Abstract:
:It has previously been shown that overexpression of the CdMDR1 gene is a major contributor to resistance in fluconazole-resistant isolates of Candida dubliniensis. However, since CdMdr1p does not mediate transport of other azole drugs such as itraconazole, we investigated the molecular mechanisms of stable resistance to itraconazole obtained in three strains of C. dubliniensis (two with nonfunctional CdCDR1 genes and one with functional CdCDR1 genes) by serial exposure to this antifungal agent in vitro. Seven derivatives that were able to grow on agar medium containing 64 micro g of itraconazole per ml were selected for detailed analysis. These derivatives were resistant to itraconazole, fluconazole, and ketoconazole but were not cross resistant to inhibitors. CdMDR1 expression was unchanged in the seven resistant derivatives and their parental isolates; however, all seven derivatives exhibited increased levels of CdERG11 expression, and six of the seven derivatives exhibited increased levels of CdCDR1 expression compared to the levels of expression by their respective parental isolates. Except for one derivative, the level of rhodamine 6G efflux was decreased in the itraconazole-resistant derivatives compared to the level of efflux in their parental isolates, suggesting altered membrane properties in these derivatives. Analysis of their membrane sterol contents was consistent with a defective sterol C5,6-desaturase enzyme (CdErg3p), which was confirmed by the identification of mutations in the alleles (CdERG3) encoding this enzyme and their lack of functional complementation in a Saccharomyces cerevisiae erg3 mutant. The results of this study show that the loss of function of CdErg3p was the primary mechanism of in vitro-generated itraconazole resistance in six of the seven the C. dubliniensis derivatives. However, the mechanism(s) of itraconazole resistance in the remaining seventh derivative has yet to be determined.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Pinjon E,Moran GP,Jackson CJ,Kelly SL,Sanglard D,Coleman DC,Sullivan DJdoi
10.1128/aac.47.8.2424-2437.2003subject
Has Abstractpub_date
2003-08-01 00:00:00pages
2424-37issue
8eissn
0066-4804issn
1098-6596journal_volume
47pub_type
杂志文章abstract::We determined the antibiotic susceptibilities of 1,785 enterococcal bloodstream isolates collected over 25 years. Antibiotic resistance emerged at a greater rate in Enterococcus faecium than in other enterococcal species, and E. faecium isolates became proportionally more common over time. Our findings confirm the pat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3676-3678.2002
更新日期:2002-11-01 00:00:00
abstract::PD 131628 is a new aminopyrrolidine-substituted fluorocyclopropyl naphthyridine quinolone which possesses high in vitro activity against a wide spectrum of bacterial species. The MICs for greater than or equal to 90% of strains were 0.125 to 0.25 microgram/ml for staphylococci, Streptococcus pyogenes, and S. pneumonia...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.1.141
更新日期:1991-01-01 00:00:00
abstract::Artemisinin-derivative combination therapies (ACT) are highly efficacious against multidrug-resistant Plasmodium falciparum malaria. Few efficacy data, however, are available for vivax malaria. With high rates of chloroquine (CQ) resistance in both vivax and falciparum malaria in Papua Province, Indonesia, new combina...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.46.12.3947-3953.2002
更新日期:2002-12-01 00:00:00
abstract::Osteoarticular mucormycosis cases are quite rare and challenging infections that are mostly due to direct inoculation during traumatic injury among immunocompetent patients. Classic management includes a combination of aggressive surgical debridement, which may lead to amputation, and long-term systemic liposomal amph...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01006-18
更新日期:2018-12-21 00:00:00
abstract::The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based com...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00073-17
更新日期:2017-06-27 00:00:00
abstract::The pharmacokinetics of a single 1-g intravenous dose of mezlocillin were examined in six functionally anephric patients undergoing hemodialysis. Hemodialysis clearance calculated by plasma extraction ratios across the dialyzer membrane and by dialysis fluid agree well, averaging 26 and 32 ml/min. Dialyzer extraction ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.5.590
更新日期:1981-11-01 00:00:00
abstract::Single amino acid substitutions in the Ω loop of KPC β-lactamases are known to lead to resistance to the ceftazidime-avibactam combination. Here, we investigate this mechanism of resistance in CTX-M enzymes, which are the most widely spread extended-spectrum β-lactamases worldwide. Nine single amino acid polymorphisms...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00357-18
更新日期:2018-08-27 00:00:00
abstract::An Ambler class A β-lactamase gene, bla(CIA-1), was cloned from the reference strain Chryseobacterium indologenes ATCC 29897 and expressed in Escherichia coli BL21. The bla(CIA-1) gene encodes a novel extended-spectrum β-lactamase (ESBL) that shared 68% and 60% identities with the CGA-1 and CME-1 β-lactamases, respect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05165-11
更新日期:2012-01-01 00:00:00
abstract::There were no significant differences in the pharmacokinetics of micafungin and expression of hepatic multidrug resistance-associated protein 2 (ABCC2/Mrp2) between analbuminemic and Sprague-Dawley rats. Micafungin bound strongly to high-density lipoprotein (HDL) and moderately to gamma globulin. These results suggest...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00396-08
更新日期:2008-09-01 00:00:00
abstract::The penetration of ciprofloxacin into heart tissue (valve and myocardium), mediastinal fat, and sternal bone marrow was the object of a prospective nonrandomized study involving 36 patients undergoing mitral and/or aortic valve replacement. Patients were divided into two groups of 18. Group 1 patients were administere...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.34.3.398
更新日期:1990-03-01 00:00:00
abstract::LpxC [UDP-3-O-(R-3-hydroxymyristoyl)-GlcNAc deacetylase] is a metalloamidase that catalyzes the first committed step in the biosynthesis of the lipid A component of lipopolysaccharide. A previous study (H. R. Onishi, B. A. Pelak, L. S. Gerckens, L. L. Silver, F. M. Kahan, M. H. Chen, A. A. Patchett, S. M. Galloway, S....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00140-06
更新日期:2006-06-01 00:00:00
abstract::Intragastric inoculation of mice with Klebsiella pneumoniae can cause liver abscesses, necrosis of liver tissues, and bacteremia. A newly isolated phage (φNK5) with lytic activity for K. pneumoniae was used to treat K. pneumoniae infection in an intragastric model. Both intraperitoneal and intragastric administration ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01123-10
更新日期:2011-04-01 00:00:00
abstract::A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing e...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01784-12
更新日期:2013-01-01 00:00:00
abstract::Antimicrobial efficacy in orthopedic device infections is diminished because of bacterial biofilms which express tolerance to antibiotics. Recently, the use of high doses of levofloxacin with rifampin has been recommended for staphylococcal infections. In the present study, we evaluated the efficacy of levofloxacin at...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00523-06
更新日期:2006-12-01 00:00:00
abstract::Toxoplasma gondii and Cryptosporidium parvum, members of the phylum Apicomplexa, are significant pathogens of both humans and animals worldwide for which new and effective therapeutics are needed. Here we describe the activity of the antibiotic boromycin against Toxoplasma and Cryptosporidium Boromycin potently inhibi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01278-20
更新日期:2021-01-19 00:00:00
abstract::The in vitro activity of a new oral antimicrobial agent, norfloxacin (MK-0366), was compared with those of nalidixic acid, nitrofurantoin, co-trimoxazole, trimethoprim, sulfamethoxazole, cinoxacin, tetracycline, ampicillin, carbenicillin, and cephalexin against 628 urinary bacterial isolates. Norfloxacin was the most ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.5.848
更新日期:1982-05-01 00:00:00
abstract::Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5'-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatm...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06050-12
更新日期:2012-07-01 00:00:00
abstract::Emtricitabine [(-)FTC] [(-)-beta-2', 3'-dideoxy-5-fluoro-3'-thiacytidine] has been shown to be an effective inhibitor of hepatitis B virus (HBV) in cell culture, with a potency and selectivity that are essentially identical to those of lamivudine. The antiviral activity of oral administration of (-)FTC against WHV rep...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1757-1760.2000
更新日期:2000-06-01 00:00:00
abstract::The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and uri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.43.12.2848
更新日期:1999-12-01 00:00:00
abstract::In enterobacteria, the ampG gene encodes a transmembrane protein (permease) that transports 1,6-GlcNAc-anhydro-MurNAc and the 1,6-GlcNAc-anhydro-MurNAc peptide from the periplasm to the cytoplasm, which serve as signal molecules for the induction of ampC β-lactamase. The role of AmpG as a transporter is also essential...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00009-10
更新日期:2010-11-01 00:00:00
abstract::Rifampin was shown in vitro to decrease the amphotericin B minimal inhibitory concentrations of all of 10 strains of Coccidioides immitis tested. These decreases ranged from two- to fourfold and occurred with rifampin concentrations of 10 to 40 mug/ml. Rifampin alone was without effect. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.6.783
更新日期:1974-12-01 00:00:00
abstract::Invasive aspergillosis (IA) is a severe condition mainly caused by Aspergillus fumigatus, although other species of the genus, such as section Nigri members, can also be involved. Voriconazole (VRC) is the recommended treatment for IA; however, the prevalence of azole-resistant Aspergillus isolates has alarmingly incr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00543-19
更新日期:2019-06-24 00:00:00
abstract::The P450 enzyme, CYP3A4, extensively metabolizes both amprenavir and clarithromycin. To determine if an interaction exists when these two drugs are coadministered, the pharmacokinetics of amprenavir and clarithromycin were investigated in healthy adult male volunteers. This was a Phase I, open-label, randomized, balan...
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.44.4.978-984.2000
更新日期:2000-04-01 00:00:00
abstract::Cyclic phosphate derivative of DHPG, 2'-nor-cGMP [9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]-guani ne phosphate-oxide] was evaluated for activity against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo cells and in guinea pigs. By virus yield reduction and plaque reduction assays,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1563
更新日期:1989-09-01 00:00:00
abstract::Chromosomally mediated penicillin resistance in Neisseria gonorrhoeae occurs in part through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. However, the genetic and molecular mechanisms of transformation of a penicillin-susceptible strain of N. gonorrhoeae to high-leve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.3.769-777.2002
更新日期:2002-03-01 00:00:00
abstract::The Capnocytophaga sputigena isolate NOR, responsible for septicemia, was resistant to amoxicillin and narrow-spectrum cephalosporins. In a cloning experiment, a new gene, bla(CSP-1), was identified; this gene encodes a novel extended-spectrum beta-lactamase (ESBL) that shares only 52% and 49% identities with the CME-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00791-09
更新日期:2010-05-01 00:00:00
abstract::The postantibiotic effect (PAE) (10 times the MIC of quinolones, 5 times the MIC of macrolides) and postantibiotic sub-MIC effect (PAE-SME) at 0.125, 0.25, and 0.5 times the MIC were determined for levofloxacin, ciprofloxacin, ofloxacin, erythromycin, azithromycin, and clarithromycin against 20 pneumococci. Quinolone ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.5.1253
更新日期:1998-05-01 00:00:00
abstract::We used multiplex PCR to determine the agr group membership of 18 European glycopeptide heterointermediate and intermediate-resistant Staphylococcus aureus strains. Of the 15 agr group I strains, 13 were resistant and 2 were susceptible to methicillin. The remaining three strains, like the United States and Japanese c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.3.1024-1027.2004
更新日期:2004-03-01 00:00:00
abstract::Mycobacterium tuberculosis and the fast-growing species Mycobacterium abscessus are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant M. tuberculosis strains and the high level of intrinsic resistance of M....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01696-17
更新日期:2018-04-26 00:00:00
abstract::The in vitro activity of tebipenem (TBM), a new oral carbapenem antibiotic, against Streptococcus pneumoniae clinical isolates (n = 202) was compared with those of 15 reference agents. The isolates were classified into five genotypic classes after PCR identification of abnormal pbp1a, pbp2x, and pbp2b genes: (i) penic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.889-894.2005
更新日期:2005-03-01 00:00:00