Abstract:
:Despite dose-limiting nephrotoxicity concerns, polymyxin B has resurged as the treatment of last resort for multidrug-resistant Gram-negative bacterial infections. However, the pharmacokinetic, pharmacodynamic, and nephrotoxic properties of polymyxin B still are not thoroughly understood. The objective of this study was to provide additional insights into the overall biodistribution and disposition of polymyxin B in an animal model. Sprague-Dawley rats were dosed with intravenous polymyxin B (3 mg/kg of body weight). Drug concentrations in the serum, urine, bile, and tissue (brain, heart, lungs, liver, spleen, kidneys, and skeletal muscle) samples over time were assayed by a validated methodology. Among all the organs evaluated, polymyxin B distribution was highest in the kidneys. The mean renal tissue/serum polymyxin B concentration ratios were 7.45 (95% confidence interval [CI], 4.63 to 10.27) at 3 h and 19.62 (95% CI, 5.02 to 34.22) at 6 h postdose. Intrarenal drug distribution was examined by immunostaining. Using a ratiometric analysis, proximal tubular cells showed the highest accumulation of polymyxin B (Mander's overlap coefficient, 0.998) among all cell types evaluated. Less than 5% of the administered dose was recovered in urine over 48 h, but all 4 major polymyxin B components were detected in the bile over 4 h. These findings corroborate previous results that polymyxin B is highly accumulated in the kidneys, but the elimination likely is via a nonrenal route. Biliary excretion could be one of the routes of polymyxin B elimination, and this should be further explored. The elucidation of mechanism(s) of drug uptake in proximal tubular cells is ongoing.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Manchandani P,Zhou J,Ledesma KR,Truong LD,Chow DS,Eriksen JL,Tam VHdoi
10.1128/AAC.02445-15subject
Has Abstractpub_date
2015-12-07 00:00:00pages
1029-34issue
2eissn
0066-4804issn
1098-6596pii
AAC.02445-15journal_volume
60pub_type
杂志文章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
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00814-06
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abstract::The incidence of triazole-resistant Aspergillus infections is increasing worldwide, often mediated through mutations in the CYP51A amino acid sequence. New classes of azole-based drugs are required to combat the increasing resistance to existing triazole therapeutics. In this study, a CYP51 reconstitution assay is des...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01806-15
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doi:10.1128/aac.36.5.962
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00373-06
更新日期:2006-10-01 00:00:00
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doi:10.1128/AAC.01325-16
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.1.6.460
更新日期:1972-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.4.383
更新日期:1973-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3676-3678.2002
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.06126-11
更新日期:2012-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.5.1186-1194.2000
更新日期:2000-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02214-15
更新日期:2016-03-25 00:00:00
abstract::The effects of trimethoprim, sulfadiazine, sulfamethoxazole, and sulfathiazole on the hemagglutination and adhesion by three Escherichia coli strains were studied. The strains were isolated from the urine of patients with acute pyelonephritis and carried P antigen-recognizing fimbriae (P fimbriae). At antimicrobial co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1982-07-01 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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doi:10.1128/AAC.01952-12
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.6.1239
更新日期:1994-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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更新日期:2001-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2020-12-16 00:00:00
abstract::Because of the widespread occurrence of resistance to sulfonamides among Enterobacteriaceae, some researchers have suggested using trimethoprim (TMP) alone instead of the combination sulfamethoxazole-trimethoprim (SMX-TMP) in treating infections with TMP-susceptible organisms. To answer whether SMX-TMP suppresses the ...
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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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1276-1281.2006
更新日期:2006-04-01 00:00:00
abstract::The use of gentamicin to control contamination in a tissue culture system for the isolation of Chlamydia was investigated. Gentamicin, at concentrations up to 100 mug/ml, did not appear to inhibit the growth of stock chlamydial strains, as judged by assays for iodine-staining inclusions. When 343 cervical and urethral...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.6.698
更新日期:1973-06-01 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:1991-01-01 00:00:00