Abstract:
:Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kidney injury using sensitive urinary biomarkers. Male Sprague-Dawley rats received clinical-grade vancomycin or normal saline as an intraperitoneal injection. Total daily doses between 0 and 400 mg/kg of body weight were administered as a single dose or 2 divided doses over a 24-h period. At least five rats were utilized for each dosing protocol. A maximum of 8 plasma samples per rat were obtained, and urine was collected over the 24-h period. Kidney injury molecule-1 (KIM-1), clusterin, osteopontin, cystatin C, and neutrophil gelatinase-associated lipocalin levels were determined using Milliplex multianalyte profiling rat kidney panels. Vancomycin plasma concentrations were determined via a validated high-performance liquid chromatography methodology. Pharmacokinetic analyses were conducted using the Pmetrics package for R. Bayesian maximal a posteriori concentrations were generated and utilized to calculate the 24-h area under the concentration-time curve (AUC), the maximum concentration (Cmax), and the minimum concentration. Spearman's rank correlation coefficient (rs ) was used to assess the correlations between exposure parameters, biomarkers, and histopathological damage. Forty-seven rats contributed pharmacokinetic and toxicodynamic data. KIM-1 was the only urinary biomarker that correlated with both composite histopathological damage (rs = 0.348, P = 0.017) and proximal tubule damage (rs = 0.342, P = 0.019). The vancomycin AUC and Cmax were most predictive of increases in KIM-1 levels (rs = 0.438 and P = 0.002 for AUC and rs = 0.451 and P = 0.002 for Cmax). Novel urinary biomarkers demonstrate that kidney injury can occur within 24 h of vancomycin exposure as a function of either AUC or Cmax.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
O'Donnell JN,Rhodes NJ,Lodise TP,Prozialeck WC,Miglis CM,Joshi MD,Venkatesan N,Pais G,Cluff C,Lamar PC,Briyal S,Day JZ,Gulati A,Scheetz MHdoi
10.1128/AAC.00416-17subject
Has Abstractpub_date
2017-10-24 00:00:00issue
11eissn
0066-4804issn
1098-6596pii
AAC.00416-17journal_volume
61pub_type
杂志文章abstract::The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was sig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1219
更新日期:1996-05-01 00:00:00
abstract::In 24 patients with hepatitic C virus (HCV) infection who participated in a randomized trial with alpha 2B interferon, HCV RNA analysis by the polymerase chain reaction with two separate primer sets was performed at weeks 0, 4, and 24 and during a follow-up period of 6 to 9 months. Prior to therapy all patients were H...
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.37.3.595
更新日期:1993-03-01 00:00:00
abstract::Suramin is 100 years old and is still being used to treat the first stage of acute human sleeping sickness, caused by Trypanosoma bruceirhodesiense Suramin is a multifunctional molecule with a wide array of potential applications, from parasitic and viral diseases to cancer, snakebite, and autism. Suramin is also an e...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
doi:10.1128/AAC.01168-19
更新日期:2020-02-21 00:00:00
abstract::Five isoforms of protein mannosyltransferase (Pmt) O-mannosylate secretory proteins in Candida albicans. pmt mutants were differentially defective for biofilm formation on plastic in static and flow-through systems, and a Pmt inhibitor blocked early stages of biofilm formation. Conceptually, Pmt inhibition may prevent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00606-06
更新日期:2006-10-01 00:00:00
abstract::The in vivo activities of imipenem, meropenem, and cefepime were studied in a model of rat pneumonia caused by a plasmid-mediated AmpC beta-lactamase ACT-1-producing Klebsiella pneumoniae strain (K. pneumoniae strain 12) and a derivative porin-deficient mutant (K. pneumoniae strain 12dp). No differences between these ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01513-05
更新日期:2006-06-01 00:00:00
abstract::A major concern of immunocompromised patients, in particular those with AIDS, is susceptibility to infection caused by opportunistic pathogens such as Pneumocystis jirovecii, which is a leading cause of pneumonia in immunocompromised patients. We report the first kinetic and structural data for 2,4-diamino-6-[(2',5'-d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00172-13
更新日期:2013-06-01 00:00:00
abstract::Administering polymyxin antibiotics in a traditional fashion may be ineffective against Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens. Here, we explored increasing the dose intensity of poly...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02831-15
更新日期:2016-06-20 00:00:00
abstract::The ampD gene product regulates the expression of AmpC beta-lactamase in gram-negative bacteria and is proposed to be involved in peptidoglycan metabolism. In this study, we sequenced the ampD wild type and three mutant genes of Enterobacter cloacae and Citrobacter freundii. They exhibited a high degree of homology wi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.224
更新日期:1993-02-01 00:00:00
abstract::The in vitro activity of PD 127,391, a dihalogenated quinolone, was compared with those of ofloxacin, ciprofloxacin, nalidixic acid, gentamicin, and cefuroxime against 525 recent isolates and well-characterized antimicrobial agent-resistant strains. The MICs of PD 127,391 against 90% of members of the family Enterobac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.8.1251
更新日期:1988-08-01 00:00:00
abstract::The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, ur...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.4.438
更新日期:1984-04-01 00:00:00
abstract::Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.2.161
更新日期:1979-02-01 00:00:00
abstract::Occidiofungin is produced by the soil bacterium Burkolderia contaminans MS14 and is structurally similar or identical to the burkholdines, xylocandins, and cepacidines. This study identified the primary cellular target of occidiofungin, which was determined to be actin. The modification of occidiofungin with a functio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01585-18
更新日期:2018-12-21 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.1.140
更新日期:1979-01-01 00:00:00
abstract::Combination therapy using drugs with different mechanisms of action is the current state of the art in antimalarial treatment. However, except for artemisinin-based combination therapies, only a few other combinations are now available. Increasing concern regarding the emergence and spread of artemisinin resistance in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02307-19
更新日期:2020-10-20 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.1.82
更新日期:1974-01-01 00:00:00
abstract::Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,meta分析,评审
doi:10.1128/AAC.01257-13
更新日期:2013-11-01 00:00:00
abstract::More than 10(6) compounds were evaluated in a human immunodeficiency virus type 1 (HIV-1) high-throughput antiviral screen, resulting in the identification of a novel HIV-1 inhibitor (UK-201844). UK-201844 exhibited antiviral activity against HIV-1 NL4-3 in MT-2 and PM1 cells, with 50% effective concentrations of 1.3 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00643-07
更新日期:2007-10-01 00:00:00
abstract::The antibacterial drug nalidixic acid (Nal) can suppress the growth of Candida albicans at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temper...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.3.485
更新日期:1976-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.10.2376
更新日期:1999-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.8.2606-2612.2002
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.12.3901-3906.2003
更新日期:2003-12-01 00:00:00
abstract::Boronic acid transition state inhibitors (BATSIs) with R1 side chains of cefotaxime and ceftazidime were assayed against SHV-1, SHV-2, SHV-5, D104K, and D104K G238S beta-lactamases. The D104K variant was the most susceptible to inhibition by the ceftazidime BATSI (Ki, 730+/-80 nM), while the D104K G238S variant was th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01293-06
更新日期:2007-04-01 00:00:00
abstract::A survey carried out in 2005 among members of a healthy population of children living in Bolivia and Peru revealed that fecal carriage of Escherichia coli strains resistant to expanded-spectrum cephalosporins was remarkably increased compared to that observed in the same settings in 2002 (1.7% in 2005 versus 0.1% in 2...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00026-07
更新日期:2007-08-01 00:00:00
abstract::Dengue fever is a severe, widespread, and neglected disease with more than 2 million diagnosed infections per year. The dengue virus NS2B/NS3 protease (PR) represents a prime target for rational drug design. At the moment, there are no clinical PR inhibitors (PIs) available. We have identified diaryl (thio)ethers as c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03543-14
更新日期:2015-02-01 00:00:00
abstract::Group B beta-hemolytic streptococci (GB-BHS) frequently cause severe infection in newborns. Previous in vitro studies showed accelerated killing of GB-BHS by ampicillin plus gentamicin as compared with ampicillin alone. To extend the in vitro observations, mice were infected experimentally with GB-BHS and treated with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.5.817
更新日期:1977-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.8.1342
更新日期:1989-08-01 00:00:00
abstract::In a randomized crossover trial, six volunteers received 200- and 400-mg doses of loracarbef (LY 163892), a new oral cephalosporin. Mean +/- standard error of the mean concentrations in serum obtained after 1.5 and 3 h were 13.2 +/- 2.8 and 4.3 +/- 0.7 mg/liter, respectively, after the 400-mg dose and 6.9 +/- 1.0 and ...
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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更新日期:1992-03-01 00:00:00
abstract::Expression of eight transporter genes of Escherichia coli K-12 and its DeltaacrAB mutant prior to and after induction of both strains to tetracycline resistance and after reversal of induced resistance were analyzed by quantitative reverse transcriptase PCR. All transporter genes were overexpressed after induced resis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.8.3578-3582.2005
更新日期:2005-08-01 00:00:00
abstract::Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom ...
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.44.3.693-696.2000
更新日期:2000-03-01 00:00:00
abstract::The penetration of intravenously administered cefuroxime into ventricular fluid was assessed in five pediatric patients with ventriculoperitoneal shunt infections and in one with a ventriculostomy infection. Patients received a total dose of 200 to 230 mg of cefuroxime per kg of body weight per day administered at 8-h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.7.1108
更新日期:1989-07-01 00:00:00