Abstract:
:Echinocandins are a preferred therapy for invasive candidiasis due to their potency and broad spectrum. Resistance, especially in Candida glabrata, is an emerging threat to their use. Pharmacodynamic (PD) studies examining reduced susceptibility secondary to fks mutations in C. glabrata are lacking. The current study explored PD targets for anidulafungin, caspofungin, and micafungin in an in vivo invasive candidiasis model against 11 C. glabrata isolates with known or putative fks mutations. The PD targets were compared to those of 8 wild-type (WT) isolates. The MIC ranges in the WT group were 0.03 to 0.25 mg/liter for anidulafungin, 0.03 to 0.25 mg/liter for caspofungin, and 0.01 to 0.06 mg/liter for micafungin. The MIC ranges for mutants were 0.06 to 4, 0.25 to 16, and 0.13 to 8 mg/liter for the same compounds, respectively. The mean free drug 24-h area under the concentration-time curve (AUCf)/MIC ratio associated with a stasis endpoint for the WT group was 13.2 for anidulafungin, 2.04 for caspofungin, and 6.78 for micafungin. Comparative values for mutants were 3.43, 2.67, and 0.90, respectively. Pharmacokinetic data from patients suggest that the C. glabrata PD targets needed for success in this model could be achieved based on MIC values of 0.25 mg/liter for anidulafungin, 2 mg/liter for caspofungin, and 0.5 mg/liter for micafungin. These values are higher than recently identified epidemiology cutoff values (ECVs). The results suggest that drug-specific MIC breakpoints could be increased for caspofungin and micafungin against C. glabrata and could include organisms with mutations in fks-1 and fks-2. While identification of genetic mutants is epidemiologically important, the phenotype (MIC) provides a better predictor of therapeutic efficacy.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Lepak A,Castanheira M,Diekema D,Pfaller M,Andes Ddoi
10.1128/AAC.01102-12subject
Has Abstractpub_date
2012-11-01 00:00:00pages
5875-82issue
11eissn
0066-4804issn
1098-6596pii
AAC.01102-12journal_volume
56pub_type
杂志文章abstract::We collected 1,353 strains of beta-hemolytic streptococci of groups A, B, C, and G (1,176 strains of which were group A) isolated in 26 institutions throughout Japan in 1972-1974. The strains were grouped and T-typed by our specific group-and T-factor sera, and the minimal inhibitory concentrations of 10 antibiotics w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.3.399
更新日期:1978-03-01 00:00:00
abstract::There are no data comparing outcomes of patients treated with ceftazidime-avibactam versus comparators for carbapenem-resistant Enterobacteriaceae infections. At our center, ceftazidime-avibactam treatment of carbapenem-resistant Klebsiella pneumoniae bacteremia was associated with higher rates of clinical success (P ...
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pub_type: 杂志文章
doi:10.1128/AAC.00883-17
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.2.253
更新日期:1987-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.23.6.831
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doi:10.1128/AAC.02532-17
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abstract::The pharmacokinetics and protein binding of ceforanide were studied in 15 patients undergoing cholecystectomies. Each patient received ceforanide (20 mg/kg) intravenously on arrival in the operating room, after which serial blood samples were collected during the elimination phase for determination of total and free c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.4.487
更新日期:1985-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.6.861
更新日期:1975-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00596-15
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.3.656
更新日期:1992-03-01 00:00:00
abstract::To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01236-13
更新日期:2013-11-01 00:00:00
abstract::Carbapenem-resistant Acinetobacter baumannii is a major source of nosocomial infections worldwide and is mainly associated with the acquisition of OXA-type carbapenemases and, to a lesser extent, metallo-β-lactamases (MBLs). In this study, 82 nonepidemiologically related Acinetobacter strains carrying different types ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03870-14
更新日期:2014-12-01 00:00:00
abstract::Enzyme-mediated immunoassay (EMIT) serum aminoglycoside assay results were accurate and precise and correlated well with radioimmunoassay, fluoroimmunoassay, and acetyltransferase and microbiological assay determinations. ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.19.6.1064
更新日期:1981-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00755-19
更新日期:2019-08-23 00:00:00
abstract::Atazanavir (Reyataz; ATV) is a well-tolerated protease inhibitor (PI) that is indicated as a once-daily treatment for HIV infections. These features of ATV, combined with its virologic potency, make it particularly desirable for the treatment of HIV-infected pediatric patients. The objective of this study was to use a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00554-11
更新日期:2011-12-01 00:00:00
abstract::The resistance-nodulation-division (RND)-type efflux pump is one of the causes of the multidrug resistance of Stenotrophomonas maltophilia. The roles of the RND-type efflux pump in physiological functions and virulence, in addition to antibiotic extrusion, have attracted much attention. In this study, the contribution...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00372-15
更新日期:2015-07-01 00:00:00
abstract::The in vitro activities of magainin analogs against Blastocystis hominis, Entamoeba histolytica, and Trypanosoma cruzi were assessed by protozoan morphological integrity and motility. The antiprotozoan activities in descending order were magainin B greater than G greater than H, the same order as the alpha-helix conte...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.34.9.1824
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2011-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1974-12-01 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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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2018-02-23 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2018-06-26 00:00:00