Abstract:
:In vitro studies of zidovudine (ZDV) phosphorylation may not accurately reflect the in vivo dose-response relationship, which is crucial to determining the relationship between ZDV exposure, efficacy, and toxicity. However, measurement of ZDV phosphorylated anabolites in peripheral blood mononuclear cells (PBMCs) from ZDV-treated human immunodeficiency virus (HIV)-infected patients would be extremely useful in the more appropriate utilization of ZDV in the treatment of HIV infection. We developed a specific and sensitive combined high-pressure liquid chromatography (HPLC)-radioimmunoassay (RIA) procedure for the determination of ZDV, ZDV-monophosphate, ZDV-diphosphate, and ZDV-triphosphate in PBMCs taken from ZDV-treated HIV-infected patients. ZDV and its anabolites were extracted from washed, Ficoll-Paque-isolated PBMCs and then separated by HPLC using a strong anion-exchange column. The anabolites were then hydrolyzed to ZDV with acid phosphatase. ZDV was then measured by using a modified commercially available RIA protocol. Our method was validated by measuring [3H]ZDV anabolites generated in Molt-4 cells radioisotopically and simultaneously by the combined HPLC-RIA procedure. The ZDV determinations correlated well (r2 = 0.97) over the range of 0.037 to 5.2 pmol (10 to 1,400 pg) per assay tube. Furthermore, we defined the stability of ZDV anabolites during ficoll isolation and the recovery after extraction and cleanup. We then measured intracellular parent ZDV and its phosphorylated anabolites in PBMCs from six ZDV-treated HIV-infected patients (PBMCs were taken 2 h after a 300-mg oral dose). The mean concentrations ( +/- standard deviations) of parent and of mono-, di-, and triphosphates were 0.15 +/- 0.08, 1.4 +/-, 0.082 +/- 0.02, and 0.081 +/- 0.03 pmol/10(6) PBMC, respectively (one pmol/10(6) PBMC represents a concentration of approximately 1 microm). Concurrent serum ZDV concentrations were between 1.3 and 7.1 microm. This method should provide a useful tool for evaluating in vivo pharmacokinetics of ZDV anabolites in PBMCs and possibly other cell types, even at the low doses of ZDV currently administered therapeutically.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Slusher JT,Kuwahara SK,Hamzeh FM,Lewis LD,Kornhauser DM,Lietman PSdoi
10.1128/aac.36.11.2473subject
Has Abstractpub_date
1992-11-01 00:00:00pages
2473-7issue
11eissn
0066-4804issn
1098-6596journal_volume
36pub_type
杂志文章abstract::In this study, the genetic organization of three novel genomic antibiotic resistance islands (AbaRs) in Acinetobacter baumannii isolates belonging to group of European clone II (EC II) comM integrated sequences of 18-, 21-, and 23-kb resistance islands were determined. These resistance islands carry the backbone of Ab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05678-11
更新日期:2012-04-01 00:00:00
abstract::We investigated whether cells derived from the fetal central nervous system can support productive infection by a human immunodeficiency virus type 1 (HIV-1) isolate termed UHC-1, produced by a cellular clone derived from HIV-1 strain HIV-IIIB chronically infected U-937 promonocytic cells, and what the effect of nucle...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.6.1305
更新日期:1993-06-01 00:00:00
abstract::Viral pathogens causing global disease burdens are often characterized by high rates of evolutionary changes. The extensive viral diversity at baseline can shorten the time to escape from therapeutic or immune selective pressure and alter mutational pathways. The impact of genotypic background on the barrier to resist...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00539-19
更新日期:2019-07-25 00:00:00
abstract::We investigated the contribution of multidrug resistance-associated protein 2 (MRP2) to the secretory transport of grepafloxacin and compared its functional role with that of P-glycoprotein (P-gp) by using Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic rats (EHBRs), in which MRP2 is hereditarily defective. In...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.2.344-349.2002
更新日期:2002-02-01 00:00:00
abstract::The in vitro activity of TR-700 (torezolid) was evaluated against a collection of 660 staphylococcal blood isolates. TR-700 showed excellent activity against all the staphylococci tested. The MIC(50) and MIC(90) values of TR-700, linezolid, daptomycin, and vancomycin against methicillin-resistant Staphylococcus aureus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01653-09
更新日期:2010-05-01 00:00:00
abstract::We compared a rigid (1-h) screening method for the detection of chloramphenicol acetyltransferase (CAT) activity with the standard spectrophotometric CAT assay to determine whether CAT-mediated chloramphenicol resistance in Haemophilus influenzae could be determined upon primary isolation. Of 58 H. influenzae cell son...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.2.168
更新日期:1981-08-01 00:00:00
abstract::Passive antibody administration is a potentially useful approach for the therapy of human Cryptococcus neoformans infections. To evaluate the efficacy of the human immunoglobulin G1 (IgG1) constant region against C. neoformans and to construct murine antibody derivatives with reduced immunogenicities and longer half-l...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1507
更新日期:1994-07-01 00:00:00
abstract::(S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP], cyclic (S)-HPMPA [(S)-cHPMPA], 9-(2-phosphonylmethoxyethoxyethyl)-2,6-diaminopurine (PMEDAP), and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were examined fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.11.2440
更新日期:1991-11-01 00:00:00
abstract::Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for beta-lactamase production. Ten children (50%) harbored, altogether, 25 beta-lactamase-positive F. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.5.1270
更新日期:1999-05-01 00:00:00
abstract::Candida albicans and Staphylococcus aureus form vigorous polymicrobial biofilms in serum, which may serve as the source of coinfection in patients. More importantly, S. aureus is highly resistant to vancomycin during polymicrobial biofilm formation, with no decreases in bacterial viability observed with up to 1,600 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00573-10
更新日期:2010-09-01 00:00:00
abstract::Using 98 clinical methicillin-susceptible Staphylococcus aureus isolates of known beta-lactamase (Bla) type, we found a pronounced inoculum effect for cephalexin (mostly Bla type A and C strains), a mild inoculum effect for cephalothin (especially types B and C), and no inoculum effects for ceftriaxone and cefuroxime....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01325-09
更新日期:2010-05-01 00:00:00
abstract::Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.8.1683
更新日期:1995-08-01 00:00:00
abstract::Since beta-lactam antibiotics have concentration-independent killing, bacterial eradication is a function of the time the serum drug concentration remains above the drug's MIC (T > MIC). We compared the serum bactericidal titers (SBTs) of ceftazidime given by continuous infusion (CI) or by intermittent bolus dosing (B...
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.40.1.61
更新日期:1996-01-01 00:00:00
abstract::In vitro activity of tebipenem, a new oral carbapenem antibiotic, against clinical Haemophilus influenzae isolates was compared with those of 8 reference agents. Isolates were classified into 6 resistance classes after PCR identification of beta-lactamase genes and ftsI gene mutations. For all isolates, the minimal co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00054-10
更新日期:2010-09-01 00:00:00
abstract::Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02109-15
更新日期:2016-03-25 00:00:00
abstract::The present study demonstrates the in vitro effectiveness of the macrolide rokitamycin and the phenothiazine compound chlorpromazine against Acanthamoeba castellanii. Growth curve evaluations revealed that both drugs inhibit trophozoite growth in dose- and time-dependent ways. The effects of both drugs when they were ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.12.4520-4527.2004
更新日期:2004-12-01 00:00:00
abstract::We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00608-09
更新日期:2009-11-01 00:00:00
abstract::Susceptibility testing of laboratory strains and clinical isolates of Borrelia burgdorferi indicates that resistance to erythromycin is present in them. Evaluation of the MICs, minimal bactericidal concentrations, and kinetics of bacterial killing of erythromycin suggests that this resistance is increased by preexposu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3637-3640.2002
更新日期:2002-11-01 00:00:00
abstract::Kinetic data on potassium release from and killing of Candida albicans by the four polyene antibiotics amphotericin B, amphotericin B methyl ester hydrochloride, nystatin, and nystatin methyl ester hydrochloride are presented. The nystatins were relatively more effective than the amphotericins in causing potassium rel...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.6.914
更新日期:1978-06-01 00:00:00
abstract::Streptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which can be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococcus-specific lysin ClyJ comprising the binding doma...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00311-20
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abstract::The incidence of measles virus (MV) infection has been significantly reduced in many nations through extensive vaccination; however, the virus still causes significant morbidity and mortality in developing countries. Measles outbreaks also occur in some developed countries that have failed to maintain high vaccine cov...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3755-3761.2005
更新日期:2005-09-01 00:00:00
abstract::We evaluated the efficacy, safety, and tolerance of cefotaxime in 35 adults (25 with pleuropulmonary infections, 7 with genitourinary tract infections, and 3 with soft tissue infections). Of these 35 patients, 18 (51.4%) were seriously or critically ill. In vitro susceptibility testing revealed that 90.4% of the patho...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.421
更新日期:1982-03-01 00:00:00
abstract::The efficacy of clarithromycin in a murine model of acute toxoplasmosis was studied. Clarithromycin was administered alone and concurrently with minocycline, and efficacy was assessed by survival rates and sequential determination of parasite burden in blood, brains, and lungs. Limited protection resulted from adminis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2852
更新日期:1992-12-01 00:00:00
abstract::Moxifloxacin has enhanced potency against Staphylococcus aureus, lower propensity to select for resistant mutants, and higher bactericidal activity against highly resistant strains than ciprofloxacin. Despite similar activity against purified S. aureus topoisomerase IV and DNA gyrase, it selects for topoisomerase IV m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.4.1410-1415.2003
更新日期:2003-04-01 00:00:00
abstract::The nonnucleoside reverse transcriptase inhibitor UC781 is under development as a potential microbicide to prevent sexual transmission of human immunodeficiency virus type 1 (HIV-1). Two gel formulations of UC781 (0.1% and 1.0%) were evaluated in a range of preclinical safety assessments, including systemic absorption...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00984-06
更新日期:2007-05-01 00:00:00
abstract::Several classes of antibiotics exert antimalarial activity. The mechanisms of action of antibiotics against malaria parasites have been unclear, and prior studies have led to conflicting results, in part because they studied antibiotics at suprapharmacological concentrations. We examined the antimalarial effects of az...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00527-07
更新日期:2007-10-01 00:00:00
abstract::Various fluoroquinolones (norfloxacin, enoxacin, ofloxacin, levofloxacin, and sparfloxacin) induce DnaK and GroEL heat shock proteins in Escherichia coli. The induction is transient, consistent with the kinetics of cellular DNA relaxation. The concentrations of fluoroquinolones required for induction are similar to th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.1.193
更新日期:1997-01-01 00:00:00
abstract::In a previous work, we described the possible relationship between a defect of purine-cytosine permease and the acquisition of a cross-resistance to the antifungal combination flucytosine (5FC) and fluconazole (FLC) in Candida lusitaniae (T. Noël, F. François, P. Paumard, C. Chastin, D. Brethes, and J. Villard, Antimi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.8.3101-3108.2005
更新日期:2005-08-01 00:00:00
abstract::Staphylococcus aureus is a major human pathogen in catheter-related infections. Modifying catheter material with interpenetrating polymer networks is a novel material technology that allows for impregnation with drugs and subsequent controlled release. Here, we evaluated the potential for combining this system with pl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00604-17
更新日期:2017-06-27 00:00:00
abstract::Bacterial susceptibility to a new organic acid related to nalidixic acid and oxolinic acid was tested. The in vitro susceptibility pattern of the new compound was found to be very similar to that of nalidixic acid. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.3.533
更新日期:1978-03-01 00:00:00