Abstract:
:Assessment of drug susceptibility has become an integral part of influenza virus surveillance. In this study, we describe the drug resistance profile of influenza A(H3N2) virus, A/Mississippi/05/2011, collected from a patient treated with oseltamivir and detected via surveillance. An MDCK cell-grown isolate of this virus exhibited highly reduced inhibition by the neuraminidase (NA) inhibitors (NAIs) oseltamivir (8,005-fold), zanamivir (813-fold), peramivir (116-fold), and laninamivir (257-fold) in the NA inhibition assay. Sequence analysis of its NA gene revealed a known oseltamivir-resistance marker, the glutamic acid-to-valine substitution at position 119 (E119V), and an additional change, threonine to isoleucine at position 148 (T148I). Unlike E119V, T148I was not detected in the clinical sample but acquired during viral propagation in MDCK cells. Using recombinant proteins, T148I by itself was shown to cause only a 6-fold increase in the zanamivir 50% inhibitory concentration (IC50) and had no effect on inhibition by other drugs. The T148I substitution reduced NA activity by 50%, most likely by affecting the positioning of the 150 loop at the NA catalytic site. Using pyrosequencing, changes at T148 were detected in 35 (23%) of 150 MDCK cell-grown A(H3N2) viruses tested, which was lower than the frequency of changes at D151 (85%), an NA residue previously implicated in cell selection. We demonstrate that culturing of the A(H3N2) viruses (n = 11) at a low multiplicity of infection delayed the emergence of the NA variants with changes at position 148 and/or 151, especially when conducted in MDCK-SIAT1 cells. Our findings highlight the current challenges in monitoring susceptibility of influenza A(H3N2) viruses to the NAI class of antiviral drugs.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Tamura D,Nguyen HT,Sleeman K,Levine M,Mishin VP,Yang H,Guo Z,Okomo-Adhiambo M,Xu X,Stevens J,Gubareva LVdoi
10.1128/AAC.01364-13subject
Has Abstractpub_date
2013-12-01 00:00:00pages
6141-6issue
12eissn
0066-4804issn
1098-6596pii
AAC.01364-13journal_volume
57pub_type
杂志文章abstract::The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cell...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.8.2636-2639.2003
更新日期:2003-08-01 00:00:00
abstract::The incidence of measles virus (MV) infection has been significantly reduced in many nations through extensive vaccination; however, the virus still causes significant morbidity and mortality in developing countries. Measles outbreaks also occur in some developed countries that have failed to maintain high vaccine cov...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3755-3761.2005
更新日期:2005-09-01 00:00:00
abstract::We found a heterozygous C2857T mutation (R953C) in polymerase gamma (Pol-γ) in an HIV-infected patient with mitochondrial toxicity. The R953C Pol-γ mutant binding affinity for dCTP is 8-fold less than that of the wild type. The R953C mutant shows a 4-fold decrease in discrimination of analog nucleotides relative to th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00976-16
更新日期:2016-08-22 00:00:00
abstract::Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patient...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.03246-14
更新日期:2014-11-01 00:00:00
abstract::Serial passage of Pseudomonas aeruginosa ATCC 27853 or Escherichia coli ATCC 25922 on agar with subinhibitory concentrations of norfloxacin rapidly produced isolates with minimal inhibitory concentrations (MICs) of norfloxacin up to 512-fold higher than that for the original strain. Although MICs of seven unrelated an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.1.188
更新日期:1983-01-01 00:00:00
abstract::The sterol 14-demethylase P450 (CYP51) of a fluconazole-resistant isolate of Candida albicans, DUMC136, showed reduced susceptibility to this azole but with little change in its catalytic activity. Twelve nucleotide substitutions, resulting in four amino acid changes, were identified in the DUMC136 CYP51 gene in compa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.5.1163
更新日期:1999-05-01 00:00:00
abstract::Sixteen weeks of treatment with clarithromycin (CLARI) alone displayed significant bactericidal activity against Mycobacterium avium complex infection in beige mice. Only two combined regimens, CLARI combined with an initial 4 or 8 weeks of amikacin (AMIKA), displayed activity greater than that displayed by CLARI alon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.3.608
更新日期:1995-03-01 00:00:00
abstract::Compounds that interact with DNA or RNA generally act as inhibitors of enzymes that unwind DNA or RNA. In the present study we describe the synthesis and properties of some nucleoside analogues that interact with double-stranded DNA but that, in contrast, facilitate the unwinding reaction mediated by West Nile (WN) vi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.5.1231-1239.2002
更新日期:2002-05-01 00:00:00
abstract::The ampD gene product regulates the expression of AmpC beta-lactamase in gram-negative bacteria and is proposed to be involved in peptidoglycan metabolism. In this study, we sequenced the ampD wild type and three mutant genes of Enterobacter cloacae and Citrobacter freundii. They exhibited a high degree of homology wi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.224
更新日期:1993-02-01 00:00:00
abstract::Unlike most antimicrobial peptides (AMPs), the main mode of action of the subclass of proline-rich antimicrobial peptides (PrAMPs) is not based on disruption of the bacterial membrane. Instead, PrAMPs exploit the inner membrane transporters SbmA and YjiL/MdtM to pass through the bacterial membrane and enter the cytoso...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00534-18
更新日期:2018-07-27 00:00:00
abstract::We have evaluated the influence of age on the intracortical accumulation kinetics of gentamicin in conscious male rats by using a short-term infusion model. Animals were infused with gentamicin over a 6-h period and achieved individual steady-state levels in serum ranging from 0.5 to 12 micrograms/ml. Young rats were ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.11.2006
更新日期:1989-11-01 00:00:00
abstract::Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio)uracil (E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replication without cytotoxicity in vitro and were more potent than azidothymidine and were as potent as E-BPU. The target of these compounds is HIV-1 reverse transcriptase. Reverse ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.2.539
更新日期:1995-02-01 00:00:00
abstract::In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin. Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and ...
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.36.3.521
更新日期:1992-03-01 00:00:00
abstract::Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.11.2633
更新日期:1994-11-01 00:00:00
abstract::The clinical vancomycin-intermediate Staphylococcus aureus (VISA) strain Mu50 carries two mutations in the vraSR and graRS two-component regulatory systems (TCRSs), namely, vraS(I5N) and graR(N197S) (hereinafter designated graR). The clinical heterogeneously vancomycin-intermediate S. aureus (hVISA) strain Mu3 shares ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00398-11
更新日期:2011-09-01 00:00:00
abstract::Clinical isolates of the Bacteroides melaninogenicus and Bacteroides fragilis groups were tested for in vitro and in vivo susceptibility to penicillin, clindamycin, and metronidazole, used singly or in combination with gentamicin. The in vitro tests consisted of determinations of minimal inhibitory concentrations (MIC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.1.71
更新日期:1984-01-01 00:00:00
abstract::Seventy nine strains of Yersinia enterocolitica resistant to one or more antimicrobials were analyzed for integrons. Only class 1 sul1 integrons containing aadA1a (28 strains), aadA1a-dfr1-sat1 (2 strains), and dfr1-aadA1a (1 strain) gene cassettes were found. The first two types were found in clinical isolates belong...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.1.421-425.2003
更新日期:2003-01-01 00:00:00
abstract::A new 3-N-aminoglycoside acetyltransferase is described, which possesses a wider substrate range than any such enzyme so far discovered in clinical isolates of antibiotic-resistant bacteria. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.6.951
更新日期:1976-06-01 00:00:00
abstract::The mechanism(s) of daptomycin (DAP) resistance (DAPr) is incompletely defined. Thickened cell walls (CWs) acting as either a mechanical barrier or an affinity trap for DAP have been purported to be a major contributor to the DAPr phenotype. To this end, we studied an isogenic set of methicillin-resistant Staphylococc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00122-10
更新日期:2010-08-01 00:00:00
abstract::The outer membrane of mycobacteria presents an effective permeability barrier for many antibiotics. Transport pathways across this membrane are unknown for most drugs. Here, we examined which antibiotics utilize the porin pathway across the outer membrane of the model organism Mycobacterium smegmatis. Deletion of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00239-08
更新日期:2008-09-01 00:00:00
abstract::Intraoperative biliary cefamandole concentrations were determined in 16 patients with hepatobiliary pathology. These included seven patients with cholelithiasis, five with acute cholecystitis, two with recurrent ascending cholangitis, and two with liver abscesses. Bile collected 0.5 to 2.5 h after the last antibiotic ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.6.1087
更新日期:1982-12-01 00:00:00
abstract::In the present study we determined the resistance patterns of anaerobic bacteria from human saliva and stool specimens and investigated whether there were significant differences in resistance between outpatients and hospitalized patients, regardless of whether they had received antimicrobial agents. No bacterial stra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.8.1665
更新日期:1993-08-01 00:00:00
abstract::Eighty-one clinical isolates of Helicobacter pylori showed no resistance to rifampin (MIC range, 0.032 to 2 microg/ml; MIC at which 50% of isolates are inhibited [MIC50], 0.25 microg/ml). The MIC50 of rifabutin was 0.008 microg/ml (n = 16). All resistant laboratory mutants of H. pylori ATCC 43504 showed amino acid exc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.6.1497
更新日期:1999-06-01 00:00:00
abstract::Three sizes of inserted regions of DNA (800, 1,000, and 1,500 bp) were shown to be common among class I integrons in unrelated clinical isolates of Enterobacteriaceae from different European hospitals. Sequencing showed that 800-bp inserted regions comprised identical sequences including aacA4, that 1,000-bp inserted ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.3.686
更新日期:1999-03-01 00:00:00
abstract::Klebsiella oxytoca 1731, which showed a wide spectrum of resistance to beta-lactams, including cefoxitin, was isolated in 1994 from a patient in Genoa, Italy. This strain contained a plasmid-mediated AmpC beta-lactamase with a pI of 7.25. Sequencing of the corresponding DNA of K. oxytoca 1731 revealed 96 and 97% ident...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::We tested the combined activity of vancomycin and seven beta-lactam antibiotics against Staphylococcus aureus clinical strain Mu3, which displays heterogeneous resistance to vancomycin. When combined with vancomycin, four of the seven tested beta-lactams exhibited an additive effect at or near their MICs, while all sh...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.4.1292-1294.2001
更新日期:2001-04-01 00:00:00
abstract::Despite the availability of >30 effective drugs for managing HIV-1 infection, no current therapy is curative, and long-term management is challenging owing to the emergence and spread of drug-resistant mutants. Identification of drugs against novel HIV-1 targets would expand the current treatment options and help to c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00646-15
更新日期:2015-09-01 00:00:00
abstract::The current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05646-11
更新日期:2012-02-01 00:00:00
abstract::Cefazolin and cephalothin disk susceptibility and minimal inhibitory concentration determinations were conducted on 591 clinical isolates. Cefazolin demonstrated superior activity, as shown by lower minimal inhibitory concentrations, and a greater percentage of isolates inhibited in the disk susceptibility test. The c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.1.63
更新日期:1974-01-01 00:00:00
abstract::Intermittent preventive treatment in infants with sulfadoxine-pyrimethamine (IPTi-SP) reduces malaria episodes by 20 to 59% across Africa. This protective efficacy, however, may be affected by the high frequency of malnutrition in African infants. We analyzed the impact of malnutrition as defined by anthropometry on t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01723-08
更新日期:2009-05-01 00:00:00