Abstract:
:Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside for the treatment of chronic hepatitis B virus (HBV) infection that exhibits potent activity against viral reverse transcriptase. We assessed the potential for mitochondrial toxicity of ETV in long-term cultures of HepG2 hepatoma cells by measuring mitochondrial function (through lactate secretion), levels of mitochondrial DNA (mtDNA), and levels of mitochondrial proteins COX II and COX IV. Furthermore, we tested the activity of ETV-triphosphate (ETV-TP) against mitochondrial DNA polymerase gamma (Pol gamma) in vitro. ETV concentrations as high as 100 times the maximal clinical exposure (C(max)) did not affect cell proliferation, levels of lactate, mitochondrial DNA, or mitochondrial proteins throughout the 15-day culture. The lack of mitochondrial toxicity was consistent with the finding that ETV-TP was not recognized by mitochondrial DNA Pol gamma and failed to be incorporated into DNA or inhibit the polymerase assay at the highest levels tested, 300 microM. Combinations of ETV with each of the other HBV NRTI antivirals, adefovir, tenofovir, and lamivudine at 10 times their respective C(max) levels also failed to result in cellular or mitochondrial toxicity. In summary, cell culture and enzymatic studies yielded no evidence that would predict mitochondrial toxicity of ETV at exposure levels in excess of those expected to be achieved clinically.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Mazzucco CE,Hamatake RK,Colonno RJ,Tenney DJdoi
10.1128/AAC.01122-07subject
Has Abstractpub_date
2008-02-01 00:00:00pages
598-605issue
2eissn
0066-4804issn
1098-6596pii
AAC.01122-07journal_volume
52pub_type
杂志文章abstract::Botulism is caused by botulinum neurotoxin (BoNT), the most poisonous substance known. BoNTs are also classified as Tier 1 biothreat agents due to their high potency and lethality. The existence of seven BoNT serotypes (A-G), which differ between 35% to 68% in amino acid sequence, necessitates the development of serot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01270-19
更新日期:2019-10-07 00:00:00
abstract::The simian immunodeficiency virus (SIV)-newborn rhesus macaque model of AIDS can be used to study directly the virulence of viral mutants which are resistant to antiviral drugs. A viral mutant called SIVmac79A6.1, isolated from an SIV-infected macaque after prolonged zidovudine treatment, was found to have a double-ba...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.2.278
更新日期:1997-02-01 00:00:00
abstract::Avibactam is a new non-β-lactam β-lactamase inhibitor that shows promising restoration of ceftazidime activity against microorganisms producing Ambler class A extended-spectrum β-lactamases (ESBLs) and carbapenemases such as KPCs, class C β-lactamases (AmpC), and some class D enzymes. To determine optimal dosing combi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01269-15
更新日期:2015-11-02 00:00:00
abstract::The treatment of choice for Stenotrophomonas maltophilia is trimethoprim-sulfamethoxazole (SXT). Fluoroquinolones (FQs) have in vitro activity against S. maltophilia; however, there is limited published information on their effectiveness. The purpose of this study is to compare the effectiveness of FQs and SXT for the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01324-13
更新日期:2014-01-01 00:00:00
abstract::A study was performed to determine the effect of parenteral treatment with four broad-spectrum cephalosporins (cefoperazone, ceftriaxone, ceftazidime, and cefepime) on the number of aerobic gram-negative rods and on the outgrowth of Candida albicans and a multiresistant strain of Citrobacter freundii in the feces of m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.5.976
更新日期:1991-05-01 00:00:00
abstract::The in vitro activities of 25 quinolones and fluoroquinolones against erythrocytic stages of Plasmodium falciparum and against liver stages of Plasmodium yoelii yoelii and P. falciparum were studied. All compounds were inhibitory for chloroquine-sensitive and chloroquine-resistant P. falciparum grown in red blood cell...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.8.2636-2639.2003
更新日期:2003-08-01 00:00:00
abstract::Endoplasmic reticulum (ER)-resident glucosidases I and II sequentially trim the three terminal glucose moieties on the N-linked glycans attached to nascent glycoproteins. These reactions are the first steps of N-linked glycan processing and are essential for proper folding and function of many glycoproteins. Because m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03999-14
更新日期:2015-01-01 00:00:00
abstract::Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefix...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05760-11
更新日期:2012-03-01 00:00:00
abstract::Pathogenic bacterial biofilms, such as those found in the lungs of patients with cystic fibrosis (CF), exhibit increased antimicrobial resistance, due in part to the inherent architecture of the biofilm community. The protection provided by the biofilm limits antimicrobial dispersion and penetration and reduces the ef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03170-14
更新日期:2014-10-01 00:00:00
abstract::The comparative in vitro activity of SMT19969, a novel, narrow-spectrum, nonabsorbable agent, was studied against 50 ribotype-defined Clostridium difficile strains, 174 Gram-positive and 136 Gram-negative intestinal anaerobes, and 40 Gram-positive aerobes. SMT19969 was one dilution more active against C. difficile iso...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01136-13
更新日期:2013-10-01 00:00:00
abstract::The effect of four macrolides against intracellular Toxoplasma gondii was determined in three different in vitro systems. Unactivated murine peritoneal macrophages were infected with the virulent RH strain of T. gondii. The activity of the macrolides was first measured with [3H]uracil, which is incorporated by the par...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.4.524
更新日期:1988-04-01 00:00:00
abstract::The stage-dependent susceptibility of Plasmodium falciparum to a short exposure to docetaxel (Taxotere) was evaluated by subjecting ring-infected, trophozoite-infected, and schizont-infected erythrocytes to a 5-h exposure to various concentrations of the drug. The schizont stage was shown to be the most sensitive stag...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.2.358
更新日期:1996-02-01 00:00:00
abstract::Cell-free amino acid incorporation using ribosomes from strains of either Clostridium perfringens or Bacteroides fragilis was shown to be susceptible to inhibition by streptomycin and gentamicin. Ribosomes bound dihydrostreptomycin as effectively as ribosomes from Escherichia coli. No inactivation of streptomycin or g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.1.7
更新日期:1979-01-01 00:00:00
abstract::We report on the cloning of the gene smeT, which encodes the transcriptional regulator of the Stenotrophomonas maltophilia efflux pump SmeDEF. SmeT belongs to the TetR and AcrR family of transcriptional regulators. The smeT gene is located upstream from the structural operon of the pump genes smeDEF and is divergently...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3386-3393.2002
更新日期:2002-11-01 00:00:00
abstract::An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells we...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1116
更新日期:1996-05-01 00:00:00
abstract::The pharmacokinetics of cefepime were studied in 12 adult patients in intensive care units during continuous venovenous hemofiltration (CVVH) or continuous venovenous hemodiafiltration (CVVHDF) with a Multiflow60 AN69HF 0.60-m(2) polyacrylonitrile hollow-fiber membrane (Hospal Industrie, Meyzieu, France). Patients (me...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.45.11.3148-3155.2001
更新日期:2001-11-01 00:00:00
abstract::Previous studies on tetracycline transport into Staphylococcus aureus identified a high-affinity, saturable uptake system for the antibiotic (Km, 4.76 microM) (B.L. Hutchings, Biochim. Biophys. Acta 174:734-738, 1969). However, the earlier results could not be confirmed using conditions that permitted energy-dependent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.12.2643
更新日期:1991-12-01 00:00:00
abstract::The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecologi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01214-08
更新日期:2009-05-01 00:00:00
abstract::A total of 201 Staphylococcus aureus isolates were surveyed for susceptibility to ciprofloxacin and trovafloxacin. Of 66 methicillin-resistant isolates, 89% were ciprofloxacin resistant and 6% were also trovafloxacin resistant. Trovafloxacin-resistant strains had unusual patterns of quinoline resistance mutations in D...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.8.2122
更新日期:1998-08-01 00:00:00
abstract::Hepatitis C virus (HCV) genotype (GT) 2 represents approximately 9% of all viral infections globally. While treatment outcomes for GT2-infected patients have improved substantially with direct-acting antiviral agents (DAAs) compared to interferon-α, the presence of polymorphisms in NS5A can impact efficacy of NS5A inh...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01269-19
更新日期:2019-09-16 00:00:00
abstract::Eravacycline is a fluorocycline antibiotic in phase 3 clinical development for complicated intra-abdominal and urinary tract infections. To support its clinical development, a study was conducted to evaluate the effects of various susceptibility test parameters on the MIC values for aerobic bacteria. The results showe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04727-14
更新日期:2015-04-01 00:00:00
abstract::In most experiments when aminoglycoside antibiotic (AG) tissue levels are measured, the AG is extracted into buffered media. The data from this study reveal that buffer extraction results in only partial recovery of AG from tissues and that total recovery can be obtained after NaOH or trichloroacetic acid treatment. T...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.4.448
更新日期:1989-04-01 00:00:00
abstract::Five patients with chronic hepatitis B were treated with 8-day courses of leukocyte (alpha) interferon (5 X 10(6) U/day) and with 8-day courses of recombinant fibroblast (betaser) interferon at dosages of 5 X 10(6), 35 X 10(6), and 105 X 10(6) U/day. Inhibition of hepatitis B virus replication as evidenced by a decrea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.29.1.122
更新日期:1986-01-01 00:00:00
abstract::Peroxide antimalarials, including artemisinin, are important for the treatment of multidrug-resistant malaria. These peroxides are known to react with iron or heme to produce reactive intermediates that are thought to be responsible for their antimalarial activities. This study investigated the potential interaction o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00363-09
更新日期:2009-08-01 00:00:00
abstract::We investigated the minimum exposure times of prazicuantel (PZQ) and albendazole sulfoxide (ABZSO) required for their activities against Taenia cysts in vitro as well as the 50 and 99% effective concentrations. The results showed that although the effects of both drugs are time and concentration dependent, ABZSO acts ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.6.2302-2304.2004
更新日期:2004-06-01 00:00:00
abstract::Cinodine, a broad-spectrum glycocinnamoylspermidine antibiotic, binds to DNA and irreversibly inhibits bacterial and phase DNA synthesis. Cinodine was found to inhibit the activity of Micrococcus luteus DNA gyrase in vitro, but it did not inhibit the activities of two other DNA-binding enzymes, namely, topoisomerase I...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1450
更新日期:1990-07-01 00:00:00
abstract::The direct or indirect interactions that antifungals have with the host immune response may play a significant role in defining their activity in vivo. However, the impact that acquired antifungal resistance has on the immunopharmacologic activity of antifungals is not well described. We assessed the immunopharmacolog...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00624-15
更新日期:2015-09-01 00:00:00
abstract::The small-colony-variant (SCV) phenotype of Staphylococcus aureus has been associated with difficult-to-treat infections, reduced antimicrobial susceptibility, and intracellular persistence. This study represents a detailed intra- and extracellular investigation of a clinical wild-type (WT) S. aureus strain and its co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00205-10
更新日期:2011-04-01 00:00:00
abstract::beta-Lactamases produced by urine isolates from patients in long-term care facilities (LTCFs), outpatient, clinics, and one hospital in a U.S. community were characterized. A total of 1.3% of all Escherichia coli and Klebsiella pneumoniae isolates collected from patients in 30 LTCFs and various outpatient clinics prod...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00877-08
更新日期:2008-10-01 00:00:00
abstract::Although often dismissed as contaminants when isolated from blood cultures, Bacillus spp. are increasingly recognized as capable of causing serious systemic infections. As part of a clinical-microbiological study, 89 strains of Bacillus spp. isolated from clinical blood cultures between 1981 and 1985 had their species...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.5.642
更新日期:1988-05-01 00:00:00