract::A clinical study was carried out to establish the influence of aluminum on the oral absorption of ofloxacin. Ten healthy volunteers were included in a crossover study based on a Latin square design. The treatments that all volunteers received were A, consisting of 400 mg of ofloxacin, and B, consisting of 400 mg of of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.38.10.2510
更新日期:1994-10-01 00:00:00
abstract::Nalidixic acid-resistant derivatives of Neisseria gonorrhoeae WR302 were identified and categorized into two classes on the basis of their susceptibilities to this antimicrobial agent. The MIC of nalidixic acid for the derivative strain MUG116 was fourfold greater than that for its isogenic parental strain WR302 (2 ve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.4.622
更新日期:1991-04-01 00:00:00
abstract::The in vitro activity of CEM-101, a new fluoroketolide, was determined against Gram-positive organisms with various macrolide susceptibility profiles. Experiments for determination of the MICs and minimum bactericidal concentrations (MBCs), timed killing, single-step and multistep mutation rates, the erythromycin indu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01662-09
更新日期:2010-05-01 00:00:00
abstract::The only human cathelicidin, the 37-residue peptide LL-37, exhibits antimicrobial activity against both gram-positive and gram-negative bacteria. We studied the ability of several fragments of LL-37, exhibiting different antimicrobial activities, to interact with membranes whose compositions mimic the cytoplasmic memb...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00321-09
更新日期:2009-09-01 00:00:00
abstract::Lysobactor enzymogenes strain OH11 is an emerging biological control agent of fungal and bacterial diseases. We recently completed its genome sequence and found it contains a large number of gene clusters putatively responsible for the biosynthesis of nonribosomal peptides and polyketides, including the previously ide...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05370-11
更新日期:2011-12-01 00:00:00
abstract::Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.02014-16
更新日期:2017-03-24 00:00:00
abstract::Novel sulfonated derivatives of poly(allylamine hydrochloride) (NSPAHs) and N-sulfonated chitosan (NSCH) have been synthesized, and their activity against influenza A and B viruses has been studied and compared with that of a series of carrageenans, marine polysaccharides of well-documented anti-influenza activity. NS...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02183-15
更新日期:2016-03-25 00:00:00
abstract::We examined an E-test-based strategy for testing the combination of itraconazole and amphotericin B, the latter given either sequentially or concomitantly, in isolates of Aspergillus fumigatus. An antagonistic interaction between the two drugs was noted, especially with the sequential administration of amphotericin B....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.10.2915-2918.2000
更新日期:2000-10-01 00:00:00
abstract::A beta-lactam-sensitive strain (C152) of Shigella dysenteriae showed two major outer membrane proteins (OMPs) with M(r)s of 43,000 and 38,000, while the clinical isolate M2 lacked the 43,000-Mr OMP, which acted as a channel for beta-lactam antibiotics. Permeability of beta-lactams across the outer membrane (OM) of M2 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.10.2302
更新日期:1997-10-01 00:00:00
abstract::Resistance to rifampin in Mycobacterium tuberculosis results from mutations in the gene coding for the beta subunit of RNA polymerase (rpoB). At least 95% of rifampin-resistant isolates have mutations in rpoB, and the mutations are clustered in a small region. About 40 distinct point mutations and in-frame insertions ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.12.3298-3301.2000
更新日期:2000-12-01 00:00:00
abstract::Etest susceptibilities to amoxicillin, chloramphenicol, and trimethoprim-sulfamethoxazole of 240 invasive isolates of Haemophilus influenzae cultured from children in rural Kenya were 66%, 66%, and 38%, respectively. Resistance increased markedly over 9 years and was concentrated among serotype b isolates. In Africa, ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.7.3021-3024.2005
更新日期:2005-07-01 00:00:00
abstract::Endogenous nitric oxide (NO) has antimycobacterial properties. We tested the hypothesis that exogenous (inhaled) NO can be safely delivered and can accelerate airway disinfection for pulmonary tuberculosis patients treated with standard therapy. Exogenous NO administered at 80 ppm for 72 h can be safely delivered but ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.1209-1212.2005
更新日期:2005-03-01 00:00:00
abstract::The class 1 integron In28, found in the multidrug resistance transposon Tn1403, was found to be located in the res site of the backbone transposon and is flanked by a 5-bp direct duplication, indicating that it reached this position by transposition. In28 has a backbone structure related to that of In4, but has lost i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.11.3014-3020.2001
更新日期:2001-11-01 00:00:00
abstract::Tedizolid and linezolid in vitro activities against 3,032 Gram-positive pathogens collected in Asia-Pacific, Eastern European, and Latin American medical centers during 2014 were assessed. The isolates were tested for susceptibility by the current reference broth microdilution methods. Due to concern over the effect o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00881-16
更新日期:2016-08-22 00:00:00
abstract::Compound 2242, also known as 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine, is the first known antivirally active nucleoside analog with the side chain substituted at the N-7 position of the purine ring system. Our purpose was to evaluate its retinal toxicity and assess the efficacy of its highest nontoxic concent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.7.1485
更新日期:1995-07-01 00:00:00
abstract::The polyene antifungal amphotericin B (AmB) is widely used to treat life-threatening fungal infections. Even though AmB resistance is exceptionally rare in fungi, most Aspergillus terreus isolates exhibit an intrinsic resistance against the drug in vivo and in vitro. Heat shock proteins perform a fundamental protectiv...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05164-14
更新日期:2015-07-01 00:00:00