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  • American Society for Microbiology  (23)
  • Pharmacy  (23)
  • 1
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    Online Resource
    Ketoconazole Inhibition of Testicular Secretion of Testosterone and Displacement of Steroid Hormones from Serum Transport Proteins
    American Society for Microbiology ; 1983
    In:  Antimicrobial Agents and Chemotherapy Vol. 23, No. 6 ( 1983-06), p. 950-950
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 23, No. 6 ( 1983-06), p. 950-950
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.23.6.950-a
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 1983
    detail.hit.zdb_id: 1496156-8
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  • 2
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    In Vivo and In Vitro Antimalarial Properties of Azithromycin-Chloroquine Combinations That Include the Resistance Reversal Agent Amlodipine
    American Society for Microbiology ; 2011
    In:  Antimicrobial Agents and Chemotherapy Vol. 55, No. 7 ( 2011-07), p. 3115-3124
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 55, No. 7 ( 2011-07), p. 3115-3124
    Abstract: Evidence of emerging Plasmodium falciparum resistance to artemisinin-based combination therapies, documented in western Cambodia, underscores the continuing need to identify new antimalarial combinations. Given recent reports of the resurgence of chloroquine-sensitive P. falciparum parasites in Malawi, after the enforced and prolonged withdrawal of this drug, and indications of a possible synergistic interaction with the macrolide azithromycin, we sought to further characterize chloroquine-azithromycin combinations for their in vitro and in vivo antimalarial properties. In vitro 96-h susceptibility testing of chloroquine-azithromycin combinations showed mostly additive interactions against freshly cultured P. falciparum field isolates obtained from Mali. Some evidence of synergy, however, was apparent at the fractional 90% inhibitory concentration level. Additional in vitro testing highlighted the resistance reversal properties of amlodipine for both chloroquine and quinine. In vivo experiments, using the Peters 4-day suppressive test in a P. yoelii mouse model, revealed up to 99.9% suppression of parasitemia following treatment with chloroquine-azithromycin plus the R enantiomer of amlodipine. This enantiomer was chosen because it does not manifest the cardiac toxicities observed with the racemic mixture. Pharmacokinetic/pharmacodynamic analyses in this rodent model and subsequent extrapolation to a 65-kg adult led to the estimation that 1.8 g daily of R -amlodipine would be required to achieve similar efficacy in humans, for whom this is likely an unsafe dose. While these data discount amlodipine as an additional partner for chloroquine-based combination therapy, our studies continue to support azithromycin as a safe and effective addition to antimalarial combination therapies.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01566-10
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2011
    detail.hit.zdb_id: 1496156-8
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  • 3
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    Comparative Genomics of an IncA/C Multidrug Resistance Plasmid from Escherichia coli and Klebsiella Isolates from Intensive Care Unit Patients and the Utility of Whole-Genome Sequencing in Health Care Settings
    American Society for Microbiology ; 2014
    In:  Antimicrobial Agents and Chemotherapy Vol. 58, No. 8 ( 2014-08), p. 4814-4825
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 58, No. 8 ( 2014-08), p. 4814-4825
    Abstract: The IncA/C plasmids have been implicated for their role in the dissemination of β-lactamases, including gene variants that confer resistance to expanded-spectrum cephalosporins, which are often the treatment of last resort against multidrug-resistant, hospital-associated pathogens. A bla FOX-5 gene was detected in 14 Escherichia coli and 16 Klebsiella isolates that were cultured from perianal swabs of patients admitted to an intensive care unit (ICU) of the University of Maryland Medical Center (UMMC) in Baltimore, MD, over a span of 3 years. Four of the FOX-encoding isolates were obtained from subsequent samples of patients that were initially negative for an AmpC β-lactamase upon admission to the ICU, suggesting that the AmpC β-lactamase-encoding plasmid was acquired while the patient was in the ICU. The genomes of five E. coli isolates and six Klebsiella isolates containing bla FOX-5 were selected for sequencing based on their plasmid profiles. An ∼167-kb IncA/C plasmid encoding the FOX-5 β-lactamase, a CARB-2 β-lactamase, additional antimicrobial resistance genes, and heavy metal resistance genes was identified. Another FOX-5-encoding IncA/C plasmid that was nearly identical except for a variable region associated with the resistance genes was also identified. To our knowledge, these plasmids represent the first FOX-5-encoding plasmids sequenced. We used comparative genomics to describe the genetic diversity of a plasmid encoding a FOX-5 β-lactamase relative to the whole-genome diversity of 11 E. coli and Klebsiella isolates that carry this plasmid. Our findings demonstrate the utility of whole-genome sequencing for tracking of plasmid and antibiotic resistance gene distribution in health care settings.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.02573-14
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1496156-8
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  • 4
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    Defects in Efflux ( oprM ), β-Lactamase ( ampC ), and Lipopolysaccharide Transport ( lptE ) Genes Mediate Antibiotic Hypersusceptibility of Pseudomonas aeruginosa Strain Z61
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 7 ( 2019-07)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 7 ( 2019-07)
    Abstract: Antibiotic hypersensitive bacterial mutants (e.g., Escherichia coli imp ) are used to investigate intrinsic resistance and are exploited in antibacterial discovery to track weak antibacterial activity of novel inhibitor compounds. Pseudomonas aeruginosa Z61 is one such drug-hypersusceptible strain generated by chemical mutagenesis, although the genetic basis for hypersusceptibility is not fully understood. Genome sequencing of Z61 revealed nonsynonymous single-nucleotide polymorphisms in 153 genes relative to its parent strain, and three candidate mutations (in oprM , ampC , and lptE ) predicted to mediate hypersusceptibility were characterized. The contribution of these mutations was confirmed by genomic restoration of the wild-type sequences, individually or in combination, in the Z61 background. Introduction of the lptE mutation or genetic inactivation of oprM and ampC genes alone or together in the parent strain recapitulated drug sensitivities. This showed that disruption of oprM (which encodes a major outer membrane efflux pump channel) increased susceptibility to pump substrate antibiotics, that inactivation of the inducible β-lactamase gene ampC contributed to β-lactam susceptibility, and that mutation of the lipopolysaccharide transporter gene lptE strongly altered the outer membrane permeability barrier, causing susceptibility to large antibiotics such as rifampin and also to β-lactams.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00784-19
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
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  • 5
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    Characterization of Klebsiella sp. Strain 10982, a Colonizer of Humans That Contains Novel Antibiotic Resistance Alleles and Exhibits Genetic Similarities to Plant and Clinical Klebsiella Isolates
    American Society for Microbiology ; 2014
    In:  Antimicrobial Agents and Chemotherapy Vol. 58, No. 4 ( 2014-04), p. 1879-1888
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 58, No. 4 ( 2014-04), p. 1879-1888
    Abstract: A unique Klebsiella species strain, 10982, was cultured from a perianal swab specimen obtained from a patient in the University of Maryland Medical Center intensive care unit. Klebsiella sp. 10982 possesses a large IncA/C multidrug resistance plasmid encoding a novel FOX AmpC β-lactamase designated FOX-10. A novel variant of the LEN β-lactamase was also identified. Genome sequencing and bioinformatic analysis demonstrated that this isolate contains genes associated with nitrogen fixation, allantoin metabolism, and citrate fermentation. These three gene regions are typically present in either Klebsiella pneumoniae clinical isolates or Klebsiella nitrogen-fixing endophytes but usually not in the same organism. Phylogenomic analysis of Klebsiella sp. 10982 and sequenced Klebsiella genomes demonstrated that Klebsiella sp. 10982 is present on a branch that is located intermediate between the genomes of nitrogen-fixing endophytes and K. pneumoniae clinical isolates. Metabolic features identified in the genome of Klebsiella sp. 10982 distinguish this isolate from other Klebsiella clinical isolates. These features include the nitrogen fixation ( nif ) gene cluster, which is typically present in endophytic Klebsiella isolates and is absent from Klebsiella clinical isolates. Additionally, the Klebsiella sp. 10982 genome contains genes associated with allantoin metabolism, which have been detected primarily in K. pneumoniae isolates from liver abscesses. Comparative genomic analysis of Klebsiella sp. 10982 demonstrated that this organism has acquired genes conferring new metabolic strategies and novel antibiotic resistance alleles, both of which may enhance its ability to colonize the human body.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01605-13
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2014
    detail.hit.zdb_id: 1496156-8
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  • 6
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    Use of Comparative Genomics To Characterize the Diversity of Acinetobacter baumannii Surveillance Isolates in a Health Care Institution
    American Society for Microbiology ; 2016
    In:  Antimicrobial Agents and Chemotherapy Vol. 60, No. 10 ( 2016-10), p. 5933-5941
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 60, No. 10 ( 2016-10), p. 5933-5941
    Abstract: Despite the increasing prevalence of the nosocomial pathogen Acinetobacter baumannii , little is known about which genomic components contribute to clinical presentation of this important pathogen. Most whole-genome comparisons of A. baumannii have focused on specific genomic regions associated with phenotypes in a limited number of genomes. In this work, we describe the results of a whole-genome comparative analysis of 254 surveillance isolates of Acinetobacter species, 203 of which were A. baumannii , isolated from perianal swabs and sputum samples collected as part of an infection control active surveillance program at the University of Maryland Medical Center. The collection of surveillance isolates includes both carbapenem-susceptible and -resistant isolates. Based on the whole-genome phylogeny, the A. baumannii isolates collected belong to two major phylogenomic lineages. Results from multilocus sequence typing indicated that one of the major phylogenetic groups of A. baumannii was comprised solely of strains from the international clonal lineage 2. The genomic content of the A. baumannii isolates was examined using large-scale BLAST score ratio analysis to identify genes that are associated with carbapenem-susceptible and -resistant isolates, as well as genes potentially associated with the source of isolation. This analysis revealed a number of genes that were exclusive or at greater frequency in each of these classifications. This study is the most comprehensive genomic comparison of Acinetobacter isolates from a surveillance study to date and provides important information that will contribute to our understanding of the success of A. baumannii as a human pathogen.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00477-16
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
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  • 7
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    Race/Ethnicity and Protease Inhibitor Use Influence Plasma Tenofovir Exposure in Adults Living with HIV-1 in AIDS Clinical Trials Group Study A5202
    American Society for Microbiology ; 2019
    In:  Antimicrobial Agents and Chemotherapy Vol. 63, No. 4 ( 2019-04)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 63, No. 4 ( 2019-04)
    Abstract: AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant ( k a ), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: k a = 2.87 h −1 , CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F ( P 〈 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.01638-18
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2019
    detail.hit.zdb_id: 1496156-8
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  • 8
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    Plasmodium falciparum Strains Harboring Dihydrofolate Reductase with the I164L Mutation Are Absent in Malawi and Zambia Even under Antifolate Drug Pressure
    American Society for Microbiology ; 2008
    In:  Antimicrobial Agents and Chemotherapy Vol. 52, No. 11 ( 2008-11), p. 3883-3888
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 52, No. 11 ( 2008-11), p. 3883-3888
    Abstract: The Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme is the target of pyrimethamine, a component of the antimalarial pyrimethamine-sulfadoxine. Resistance to this drug is associated primarily with mutations in the Pf dhfr gene. The I164L mutant allele is of particular interest, because strains possessing this mutation are highly resistant to pyrimethamine and to chlorproguanil, a component of chlorproguanil-dapsone. A recent study from Malawi reported this mutation at a prevalence of 4.7% in parasites from human immunodeficiency virus-positive pregnant women by using a real-time PCR method. These observations have huge implications for the use of pyrimethamine-sulfadoxine, chlorproguanil-dapsone, and future antifolate-artemisinin combinations in Africa. It was imperative that this finding be rigorously tested. We identified a number of critical limitations in the original genotyping strategy. Using a refined and validated real-time PCR strategy, we report here that this mutation was absent in 158 isolates from Malawi and 42 isolates from Zambia collected between 2003 and 2005.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00431-08
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2008
    detail.hit.zdb_id: 1496156-8
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  • 9
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    Genomic Analysis of Multidrug-Resistant Escherichia coli from North Carolina Community Hospitals: Ongoing Circulation of CTX-M-Producing ST131- H 30Rx and ST131- H 30R1 Strains
    American Society for Microbiology ; 2017
    In:  Antimicrobial Agents and Chemotherapy Vol. 61, No. 8 ( 2017-08)
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 61, No. 8 ( 2017-08)
    Abstract: Escherichia coli sequence type 131 (ST131) predominates globally among multidrug-resistant (MDR) E. coli strains. We used whole-genome sequencing (WGS) to investigate 63 MDR E. coli isolates from 7 North Carolina community hospitals (2010 to 2015). Of these, 39 (62%) represented ST131, including 37 (95%) from the ST131- H 30R subclone: 10 (27%) from its H 30R1 subset and 27 (69%) from its H 30Rx subset. ST131 core genomes differed by a median of 15 (range, 0 to 490) single-nucleotide variants (SNVs) overall versus only 7 within H 30R1 (range, 3 to 12 SNVs) and 11 within H 30Rx (range, 0 to 21). The four isolates with identical core genomes were all H 30Rx. Epidemiological and clinical characteristics did not vary significantly by strain type, but many patients with MDR E. coli or H 30Rx infection were critically ill and had poor outcomes. H 30Rx isolates characteristically exhibited fluoroquinolone resistance and CTX-M-15 production, had a high prevalence of trimethoprim-sulfamethoxazole resistance (89%), sul1 (89%), and dfrA17 (85%), and were enriched for specific virulence traits, and all qualified as extraintestinal pathogenic E. coli . The high overall prevalence of CTX-M-15 appeared to be possibly attributable to its association with the ST131- H 30Rx subclone and IncF[F2:A1:B−] plasmids. Some phylogenetically clustered non-ST131 MDR E. coli isolates also had distinctive serotypes/ fimH types, fluoroquinolone mutations, CTX-M variants, and IncF types. Thus, WGS analysis of our community hospital source MDR E. coli isolates suggested ongoing circulation and differentiation of E. coli ST131 subclones, with clonal segregation of CTX-M variants, other resistance genes, Inc-type plasmids, and virulence genes.
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00912-17
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 1496156-8
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  • 10
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    Design, Synthesis, and Evaluation of 10-N-Substituted Acridones as Novel Chemosensitizers in Plasmodium falciparum
    American Society for Microbiology ; 2007
    In:  Antimicrobial Agents and Chemotherapy Vol. 51, No. 11 ( 2007-11), p. 4133-4140
    Details
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 51, No. 11 ( 2007-11), p. 4133-4140
    Abstract: A series of novel 10-N-substituted acridones, bearing alkyl side chains with tertiary amine groups at the terminal position, were designed, synthesized, and evaluated for the ability to enhance the potency of quinoline drugs against multidrug-resistant (MDR) Plasmodium falciparum malaria parasites. A number of acridone derivatives, with side chains bridged three or more carbon atoms apart between the ring nitrogen and terminal nitrogen, demonstrated chloroquine (CQ)-chemosensitizing activity against the MDR strain of P. falciparum (Dd2). Isobologram analysis revealed that selected candidates demonstrated significant synergy with CQ in the CQ-resistant (CQR) parasite Dd2 but only additive (or indifferent) interaction in the CQ-sensitive (CQS) D6. These acridone derivatives also enhanced the sensitivity of other quinoline antimalarials, such as desethylchloroquine (DCQ) and quinine (QN), in Dd2. The patterns of chemosensitizing effects of selected acridones on CQ and QN were similar to those of verapamil against various parasite lines with mutations encoding amino acid 76 of the P. falciparum CQ resistance transporter (PfCRT). Unlike other known chemosensitizers with recognized psychotropic effects (e.g., desipramine, imipramine, and chlorpheniramine), these novel acridone derivatives exhibited no demonstrable effect on the uptake or binding of important biogenic amine neurotransmitters. The combined results indicate that 10-N-substituted acridones present novel pharmacophores for the development of chemosensitizers against P. falciparum .
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    URL: Article
    DOI: 10.1128/AAC.00669-07
    RVK:
    XA 24552
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2007
    detail.hit.zdb_id: 1496156-8
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