Abstract:
:Invasive pulmonary aspergillosis (IPA) is a devastating disease of immunocompromised patients. Pharmacodynamic (PD) examination of antifungal drug therapy in IPA is one strategy that may improve outcomes. The current study explored the PD target of posaconazole in an immunocompromised murine model of IPA against 10 A. fumigatus isolates, including 4 Cyp51 wild-type isolates and 6 isolates carrying Cyp51 mutations conferring azole resistance. The posaconazole MIC range was 0.25 to 8 mg/liter. Following infection, mice were given 0.156 to 160 mg/kg of body weight of oral posaconazole daily for 7 days. Efficacy was assessed by quantitative PCR (qPCR) of lung homogenate and survival. At the start of therapy, mice had 5.59 ± 0.19 log(10) Aspergillus conidial equivalents (CE)/ml of lung homogenate, which increased to 7.11 ± 0.29 log(10) CE/ml of lung homogenate in untreated animals. The infection was uniformly lethal prior to the study endpoint in control mice. A Hill-type dose response function was used to model the relationship between posaconazole free drug area under the concentration-time curve (AUC)/MIC and qPCR lung burden. The static dose range was 1.09 to 51.9 mg/kg/24 h. The free drug AUC/MIC PD target was 1.09 ± 0.63 for the group of strains. The 1-log kill free drug AUC/MIC was 2.07 ± 1.02. The PD target was not significantly different for the wild-type and mutant organism groups. Mortality mirrored qPCR results, with the greatest improvement in survival noted at the same dosing regimens that produced static or cidal activity. Consideration of human pharmacokinetic data and the current static dose PD target would predict a clinical MIC threshold of 0.25 to 0.5 mg/liter.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Lepak AJ,Marchillo K,Vanhecker J,Andes DRdoi
10.1128/AAC.01279-12subject
Has Abstractpub_date
2013-01-01 00:00:00pages
579-85issue
1eissn
0066-4804issn
1098-6596pii
AAC.01279-12journal_volume
57pub_type
杂志文章abstract::The post-β-lactamase-inhibitor effect (PBLIE) of tazobactam combined with ceftolozane was evaluated by time-kill assays on two clinical Escherichia coli strains producing CTX-M-15 with or without TEM-1. The organisms were exposed (2 h) to 4 μg/ml/4 μg/ml of ceftolozane-tazobactam (4× MIC), 4 μg/ml of ceftolozane, and ...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::We have developed a new recombinant retroviral system in which a library of infectious molecular clones of human immunodeficiency virus type 1 (HIV-1) is constructed with reverse transcriptase (RT) genes derived from viral RNA sequences in plasma. HIV-1 RT is amplified from plasma HIV-1 RNA by nested RT-PCR and cloned...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.41.12.2781
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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
pub_type: 杂志文章
doi:10.1128/AAC.45.1.166-169.2001
更新日期:2001-01-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.5.1456-1462.2001
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.6.965
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1980-02-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.4.519
更新日期:1980-10-01 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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更新日期:1995-11-01 00:00:00
abstract::An antibiotic-producing pseudomonad was isolated from a seawater sample from a La Jolla, Calif., tidepool. The pseudomonad produces two novel antibacterial compounds, 2-n-pentyl-4-quinolinol and 2-n-heptyl-4-quinolinol. It also synthesizes indole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and the known antibiot...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1988-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3610-3612.2004
更新日期:2004-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
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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
pub_type: 杂志文章
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更新日期:2003-10-01 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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更新日期:1989-05-01 00:00:00
abstract::The NS3/4A protease from hepatitis C virus (HCV) plays a key role in viral replication. We report a system for monitoring the activity of this enzyme in single living mammalian cells. We constructed a fluorescence resonance energy transfer (FRET) probe that consists of an enhanced cyan fluorescent protein-citrine fusi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2009-02-01 00:00:00